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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]

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]

The goal of this study was to develop strategies to localize human collagen-based hydrogels within an infarcted mouse heart, as well as analyze its impact on endogenous extracellular matrix (ECM) remodeling. Collagen is a natural polymer that is abundantly used in bioengineered hydrogels because of its biocompatibility, cell permeability, and biodegradability. However, without the use of tagging techniques, collagen peptides derived from hydrogels can be difficult to differentiate from the endogenous ECM within tissues. Imaging mass spectrometry is a robust tool capable of visualizing synthetic and natural polymeric molecular structures yet is largely underutilized in the field of biomaterials outside of surface characterization. In this study, our group leveraged a recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technique to enzymatically target collagen and other ECM peptides within the tissue microenvironment that are both endogenous and hydrogel-derived. Using a multimodal approach of fluorescence microscopy and ECM-IMS techniques, we were able to visualize and relatively quantify significantly abundant collagen peptides in an infarcted mouse heart that were localized to regions of therapeutic hydrogel injection sites. On-tissue MALDI MS/MS was used to putatively identify sites of collagen peptide hydroxyproline site occupancy, a post-translational modification that is critical in collagen triple helical stability. Additionally, the technique could putatively identify over 35 endogenously expressed ECM peptides that were expressed in hydrogel-injected mouse hearts. Our findings show evidence for the use of MALDI-IMS in assessing the therapeutic application of collagen-based biomaterials. [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]

The physical and psychological side effects of breast cancer therapies can have substantial impact on survivors' physical and social functioning. Roughly half of the more than 3 million Americans alive with a history of breast cancer report adverse, function-degrading sequelae related to their oncologic treatments. Care delivery models for the timely delivery of rehabilitation services have been proposed yet limitedly vetted or implemented. These include the prospective surveillance model, procedure-linked referrals, survivorship care plans, and risk stratification. Patients' capacity to engage in the rehabilitative process varies during cancer therapy and into survivorship. Perioperative attention generally focuses on managing premorbid impairments and normalizing shoulder function. In contrast, during chemotherapy and radiation therapy, symptom control, constructive coping, and role preservation may become more salient. Risk-stratified, individualized screening and prevention activities for specific impairments have become increasingly feasible through predictive models and analytics. Impairments' severity deleterious impact can be mitigated, as has been established for lymphedema, shoulder dysfunction, chemotherapy-induced peripheral neuropathy, cognitive dysfunction, fatigue, and sexual side effects. Integrated rehabilitative programs, often initiated after the completion of cancer treatment, are available in some countries outside of the United States and may offer survivors vital vocation and avocation-directed services. [ABSTRACT FROM AUTHOR]

Introduction: MEAAP, a charitable organisation, used an "Asset Based Community Development" approach to collaborate with local Health Care Practitioners and Commissioners to develop an integrated care model which aimed to improve quality of life for older people in our community by putting wellbeing on a par with medical needs, namely IMPACTAgewell®. MEAAP secured an investment of £1,000,000 in 2016 to 'prove' the IMPACTAgewell® multidisciplinary model of care, over a 3 year period. This was awarded via The Dunhill Medical Trust's UK-wide call for proposals to deliver a "bottom-up, community asset based approach to delivering social care for Older People. Aims Objectives Theory or Methods: Six 'Locality Hubs' were established in 2017, meeting monthly in GP Practices with a Community Pharmacist, Social Worker and their IMPACTAgewell® Officer. Together, the members identify Older People, 65 years old and over, who are most at risk and/or vulnerable, to secure initial consent. This allows the IMPACTAgewell® Officer to commence support over a 6 month period. The Older Person is supported by their Locality Hub to develop a 'Health and Well-being Action Plan' namely their "My IMPACTAgewell Plan", based on the social determinants of health, focusing on their home, wellbeing, health, community and future. Highlights or Results or Key Findings: By March 2020, IMPACTAgewell® has expanded to 16 Locality Hubs, received 1,300 referrals and published our 'Action Research Evaluation' results: • Fiscal Return on Investment (FROI) - for every £1 invested, £1.87 of savings has been generated in terms of unscheduled health and social care. • Social Return on Investment (SROI) - for every £1 invested, £2.52 of a social return on investment has been achieved when considering all service users, health care practitioners and carers. • Community Pharmacy Ratio - for every £1 spent on community pharmacists within the project they delivered savings of £3.86. • Older People Surveys - Increasing satisfaction suggests that older people were accessing support they hadn't previously. • Health Care Practitioners - A significant increase in "Stronger partnerships" (15% net) and "improvement in Skills and Knowledge" (11% net), with a marginal increase in "increasing job satisfaction" (3% net). This was despite a small "increase in time pressures" (-3.3% net). Conclusions: An "Asset Based Community Development" approach and strong partnerships ensured IMPACTAgewell® could adapt to the COVID-19 pandemic. A scoping exercise gained feedback for what support was needed for service users and health care practitioners. This led to offering multiple services of support via telephone, doorstep/home visits and video conferencing. Implications for applicability/transferability sustainability and limitations: MEAAP secured commitment from the Health & Social Care Board to sustain IMPACTAgewell® in partnership with The Dunhill Medical Trust, fund the scale and spread of the model and allow MEAAP to establish a trading subsidiary to potentially cascade the learning to extend IMPACTAgewell® beyond Mid & East Antrim. [ABSTRACT FROM AUTHOR]

