Multimodality Imaging of Benign and Malignant Diseases of the Nipple-Areolar Complex.

The nipple-areolar complex (NAC), a unique anatomic structure of the breast, encompasses the terminal intramammary ducts and skin appendages. Several benign and malignant diseases can arise within the NAC. As several conditions have overlapping symptoms and imaging findings, understanding the distinctive nipple anatomy, as well as the clinical and imaging features of each NAC disease process, is essential. A multimodality imaging approach is optimal in the presence or absence of clinical symptoms. The authors review the ductal anatomy and anomalies, including congenital abnormalities and nipple retraction. They then discuss the causes of nipple discharge and highlight best practices for the imaging workup of pathologic nipple discharge, a common condition that can pose a diagnostic challenge and may be the presenting symptom of breast cancer. The imaging modalities used to evaluate and differentiate benign conditions (eg, dermatologic conditions, epidermal inclusion cyst, mammary ductal ectasia, periductal mastitis, and nonpuerperal abscess), benign tumors (eg, papilloma, nipple adenoma, and syringomatous tumor of the nipple), and malignant conditions (eg, breast cancer and Paget disease of the breast) are reviewed. Breast MRI is the current preferred imaging modality used to evaluate for NAC involvement by breast cancer and select suitable candidates for nipple-sparing mastectomy. Different biopsy techniques (US -guided biopsy and stereotactic biopsy) for sampling NAC masses and calcifications are described. This multimodality imaging approach ensures an accurate diagnosis, enabling optimal clinical management and patient outcomes. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Longitudinal dynamic contrast-enhanced MRI radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer.

Early prediction of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) patients could help oncologists select individualized treatment and avoid toxic effects associated with ineffective therapy in patients unlikely to achieve pathologic complete response (pCR). The objective of this study is to evaluate the performance of radiomic features of the peritumoral and tumoral regions from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquired at different time points of NAST for early treatment response prediction in TNBC. This study included 163 Stage I-III patients with TNBC undergoing NAST as part of a prospective clinical trial (NCT02276443). Peritumoral and tumoral regions of interest were segmented on DCE images at baseline (BL) and after two (C2) and four (C4) cycles of NAST. Ten first-order (FO) radiomic features and 300 gray-level-co-occurrence matrix (GLCM) features were calculated. Area under the receiver operating characteristic curve (AUC) and Wilcoxon rank sum test were used to determine the most predictive features. Multivariate logistic regression models were used for performance assessment. Pearson correlation was used to assess intrareader and interreader variability. Seventy-eight patients (48%) had pCR (52 training, 26 testing), and 85 (52%) had non-pCR (57 training, 28 testing). Forty-six radiomic features had AUC at least 0.70, and 13 multivariate models had AUC at least 0.75 for training and testing sets. The Pearson correlation showed significant correlation between readers. In conclusion, Radiomic features from DCE-MRI are useful for differentiating pCR and non-pCR. Similarly, predictive radiomic models based on these features can improve early noninvasive treatment response prediction in TNBC patients undergoing NAST.

Triple-Negative Breast Cancer: Histopathologic Features, Genomics, and Treatment.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive group of tumors that are defined by the absence of estrogen and progesterone receptors and lack of ERBB2 (formerly HER2 or HER2/neu) overexpression. TNBC accounts for 8%-13% of breast cancers. In addition, it accounts for a higher proportion of breast cancers in younger women compared with those in older women, and it disproportionately affects non-Hispanic Black women. TNBC has high metastatic potential, and the risk of recurrence is highest during the 5 years after it is diagnosed. TNBC exhibits benign morphologic imaging features more frequently than do other breast cancer subtypes. Mammography can be suboptimal for early detection of TNBC owing to factors that include the fast growth of this cancer, increased mammographic density in young women, and lack of the typical features of malignancy at imaging. US is superior to mammography for TNBC detection, but benign-appearing features can lead to misdiagnosis. Breast MRI is the most sensitive modality for TNBC detection. Most cases of TNBC are treated with neoadjuvant chemotherapy, followed by surgery and radiation. MRI is the modality of choice for evaluating the response to neoadjuvant chemotherapy. Survival rates for individuals with TNBC are lower than those for persons with hormone receptor-positive and human epidermal growth factor receptor 2-positive cancers. The 5-year survival rates for patients with localized, regional, and distant disease at diagnosis are 91.3%, 65.8%, and 12.0%, respectively. The early success of immunotherapy has raised hope regarding the development of personalized strategies to treat TNBC. Imaging and tumor biomarkers are likely to play a crucial role in the prediction of TNBC treatment response and TNBC patient survival in the future. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Deep Learning for Fully Automatic Tumor Segmentation on Serially Acquired Dynamic Contrast-Enhanced MRI Images of Triple-Negative Breast Cancer.

