Abstract

Abstract The aim of this study was to determine if fluorescence-guided surgery (FGS) could improve surgical outcomes, reduce recurrence rates and improve overall survival in orthotopic mouse models of human pancreatic cancer. Orthotopic mouse models of human pancreatic cancer were established using the BxPC-3 RFP-expressing pancreatic cancer cell line in nude mice. Two weeks after implantation, the mice were randomized to undergo bright light surgery (BLS) or fluorescence-guided surgery (FGS). Pre- and postoperative images were obtained with the Olympus OV-100 Small Animal Imaging System to assess completeness of surgical resection. Whole body imaging of the mice was performed weekly in the postoperative period to assess for recurrence and follow tumor progression. Additionally, half of the mice were randomly selected to undergo 4 weeks of postoperative gemcitabine treatment. At six weeks postoperatively, or when premorbid, the mice were sacrificed and primary pancreatic tumor burden was measured using ImageJ v1.440. A more complete resection of pancreatic cancer was achieved using FGS compared to BLS: 98.9% vs 77.1%, p=0.005. Sixty-three percent of the mice undergoing BLS had evidence of gross residual disease, whereas 20% of mice undergoing FGS received a complete resection and an additional 75% of the mice were left with minimal residual disease (p=0.0001). At six weeks, the primary pancreatic tumor burden was significantly less with FGS compared to BLS: 19.341 ± 5.26 mm2 vs. 6.194 ± 3.61 mm2, p=0.048. In a pilot survival study, FGS alone was associated with a decreased risk of tumor recurrence (HR=0.093, 95% CI 0.013-0.645), and mean overall survival was lengthened from 18.5 weeks to 28.2 weeks. The addition of adjuvant gemcitabine (GEM) to FGS further lengthened mean overall survival to 42.75 weeks (p=0.019). Three of the four mice in the FGS with adjuvant gemcitabine group were alive at 12 months postoperatively and all of the mice (n=4) were free of tumor at time of sacrifice. In this study, we achieved improved surgical outcomes in primary pancreatic cancer under fluorescence-guidance. FGS afforded a more complete resection of primary tumor and improved disease-free survival and overall survival. The combination of FGS and GEM lengthened disease-free survival and improved overall survival. This novel approach has potential to improve outcomes in the surgical treatment of pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 375. doi:1538-7445.AM2012-375

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