Recent Evolution in the Management of Lymph Node Metastases in Melanoma

Introduction. Based upon two large randomized international clinical trials (German Dermatologic Cooperative Oncology Group (DeCOG-SLT) and Multicenter Selective Lymphadenectomy Trial II (MSLT-II)) which were published in 2016 and 2017, respectively, active surveillance has been demonstrated to have equivalent survival outcomes to completion lymphadenectomy (CLND) for a subset of patients who have microscopic lymph node disease. In this study, we examined the changes in national practice patterns regarding the utilization of CLND after positive sentinel lymph node biopsy (SLNB). Methods. Using the National Cancer Database, we examined CLND utilization in SLN-positive patients diagnosed with melanoma between 2012 and 2016. A hierarchal logistical regression model with hospital-level random intercepts was constructed to examine the factors associated with SLNB followed by observation vs. SLNB with CLND. Results. Of the 148,982 patients identified, 43% (n = 63,358) underwent SLNB, and 10.3% (n = 6,551) had a SLNB with microscopic disease. CLND was performed for 57% (n = 2,817) of these patients. Patients were more likely to undergo CLND if they were < 55 years of age (OR, 0.687;  p = <0.0001), ages 56 - 65 (OR, 0.886; p = 0.0237), Charlson Deyo Score = 0 (OR, 0.859; p = 0.0437), or were diagnosed with melanoma in 2012 (OR, 0.794, p = <0.0001). Conclusions. We found the utilization of CLND among patients with microscopic nodal melanoma to be significantly lower in 2016 compared to 2012. Younger age, lack of comorbidities, and primary tumor location on the trunk or head/neck were associated with higher utilization of CLND

Informing the surgical workforce pathway: how rural community characteristics matter

Introduction: Rural areas worldwide face a general surgeon shortage, limiting rural populations' access to surgical care. While individual and practice-related factors have been well-studied in the US, we need a better understanding of the role of community characteristics in surgeons' location choices. This study aimed to understand the deeper meanings surgeons associated with community characteristics in order to inform efforts spanning the rural surgeon workforce pathway, from early educational exposures, and undergraduate and graduate medical education, to recruitment and retention. Methods: We conducted a qualitative, descriptive interview study with general surgeons in the Midwestern US about the role and meaning of community characteristics, exploring their backgrounds, education, practice location choices, and future plans. We focused on rural surgeons and used an urban comparison group. We used convenience and snowball sampling, then conducted interviews in-person and via phone, and digitally recorded and professionally transcribed them. We coded inductively and continued collecting data until reaching code saturation. We used thematic network analysis to organize codes and draw conclusions. Results: A total of 37 general surgeons (22 rural and 15 urban) participated. Interviews totaled over 52 hours. Three global themes described how rural surgeons associated different, often deeper, meanings with certain community characteristics compared to their urban colleagues: physical environment symbolism, health resources' relationship to scope of practice, and implications of intense role overlap (professional and personal roles). All interviewees spoke to all three themes, but the meanings they found differed importantly between urban and rural surgeons. Physical landscapes and community infrastructure were representative of autonomy and freedom for rural surgeons. They also shared how facilities, equipment, staff, staff education, and surgical partners combined to create different scopes of practice than their urban counterparts experienced. Often, rural surgeons found these resources dictated when they needed to transfer patients to higher-acuity facilities. Rural surgeons experienced role overlap intensely, as they cared for patients who were also friends and neighbors. Conclusion: Rural surgeons associated different meanings with certain community characteristics than their urban counterparts. As they work with prospective rural surgeons, educators and rural communities should highlight how health resources can translate into desired scopes of practice. They also should share with trainees the realities of role overlap, both how intense and stressful it can be but also how gratifying. Educators should include the rural social context in medical and surgical education, looking for even more opportunities to collaborate with rural communities to provide learners with firsthand experiences of rural environments, resources, and role overlap

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

Ischemia /reperfusion injury in the intestine: Important roles for PKC, MAPK, and adenosine

Ischemic stress is a central characteristic of a variety of pathologic conditions. Ischemic stress results from an imbalance of energy demands with associated supply during the ischemic phase, followed by the injury associated with reperfusion. While certain systems, particularly the cardiovascular system, have been studied in depth, little is understood about the cellular response to ischemic stress in intestinal epithelial cells. In this series of studies, we sought to describe the signaling that occurs in intestinal epithelial cells during ischemic stress. Protein Kinase C is known to be important in signaling during ischemic stress in cardiomyocytes. In my first series of experiments, I studied the activation of various protein kinase C isoforms in response to ischemic stress. Ischemic stress resulted only in the activation of the epsilon isoform in a manner distinct from its activation in response to pharmacologic agents, particularly phorbol ester. In my second series of experiments, I sought to understand the relationship of protein kinase C and the mitogen antigen peptide kinases (MAPK’s). The sustained activation of MAPK’s, particularly ERK 1/2, has been found in other model systems to be important in regulating cell survival. I demonstrated that ERK 1/2 is activated in response to ischemic stress in intestinal epithelial cells, but PKC inhibition did not appear to affect this pathway. Another critical protein in signaling in ischemia, the epidermal growth factor receptor (EGFR), appears to have an important role in regulating ERK 1/2 activation during ischemic stress. This regulation appears to be largely independent of ligand binding to the EGFR itself. The final series of experiments investigated the role of extracellular adenosine on ERK 1/2 activation. Extracellular adenosine does not appear to enhance ERK 1/2 phosphorylation, but it absence prevents full activation. This regulation of ERK 1/2 activation does not appear to be through an adenosine receptor dependent route. I sought to delineate several signaling pathways important in ischemic stress in intestinal epithelial cells. The epsilon isoform of protein kinase C is activated in a manner distinct from its activation by pharmacologic agents. ERK 1/2, an important protein in signaling during ischemic stress, is not activated by PKC, but rather mostly through a non-EGFR ligand dependent EGFR pathway. Finally, adenosine appears to be important in ERK 1/2, but its mechanism of regulation appears to be adenosine receptor independent

Automated test system for laser control circuit boards

The purpose of this project was to develop an automated test system for laser control circuit board assemblies. By providing a system with which IPG Photonics can test their laser control boards, other related Fiber Optic Amplifier hardware will be shielded from destructive board failures. We built a custom software and hardware package to measure various parameters of the laser control boards verifying correct modular operation. The scalable LabVIEW-based on solution was designed to include a user defined pass-fail criteria and a board failure analysis tool. Analysis of verification tests prove that the test system is reliable