Feasibility and Reliability of Pancreatic Cancer Staging Using Fiberoptic Confocal Fluorescence Microscopy in Rats
Received 12 August 2008; accepted 10 July 2009. published online 27 July 2009.
Background & Aims
Surgical management of pancreatic cancer depends on tumor resectability and staging. This study evaluated a new in vivo technique, fiberoptic confocal fluorescence microscopy (FCFM), for detection and staging of pancreatic tumors in rats.
Methods
FCFM was used with a protease-activated fluorescent marker (ProSense; VisEn Medical Inc, Woburn, MA) for in vivo imaging of solid organs (1.8-μm resolution) in a rat model of pancreatic ductal adenocarcinoma. A preliminary study described the FCFM rendering of normal and pathologic tissues. Subsequently, 2 double-blind studies compared FCFM to standard histology in (1) detection of tumors in rat models of cancer and controls and (2) detection of nodal involvement (splenic, celiac, mesenteric, and colic) 4, 5, and 6 weeks after tumor induction vs controls.
Results
Tumor cells displayed a fluorescent ductal pattern compared with non-fluorescent normal pancreas or normal follicular pattern of lymph nodes (LNs). FCFM detected all the pancreatic tumors (1.7-mm mean diameter) and identified 23 LNs that contained metastases of 99 LNs examined. Standard histologic analyses resulted in 1 false-negative result in tumor detection and 2 false negatives in LN detection, whereas FCFM produced no false-negative results. Additional serial sectioning confirmed all tumors and 16 metastatic LNs; FCFM had a negative predictive value of 100% and a positive predictive value of 69.6%.
Conclusions
Real-time “virtual biopsy” using FCFM detects tumors and LN metastases with 100% sensitivity and 92.2% specificity in rats, making it a reliable technique for detection and staging of pancreatic cancer.
∥Centre Hospitalier Emile Muller, Service de Pathologie, Mulhouse, France
¶Hôpitaux Universitaires, Chirurgie Digestive et Endocrinienne, NHC, Strasbourg, France
Reprint requests Address requests for reprints to: Jacques Marescaux, MD, FRCS, FACS, IRCAD, 1 place de l'hôpital, 67091 Strasbourg, France. fax: (33) 388 119 096
Conflicts of interest The authors disclose no conflicts.
Funding Supported by Association pour la Recherche sur le Cancer, project P08/2-02/07/08 (to I.M.).
ABSTRACT
Feasibility and Reliability of Pancreatic Cancer Staging Using Fiberoptic Confocal Fluorescence Microscopy in Rats