Image directed lymph node sampling for lung cancer staging

http://deepblue.lib.umich.edu/bitstream/2027.42/117374/1/40644_2014_Article_102.pd

Minimally invasive transhiatal esophagectomy

While traditionally performed through an open approach, the role of minimally invasive technologies has evolved in its application to esophageal resection. Esophagectomy is associated with significant morbidity, which has led to interest in developing minimally invasive esophagectomy (e.g., laparoscopic/thoracoscopic approaches) to address this issue. As a result, the role of minimally invasive approaches for esophageal resection has evolved, with a growing body of literature describing these techniques. Minimally invasive approaches have been applied to transhiatal esophagectomy, with application of both laparoscopic and robotic-assisted techniques. Although minimally invasive esophagectomy approaches are well-described in the literature for esophageal malignancies, the efficacy of robotic-assisted esophagectomy is not as well established. Since the initial reports of this application, the adoption of this technology for esophagectomy has continued to expand. As the role for robotic techniques has expanded across esophageal resection approaches, a more defined application to minimally invasive transhiatal esophagectomy (MI-THE) has developed. Our group has sought to adapt laparoscopic and robotic techniques to the transhiatal approach for both malignant and end-stage benign esophageal disease. With growing MI-THE experience, operative technique has been further refined. This report describes the operative technique and best practices for robotic-assisted transhiatal esophagectomy with cervical esophagogastric anastomosis, including preoperative preparation, operative technique, postoperative care, and perioperative outcomes

Treatment of asymptomatic carotid artery disease: Similar early outcomes after carotid stenting for high-risk patients and endarterectomy for standard-risk patients

BackgroundThe role of carotid angioplasty and stenting (CAS) in the treatment of asymptomatic patients with carotid disease remains controversial. The purpose of this report is to compare outcomes in asymptomatic patients treated with CAS and carotid endarterectomy (CEA). This was the initial experience performing CAS for most of the surgeons. For comparison, we also report our outcomes in standard-risk patients treated concurrently with CEA during the same period of time.MethodsA retrospective, nonrandomized review of asymptomatic patients undergoing CEA or CAS at Washington University Medical Center in St. Louis was done. Patients with >70% asymptomatic carotid stenosis treated between September 2003 and April 2005 were identified. CEA was the first therapeutic consideration in all patients. CAS was reserved for high-risk patients. Thirty-day outcomes of stroke or death were recorded. During this time interval, 248 patients were treated including with 93 CAS and with 145 CEA. Symptomatic or clinically detected adverse outcomes such as myocardial infarction (MI), arrhythmia, renal failure, or pulmonary complications were noted but were not the primary end points of this review. This study addresses only the periprocedural outcomes of CEA and CAS in asymptomatic patients. No data >30-day follow-up are included.ResultsDuring this period, 93 CAS and 145 CEA procedures were done in asymptomatic patients. Patient characteristics in both groups were similar. Carotid protection devices were used in 91.4% of CAS patients. The results in the CAS group showed one death (1.1%) and one stroke (1.1%). In the CEA group, three strokes occurred (2.1%, P = 0.9999), one associated with death (0.7%, P = 0.9999). The CAS group had 1.34 ± 0.83 risk factors vs 0.39 ± 0.58 in the CEA group (P < .0001). Median CAS and CEA length of stay was 1 day.ConclusionsCAS for asymptomatic carotid stenosis demonstrated equivalent outcomes compared with CEA, despite CAS being reserved for use in a disadvantaged subset of high-risk patients owing to anatomic risk factors or medical comorbidities. These results suggest CAS should be considered a reasonable treatment option in the high-risk but asymptomatic patient. Enthusiasm for CAS should be tempered by the recognition that long-term outcomes in CAS-treated asymptomatic patients remain unknown

A Radial Flow Microfluidic Device for Ultra‐High‐Throughput Affinity‐Based Isolation of Circulating Tumor Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/1/smll201400719.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110045/2/smll201400719-sup-0001-S1.pd

Characterizing isoform switching events in esophageal adenocarcinoma

Isoform switching events with predicted functional consequences are common in many cancers, but characterization of switching events in esophageal adenocarcinoma (EAC) is lacking. Next-generation sequencing was used to detect levels of RNA transcripts and identify specific isoforms in treatment- naïve esophageal tissues ranging from premalignant Barrett’s esophagus (BE), BE with low- or high-grade dysplasia (BE.LGD, BE.HGD), and EAC. Samples were stratified by histopathology and TP53 mutation status, identifying significant isoform switching events with predicted functional consequences. Comparing BE.LGD with BE.HGD, a histopathology linked to cancer progression, isoform switching events were identified in 75 genes including KRAS, RNF128, and WRAP53. Stratification based on TP53 status increased the number of significant isoform switches to 135, suggesting switching events affect cellular functions based on TP53 mutation and tissue histopathology. Analysis of isoforms agnostic, exclusive, and shared with mutant TP53 revealed unique signatures including demethylation, lipid and retinoic acid metabolism, and glucuronidation, respectively. Nearly half of isoform switching events were identified without significant gene-level expression changes. Importantly, two TP53-interacting isoforms, RNF128 and WRAP53, were significantly linked to patient survival. Thus, analysis of isoform switching events may provide new insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC

Characterizing isoform switching events in esophageal adenocarcinoma

Isoform switching events with predicted functional consequences are common in many cancers, but characterization of switching events in esophageal adenocarcinoma (EAC) is lacking. Next-generation sequencing was used to detect levels of RNA transcripts and identify specific isoforms in treatment- naïve esophageal tissues ranging from premalignant Barrett’s esophagus (BE), BE with low- or high-grade dysplasia (BE.LGD, BE.HGD), and EAC. Samples were stratified by histopathology and TP53 mutation status, identifying significant isoform switching events with predicted functional consequences. Comparing BE.LGD with BE.HGD, a histopathology linked to cancer progression, isoform switching events were identified in 75 genes including KRAS, RNF128, and WRAP53. Stratification based on TP53 status increased the number of significant isoform switches to 135, suggesting switching events affect cellular functions based on TP53 mutation and tissue histopathology. Analysis of isoforms agnostic, exclusive, and shared with mutant TP53 revealed unique signatures including demethylation, lipid and retinoic acid metabolism, and glucuronidation, respectively. Nearly half of isoform switching events were identified without significant gene-level expression changes. Importantly, two TP53-interacting isoforms, RNF128 and WRAP53, were significantly linked to patient survival. Thus, analysis of isoform switching events may provide new insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC

High-Throughput Label-Free Isolation of Heterogeneous Circulating Tumor Cells and CTC Clusters from Non-Small-Cell Lung Cancer Patients.

(1) Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers and current methods for isolation of clusters may fall short. (2) Methods: We applied an inertial microfluidic Labyrinth device for high-throughput, biomarker-independent, size-based isolation of CTCs/CTC clusters from patients with metastatic non-small-cell lung cancer (NSCLC). (3) Results: Using Labyrinth, CTCs (PanCK+/DAPI+/CD45-) were isolated from patients (n = 25). Heterogeneous CTC populations, including CTCs expressing epithelial (EpCAM), mesenchymal (Vimentin) or both markers were detected. CTCs were isolated from 100% of patients (417 +/- 1023 CTCs/mL). EpCAM- CTCs were significantly greater than EpCAM+ CTCs. Cell clusters of \u3e/=2 CTCs were observed in 96% of patients-of which, 75% were EpCAM-. CTCs revealed identical genetic aberrations as the primary tumor for RET, ROS1, and ALK genes using fluorescence in situ hybridization (FISH) analysis. (4) Conclusions: The Labyrinth device recovered heterogeneous CTCs in 100% and CTC clusters in 96% of patients with metastatic NSCLC. The majority of recovered CTCs/clusters were EpCAM-, suggesting that these would have been missed using traditional antibody-based capture methods

Expectations of and for Clerkship Directors 2.0: A Collaborative Statement from the Alliance for Clinical Education

This article presents an update of the collaborative statement on clerkship directors (CDs), first published in 2003, from the national undergraduate medical education organizations that comprise the Alliance for Clinical Education (ACE). The clerkship director remains an essential leader in the education of medical students on core clinical rotations, and the role of the CD has and continues to evolve. The selection of a CD should be an explicit contract between the CD, their department, and the medical school, with each party fulfilling their obligations to ensure the success of the students, the clerkship and of the CD. Educational innovations and accreditation requirements have evolved in the last two decades and therefore this article updates the 2003 standards for what is expected of a CD and provides guidelines for the resources and support to be provided. In their roles as CDs, medical student educators engage in several critical activities: administration, education/teaching, coaching, advising, and mentoring, faculty development, compliance with accreditation standards, and scholarly activity. This article describes (a) the work products that are the primary responsibility of the CD; (b) the qualifications for the CD; (c) the support structure, resources, and personnel that are necessary for the CD to accomplish their responsibilities; (d) incentives and career development for the CD; and (e) the dedicated time that should be provided for the clerkship and the CD to succeed. Given all that should rightfully be expected of a CD, a minimum of 50% of a full-time equivalent is recognized as appropriate. The complexity and needs of the clerkship now require that at least one full-time clerkship administrator (CA) be a part of the CD’s team. To better reflect the current circumstances, ACE has updated its recommendations for institutions and departments to have clear standards for what is expected of the director of a clinical clerkship and have correspondingly clear guidelines as to what should be expected for CDs in the support they are provided. This work has been endorsed by each of the eight ACE member organizations

Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity

The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a mutational signature defined by a high prevalence of A to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis

Health Disparities in Patients with Esophageal Cancer

Part of Virtual Roundtable: Population Health and Health Equity in the Upper MidwestBristol Meyers Squibhttp://deepblue.lib.umich.edu/bitstream/2027.42/177043/2/Health Disparities in Patients with Esophageal Cancer-6-14-23.ppt