Accurate tumor segmentation is required for quantitative image analyses, which are increasingly used for evaluation of tumors. We developed a fully automated and high-performance segmentation model of triple-negative breast cancer using a self-configurable deep learning framework and a large set of dynamic contrast-enhanced MRI images acquired serially over the patients' treatment course. Among all models, the top-performing one that was trained with the images across different time points of a treatment course yielded a Dice similarity coefficient of 93% and a sensitivity of 96% on baseline images. The top-performing model also produced accurate tumor size measurements, which is valuable for practical clinical applications.

Assessment of Response to Neoadjuvant Systemic Treatment in Triple-Negative Breast Cancer Using Functional Tumor Volumes from Longitudinal Dynamic Contrast-Enhanced MRI.

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann-Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 (p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients.

Evaluation of a Surgical Navigation System for Localization and Excision of Nonpalpable Lesions in Breast and Axillary Surgery.

Introduction: Elucent Medical has introduced a novel EnVisio™ Surgical Navigation system which uses SmartClips™ that generate a unique electromagnetic signal triangulated in 3 dimensions for real-time navigation. The purpose of this study was to evaluate the efficacy and feasibility of the EnVisio Surgical Navigation system in localizing and excising nonpalpable lesions in breast and axillary surgery. Methods: This pilot study prospectively examined patients undergoing breast and nodal localization using the EnVisio Surgical Navigation system. SmartClips were placed by designated radiologists using ultrasound (US) or mammographic (MMG) guidance. The technical evaluation focused on successful deployment and subsequent excision of all localized lesions including SmartClips and biopsy clips. Results: Eleven patients underwent localization using 27 SmartClips which included bracketed multifocal disease (n = 4) and clipped lymph node (n = 1). The bracketed cases were each localized with 2 SmartClips. Mammography and ultrasound were used (n = 8 and n = 19, respectively) to place the SmartClips. All 27 devices were successfully deployed within 5 mm of the targeted lesion or biopsy clip. All SmartClip devices were identified and retrieved intraoperatively. No patients required a second operation for margin excision. Conclusion: In a limited sample, the EnVisio Surgical Navigation system was a reliable technology for the localization of breast and axillary lesions planned for surgical excision. Further comparative studies are required to evaluate its efficacy in relation to the other existing localization modalities.

First-in-human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy.

BACKGROUND: Polymerized allergens conjugated to non-oxidized mannan (PM-allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM-allergoids are readily taken up by DCs and induce Treg cells. This first-in-human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM-allergoid (PM-HDM) administered subcutaneously (SC) or sublingually (SL). METHODS: In a randomized, double-blind, double-dummy, placebo-controlled trial, 196 subjects received placebo or PM-HDM at 500, 1000, 3000, or 5000 mannan-conjugated therapeutic units (mTU)/mL in 9-arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. RESULTS: No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. CONCLUSIONS: PM-HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.

Adult pancreatic islet endocrine cells emerge as fetal hormone-expressing cells.

The precise developmental dynamics of the pancreatic islet endocrine cell types, and their interrelation, are unknown. Some authors claim the persistence of islet cell differentiation from precursor cells after birth ("neogenesis"). Here, using four conditional cell lineage tracing ("pulse-and-chase") murine models, we describe the natural history of pancreatic islet cells, once they express a hormone gene, until late in life. Concerning the contribution of early-appearing embryonic hormone-expressing cells to the formation of islets, we report that adult islet cells emerge from embryonic hormone-expressing cells arising at different time points during development, without any evidence of postnatal neogenesis. We observe specific patterns of hormone gene activation and switching during islet morphogenesis, revealing that, within each cell type, cells have heterogeneous developmental trajectories. This likely applies to most maturating cells in the body, and explains the observed phenotypic variability within differentiated cell types. Such knowledge should help devising novel regenerative therapies.

Team Science: A Practical Approach to Starting Collaborative Projects.

