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Background: Immediate lymphatic reconstruction (ILR) has been proposed to decrease lymphedema rates. The primary aim of our study was to determine whether ILR decreased the incidence of lymphedema in patients undergoing axillary lymph node dissection (ALND). Methods: We conducted a two-site pragmatic study of ALND with or without ILR, employing surgeon-level cohort assignment, based on breast surgeons' preferred standard practice. Lymphedema was assessed by limb volume measurements, patient self-reporting, provider documentation, and International Classification of Diseases, Tenth Revision (ICD-10) codes. Results: Overall, 230 patients with breast cancer were enrolled; on an intention-to-treat basis, 99 underwent ALND and 131 underwent ALND with ILR. Of the 131 patients preoperatively planned for ILR, 115 (87.8%) underwent ILR; 72 (62.6%) were performed by one breast surgical oncologist and 43 (37.4%) by fellowship-trained microvascular plastic surgeons. ILR was associated with an increased risk of lymphedema when defined as ≥10% limb volume change on univariable analysis, but not on multivariable analysis, after propensity score adjustment. We did not find a statistically significant difference in limb volume measurements between the two cohorts when including subclinical lymphedema (≥5% inter-limb volume change), nor did we see a difference in grade between the two cohorts on an intent-to-treat or treatment received basis. For all patients, considering ascertainment strategies of patient self-reporting, provider documentation, and ICD-10 codes, as a single binary outcome measure, there was no significant difference in lymphedema rates between those undergoing ILR or not. Conclusion: We found no significant difference in lymphedema rates between patients undergoing ALND with or without ILR. [ABSTRACT FROM AUTHOR]

This article discusses the importance of understanding research paradigms in medical education and provides a method for novice researchers to deconstruct their own paradigms. The authors use gamification techniques and Socratic questioning to guide researchers in thinking openly about their assumptions and improving the conduct of research. The article emphasizes the need for healthcare professionals to be aware of different paradigms, such as positivism, interpretivism, and critical theory, and how these paradigms can influence research methodology. The authors believe that their approach can be applied to researchers in other disciplines and can help educators teach the philosophy of research practice. [Extracted from the article]

Purpose:Although fertility preservation for patients with childhood and adolescent cancer is considered standard of care in the high-resource settings, it is rarely offered in low-resource settings. This study explores the experiences and perspectives of oncology health care professionals in Uganda to identify contextual barriers and facilitators to addressing oncofertility in low-resource settings. Methods: Using ground theory, we conducted in-depth face-to-face interviews of health care professionals managing pediatric patients at the Uganda Cancer Institute (UCI). Using a systematic, semi-structured interview guide, participants were asked open-ended questions about their understanding of fertility preservation and their perspectives on implementing this care at their institution. Although all the eligible health care providers were interviewed, interview transcripts were uploaded into NVivo version 12 and openly coded as per theoretical requirements. Codes were refined into categories and later into structured themes. Results: Twelve health care professionals were interviewed. Most participants identified as female (n = 9). Their role in the medical team varied from nurses (n = 6), medical officers (n = 3), pediatric oncologists (n = 2), and pediatric oncology fellow (n = 1). Six themes were noted as follows: (1) importance of information, (2) importance of future fertility, (3) inadequate consideration to future fertility, (4) communication barriers, (5) inadequate knowledge, and (6) resource barriers. Conclusion: Although health care providers at the UCI face contextual barriers to addressing future fertility among patients with pediatric cancer, they value preserving fertility in this population. Future initiatives that aim to introduce oncofertility care in low-resource settings should prioritize educating providers and building capacity to meet the oncofertility needs in this setting. [ABSTRACT FROM AUTHOR]

CD36 expression in both immune and non-immune cells is known to be directly involved in cancer metastasis. Extracellular vesicles (EVs) secreted by malignant melanocytes play a vital role in developing tumor-promoting microenvironments, but it is unclear whether this is mediated through CD36. To understand the role of CD36 in melanoma, we first analyzed the SKCM dataset for clinical prognosis, evaluated the percentage of CD36 in lymphatic fluid-derived EVs (LEVs), and tested whether melanoma-derived EVs increase CD36 expression and induce M2-macrophage-like characteristics. Furthermore, we performed a multiplex immunofluorescence (MxIF) imaging analysis to evaluate the CD36 expression and its colocalization with various other cells in the lymph node (LN) of patients and control subjects. Our findings show that cutaneous melanoma patients have a worse clinical prognosis with high CD36 levels, and a higher percentage of CD36 in total LEVs were found at baseline in melanoma patients compared to control. We also found that monocytic and endothelial cells treated with melanoma EVs expressed more CD36 than untreated cells. Furthermore, melanoma-derived EVs can regulate immunosuppressive macrophage-like characteristics by upregulating CD36. The spatial imaging data show that cells in tumor-involved sentinel LNs exhibit a higher probability of CD36 expression than cells from control LNs, but this was not statistically significant. Conclusively, our findings demonstrated that CD36 plays a vital role in controlling the immunosuppressive microenvironment in the LN, which can promote the formation of a protumorigenic niche. [ABSTRACT FROM AUTHOR]

