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Fluorescence-Guided Surgery Allows for More Complete Resection of Pancreatic Cancer, Resulting in Longer Disease-Free Survival Compared with Standard Surgery in Orthotopic Mouse Models - 21/06/12

Doi : 10.1016/j.jamcollsurg.2012.02.021 
Cristina A. Metildi, MD a, Sharmeela Kaushal, PhD a, Chanae R. Hardamon, BSc a, Cynthia S. Snyder, MD a, Minya Pu, PhD a, Karen S. Messer, PhD a, Mark A. Talamini, MD, FACS a, Robert M. Hoffman, PhD a, b, Michael Bouvet, MD, FACS a,
a Department of Surgery, University of California San Diego, San Diego, CA 
b AntiCancer, Inc, San Diego, CA 

Correspondence address: Michael Bouvet, MD, FACS, Department of Surgery, UCSD Moores Cancer Center, 3855 Health Science Dr #0987, La Jolla, CA 92093-0987

Riassunto

Background

Negative surgical margins are vital to achieve cure and prolong survival in patients with pancreatic cancer. We inquired if fluorescence-guided surgery (FGS) could improve surgical outcomes and reduce recurrence rates in orthotopic mouse models of human pancreatic cancer.

Study Design

A randomized active-control preclinical trial comparing bright light surgery (BLS) to FGS was used. Orthotopic mouse models of human pancreatic cancer were established using the BxPC-3 pancreatic cancer cell line expressing red fluorescent protein (RFP). Two weeks after orthotopic implantation, tumors were resected with BLS or FGS. Pre- and postoperative images were obtained with the OV-100 Small Animal Imaging System to assess completeness of surgical resection in real time. Postoperatively, noninvasive whole body imaging was done to assess recurrence and follow tumor progression. Six weeks postoperatively, mice were sacrificed to evaluate primary pancreatic and metastatic tumor burden at autopsy.

Results

A more complete resection of pancreatic cancer was achieved using FGS compared with BLS: 98.9% vs 77.1%, p = 0.005. The majority of mice undergoing BLS (63.2%) had evidence of gross disease with no complete resections; 20% of mice undergoing FGS had complete resection and an additional 75% had only minimal residual disease (p = 0.0001). The mean postoperative tumor burden was significantly less with FGS compared with BLS: 0.08 ± 0.06 mm2 vs 2.64 ± 0.63 mm2, p = 0.001. The primary tumor burden at termination was significantly less with FGS compared with BLS: 19.3 ± 5.3 mm2 vs 6.2 ± 3.6 mm2, p = 0.048. FGS resulted in significantly longer disease-free survival than BLS (p = 0.02, hazard ratio = 0.39, 95% CI 0.17, 0.88).

Conclusions

Surgical outcomes were improved in pancreatic cancer using fluorescence-guidance. This novel approach has significant potential to improve surgical treatment of cancer.

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Abbreviations and Acronyms : BLS, FGS, GFP, RFP


Mappa


 Work supported in part by grants from the National Cancer Institute CA142669 and CA132971 (to Dr Bouvet and AntiCancer, Inc) and T32 training grant CA121938-5 (to Dr Metildi).
 Disclosure Information: Dr Hoffman is a stockholder and is president of AntiCancer, Inc, but does not receive a salary. All other authors have nothing to disclose.


© 2012  American College of Surgeons. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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Vol 215 - N° 1

P. 126-135 - luglio 2012 Ritorno al numero
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