A collaborative approach to treating patients is well taught in medical training. However, collaboration and team building in clinical and laboratory research may have been given less emphasis. More scientific discoveries are now being made with multidisciplinary teams, requiring a thoughtful approach in order to achieve research goals while mitigating potential conflicts. Specific steps for a successful team science project include building the team, assigning roles and responsibilities, allocating rules, and discussing authorship guidelines. Building a team involves bringing individuals together and developing a common research goal while establishing psychological safety for all members of the team. Clear assignment of roles and responsibilities avoids confusion and allows each member's contributions to be acknowledged. Allocating rules involves discussing how decisions in the team will be made, how data and knowledge sharing will occur, and how potential conflicts will be resolved. Discussing authorship at the start of the project ensures that the entire team knows what work must be completed for authorship to be obtained.

Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production.

The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by ß-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse γ-cells. Using different approaches, we identified a set of genes and pathways defining their functional identity. We found that the γ-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional γ-cell ablation did not alter glycemia nor body weight. Interestingly, upon ß-cell injury induction, γ-cells exhibited gene expression changes and some of them engaged insulin production, like α- and δ-cells. In conclusion, we provide a comprehensive characterization of γ-cells and highlight their plasticity and therapeutic potential.

Ultrasound Evaluation of the Axilla in the Breast Imaging Setting.

ABSTRACT: Ultrasound evaluation of the axilla plays a critical role in the setting of newly diagnosed breast cancer as surgical management evolves toward more targeted axillary nodal resection. Regional nodal involvement by metastatic carcinoma is one of most important prognostic factors in breast cancer and guides local, regional, and systemic treatment. Ultrasound also evaluates response to neoadjuvant chemotherapy. This article will review ultrasound techniques and the anatomy and the morphology of axillary lymph nodes. Lymph node staging in breast cancer will also be discussed. Ultrasound-guided interventions and localizations and emerging technologies of elastography and contrast-enhanced ultrasound will be discussed. In addition, this article will discuss the role of ultrasound as it applies to management of the axilla since the American College of Surgeons Oncology Group Z011 and Z1071 trials. Finally, other causes of benign and malignant axillary lymphadenopathy, not related to breast cancer, are discussed.

Pregnancy Associated Breast Cancer.

Pregnancy associated breast cancer (PABC) is a subset of cancer that is too often diagnosed at a more advanced stage due to physiologic changes of the breast and lack of awareness among patients and physicians, resulting in higher mortality rates. While PABC is rare, it is postulated that as women delay childbearing, the rate of PABC may increase. Therefore, it is important to discuss appropriate workup, safety of mammography during pregnancy, and biopsy techniques.

Pollen-induced allergic asthma and rhinoconjunctivitis: differences in outcome between seasonal and nonseasonal exposure to allergens under real-life conditions (The LANDSCAPE Study)

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Detached Leaf Assays to Simplify Gene Expression Studies in Potato During Infestation by Chewing Insect Manduca sexta.

The multitrophic nature of gene expression studies of insect herbivory demands large numbers of biological replicates, creating the need for simpler, more streamlined herbivory protocols. Perturbations of chewing insects are usually studied in whole plant systems. While this whole organism strategy is popular, it is not necessary if similar observations can be replicated in a single detached leaf. The assumption is that basic elements required for signal transduction are present within the leaf itself. In the case of early events in signal transduction, cells need only to receive the signal from the perturbation and transmit that signal to neighboring cells which are assayed for gene expression. The proposed method simply changes the timing of the detachment. In whole plant experiments, larvae are confined to a single leaf which is eventually detached from the plant and assayed for gene expression. If the order of excision is reversed, from last in whole plant studies, to first in the detached study, the feeding experiment is simplified. Solanum tuberosum var. Kennebec is propagated by nodal transfer in a simple tissue culture medium and transferred to soil for further growth if desired. Leaves are excised from the parent plant and relocated to Petri dishes where the feeding assay is conducted with the larval stages of M. sexta. Damaged leaf tissue is assayed for the expression of relatively early events in signal transduction. Gene expression analysis identified infestation-specific Cys2-His2 (C2H2) transcription factors, confirming the success of using detached leaves in early response studies. The method is easier to perform than whole plant infestations and uses less space.

Clinical and non-clinical factors that predict discharge disposition after a fall.