Background: Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied. Methods: Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal–Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC. Results: There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response. Conclusions: Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer. Trial registration: NCT02022202. Registered 20 December 2013. [ABSTRACT FROM AUTHOR]

Introduction: Persistent pain following breast surgery is common and may be challenging to treat. In patients refractory to conservative treatments, ultrasound‐guided fascial plane blocks of thoracic nerves can be a useful option. Results: This type of neuro blockade technique provides advantages in terms of safety and efficacy that are convenient for physicians managing refractory and complex cases of post‐breast surgery syndrome. Conclusion: This technical review aims to present an up‐to‐date summary of the most common ultrasound‐guided fascial plane blocks for chronic pain in post‐breast surgery patients, provide a detailed technical description of each intervention, and propose preferred injections based on the anatomical location of the pain. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare the overall survival (OS) of upfront surgery followed by adjuvant chemotherapy (ACT) versus neoadjuvant chemotherapy (NACT) followed by surgery in patients with clinical T1 clinically node negative triple negative breast cancer (TNBC). Patients and Methods: We retrospectively reviewed 48,329 women with cT1N0 TNBC from 2006 to 2016 in the National Cancer Database (NCDB). Patients were categorized into five pathologic subgroups based on ACT versus NACT and definitive pathologic stage after surgery: ACT with unchanged stage (pT0–1N0), ACT with pathologic upstage (any nodal disease, > pT1N0), NACT with pCR (ypT0–isN0), NACT with stable disease (SD) (ypT1N0), and NACT with progressive disease (PD) (any nodal disease, > ypT1N0). The primary outcome was 5 year OS. Results: Patients with TNBC who underwent upfront surgery followed by ACT had better OS compared with those who received NACT (p < 0.001). The hazard ratio (HR) for death for NACT compared with ACT was 1.42 (95% CI 1.26–1.59, p < 0.001) on multivariate analysis. Patients who underwent upfront surgery followed by ACT and whose pathological stage was unchanged from clinical stage had similar outcomes compared with those who received NACT and attained pCR with 5 year OS of 92.7% versus 93.3% (p = 0.34). Patients with clinical T1cN0 tumors who underwent NACT with pCR had better outcomes compared with those who underwent ACT with unchanged stages. (p = 0.025). Conclusions: For cT1N0 TNBC patients, OS of upfront surgery followed by ACT was not inferior to those who underwent NACT. Neoadjuvant chemotherapy was associated with better outcomes in cT1c patients who attained pCR. [ABSTRACT FROM AUTHOR]