Modeling metastasis in vivo with animals is a priority for both revealing mechanisms of tumor dissemination and developing therapeutic methods. While conventional intravenous injection of tumor cells provides an efficient and consistent system for studying tumor cell extravasation and colonization, studying spontaneous metastasis derived from orthotopic tumor sites has the advantage of modeling more aspects of the metastatic cascade, but is challenging as it is difficult to detect small numbers of metastatic cells. In this work, we developed an approach for quantifying spontaneous metastasis in the syngeneic mouse B16 system using real time PCR. We first transduced B16 cells with lentivirus expressing firefly luciferase Luc2 gene for bioluminescence imaging. Next, we developed a real time quantitative PCR (qPCR) method for the detection of luciferase-expressing, metastatic tumor cells in mouse lungs and other organs. To illustrate the approach, we quantified lung metastasis in both spontaneous and experimental scenarios using B16F0 and B16F10 cells in C57BL/6Ncrl and NOD-Scid Gamma (NSG) mice. We tracked B16 melanoma metastasis with both bioluminescence imaging and qPCR, which were found to be self-consistent. Using this assay, we can quantitatively detect one Luc2 positive tumor cell out of 104 tissue cells, which corresponds to a metastatic burden of 1.8 × 104 metastatic cells per whole mouse lung. More importantly, the qPCR method was at least a factor of 10 more sensitive in detecting metastatic cell dissemination and should be combined with bioluminescence imaging as a high-resolution, end-point method for final metastatic cell quantitation. Given the rapid growth of primary tumors in many mouse models, assays with improved sensitivity can provide better insight into biological mechanisms that underpin tumor metastasis. [ABSTRACT FROM AUTHOR]

Background: Human triple-negative breast cancer has limited therapeutic choices. Breast tumor cells have depolarized plasma membrane potential. Using this unique electrical property, we aim to develop an effective selective killing of triple-negative breast cancer.Methods: We used an engineered L-type voltage-gated calcium channel (Cec), activated by membrane depolarization without inactivation, to induce excessive calcium influx in breast tumor cells. Patch clamp and flow cytometry were used in testing the killing selectivity and efficiency of human breast tumor cells in vitro. Bioluminescence and ultrasound imaging were used in studies of human triple-negative breast cancer cell MDA-MB-231 xenograft in mice. Histological staining, immunoblotting and immunohistochemistry were used to investigate mechanism that mediates Cec-induced cell death.Results: Activating Cec channels expressed in human breast cancer MCF7 cells produced enormous calcium influx at depolarized membrane. Activating the wild-type Cav1.2 channels expressed in MCF7 cells also produced a large calcium influx at depolarized membrane, but this calcium influx was diminished at the sustained membrane depolarization due to channel inactivation. MCF7 cells expressing Cec died when the membrane potential was held at -10 mV for 1 hr, while non-Cec-expressing MCF7 cells were alive. MCF7 cell death was 8-fold higher in Cec-expressing cells than in non-Cec-expressing cells. Direct injection of lentivirus containing Cec into MDA-MB-231 xenograft in mice inhibited tumor growth. Activated caspase-3 protein was detected only in MDA-MB-231 cells expressing Cec, along with a significantly increased expression of activated caspase-3 in xenograft tumor treated with Cec.Conclusions: We demonstrated a novel strategy to induce constant calcium influx that selectively kills human triple-negative breast tumor cells. [ABSTRACT FROM AUTHOR]