BACKGROUND: Falls can result in injuries that require rehabilitation and long-term care after hospital discharge. Identifying factors that contribute to prediction of discharge disposition is crucial for efficient resource utilization and reducing cost. Several factors may influence discharge location after hospitalization for a fall. The aim of this study was to examine clinical and non-clinical factors that may predict discharge disposition after a fall. We hypothesized that age, injury type, insurance type, and functional status would affect discharge location. METHODS: This two-year retrospective study was performed at an urban, adult level-1 trauma center. Fall patients who were discharged home or to a facility after hospital admission were included in the study. Data was obtained from the trauma registry and electronic medical records. Logistic regression modeling was used to assess independent predictors. RESULTS: A total of 1,121 fallers were included in the study. 621 (55.4%) were discharged home and 500 (44.6%) to inpatient rehabilitation (IRF)/skilled nursing facility (SNF). The median age was 64 years (IQR: 49-79) and 48.4% (543) were male. The median length of hospital stay was 5 days (IQR: 2.5-8). Increasing age (p < 0.001), length of stay in the ICU (p < 0.001), injury severity (p < 0.001), number of comorbidities (p = 0.038), having Medicare insurance (p = 0.025), having a fracture at any body region (p < 0.001), and ambulation status (p = 0.025) significantly increased the odds of being discharged to IRF/SNF compared to home. The removal of injury severity score and ICU length of stay from the "late/regular discharge" model, to create an "early discharge" model, decreased the accuracy of the prediction rate from 78.5% to 74.9% (p < 0.001). CONCLUSION: A combination of demographic, clinical, social, economic, and functional factors can together predict discharge disposition after a fall. The majority of these factors can be assessed early in the hospital stay, which may facilitate a timely discharge plan and shorter stays in the hospital.

[Analysis of clinical safety in the units of Allergy of the Valencian Community]. / Análisis de la seguridad clínica en las unidades de Alergología de la Comunidad Valenciana.

The introduction of new diagnostic and therapeutic procedures involving allergen exposure may increase the risk of allergic reactions. We designed and distributed an anonymous questionnaire among the allergy units of the Valencian Community in order to collect information on measures to ensure clinical safety. Twelve hospital outpatient clinics and 8 ambulatory care centres reported similar patterns of activities, including the use of critical care units, emergency rooms or day hospitals for higher risk techniques. The provision of security-related instruments is broader in hospital outpatient clinics and included: oxygen (91.7%), pulse oximeter (75.0%) or vital signs monitor (8.3%), resuscitation material (91.7%) and defibrillator (83.3%). The response time for emergencies is set in 50% of clinics. The resuscitation material is systematically reviewed and informed consent signed. Security is more limited in ambulatory care centres. It is necessary to set down the conditions for clinical safety in allergology. Key words. Allergy. Ambulatory care. Clinical safety. Health services. Hospital outpatient clinic.

Análisis de la seguridad clínica en las unidades de Alergología de la Comunidad Valenciana / Analysis of clinical safety in the Allergy Units of the Valencian Community

La introducción de procedimientos diagnósticos y terapéuticos que implican exposición alergénica conlleva riesgos. Para evaluar la seguridad clínica en las unidades de Alergología de la Comunidad Valenciana se diseñó y distribuyó un cuestionario anónimo, obteniendo respuesta de doce unidades hospitalarias y ocho centros de especialidades. La distribución de prestaciones entre los diversos entornos fue homogénea, así como la utilización de unidades de críticos, urgencias u hospitales de día para técnicas de mayor riesgo. La dotación de instrumentos relacionados con la seguridad es más amplia en las consultas hospitalarias e incluye fuente de oxígeno (91,7%), pulsioxímetro (75,0%) o monitor (8,3%), carro de paradas (91,7%) y desfibrilador (83,33%). El tiempo de respuesta para emergencias está pactado en el 50%. Sistemáticamente se revisa el material para resucitación y se firma consentimiento informado. La seguridad es más limitada en los centros de especialidades. Se deberían establecer las condiciones idóneas de seguridad clínica en Alergología (AU)

The introduction of new diagnostic and therapeutic procedures involving allergen exposure may increase the risk of allergic reactions. We designed and distributed an anonymous questionnaire among the allergy units of the Valencian Community in order to collect information on measures to ensure clinical safety. Twelve hospital outpatient clinics and 8 ambulatory care centres reported similar patterns of activities, including the use of critical care units, emergency rooms or day hospitals for higher risk techniques. The provision of security-related instruments is broader in hospital outpatient clinics and included: oxygen (91.7%), pulse oximeter (75.0%) or vital signs monitor (8.3%), resuscitation material (91.7%) and defibrillator (83.3%). The response time for emergencies is set in 50% of clinics. The resuscitation material is systematically reviewed and informed consent signed. Security is more limited in ambulatory care centres. It is necessary to set down the conditions for clinical safety in allergology (AU)