Background: Axillary reverse mapping (ARM) was introduced in 2007 to identify and selectively preserve upper-extremity lymphatics during axillary lymph node surgery to decrease the risk of lymphedema. The patient population in which an ARM lymph node (LN) can be preserved during an axillary lymph node dissection (ALND) has not been established to date. This study aimed to determine the frequency of metastatic involvement of an ARM LN among patients undergoing ALND. Methods: Patients undergoing ALND with or without immediate lymphatic reconstruction (ILR) were enrolled in a prospective trial at two institutional sites between April 2018 and Decemeber 2022. This report analyzes the ARM node positivity and total LN positivity rates during ALND for the cohort of patients enrolled in the ILR intervention arm of the study. Results: The inclusion criteria were met by 139 patients, who made up the study population (133 with breast cancer and 6 with other disease). Of the breast cancer patients, 99.2% were female, 35.3% (47/133) were cT3 or greater, and 96.2% (128/133) had cN1 or greater disease. For 55 of the 133 patients (41.4%), the ARM nodes were marked and specified in the pathology report. Of the 55 patients, 39 (70.9%) had a positive LN at ALND. Of these 55 patients, 11 (20%) had positive ARM nodes. The ARM LN was the only positive node in 3 of the 11 patients. Conclusion: In the contemporary patient population undergoing ALND, the positivity rate of the ARM LN was relatively high, suggesting that leaving ARM LNs in patients undergoing ALND may not be oncologically safe. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Patients with TNBC are primarily treated with neoadjuvant chemotherapy (NAC). The response to NAC is prognostic, with reductions in overall survival and disease-free survival rates in those patients who do not achieve a pathological complete response (pCR). Based on this premise, we hypothesized that paired analysis of primary and residual TNBC tumors following NAC could identify unique biomarkers associated with post-NAC recurrence. Methods and results: We investigated 24 samples from 12 non-LAR TNBC patients with paired pre- and post-NAC data, including four patients with recurrence shortly after surgery (< 24 months) and eight who remained recurrence-free (> 48 months). These tumors were collected from a prospective NAC breast cancer study (BEAUTY) conducted at the Mayo Clinic. Differential expression analysis of pre-NAC biopsies showed minimal gene expression differences between early recurrent and nonrecurrent TNBC tumors; however, post-NAC samples demonstrated significant alterations in expression patterns in response to intervention. Topological-level differences associated with early recurrence were implicated in 251 gene sets, and an independent assessment of microarray gene expression data from the 9 paired non-LAR samples available in the NAC I-SPY1 trial confirmed 56 gene sets. Within these 56 gene sets, 113 genes were observed to be differentially expressed in the I-SPY1 and BEAUTY post-NAC studies. An independent (n = 392) breast cancer dataset with relapse-free survival (RFS) data was used to refine our gene list to a 17-gene signature. A threefold cross-validation analysis of the gene signature with the combined BEAUTY and I-SPY1 data yielded an average AUC of 0.88 for six machine-learning models. Due to the limited number of studies with pre- and post-NAC TNBC tumor data, further validation of the signature is needed. Conclusion: Analysis of multiomics data from post-NAC TNBC chemoresistant tumors showed down regulation of mismatch repair and tubulin pathways. Additionally, we identified a 17-gene signature in TNBC associated with post-NAC recurrence enriched with down-regulated immune genes. [ABSTRACT FROM AUTHOR]

Root exudates are plant-derived, exported metabolites likely shaping root-associated microbiomes by acting as nutrients and signals. However, root exudation dynamics are unclear and thus also, if changes in exudation are reflected in changes in microbiome structure. Here, we assess commonalities and differences between exudates of different plant species, diurnal exudation dynamics, as well as the accompanying methodological aspects of exudate sampling. We find that exudates should be collected for hours rather than days as many metabolite abundances saturate over time. Plant growth in sterile, nonsterile, or sugar-supplemented environments significantly alters exudate profiles. A comparison of Arabidopsis thaliana, Brachypodium distachyon, and Medicago truncatula shoot, root, and root exudate metabolite profiles reveals clear differences between these species, but also a core metabolome for tissues and exudates. Exudate profiles also exhibit a diurnal signature. These findings add to the methodological and conceptual groundwork for future exudate studies to improve understanding of plant-microbe interactions. Root exudates display a diurnal signature, change with growth environment, and can be divided into a core metabolome common to multiple plant species, and specialized exudates produced by distinct species. [ABSTRACT FROM AUTHOR]

Background: To evaluate risk factors (treatment-related, comorbidities, and lifestyle) for breast cancer-related lymphedema (BCRL) within the context of a Prospective Surveillance and Early Intervention (PSEI) model of care for subclinical BCRL.Methods: The parent randomized clinical trial assigned patients newly diagnosed with breast cancer to PSEI with either bioimpedance spectroscopy (BIS) or tape measurement (TM). Surgical, systemic and radiation treatments, comorbidities, and lifestyle factors were recorded. Detection of subclinical BCRL (change from baseline of either BIS L-Dex ≥6.5 or tape volume ≥ 5% and < 10%) triggered an intervention with compression therapy. Volume change from baseline ≥10% indicated progression to chronic lymphedema and need for complex decongestive physiotherapy. In this secondary analysis, multinomial logistic regressions including main and interaction effects of the study group and risk factors were used to test for factor associations with outcomes (no lymphedema, subclinical lymphedema, progression to chronic lymphedema after intervention, progression to chronic lymphedema without intervention). Post hoc tests of significant interaction effects were conducted using Bonferroni-corrected alphas of .008; otherwise, an alpha of .05 was used for statistical significance.Results: The sample (n = 918; TM = 457; BIS = 461) was female with a median age of 58.4 years. Factors associated with BCRL risk included axillary lymph node dissection (ALND) (p < .001), taxane-based chemotherapy (p < .001), regional nodal irradiation (RNI) (p ≤ .001), body mass index >30 (p = .002), and rurality (p = .037). Mastectomy, age, hypertension, diabetes, seroma, smoking, and air travel were not associated with BCRL risk.Conclusions: Within the context of 3 years of PSEI for subclinical lymphedema, variables of ALND, taxane-based chemotherapy, RNI, body mass index >30, and rurality increased risk. [ABSTRACT FROM AUTHOR]

The article provides information on a learning activity for medical students that uses Play-Doh as a tool to teach creative data collection. Topics discussed include steps involved in the learning activity, reason for including a variety of colours when purchasing more Play-Doh for the next cohort, and lessons learned from the activity.

