Involved margins after lumpectomy for breast cancer: Always to be re-excised?

Background: The oncologic benefit of upfront re-excision of involved margins after breast-conserving surgery in the context of current multimodal clinical management of breast cancer is unclear. The aim of the present study was to assess the 5-years locoregional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in patients not undergoing re-excision of positive margins after lumpectomy for breast cancer. Methods: A cohort of 104 patients with positive margins not undergoing re-excision was matched by propensity score with a cohort of 2006 control patients with clear margins after breast-conserving surgery, treated between 2008 and 2018. A multivariate survival analysis was performed accounting for all variables related to LRR and DM, including adjuvant treatments. Results: After adjusting for potential confounders, avoiding to re-excise a positive margin after lumpectomy had no effect on 5-years LRR-free survival probability (HR 0.98, 95%CI 0.36-2.67, p = 0.96) or 5-years DM-free survival probability (HR 0.37, 95%CI 0.08-1.61, p = 0.18). No correlation was found between occurrence of LRR and number of involved margins (HR 1.28, 95%CI 0.10-12.4, Log-rank p = 0.83), or extension of infiltrating disease (HR 1.21, 95%CI 0.20-7.40, Log-rank p = 0.83), but a trend toward higher LRR probability was found for invasive ductal (HR 6.92, 95%CI 0.7-68.8, Log-rank p = 0.10) and invasive lobular cancer (HR 12.95, 95%CI 0.79-213.6, Log-rank p = 0.07) on positive margins. Conclusions: In the era of multimodal treatment of breast cancer and accurate strategies to reduce the probability of residual disease in the post-lumpectomy cavity, re-excision of positive margins might be omitted in selected patients with low-risk breast cancers

Hippocampal Memory Recovery After Acute Stress: A Behavioral, Morphological and Molecular Study

Indexación: Scopus.Laboratory of Neuroplasticity and Neurogenetics, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile, 2Laboratorio Farmacología del Comportamiento, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile, 3Department of Kinesiology, Faculty of Health Sciences, Universidad Católica del Maule, Talca, Chile, 4Facultad de Psicología, Universidad de Talca, Talca, Chile, 5Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile, 6Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.This study was supported by the following grants: Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) 1120528 (JLF), Fondo Central de Investigación, Universidad de Chile ENL025/16 (JLF).Several studies have shown that a single exposure to stress may improve or impair learning and memory processes, depending on the timing in which the stress event occurs with relation to the acquisition phase. However, to date there is no information about the molecular changes that occur at the synapse during the stress-induced memory modification and after a recovery period. In particular, there are no studies that have evaluated—at the same time—the temporality of stress and stress recovery period in hippocampal short-term memory and the effects on dendritic spine morphology, along with variations in N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. The aim of our study was to take a multidimensional approach to investigate concomitant behavioral, morphological and molecular changes induced by a single restraint stress exposure (2.5 h) and a recovery period of 6 and 24 h in rats. We found that acute stress elicited a reduced preference to explore an object placed in a novel position (a hippocampal-dependent task). These changes were accompanied by increased activity of LIM kinase I (LIMK; an actin-remodeling protein) and increased levels of NR2A subunits of NMDA receptors. After 6 h of recovery from stress, rats showed similar preference to explore an object placed in a novel or familiar position, but density of immature spines increased in secondary CA1 apical dendrites, along with a transient rise in GluA2 AMPA receptor subunits. After 24 h of recovery from stress, the animals showed a preference to explore an object placed in a novel position, which was accompanied by a normalization of NMDA and AMPA receptor subunits to control values. Our data suggest that acute stress produces reversible molecular and behavioral changes 24 h after stress, allowing a full reestablishment of hippocampal-related memory. Further studies need to be conducted to deepen our understanding of these changes and their reciprocal interactions.Adaptive stress responses are a promising avenue to develop interventions aiming at restoring hippocampal function impaired by repetitive stress exposure. © 2018 Aguayo, Tejos-Bravo, Díaz-Véliz, Pacheco, García-Rojo, Corrales, Olave, Aliaga, Ulloa, Avalos, Román-Albasini, Rojas and Fiedler.https://www.frontiersin.org/articles/10.3389/fnmol.2018.00283/ful