We have developed a rapid colorimetric method to determine the concentration of denatured collagen in solution, which is based on the collagen-silver nanoparticle corona formation. Using the proposed method, the lowest detectable concentration of denatured collagen protein in a solution of pure collagen was 14.7, 8.5, and 8.6 μg mL for porcine (PCOL), rat tail (RCOL), and type I human recombinant (HCOL) collagen, respectively. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Epidemiological studies provide strong evidence that obesity and the associated adipose tissue inflammation are risk factors for breast cancer; however, the molecular mechanisms are poorly understood. We evaluated the effect of a high-fat/high-calorie diet on mammary carcinogenesis in the immunocompetent MMTV-PyMT murine model. Four-week old female mice (20/group) were randomized to receive either a high-fat (HF; 60% kcal as fat) or a low-fat (LF; 16% kcal) diet for eight weeks. Body weights were determined, and tumor volumes measured by ultrasound, each week. At necropsy, the tumors and abdominal visceral fat were weighed and plasma collected. The primary mammary tumors, adjacent mammary fat, and lungs were preserved for histological and immunohistochemical examination and quantification of infiltrating macrophages, crown-like structure (CLS) formation, and microvessel density. The body weight gains, visceral fat weights, the primary mammary tumor growth rates and terminal weights, were all significantly greater in the HF-fed mice. Adipose tissue inflammation in the HF group was indicated by hepatic steatosis, pronounced macrophage infiltration and CLS formation, and elevations in plasma monocyte chemoattractant protein-1 (MCP-1), leptin and proinflammatory cytokine concentrations. HF intake was also associated with higher tumor-associated microvascular density and the proangiogenic factor MCP-1. This study provides preclinical evidence in a spontaneous model of breast cancer that mammary adipose tissue inflammation induced by diet, enhances the recruitment of macrophages and increases tumor vascular density suggesting a role for obesity in creating a microenvironment favorable for angiogenesis in the progression of breast cancer. [ABSTRACT FROM AUTHOR]

Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO) and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular) lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA) biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl). Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy. [ABSTRACT FROM AUTHOR]

Aurora A kinase (AURKA) is overexpressed in 96% of human cancers and is considered an independent marker of poor prognosis. While the majority of tumors have elevated levels of AURKA protein, few have AURKA gene amplification, implying that posttranscriptional mechanisms regulating AURKA protein levels are significant. Here, we show that NEDD9, a known activator of AURKA, is directly involved in AURKA stability. Analysis of a comprehensive breast cancer tissue microarray revealed a tight correlation between the expression of both proteins, significantly corresponding with increased prognostic value. A decrease in AURKA, concomitant with increased ubiquitination and proteasome-dependent degradation, occurs due to depletion or knockout of NEDD9. Reexpression of wild-type NEDD9 was sufficient to rescue the observed phenomenon. Binding of NEDD9 to AURKA is critical for AURKA stabilization, as mutation of S296E was sufficient to disrupt binding and led to reduced AURKA protein levels. NEDD9 confers AURKA stability by limiting the binding of the cdh1-substrate recognition subunit of APC/C ubiquitin ligase to AURKA. Depletion of NEDD9 in tumor cells increases sensitivity to AURKA inhibitors. Combination therapy with NEDD9 short hairpin RNAs and AURKA inhibitors impairs tumor growth and distant metastasis in mice harboring xenografts of breast tumors. Collectively, our findings provide rationale for the use of AURKA inhibitors in treatment of metastatic tumors and predict the sensitivity of the patients to AURKA inhibitors based on NEDD9 expression. [ABSTRACT FROM AUTHOR]