Methylglyoxal (MG) production after myocardial infarction (MI) leads to advanced glycation end‐product formation, adverse remodeling, and loss of cardiac function. The extracellular matrix (ECM) is a main target for MG glycation. This suggests that ECM‐mimicking biomaterial therapies may protect the post‐MI environment by removing MG. In this study, mechanisms by which a recombinant human collagen type I hydrogel therapy confers cardioprotection are investigated. One‐week post‐MI, mice receive intramyocardial injection of hydrogel or PBS. The hydrogel improves border zone contractility after 2 days, which is maintained for 28 days. RNA sequencing shows that hydrogel treatment decreases the expression of erythroid differentiation regulator 1, a factor associated with apoptosis. Hydrogel treatment reduces cardiomyocyte apoptosis and oxidative stress at 2 days with greater myocardial salvage seen at 28 days. The hydrogel located at the epicardial surface is modified by MG, and less MG‐modified proteins are observed in the underlying myocardium of hydrogel‐treated mice. Biomaterials that can be a target for MG glycation may act as a sponge to remove MG from the myocardium post‐MI. This leads to less oxidative stress, greater survival and contractility of cardiomyocytes, which altogether suggests a novel mechanism by which biomaterials improve function of the infarcted heart. [ABSTRACT FROM AUTHOR]

Although pectoralis (PECS) blocks are commonly used for breast surgery, recommendations regarding the efficacy of these blocks have thus far not been developed by any professional anesthesia society. Given the potential impact of PECS blocks on analgesia after outpatient breast surgery, The Society for Ambulatory Anesthesia (SAMBA) convened a task force to develop a practice advisory on the use of this analgesic technique. In this practice advisory, we compare the efficacy of PECS blocks with systemic analgesia, local infiltration anesthesia, and paravertebral blockade. Our objectives were to advise on two clinical questions. (1) Does PECS-1 and/or -2 blockade provide more effective analgesia for breast-conserving surgery than either systemic analgesics or surgeon-provided local infiltration anesthesia? (2) Does PECS-1 and/or -2 blockade provide equivalent analgesia for mastectomy compared with a paravertebral block (PVB)? Among patients undergoing breast-conserving surgery, PECS blocks moderately reduce postoperative opioid use, prolong time to analgesic rescue, and decrease postoperative pain scores when compared with systemic analgesics. SAMBA recommends the use of a PECS-1 or -2 blockade in the absence of systemic analgesia (Strength of Recommendation A). No evidence currently exists that strongly favors the use of PECS blocks over surgeon-performed local infiltration in this surgical population. SAMBA cannot recommend PECS blocks over surgical infiltration (Strength of Recommendation C). For patients undergoing a mastectomy, a PECS block may provide an opioid-sparing effect similar to that achieved with PVB; SAMBA recommends the use of a PECS block if a patient is unable to receive a PVB (Strength of Recommendation A). [ABSTRACT FROM AUTHOR]