Building capacity to provide innovative interventions for early psychosis in mental health professionals

Abstract Despite international guidelines, cognitive behavioural therapy for early psychosis (CBTep) is still under-used in daily clinical practice, mainly due to the lack of specific skills among mental health professionals. The aim of the study was to evaluate the feasibility and efficacy of a CBTep training course and to investigate the impact of trainees' variables on the level of skills acquisition. An intensive and graded CBTep training programme consisting of 112 hours of plenary lectures, 30 hours of group supervision and 3 months of practical training was offered to mental health professionals of 65 Italian community Mental Health Centers (CMHCs). CBT expert psychologists were used as the comparison group. Participants underwent pre-planned exams to test the level of skills acquisition and were requested to complete a satisfaction survey. The vast majority of participants (93%) completed the training with medium–high evaluation scores and reported to be highly satisfied with the course. CMHCs staff members achieved high scores in the examinations and no major differences between them and CBT expert psychologists were found in most of the final exam scores. Our results support the feasibility and the efficacy of the training to build specific CBTep capacity in a large cohort of professionals working in Italian Generalist Mental Health Services. Key learning aims (1) To understand the capacity building of a short training programme in CBT for early psychosis dedicated to community mental health professionals. (2) To consider the optimal characteristics of a CBT training programme for early psychosis. (3) To reflect on the feasibility of a CBT training programme for early psychosis in the context of Italian Community Mental Health Services

Raman spectroscopy reveals that biochemical composition of breast microcalcifications correlates with histopathologic features

Breast microcalcifications are a common mammographic finding. Microcalcifications are considered suspicious signs of breast cancer and a breast biopsy is required, however, cancer is diagnosed in only a few patients. Reducing unnecessary biopsies and rapid characterization of breast microcalcifications are unmet clinical needs. In this study, 473 microcalcifications detected on breast biopsy specimens from 56 patients were characterized entirely by Raman mapping and confirmed by X-ray scattering. Microcalcifications from malignant samples were generally more homogeneous, more crystalline, and characterized by a less substituted crystal lattice compared with benign samples. There were significant differences in Raman features corresponding to the phosphate and carbonate bands between the benign and malignant groups. In addition to the heterogeneous composition, the presence of whitlockite specifically emerged as marker of benignity in benign microcalcifications. The whole Raman signature of each microcalcification was then used to build a classification model that distinguishes microcalcifications according to their overall biochemical composition. After validation, microcalcifications found in benign and malignant samples were correctly recognized with 93.5% sensitivity and 80.6% specificity. Finally, microcalcifications identified in malignant biopsies, but located outside the lesion, reported malignant features in 65% of in situ and 98% of invasive cancer cases, respectively, suggesting that the local microenvironment influences microcalcification features. This study confirms that the composition and structural features of microcalcifications correlate with breast pathology and indicates new diagnostic potentialities based on microcalcifications assessment. Significance: Raman spectroscopy could be a quick and accurate diagnostic tool to precisely characterize and distinguish benign from malignant breast microcalcifications detected on mammography

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients

Background: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. Patients and methods: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). Results: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75\u20130.80). After external validation the accuracy of the nomogram was confirmed. Conclusion: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients

Differential planar antennas for 2.4/5.2 GHz WLAN applications

In this paper, three different configurations of planar antennas with a 100 Omega differential input impedance for dual-band WLAN applications, have been designed and compared. The proposed antennas provide dual-band operation in the 802.11a/b/g frequency bands without using a balun (balanced feeding). The best return loss performance has been obtained with the dual-band printed dipoles which are also characterized by a relatively straightforward design and tuning procedure. Measurements on constructed prototypes are shown at the conferenc