Background: Lymphedema is a feared complication of breast cancer surgery. We evaluated the trends in lymphedema development, patient worry, and risk reduction behaviors. Study Design: We prospectively enrolled 120 women undergoing sentinel node biopsy (SLNB) or axillary node dissection (ALND) for breast cancer and assessed lymphedema by upper extremity volume preoperatively and at 6 and 12 months postoperatively. We defined lymphedema as a >10% volume change from baseline relative to the contralateral upper extremity. Patients completed a validated instrument evaluating lymphedema worry and risk reducing behaviors. Associations were determined by Fisher''s exact and signed rank tests. Results: At 6 months, lymphedema was similar between ALND and SLNB patients (p = 0.22), but was higher in ALND women at 12 months (19% vs 3%, p = 0.005). A clear relationship exists between relative change in upper extremity volume at 6 and 12 months (Kendall tau coefficient 0.504, p < 0.001). Among the women with 0 to 9% volume change at 6 months, 22% had progressive swelling, and 18% resolved their volume changes at 12 months. Overall, 75% of ALND and 50% of SLNB patients had persistent worry about lymphedema at follow-up, and no difference existed in the number of risk reducing behaviors practiced among the 2 groups (p > 0.34). Conclusions: Upper extremity volumes fluctuate, and there is a period of latency before development of lymphedema. Despite the low risk of lymphedema after SLNB, most women worry about lymphedema and practice risk reducing behaviors. Additional study into early upper extremity volume changes is warranted to allay the fears of most women and better predict which women will progress to lymphedema. [Copyright &y& Elsevier]

Lymphedema is a chronic debilitating condition affecting many long-term breast cancer survivors. The incidence of lymphedema is reported to range from 6% to 70% after axillary surgery for breast cancer; however, its true incidence has been difficult to quantify because of the lack of standard diagnostic and universal assessment criteria. Extent of nodal dissection, axillary radiation, injury, and infection in the ipsilateral upper extremity remain significant risk factors for the development of lymphedema. Current changes in axillary management, including the adoption of sentinel node biopsy, the selective omission of completion axillary dissection after a positive sentinel node, and the elimination of axillary staging, have been proposed to further reduce axillary morbidity. Early research on lymphedema risk reduction focuses on supervised weight training after axillary surgery, axillary reverse mapping to avoid removal of lymph nodes draining the upper extremity, and incorporation of fused single photon emission computed tomography (SPECT)-CT axillary nodal images to better plan adjuvant radiation treatments. [ABSTRACT FROM AUTHOR]

Abstract: Background: The accuracy of magnetic resonance imaging (MRI) in identifying residual disease after breast conservation therapy (BCT) is unclear. Method: Review of an institutional database identified patients with positive or close (≤2 mm) margins undergoing MRI before re-excision. Histopathologic correlation was performed. Results: Forty-three women underwent MRI after BCT. MRI suggested residual disease in 29 patients, of whom 20 (69%) had residual carcinoma pathologically. Nine patients had false-positive MRI as seen by benign pathology findings. Fourteen MRIs indicated no residual disease, of which 6 had residual disease pathologically. The sensitivity and positive predictive value of MRI was 77% and 69%, respectively. MRI conducted within 28 days of the original surgery was 85% sensitive. MRI performed after 28 days was 69% sensitive. Conclusions: MRI is able to detect residual disease among most patients undergoing re-excision. False-positive results may be caused by inflammatory processes that resemble residual disease. [Copyright &y& Elsevier]

The article discusses a study on the cost-effectiveness of preoperative magnetic resonance imaging (MRI) in selecting patients for prophylactic mastectomy (PM) with or without sentinel lymph node biopsy (SLNB). Six hundred-thirteen PMs were performed in 529 study population between January 1999 and January 2006. Such a surgical operation is frequently recommended as an alternative to intensive screening for patients with known mutations of the BRCA1 or BRCA2 genes. Characteristics of patients who underwent PM with or without SLNB are also cited.