Controversy exists regarding the influence of breast cancer–related lymphedema (BCRL) in the development of peripheral neuropathies. Our aim was to evaluate the association of secondary lymphedema with peripheral neuropathies in patients with breast cancer. We performed a systematic review by querying PubMed, EMBASE, Ovid Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Cochrane Central Register of Controlled Trials databases. The keywords "lymphedema" AND ("neuropathy" OR "carpal tunnel syndrome" OR "cubital tunnel syndrome" OR "neuropathic pain") and synonyms in titles and abstracts were used to perform the search. Seventeen articles met the inclusion criteria. Discrepancies were found in studies that analyzed whether a cause-effect association exists between carpal tunnel syndrome (CTS) and secondary lymphedema. No evidence indicated that lymphedema predisposes to developing peripheral neuropathies such as CTS or brachial plexopathy. No studies found an association between patients with breast cancer at risk of or with lymphedema and the development or worsening of CTS. Carpal tunnel release can be safely performed in patients with BCRL. Neuropathic pain worsens with lymphedema, and treatment seems to improve the pain. Our study did not find enough evidence to conclude that BCRL is associated with the development of peripheral neuropathies. Carpal tunnel release is a safe procedure that can be performed in patients with BCRL and does not influence the development or worsening of lymphedema. Neuropathic pain seems to worsen after development of lymphedema, and treatment has been found to improve neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Preoperative breast MRI is indicated for staging but can lead to complex imaging workups. This study reviewed imaging recommendations made on preoperative MRI exams, to simplify management approaches for patients with newly diagnosed breast cancer. Methods: This retrospective single-institution review was restricted to women with breast cancer who underwent staging MRI. Additional breast lesions, separate from index tumors, recommended for additional workup or surveillance were assessed to see which were detected and which characteristics predicted success in detection. Univariate mixed-effects logistic modeling predicted the likelihood of finding lesions using MRI-directed ultrasound (US), with odds ratios reported. Tests were two-sided, with a p value lower than 0.05 considered significant. Results: In this study, 534 (39.6%) patients had recommendations for additional workup after preoperative MRI. MRI detected additional malignancy in 178 patients (33.3%). Half of the 66 patients who refused an additional workup and opted for mastectomy had additional malignancies at mastectomy. MRI-directed US was 14 times more likely to detect masses than nonmass enhancement (NME) (p < 0.001). NME was detected on US in only 16% of cases, with one third of subsequent biopsy results considered discordant. Probably benign assessments were given to 35 patients, with 23% not returning for follow-up evaluation and 7% returning at least 6 months later than recommended. Conclusion: Use of preoperative breast MRI has increased. Although it can add value, institutions should establish indications and expectations to prevent unnecessary workups. Limiting MRI-directed US to masses, avoiding probably benign assessments, and consulting with patients after MRI but prior to workups can prevent unnecessary exams and confusion. [ABSTRACT FROM AUTHOR]

Cell Communication Network factor 4 (CCN4/WISP1) is a matricellular protein secreted by cancer cells that promotes metastasis by inducing the epithelial–mesenchymal transition. While metastasis limits survival, limited anti‐tumor immunity also associates with poor patient outcomes with recent work linking these two clinical correlates. Motivated by increased CCN4 correlating with dampened anti‐tumor immunity in primary melanoma, we test for a direct causal link by knocking out CCN4 (CCN4 KO) in the B16F0 and YUMM1.7 mouse melanoma models. Tumor growth is reduced when CCN4 KO melanoma cells are implanted in immunocompetent but not in immunodeficient mice. Correspondingly, CD45+ tumor‐infiltrating leukocytes are significantly increased in CCN4 KO tumors, with increased natural killer and CD8+ T cells and reduced myeloid‐derived suppressor cells (MDSC). Among mechanisms linked to local immunosuppression, CCN4 suppresses IFN‐gamma release by CD8+ T cells and enhances tumor secretion of MDSC‐attracting chemokines like CCL2 and CXCL1. Finally, CCN4 KO potentiates the anti‐tumor effect of immune checkpoint blockade (ICB) therapy. Overall, our results suggest that CCN4 promotes tumor‐induced immunosuppression and is a potential target for therapeutic combinations with ICB. Synopsis: Cell Communication Network factor 4, a secreted matricellular protein that promotes metastasis in melanoma, also suppresses anti‐tumor immunity via autocrine and paracrine mechanisms. CCN4 is a potential target in combination with immune checkpoint blockade therapy. Knockout of CCN4 reduces tumor growth and increases overall survival only in immunocompetent mice.CCN4 suppresses antitumor immunity by promoting CCL2 and CXCL1 secretion, leading to increased MDSC infiltration.CCN4 suppresses IFN‐γ release by CD8+ T cells through a paracrine mechanism resulting in lower CD45+ cell numbers.Knockout of CCN4 complements immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

Background: Plasmodium interspersed repeat (pir) is the largest multigene family in the genomes of most Plasmodium species. A variety of functions for the PIR proteins which they encode have been proposed, including antigenic variation, immune evasion, sequestration and rosetting. However, direct evidence for these is lacking. The repetitive nature of the family has made it difficult to determine function experimentally. However, there has been some success in using gene expression studies to suggest roles for some members in virulence and chronic infection. Methods: Here pir gene expression was examined across the life cycle of Plasmodium berghei using publicly available RNAseq data-sets, and at high resolution in the intraerythrocytic development cycle using new data from Plasmodium chabaudi. Results: Expression of pir genes is greatest in stages of the parasite which invade and reside in red blood cells. The marked exception is that liver merozoites and male gametocytes produce a very large number of pir gene transcripts, notably compared to female gametocytes, which produce relatively few. Within the asexual blood stages different subfamilies peak at different times, suggesting further functional distinctions. Representing a subfamily of its own, the highly conserved ancestral pir gene warrants further investigation due to its potential tractability for functional investigation. It is highly transcribed in multiple life cycle stages and across most studied Plasmodium species and thus is likely to play an important role in parasite biology. Conclusions: The identification of distinct expression patterns for different pir genes and subfamilies is likely to provide a basis for the design of future experiments to uncover their function. [ABSTRACT FROM AUTHOR]

