Request for Funding

Medical Student Research Fellowship for Summer 2002

Mentor: Jason B. Fleming, MD
Department: Surgery
Room number: E6.220
Mail Code: 9155
Phone number: 214-648-6357
E-mail: jflemi@utsouthwestern.edu
Project title: Evaluation of Vascular Endothelial Growth Factor (VEGF) in Peritoneal Washings Obtained During Diagnostic Laparoscopy of Patients with Upper Gastrointestinal Malignancies.

Human subjects IRB approved project number (where applicable): 0898-33100

Animal subjects IRB approved project number (where applicable):

Project Type patient-based research

Brief Description of Project:
Cancer of the upper gastrointestinal tract (esophagus, stomach, pancreas and liver) represent some of the most lethal solid tumors. Some patients succumb to their disease rapidly after diagnosis while others survive longer; however, it is difficult to predict the patient's outcome using conventional cancer staging methods. The only chance for cure for these patients is the successful removal of the tumor through a major operative procedure. Information that would predict tumor behavior and patient outcome would be useful to the surgeon contemplating a curative operative approach.
Laparoscopy is an effective tool for the diagnosis and staging of intra-abdominal malignancies; it adds to the information provided by other noninvasive diagnostic modalities and may spare the patient the morbidity of a non-therapeutic laparotomy. When routinely used in the staging of upper gastrointestinal malignancies, we have demonstrated an increase in clinical tumor stage in 19-36% of patients. Furthermore, the presence of malignant cells predicts a significantly decreased overall survival in the affected patients. Molecular analysis of tumor suppressor genes from DNA harvested from epithelial cells within the washings has also been evaluated; however, this data does not appear to correlate with tumor recurrence or patient survival.
Angiogenesis, the formation of new blood vessels from the existing vascular network, is essential for continued tumor growth and metastasis. One of the most potent and specific angiogenic factors is vascular endothelial growth factor (VEGF). Evidence for the pivotal role of this cytokine in tumor angiogenesis includes the observations of increased expression in tumor cells of numerous human cancers. VEGF has been assayed and found to be elevated in ascites associated with gastrointestinal malignancies and the level of cytokine present is associated with patient outcome. Similarly, the level of VEGF expression in primary gastrointestinal tumors is associated with cancer stage and outcome.
The purpose of this proposal funded by the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) is to establish a method of analysis of peritoneal washings obtained at staging laparoscopy that reflects the biology of the primary tumor and predicts patient outcome. Our hypothesis is two fold: 1) Vascular endothelial growth factor (VEGF) can be measured in peritoneal washings obtained during staging laparoscopic examination of patients with upper gastrointestinal epithelial malignancies. 2) The level of VEGF in the peritoneal fluid will reflect the clinical/pathologic stage of the malignancy and predict cancer-related morbidity and mortality.

Previous Research Activities or Publications with Medical Students:

Development of an animal model of Laparoscopic Radiofrequency Ablation of Liver Tumors

Scott DJ MD, Young WN, Watumull LM, Lindberg G, Fleming JB, Rege RV, Brown RJ, Jones DB. Development of an in vivo tumor-mimic model for learning radiofrequency ablation. J Gastrointest Surg. 2000 Nov-Dec;4(6):620-5.

Scott DJ, Young WN, Watumull LM, Lindberg G, Fleming JB, Huth JF, Rege RV, Jeyarajah DR, Jones DB. Accuracy and effectiveness of laparoscopic vs open hepatic radiofrequency ablation. Surg Endosc. 2001 Feb;15(2):135-40.

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