Background: Frozen-section analysis (FS) of the sentinel lymph node (SLN) is performed to avoid reoperation for axillary lymph node dissection (ALND), but it can miss micrometastatic disease, is labor intensive for the pathologist, and does not alter the number of breast-conservation therapy (BCT) patients needing reoperation for positive margins. The purpose of this study was to determine if eliminating FS would change reoperation rates in BCT patients. Study Design: Between January 2004 and December 2005, 1,218 patients had simultaneous BCT and SLN biopsy for invasive breast cancer. FS of the SLN was used selectively at the surgeon’s discretion. Clinical and pathologic data were collected. Results: Overall, 542 of 1,218 (44%) patients had positive margins. FS of the SLN was performed in 931 of 1,218 (76%) patients. In those having FS, the SLN positivity rate was 33% (306 of 931). FS identified the positive SLN in 170 of 306 (56%) patients with positive nodes, allowing for immediate ALND. But 101 of these 170 patients had positive lumpectomy margins; and FS of the SLN saved 69 of 931 (7%) patients a second operation. Of patients not having FS, 48 of 287 (17%) had a positive SLN on final pathology. Only 18 of 48 (those seen on routine hematoxylin and eosin) might have been seen on FS, potentially sparing reoperation. Half of patients not having FS required reexcision for positive margins. FS would have spared reoperation for only 8 of 287 (3%) patients in this group. Overall, of 354 of 1,218 patients with SLN metastases, 170 had immediate ALND and 98 had delayed ALND. Of those having delayed ALND, 68 of 98 also had positive margins. Conclusions: Among patients having BCT with SLN biopsy, FS identified the positive SLN in 56% of patients with positive SLNs, allowing immediate ALND, and was false negative in 44%. Margin status remains a frequent indication for reoperation in BCT; routine FS analysis of the SLN ultimately saves only a minority of patients a second operation. [Copyright &y& Elsevier]

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]

Pneumatosis intestinalis, or air within the wall of the gastrointestinal tract, has been documented from the esophagus to the rectum. Its presence can suggest gangrenous changes of the stomach or colon and represents a surgical emergency. However, pneumatosis intestinalis can also occur as a result of a benign, nongangrenous condition. We report the conservative management of a patient with nongangrenous gastric and esophageal pneumatosis. [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]

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]

Introduction: Contiguous non-mass enhancement (NME) often coexists with a solid tumor component on MRI, but it can be challenging to predict whether NME represents invasive breast cancer, ductal carcinoma in situ (DCIS), benign disease, or biopsy site reaction. The purpose of this study was to determine the association between the size/extent of NME and the presence of invasive cancer and/or DCIS on final pathology. Methods: This was a single institution retrospective analysis of a prospectively maintained breast cancer registry (2010- 2020). Female patients who underwent surgical resection were included if they had a diagnosis of invasive breast cancer (with or without DCIS) and had an MRI showing both a solid mass and contiguous NME. The size of NME on MRI was compared with the size of invasive cancer and/or DCIS on the final pathology. Results: From a total of 3443 patients, 225 patients were included. 86.2% had invasive ductal carcinoma (IDC), and 12.0% had invasive lobular carcinoma 76.9% were ER+, 16.4% were HER2+, and 13.3% were triple negative breast cancer (TNBC). 18.7% received neoadjuvant chemotherapy (NCT) of whom 31% achieved a complete radiographic/pathologic response. Pearson correlation coefficients (r) between the size of NME and invasive cancer/DCIS showed a strong and positive correlation of MRI NME with DCIS on pathology in patients without NCT. Subgroup analysis showed the strongest correlations for NME and DCIS among non-white (r = .70) and HER2 + patients (r = .74) who did not receive NCT. Conclusions: Strong correlations between NME and DCIS were found for HER2 + disease and non-white patients, but only modest correlations were found for other patient/disease characteristics. These correlations may impact decisions in surgical approach. [ABSTRACT FROM AUTHOR]

Recently, several professional groups have recommended a change from chart-based to instrument-based screening for preschool-age children, but the effect of this change on health care utilization is unknown. We performed a secondary analysis of a site-randomized quality improvement project on transitioning from chart-based to instrument-based vision screening for 3- to 5-year-old children in primary care. We analyzed visit rates to ophthalmologists and optometrists and costs of such care before and after implementation of instrument-based vision screening with comparison to nonparticipating practices. The implementation of instrument-based vision screening resulted in a decrease in visits to eye care specialists from 83.1 visits per 1000 children per year to 55.0, a reduction of 33.8%; no comparable reduction was seen in nonparticipating practices. The cost of services by eye care specialists fell from $65 715 per 1000 children per year prior to $55 740, a decline of 15.2%; similar costs among control practices rose 13.4%. [ABSTRACT FROM AUTHOR]

