Skin diseases of the breast and nipple: Benign and malignant tumors.

The evaluation and management of dermatologic diseases of the breast and nipple requires an understanding of the unique anatomy of the breast and nipple and an awareness of the significant emotional, cultural, and sexual considerations that may come into play when treating this anatomic area. The first article in this continuing medical education series reviews breast anatomy, congenital breast anomalies, and benign and malignant breast tumors. An emphasis is placed on inflammatory breast cancer and breast cancer with noninflammatory skin involvement and on cutaneous metastases to the breast and from breast cancer. Familiarity of the dermatologist with the cutaneous manifestations of breast cancer will facilitate the diagnosis of breast malignancy and assist with staging, prognostication, and evaluation for recurrence. This article also discusses genodermatoses that predispose to breast pathology and provides imaging recommendations for evaluating a palpable breast mass.

Discovery of putative breast cancer antigens using an integrative platform of genomics-driven immunoproteomics.

Recent advances in cancer immuno-therapeutics such as checkpoint inhibitors, chimeric antigen-receptor T cells, and tumor infiltrating T cells (TIL) are now significantly impacting cancer patients in a positive manner. Although very promising, reports indicate no more than 25% of cases result in complete remission. One of the limitations of these treatments is the identity of putative cancer antigens in each patient, as it is technically challenging to identify cancer antigens in a rapid fashion. Thus, identification of cancer antigens followed by targeted treatment will increase the efficacy of cancer immunotherapies. To achieve this goal, a combined technologies platform of deep genomic sequencing and personalized immune assessment was devised, termed Genomics Driven Immunoproteomics (GDI). Using this technological platform, we report the discovery of 149 tumor antigens from human breast cancer patients. Significant number of these putative cancer antigens arise from single nucleotide variants (SNVs), as well as insertions and deletions that results into frame-shift mutations. We propose a general model of anti-cancer immunity and suggest that the GDI platform may help identify patient-specific tumor antigens in a timely fashion for precision immunotherapies.

The role of margin status and reexcision in local recurrence following breast conservation surgery.

INTRODUCTION: Breast conservation surgery (BCS) results in survival equal to mastectomy for early-stage breast cancer. Ipsilateral breast tumor recurrence (IBTR) after BCS is thought to be related to margin status. At our institution, reexcision is performed only if tumor is at inked margin or with extensive disease close to multiple margins. The purpose of this study was to determine rates of reexcision and recurrences among BCS patients using this policy. METHODS: We performed an institutional review board-approved retrospective analysis of BCS patients who underwent surgery between January 2001 and June 2005. We identified patients who had a second breast excision within 8 weeks of the first, and those patients with an IBTR. Clinical and pathologic features of patients' tumors were reviewed. RESULTS: We identified 543 patients who underwent BCS, 84 patients (15.5 %) underwent reexcision for margin status. The crude IBTR rate was 3.4 %, and the 5-year local recurrence-free survival of the reexcised group was 90.6 % compared with 97.4 % in the non-reexcised group (p = 0.0097). Of the 64 reexcision patients, 6 (9.4 %) had an IBTR versus 12 (2.6 %) of the 459 non-reexcised patients (p = 0.0151). DISCUSSION: Our reexcision rate is low compared with other reports. This results from a policy that defines "no tumor on ink" as an adequate margin for BCS, and the use of selective irradiation boosts based on margins assessed by our pathologists. Our local recurrence rate compares favorably with those seen in other studies while minimizing the need for additional operations. A higher IBTR rate after reexcision likely reflects tumor biology.

Patient factors affecting operative times for single-incision trans-axillary robotic-assisted (STAR) thyroid lobectomy: does size matter?

BACKGROUND: Single-incision, transaxillary, robotic-assisted (STAR) thyroid lobectomy using a robotic surgical system is a novel surgical approach that is extensively described in Korean patients. Some have suggested that this experience will not translate into the American population because of differing body habitus and because the mean size of the thyroid nodules removed in Korea are <1 cm. We reviewed our experience with STAR thyroid lobectomy. METHODS: We retrospectively reviewed our prospectively collected data on consecutive cases of STAR thyroid lobectomy performed by a single surgeon. Operative times and patient outcomes were evaluated. RESULTS: Seventeen operations were performed on 15 patients. Mean total operative time was 219.3 (range, 183-256) minutes. All patients were discharged on postoperative day 1. Postoperative complications were seromas (n = 2) and cellulitis (n = 2). Operative time did not vary with the size or volume of the nodule or gland. The mean nodule diameter was 1.9 (range, 0.5-3.1) cm. The mean nodule volume and thyroid volume were 5.0 (range, 0.1-16.7) cm(3) and 20.7 (range, 11.8-45.8) cm(3), respectively. When stratified by body mass index (range, 19.6-37.8), normal versus overweight or obese, total operative time increased from 204 to 225 min, and console time from 114 to 125 min. CONCLUSIONS: STAR thyroid surgery is a feasible technique. Factors, such as mass size, specimen volume, and patient body mass index, had little effect on operative times. These differences should not hinder the adoption of this procedure in North America, because new retractor systems help to overcome them. Further evaluation of this procedure is reasonable and safe.

Bevacizumab and breast cancer: what does the future hold?