Background: In 2017, the American Society of Breast Surgeons (ASBrS) published expert panel recommendations for patients at risk for breast cancer-related lymphedema (BCRL) and those affected by BCRL. This study sought to determine BCRL practice patterns. Methods: A survey was sent to 2975 ASBrS members. Questions evaluated members' clinical practice type, practice duration, and familiarity with BCRL recommendations. Descriptive statistics, the chi-square test, and Fisher's exact test were used. Results: Of the ASBrS members surveyed, 390 (13.1%) responded. Most of the breast surgeons (58.5%, 228/390) indicated unfamiliarity with recommendations. Nearly all respondents (98.7%, 385/390) educate at-risk patients. Most (60.2%, 234/389) instruct patients to avoid venipuncture, injection or blood pressure measurements in the at-risk arm, and 35.6% (138/388) recommend prophylactic compression sleeve use during air travel. Nearly all (97.7%, 380/389) encourage those at-risk to exercise, including resistance exercise (86.2%, 331/384). Most do not perform axillary reverse mapping (ARM) (67.9%, 264/389) or a lymphatic preventive healing approach (LYMPHA) (84.9%, 331/390). Most (76.1%, 296/389) screen at-risk patients for BCRL. The most frequently used screening tools include self-reported symptoms (81%, 255/315), circumferential tape measure (54%, 170/315) and bioimpedance spectroscopy (27.3%, 86/315). After a BCRL diagnosis, most (90%, 351/390) refer management to a lymphedema-certified physical therapist. For affected patients, nearly all encourage exercise (98.7%, 384/389). Many (49%, 191/390) refer affected patients for consideration of lymphovenous bypass or lymph node transfer. Conclusion: Most respondents were unfamiliar with the ASBrS expert panel recommendations for patients at risk for BCRL and those affected by BCRL. Opportunities exist to increase awareness of best practices and to acquire ARM and LYMPHA technical expertise. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bioimpedance spectroscopy has been suggested as a useful tool for early diagnosis of breast cancer–related lymphedema (BCRL). We aimed to describe the outcomes of published studies that evaluated bioimpedance analysis as a method for prospective surveillance and early diagnosis of BCRL. METHODS: We queried the PubMed, Ovid Medline, and EMBASE databases to identify studies that evaluated use of bioimpedance spectroscopy as a diagnostic tool. We used the keywords "bioimpedance" AND ("lymphedema" OR "lymphoedema") in the search. Only English-language studies that reported quantitative outcomes for patients with BCRL were included. RESULTS: Of 152, 235 and 116 identified articles in PubMed, Ovid Medline and EMBASE databases, only 22 were included. Use of bioimpedance analysis for prospective surveillance has been shown to prevent chronic BCRL. All the cross-sectional and retrospective studies that evaluated bioimpedance for diagnosis of BCRL reported significantly different L-Dex scores between lymphedema patients and healthy participants; in addition, bioimpedance scores were positively correlated with volume of lymphedema. CONCLUSION: Bioimpedance analysis is a potential tool with demonstrated benefits for prevention of chronic BCRL and may be an economic and great alternative for early diagnosis of BCRL. [ABSTRACT FROM AUTHOR]

Purpose: Study objectives were to examine: (a) biomarker trajectories (change from presurgical baseline values of Lymphedema index (L‐Dex) units and arm volume difference) and symptom cluster scores 24 months after breast cancer surgery and (b) associations of these objective biomarkers and symptom cluster scores. Patient/treatment characteristics influencing trajectories were also evaluated. Methods: A secondary analysis of data from the published interim analysis of a randomized parent study was undertaken using trajectory analysis. Five hundred and eight participants included in the prior analysis with 24 months of postsurgical follow‐up were initially measured with bioelectric impedance spectroscopy (BIS) and tape measure (TM) and completed self‐report measures. Patients were reassessed postsurgery for continuing eligibility and then randomized to either BIS or TM groups and measured along with self‐report data at regular and optional* visits 3, 6,12,15*,18, 21*, and 24‐months. Results: Three subclinical trajectories were identified for each biomarker (decreasing, stable, increasing) and symptom cluster scores (stable, slight increase/decrease, increasing). Subclinical lymphedema was identified throughout the 24‐month period by each biomarker. An L‐Dex increase at 15 months in the BIS group was noted. The self‐report sets demonstrated contingency coefficients of 0.20 (LSIDS‐A soft tissue, P =.031) and 0.19 (FACTB+4, P =.044) with the L‐Dex unit change trajectories. Conclusions: These data support the need for long‐term (24 months) prospective surveillance with frequent assessments (every 3 months) at least 15 months after surgery. Statistically significant convergence of symptom cluster scores with L‐Dex unit change supports BIS as beneficial in the early identification of subclinical lymphedema. [ABSTRACT FROM AUTHOR]