Besides intrinsic changes, malignant cells also release soluble signals that reshape their microenvironment. Among these signals is WNT1-inducible signaling pathway protein 1 (WISP1), a secreted matricellular protein whose expression is elevated in several cancers, including melanoma, and is associated with reduced survival of patients diagnosed with primary melanoma. Here, we found that WISP1 knockout increases cell proliferation and represses wound healing, migration, and invasion of mouse and human melanoma cells in multiple in vitro assays. Metastasis assays revealed that WISP1 knockout represses tumor metastasis of B16F10 and YUMM1.7 melanoma cells in both C57BL/6Ncrl and NOD-scid IL2Rγnull (NSG) mice. WT B16F10 cells having an invasion phenotype in a transwell assay possessed a gene expression signature similar to that observed in the epithelial-mesenchymal transition (EMT), including E-cadherin repression and fibronectin and N-cadherin induction. Upon WISP1 knockout, expression of these EMT signature genes went in the opposite direction in both mouse and human cell lines, and EMT-associated gene expression was restored upon exposure to media containing WISP1 or to recombinant WISP1 protein. In vivo, Wisp1 knockout-associated metastasis repression was reversed by the reintroduction of either WISP1 or snail family transcriptional repressor 1 (SNAI1). Experiments testing EMT gene activation and inhibition with recombinant WISP1 or kinase inhibitors in B16F10 and YUMM1.7 cells suggested that WISP1 activatesAKTSer/Thr kinase and that MEK/ERK signaling pathways shift melanoma cells from proliferation to invasion. Our results indicate that WISP1 present within the tumor microenvironment stimulates melanoma invasion and metastasis by promoting an EMT-like process. [ABSTRACT FROM AUTHOR]

Acute nipple inversion can be unsettling for patients and is sometimes associated with an underlying breast malignancy. It also poses a diagnostic challenge with lack of consensus management guidelines. This study reviewed institutional experience with new nipple inversion, including malignant association, imaging utilization, and outcomes, in an effort to improve management. A multisite institutional retrospective review was conducted of all breast imaging reports from 1/2010 to 6/2022 mentioning nipple inversion as an indication or finding. Patients with new nipple inversion, defined as arising since the time of last breast imaging exam or if reported as new by the patient/provider, were included for analysis. Retroareolar imaging findings, BI-RADS assessments/recommendations, pathology obtained from percutaneous or excisional biopsies, and follow-up imaging and clinical exams were collated. Cases of chronic or stable nipple inversion were excluded. Descriptive statistics were performed. A total of 414 patients had new nipple inversion, 387/414 (93.5 %) with benign or negative results at initial imaging and 27/414 (6.5 %) with malignant lesions. Diagnostic mammography/ultrasound detected 25/27 (92.6 %) cancers (sensitivity 92.6 %, specificity 75.5 %, PPV 20.8 %, NPV 99.3 %). Of 62 breast MRI exams performed in patients with negative mammogram/ultrasound, no cancers were detected in the retroareolar space with 2 incidental malignant lesions discovered distant from the nipple. Diagnostic mammography/ultrasound is reliable in workups of acute nipple inversion, with a high sensitivity and NPV for excluding malignancy. Breast MRI and surgical referral should be reserved for patients with suspicious associated symptoms or clinical findings. • New nipple inversion is a concerning clinical finding for patients and providers. • Various etiologies and presentations result in diagnostic and management challenges. • Diagnostic mammography/ultrasound is reliable in workups of acute nipple inversion. • Breast MRI may be reserved for those with associated suspicious symptoms. [ABSTRACT FROM AUTHOR]

