Medicine and Health Sciences Commons^™

Growth Inhibition Of Human Hepatocellular Carcinoma Cells By Overexpression Of G Protein-Coupled Receptor Kinase 2, Zhengyu Wei, Reginald Hurtt, Cataldo Doria

Department of Surgery Faculty Papers

Summary:

In this study, we investigated a novel approach for HCC treatment by inducing overexpression of GRK2 in human HCC cells. We found that overexpression of GRK2 through recombinant adenovirus transduction inhibits the growth of human HCC cells. BrdU incorporation assay showed that the growth inhibition caused by elevated GRK2 level was due tot he reduced cell proliferation but not apoptosis. To examine the anti-proliferative function of increased GRK2 level, we performed cell cycle analysis using propidium iodide staining. We found that the proliferation suppression was associated with G2/M phase cell cycle arrest by the wild type GRK2 but not …

Utilizing Livers From Donors Older Than 65: A Single Center Experience, Krishnaraj Mahendraraj, Jorge H. Castro, Sean Devitt, Chad Gorn, Cataldo Doria, Adam Frank, Warren Maley, Carlo G. Ramirez

Department of Surgery Faculty Papers

Conclusions:

Use of liver grafts from older donors presents similar survival outcomes as grafts from younger donor age. Therefore, it offers a viable option to expand the donor pool and increase number of OLTs.

However, there is higher incidence of retransplantation due to primary graft non-function, and longer hospital length of stay observed in the older donor age group.

Further studies using larger patient populations are needed to validate our results.

Oncogene-Induced Nrf2 Transcription Promotes Ros Detoxification And Tumorigenesis., Gina M. Denicola, Florian A. Karreth, Timothy J. Humpton, Aarthi Gopinathan, Cong Wei, Kristopher Frese, Dipti Mangal, Kenneth H. Yu, Charles J. Yeo, Eric S. Calhoun, Francesca Scrimieri, Jordan M. Winter, Ralph H. Hruban, Christine Iacobuzio-Donahue, Scott E. Kern, Ian A Blair, David A. Tuveson

Department of Surgery Faculty Papers

Reactive oxygen species (ROS) are mutagenic and may thereby promote cancer. Normally, ROS levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors and is predominantly regulated by the transcription factor Nrf2 (also known as Nfe2l2) and its repressor protein Keap1 (refs 2-5). In contrast to the acute physiological regulation of Nrf2, in neoplasia there is evidence for increased basal activation of Nrf2. Indeed, somatic mutations that disrupt the Nrf2-Keap1 interaction to stabilize Nrf2 and increase the constitutive transcription of Nrf2 target genes were recently identified, indicating that enhanced ROS detoxification and additional Nrf2 functions may …

Endothelial Differentiation Of Adipose-Derived Stem Cells From Elderly Patients With Cardiovascular Disease., Ping Zhang, Neil Moudgill, Eric Hager, Nicolas Tarola, Christopher Dimatteo, Stephen Mcilhenny, Thomas Tulenko, Paul J Dimuzio

Department of Surgery Faculty Papers

Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50-89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 for up to 3 weeks formed cords upon Matrigel and demonstrated acetylated-low-density lipoprotein and lectin uptake. Further stimulation with vascular endothelial growth factor and shear stress upregulated endothelial cell-specific markers (CD31, …

Evaluation Of The Use Of Patient-Focused Simulation For Student Assessment In A Surgery Clerkship., Gerald A Isenberg, Katherine W Berg, Judith A Veloski, Dale D Berg, J J. Veloski, Charles Yeo

Department of Surgery Faculty Papers

BACKGROUND: The purpose of this study was to evaluate the use of simulated patients in conjunction with anatomic and tissue task-training models to assess skills.

METHODS: Faculty reviewed the objectives of the clerkship to identify skills to be acquired. Three cases were developed related to rectal examination, suturing, and inserting intravenous lines and nasogastric tubes. Student scores were based on their ability to gather data from simulated patients and perform procedures on simulation models.

RESULTS: A total of 670 students were assessed between 2006 and 2009. Alpha reliability coefficients were .97 for Communication/Interpersonal Skills, .71 for Procedures, and .58 for …

From Bench To Bedside And Beyond: Potential Uses Of Vivo In An Academic Medical Center, John C. Kairys, Md, Facs, Jack London, Phd, Karl Steiner, Phd

Department of Surgery Faculty Papers

PowerPoint presentation: From Bench to Bedside and Beyond:Potential Uses of VIVO in an Academic Medical Center.

Oncologic Efficacy Is Not Compromised, And May Be Improved With Minimally Invasive Esophagectomy., Adam C Berger, Aaron Bloomenthal, Benny Weksler, Nathaniel Evans, Karen A Chojnacki, Charles J Yeo, Ernest L Rosato

Department of Surgery Faculty Papers

BACKGROUND: Major morbidity and mortality rates continue to be high in large series of transthoracic esophagectomies. Minimally invasive approaches are being increasingly used. We compare our growing series of minimally invasive (combined thoracoscopic and laparoscopic) esophagectomies (MIEs) with a series of open transthoracic esophagectomies.