BACKGROUND: Paget's disease of the breast is rare. The National Cancer Database (NCDB) is one of the largest tumor databases in the United States. METHODS: We queried the NCDB to identify male and female patients with Paget's disease of the breast who were treated from January 1, 2004, through December 31, 2015. No age limitations were applied. Descriptive statistical analysis and survival analysis were performed. RESULTS: We analyzed the demographic, disease, and treatment characteristics of 7,191 patients with Paget's disease of the breast. The median (range) age was 64 (20–90) years. Only 2.1% of patients were men, and 85.4% were white. The most common treatment was complete mastectomy (65.3%), followed by partial mastectomy (30.3%). Tumor destruction was performed in 0.1% of patients, and 4.3% of patients did not undergo any surgery. We examined survival in the subset of 6,864 patients who were treated surgically with complete mastectomy or partial mastectomy. The 5-year survival rate after surgery was 82.5% (95% CI, 81.1%–83.9%). Factors associated with shorter survival were older age, black race/ethnicity, higher tumor grade, regional lymph node metastasis, higher cancer stage, metastatic cancer, and larger tumor size. CONCLUSIONS: Paget's disease of the breast usually affects patients older than 60 years, and the most common treatment is complete mastectomy. The 5-year overall survival rate of patients with Paget's disease of the breast is greater than 80% but is lower among older and black people. [ABSTRACT FROM AUTHOR]

Background and Objectives: Omission of routine axillary staging and adjuvant radiation (XRT) in women ≥ 70 years old with early stage, hormone receptor‐positive, clinically node‐negative breast cancer has been endorsed based on several landmark studies. We sought to determine how much omission of axillary staging/XRT has been adopted. Methods: Using the National Cancer Data Base, we selected malignant breast cancer cases in women ≥ 70 with ER + tumors, ≤2 cm with clinically negative lymph nodes who underwent breast conservation and had known XRT status in 2005‐2015. The use of sentinel lymph node biopsy (SNB) and XRT status was summarized by year to determine trends over time. Results: In total, 57 230/69 982 patients underwent SNB. Of the 12 752 patients in whom SNB was omitted, 6296 were treated at comprehensive community cancer programs. Regarding XRT, 33 891/70 114 received adjuvant XRT. There were no significant trends with regards to patients receiving SNB or those receiving XRT. Conclusion: Since 2005, there has been no change in SNB or XRT for early stage ER + breast tumors. However, there was a difference in omission of SNB based on facility type and setting. Future monitoring is needed to determine if these trends persist following the recently released Choosing Wisely® recommendations. [ABSTRACT FROM AUTHOR]

Breast cancer treatment-related lymphedema (BCRL) is a common comorbidity in breast cancer survivors. Although magnetic resonance imaging (MRI) is widely used to evaluate therapeutic response of patients with various medical conditions, it is not routinely used to evaluate lymphedema patients. We conducted a systematic review of the literature to identify studies on the use of MRI to evaluate therapy for BCRL. We hypothesized that MRI could provide information otherwise not possible through other examinations. On October 21, 2019, we conducted a systematic review on the PubMed/MEDLINE and Scopus databases, without time frame or language limitations, to identify studies on the use of MRI to evaluate therapy for BCRL. We excluded studies that investigated other applications of MRI, such as lymphedema diagnosis and surgical planning. Of 63 potential articles identified with the search, three case series fulfilled the eligibility criteria. In total, 53 patients with BCRL were included and quantitatively evaluated with MRI before and after manual lymphatic drainage. Authors used MRI or MR lymphagiography to investigate factors such as lymphatic vessel cross-sectional area, tissue water relaxation time (T2), and chemical exchange saturation transfer. The only study that compared MRI measurement with standard examinations reported that MRI added information to the therapy evaluation. MRI seems to be a promising tool for quantitative measurement of therapeutic response in patients with BCRL. However, the identified studies focused on only manual lymphatic drainage and were limited by the small numbers of patients. More studies are necessary to shed light on the topic. [ABSTRACT FROM AUTHOR]