Outline a quality initiative establishing an institutional service line for neonatal transcatheter device closure of the patent ductus arteriosus (TDC-PDA). A retrospective descriptive observational study surrounds programmatic approach to TDC-PDA in premature neonates with process measure spanning education, implementation, referral, and post-procedural care. Metrics tracked pre- and post-program creation with statistical analyses performed. Neonatal TDC-PDA referrals increased exponentially since program inception (n = 13 in year prior; n = 42 year 1; n = 74 year 2), especially in patients weighing less than 1.3 kg (12.5%; 55%; 50%), and were associated with an increased procedural success rate (81%; 95%; 99%). Procedural checklist creation decreased procedural “out of isolette” time (median 93 min; 59; 52), and procedural-related complication or clinical sequelae (19%; 12%; 4%). A multidisciplinary service line and program dedicated to neonatal TDC-PDA can result in a significant increase in referrals as well as procedural efficacy and safety for this medically fragile population. [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]

BACKGROUND. TGF-β has potent profibrotic activity in vitro and has long been implicated in systemic sclerosis (SSc), as expression of TCF-FJ-regulated genes is increased in the skin and lungs of patients with SSc. Therefore, inhibition of TGF-β may benefit these patients. METHODS. Patients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab, a high-affinity neutralizing antibody that targets all 3 TGF-β-isoforms. Seven patients received two 1 mg/kg doses of fresolimumab, and eight patients received one 5 mg/kg dose of fresolimumab. Serial mid-forearm skin biopsies, performed before and after treatment, were analyzed for expression of the TGF-β-regulated biomarker genes thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) and stained for myofibroblasts. Clinical skin disease was assessed using the modified Rodnan skin score (MRSS). RESULTS. In patient skin, THBS1 expression rapidly declined after fresolimumab treatment in both groups (P = 0.0313 at 7 weeks and P = 0.0156 at 3 weeks), and skin expression of COMP exhibited a strong downward trend in both groups. Clinical skin disease dramatically and rapidly decreased (P < 0.001 at all time points). Expression levels of other TGF-β-regulated genes, including SERPINE1 and CTGF, declined (P = 0.049 and P = 0.012, respectively), and a 2-gene, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment (P = 0.0067). Dermal myofibroblast infiltration also declined in patient skin after fresolimumab (P < 0.05). Baseline levels of THBS1 were predictive of reduced THBS1 expression and improved MRSS after fresolimumab treatment. CONCLUSION. The rapid inhibition of TGF-β-regulated gene expression in response to fresolimumab strongly implicates TGF-β in the pathogenesis of fibrosis in SSc. Parallel improvement in the MRSS indicates that fresolimumab rapidly reverses markers of skin fibrosis. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ (DCIS) of the breast represents a complex, heterogeneous pathologic condition in which malignant epithelial cells are confined within the ducts of the breast without evidence of invasion. The increased use of screening mammography has led to a significant shift in the diagnosis of DCIS, accounting for approximately 27% of all newly diagnosed cases of breast cancer in 2011, with an overall increase in incidence. As the incidence of DCIS increases, the treatment options continue to evolve. Consistent pathologic evaluation is crucial in optimizing treatment recommendations. Surgical treatment options include breast-conserving surgery (BCS) and mastectomy. Postoperative radiation therapy in combination with breast-conserving surgery is considered the standard of care with demonstrated decrease in local recurrence with the addition of radiation therapy. The role of endocrine therapy is currently being evaluated. The optimization of diagnostic imaging, treatment with regard to pathological risk assessment, and the role of partial breast irradiation continue to evolve [ABSTRACT FROM AUTHOR]