Breast cancer is a major health concern for many women, but despite the current standard therapies, many women still die of metastatic disease. Angiogenesis has been evaluated as a possible target for therapy and bevacizumab (Avastin(®), Genentech/Roche, CA, USA), a monoclonal antibody against VEGF-A, has been developed to target this. Current clinical trials utilizing bevacizumab have shown an increase in progression-free survival, but this has not translated to an increase in overall survival in breast cancer patients. In this article, we summarize the currently published trials utilizing bevacizumab in the treatment of breast cancer and describe various methods of measuring angiogenesis in vitro and in vivo. We also describe the related process of lymphangiogenesis, as this may contribute to the mechanism of cancer progression and may be a potential target for therapy in the future. Understanding these processes may help us develop new treatments for breast cancer.

The development and measurement properties of the trauma NOn-TECHnical skills (T-NOTECHS) scale: A scoping review.

PURPOSE: Conduct a scoping review to critically appraise the development and summarize the evidence on the measurement properties of T-NOTECHS including sensibility, reliability, and validity. METHODS: A literature search was performed using Pubmed and Ovid databases. Studies that described the development process of T-NOTECHS and primary studies that presented evidence of reliability and validity were identified and included. Measurement properties of T-NOTECHS was assessed and summarized under the following: scale development, sensibility, reliability, and validity. RESULTS: The literature search yielded 245 articles with 24 studies meeting inclusion criteria. The T-NOTECHS was developed with an acceptable robust methodology. It has good sensibility with adequate content, face validity, and feasibility. It is a reliable measure of non-technical skills in the setting of trauma video review, which improves with expert raters or extensive training. The T-NOTECHS is a valid discriminative and evaluative instrument that measures non-technical skills of multidisciplinary trauma teams. CONCLUSIONS: T-NOTECHS provides reliable and valid measurements of non-technical skills of trauma teams, particularly when assessing trauma video review and non-technical skills training interventions by expert raters.

A scoping review of nontechnical skill assessment tools to evaluate trauma team performance.

BACKGROUND: The objective of this scoping review was to identify assessment tools of trauma team performance (outside of technical skills) and assess the validity and reliability of each tool in assessing trauma team performance. METHODS: We searched Embase, Cochrane Library, Web of Science, Ovid Medline, and Cumulative Index to Nursing and Allied Health Literature from inception to June 1, 2021. English studies that evaluated trauma team performance using nontechnical skill assessment tools in a simulation or real-world setting were included. Studies were assessed by two independent reviewers for meeting inclusion/exclusion criteria. Data regarding team assessment tools were extracted and synthesized into behavior domains. Each tool was then assessed for validity and reliability. RESULTS: The literature search returned 4,215 articles with 29 meeting inclusion criteria. Our search identified 12 trauma team performance assessment tools. Most studies were conducted in the United States (n = 20 [69%]). Twenty studies (69%) assessed trauma team performance in a simulation setting; Team Emergency Assessment Measure (TEAM) and Trauma Nontechnical Skills Scale (T-NOTECHS) were the only tools to be applied in a simulation and real-world setting. Most studies assessed trauma team performance using video review technology (n = 17 [59%]). Five overarching themes were designed to encompass behavioral domains captured across the 12 tools: (1) Leadership, (2) Communication, (3) Teamwork, (4) Assessment, and (5) Situation Awareness. The reliability and validity of T-NOTECHS were investigated by the greatest number of studies (n = 13); however, TEAM had the most robust evidence of reliability and validity. CONCLUSION: We identified 12 trauma team performance tools that assessed nontechnical skills to varying degrees. Trauma Nontechnical Skills Scale and TEAM tools had the most evidence to support their reliability and validity. Considering the limited research in the impact of trauma team performance on patient outcomes, future studies could use video review technology in authentic trauma cases to further study this important relationship. LEVEL OF EVIDENCE: Systematic reviews and meta-analyses, level IV.

Eliciting Narratives to Inform Care for Infants With Trisomy 18.

: media-1vid110.1542/5804913218001PEDS-VA_2018-0321Video Abstract.

Targeting sphingosine-1-phosphate in hematologic malignancies.

Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that regulates several processes important for hematologic cancer progression. S1P is generated by two sphingosine kinases, SphK1 and SphK2, and is exported outside the cell, where it activates specific cell surface S1P G-protein coupled receptors in autocrine/paracrine manner, coined "inside-out signaling". In this review, we highlight the importance of SphK1 and inside-out signaling by S1P in hematologic malignancy. We also summarize the results of studies targeting the SphK1/S1P/S1P receptor axis and the effects of the S1P receptor modulator, FTY720, in hematologic malignancy.

Functional characterization of filamin a interacting protein 1-like, a novel candidate for antivascular cancer therapy.

Inhibiting angiogenesis has become a major therapeutic strategy for cancer treatment. To identify common intracellular mediators, we previously analyzed gene expression profiles of endothelial cells after treatment with angiogenesis inhibitors. Filamin A interacting protein 1-like (FILIP1L; previously known as down-regulated in ovarian cancer 1) was identified as one of the genes up-regulated in endothelial cells in response to these inhibitors. However, the expression and function of FILIP1L protein is uncharacterized. Here, we provide the first description of the expression and specific subcellular localization of FILIP1L protein in human tissue. Overexpression of FILIP1L resulted in inhibition of cell proliferation and migration and increased apoptosis. In addition, overexpression of FILIP1L truncation mutants showed differential antiproliferative activity. A COOH terminal truncation mutant (FILIP1LDeltaC103) was more potent than wild-type FILIP1L in mediating this activity. Targeted expression of FILIP1LDeltaC103 in tumor vasculature inhibited tumor growth in vivo. Overall, these findings suggest that the novel protein FILIP1L may be an important mediator of the effects of angiogenesis inhibitors and that FILIP1L has the potential to be an antivascular reagent for cancer therapy.