Background: Unlike other breast cancer subtypes that may be treated with a variety of hormonal or targeted therapies, there is a need to identify new, effective targets for triple-negative breast cancer (TNBC). It has recently been recognized that membrane potential is depolarized in breast cancer cells. The primary objective of the study is to explore whether hyperpolarization induced by opening potassium channels may provide a new strategy for treatment of TNBC.Methods: Breast cancer datasets in cBioPortal for cancer genomics was used to search for ion channel gene expression. Immunoblots and immunohistochemistry were used for protein expression in culture cells and in the patient tissues. Electrophysiological patch clamp techniques were used to study properties of BK channels in culture cells. Flow cytometry and fluorescence microscope were used for cell viability and cell cycle studies. Ultrasound imaging was used to study xenograft in female NSG mice.Results: In large datasets of breast cancer patients, we identified a gene, KCNMA1 (encoding for a voltage- and calcium-dependent large-conductance potassium channel, called BK channel), overexpressed in triple-negative breast cancer patients. Although overexpressed, 99% of channels are closed in TNBC cells. Opening BK channels hyperpolarized membrane potential, which induced cell cycle arrest in G2 phase and apoptosis via caspase-3 activation. In a TNBC cell induced xenograft model, treatment with a BK channel opener significantly slowed tumor growth without cardiac toxicity.Conclusions: Our results support the idea that hyperpolarization induced by opening BK channel in TNBC cells can become a new strategy for development of a targeted therapy in TNBC. [ABSTRACT FROM AUTHOR]

Introduction: Cellular communication network factor 4 (CCN4/WISP1) is a secreted matricellular protein that stimulates metastasis in multiple malignancies but has an unclear impact on phenotypic changes in melanoma. Recent data using cells edited via a double-nickase CRISPR/Cas9 approach suggest that CCN4/WISP1 stimulates invasion and metastasis of melanoma cells. While these data also suggest that loss of CCN4/WISP1 increases cell proliferative, the CRISPR approach used may be an alternative explanation rather than the loss of gene function. Methods: To test whether CCN4/WISP1 also influences the proliferative phenotype of melanoma cells, we used mouse melanoma models and knocked out Ccn4 using a homology-directed repair CRISPR/Cas9 system to generate pools of Ccn4-knockout cells. The resulting edited cell pools were compared to parental cell lines using an ensemble of in vitro and in vivo assays. Results: In vitro assays using knockout pools supported previous findings that CCN4/WISP1 promoted an epithelial–mesenchymal-like transition in melanoma cells and stimulated invasion and metastasis. While Ccn4 knockout also enhanced cell growth in optimal 2D culture conditions, the knockout suppressed certain cell survival signaling pathways and rendered cells less resistant to stress conditions. Tumor cell growth assays at sub-optimal conditions in vitro, quantitative analysis of tumor growth assays in vivo, and transcriptomics analysis of human melanoma cell lines were also used to quantify changes in phenotype and generalize the findings. Conclusions: In addition to stimulating invasion and metastasis of melanoma cells, the results suggested that CCN4/WISP1 repressed cell growth and simultaneously enhanced cell survival. [ABSTRACT FROM AUTHOR]

Background  Lymphedema is an accumulation of protein-rich fluid in the interstitial spaces resulting from impairment in the lymphatic circulation that can impair quality of life and cause considerable morbidity. Lower extremity lymphedema (LEL) has an overall incidence rate of 20%. Conservative therapies are the first step in treatment of LEL; however, they do not provide a cure because they fail to address the underlying physiologic dysfunction of the lymphatic system. Among several surgical alternatives, lymphaticovenous anastomosis (LVA) has gained popularity due to its improved outcomes and less invasive approach. This study aims to review the published literature on LVA for LEL treatment and to analyze the surgical outcomes. Methods  PubMed database was used to perform a comprehensive literature review of all articles describing LVA for treatment of LEL from Novemeber 1985 to June 2019. Search terms included "lymphovenous" OR "lymphaticovenous" AND "bypass" OR "anastomosis" OR "shunt" AND "lower extremity lymphedema." Results  A total of 95 articles were identified in the initial query, out of which 58 individual articles were deemed eligible. The studies included in this review describe notable variations in surgical techniques, number of anastomoses, and supplementary interventions. All, except one study, reported positive outcomes based on limb circumference and volume changes or subjective clinical improvement. The largest reduction rate in limb circumference and volume was 63.8%. Conclusion  LVA demonstrated a considerable reduction in limb volume and improvement in subjective findings of lymphedema in the majority of patients. The maintained effectiveness of this treatment modality in long-term follow-up suggests great efficacy of LVA in LEL treatment. [ABSTRACT FROM AUTHOR]