Evaluate utilization of MRI-directed breast ultrasound (US) in patients with newly diagnosed breast cancer and refine practices to increase success of sonographic lesion detection. This retrospective single-institution review was restricted to women with breast cancer who underwent MRI from November 2006 to January 2017. Enhancing breast lesions, separate from the index tumor, recommended for MRI-directed US were assessed to see which were detected and which characteristics predicted success in detection. Univariate mixed-effects logistic modeling predicted likelihood of finding breast lesions with US, with odds ratios reported. All tests were two-sided with p < 0.05 considered significant. A total of 275 patients underwent MRI-directed US for 361 breast lesions, of which 187 (51.8%) were found on US. Of those detected, 171 (91.4%) were masses and 16 (8.6%) were nonmass enhancement (NME), with masses 14 times more likely to be seen (p < 0.001). Size alone was not a significant predictor but achieved significance when associated with lesion type (mass size, p < 0.001). Masses with irregular shapes or margins and invasive carcinomas were more frequently detected. Patient age, internal enhancement pattern, and distribution of NME were not significant predictors in sonographic detection. A presumed sonographic correlate for NME was found for 16 (16.2%) of 99 attempted lesions. As MRI access expands, utilization of MRI-directed US should be scrutinized to avoid downstream practice inefficiencies. Sonographic detection rates for NME remain low for women undergoing MRI for disease extent, with NME often better suited for MRI-guided biopsy. • Success rates of MRI-directed breast US in detecting a correlate are wide-ranging. • Masses significantly more likely to be found on US than nonmass enhancement (NME). • Larger, irregular, and malignant masses portend success in sonographic detection. • Rare to detect sonographic correlate for NME, including for preoperative MRI. • Proceeding directly to MRI biopsy should be considered for NME in preoperative MRI. [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: 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]

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 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]

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]

Background: It is assumed that axillary ultrasound (AxUS) is the best method for axillary nodal evaluation in newly diagnosed breast cancer patients. However, few have evaluated the efficacy of preoperative axillary MRI. We compared the statistical accuracy of AxUS and MRI in detecting nodal metastases among breast cancer patients who were selected for neoadjuvant chemotherapy.Study Design: We retrospectively analyzed 219 breast cancer patients undergoing neoadjuvant chemotherapy from 2007 to 2015, all of whom had AxUS and breast MRI before chemotherapy. Two breast radiologists, blinded to clinical, pathologic, and AxUS findings, re-reviewed all breast MRIs, specifically focusing on axillary nodal characteristics. We correlated clinico-pathologic characteristics, AxUS, and MRI findings, and quantified predictive values of both imaging modalities.Results: Overall, 101 of 219 (47%) patients had T2 tumors. The most common abnormal nodal finding was size >10 mm. Axillary ultrasound and MRI agreed on nodal status in 192 of 219 patients (87.6%). When correlated with pre-chemotherapy needle biopsy in 129 patients, AxUS and axillary MRI performed similarly (sensitivity of 99.1% vs 97.4% and specificity 15.4% vs 15.4%, respectively). Only 4 of 129 (3.1%) patients had a negative MRI and positive AxUS; 3 of 4 of these patients (75%) had a positive biopsy and 2 of 3 had positive lymph nodes on final pathology, therefore suggesting MRI missed clinically significant disease in only 2 of 129 (1.5%) patients.Conclusions: In a high-risk patient population, AxUS and MRI have similar statistical profiles in evaluating axillary nodal status. Routine use of AxUS after a normal axillary MRI is not warranted. [ABSTRACT FROM AUTHOR]

Background: Breast cancer patients with ptotic breasts pursuing mastectomy with immediate reconstruction can present challenges. A wise pattern (inverted‐T) mastectomy incision (WPM) has been suggested as an alternative to the standard horizontal elliptical mastectomy (EM) to reduce redundant skin and correct ptosis. Herein, we sought to examine the differences in morbidity between the two techniques. Methods: We performed a retrospective review of women undergoing mastectomy with immediate reconstruction at our institution from June 2007 to January 2016. We compared those undergoing WPM to a control population undergoing EM. Statistical analysis was performed evaluating clinical, pathological, and surgical outcome variables according to patient and per breast. All tests were two‐sided with alpha level set at 0.05 for statistical significance. Results: A total of 241 women underwent mastectomy and reconstruction in 421 breasts; 78/241 (32%) had WPM (149 breasts), 163/241 (68%) had EM (272 breasts). Both groups were similar in age, smoking status, diabetes, race, tumor type, and pathologic stage (all P > 0.07). Skin flap necrosis was the most frequently encountered complication, occurring in 58/149 (38.9%) of WPM breasts and in 24/272 (8.9%) of EM breasts (P < 0.0001). There was no difference in the need for revisional procedures between the groups (WPM: 24.1% vs EM: 17.6%, P = 0.207). Conclusion: Patients should be counseled WPM is associated with higher rates of skin flap necrosis. However, this does not translate into higher rates of revisional procedures or return to OR. [ABSTRACT FROM AUTHOR]