STUDY DESIGN: We identified 65 patients who underwent an MIE with thoracoscopy/laparotomy (n = 11), Ivor Lewis (n = 2), or 3-hole approach (n = 52). These patients were compared with 53 patients who underwent open Ivor-Lewis esophagectomy (n = 15) or 3-hole esophagectomy (n = 38) over the past 10 years.

RESULTS: The MIE and …

Ercc1 And Rrm1 As Predictors Of Survival And Response In Pancreatic Ductal Adenocarcinoma Treated With Gemcitabine-Based Chemotherapy, Thomas Holdbrook, Kathleen D. Danenberg, Suneeta Satti, Jessica Kline, Charles J. Yeo, Jonathan R. Brody, Peter Mccue, Agnieszka K. Witkiewicz

Department of Surgery Faculty Papers

Conclusion:

In this study, we used RT-PCR and IHC to analyze RRM1 and ERCC1 mRNA and protein expression in PDA specimens. PDA patients with low expression of RRM1 by IHC derived benefit from gemcitabine-based chemotherapy. Assessment of RRM1 mRNA expression was limited by the small sample size. Low ERCC1 expression by RT-PCR was associated with a 2.5 times higher risk of mortality than high expression (p=0.031). There was no association between ERCC1 expression by IHC and survival; however, agreement between mRNA and protein expression was poor for ERCC1. This study demonstrates the ERCC1 and RRM1 expression have an impact on …

Conventional Aortic Valve Replacement For Elderly Patients In The Current Era., Kentaro Yamane, Hitoshi Hirose, Benjamin A Youdelman, Linda J Bogar, James T. Diehl

Department of Surgery Faculty Papers

BACKGROUND: Because of the rising expectation of prolonged life in the general population and the recent recognition of undertreated aortic valve disease in the elderly, updating the available results of aortic valve surgery is imperative, especially considering the rapid evolution of the transcatheter valve implantation procedure.

METHODS AND RESULTS: Between 1997 and 2010, 308 patients aged 70 years or older underwent aortic valve replacement (AVR) for aortic stenosis (AS). Short- and long-term results were analyzed and risk factors for long-term mortality were determined. Mean age was 78.5 years and 124 patients were aged 80 or older. Concomitant coronary artery bypass …

Ventral Hernia Repairs: 10 Year Single Institution Review At Thomas Jefferson University Hospital, Frederick C. Sailes, Md, Jason Walls, Md, Daria Guelig, Md, Mike Mirzabeigi, Ma, William D. Long, Ms, Albert Crawford, Phd, John H. Moore Jr, Md, Facs, Steven E. Copit, Md, Gary A. Tuma, M.D, James Fox, Md

Department of Surgery Faculty Papers

Abstract

Background Definitive repair of recurrent ventral hernias using abdominal wall reconstruction techniques is an essential tool in the armentarium for general and plastic surgeons. Ramirez 1 et al describes the “component separation” technique to mobilize the rectus-abdominus internal oblique and external oblique flap to correct the defect. The recurrence rate of incisional hernias increases to 20% after gastric bypass or extensive weight loss.2 The incidence of ventral hernias after failed recurrent hernia repair increases to 40%.3 It has been reported that utilizing the sliding myofascial flap repair technique, the recurrence rate was reduced to 8.5%.4

Materials and Methods This …

Serum Monocyte Chemoattractant Protein-1 In Pancreatic Cancer., Jennifer Sullivan, Qiaoke Gong, Terry Hyslop, Harish Lavu, Galina Chipitsyna, Charles Yeo, Hwyda A Arafat

Department of Surgery Faculty Papers

Background/Aims. Pancreatic ductal adenocarcinoma (PDA) has etiological association with chronic inflammation. Elevated circulating levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), are found in obese individuals. We hypothesized that serum MCP-1 levels are elevated in obese PDA patients. Methods. ELISA was used to analyze MCP-1 serum levels in PDA (n = 62) and intraductal papillary mucinous neoplasms (IPMN) (n = 27). Recursive partitioning statistical analysis investigated the relationship between log MCP-1 and clinicopathological parameters. Results. Log MCP-1 values were significantly (P < 0.05) elevated in patients with BMI ≥ 37.5. In patients with BMI < 37.5, average log MCP-1 values were significantly elevated in PDA patients when compared to IPMN patients. Within the IPMN group, higher log MCP-1 levels correlated with increased age. Recursive partitioning analysis of IPMN versus PDA revealed a strategy of predicting characteristics of patients who are more likely to have cancer. This strategy utilizes log MCP-1 as the primary factor and also utilizes smoking status, gender, and age. Conclusion. MCP-1 is a promising biomarker in pancreatic cancer. The potential of using MCP-1 to distinguish PDA from IPMN patients must be studied in larger populations to validate and demonstrate its eventual clinical utility.