Journal
LASERS IN SURGERY AND MEDICINE
Volume 49, Issue 3, Pages 280-292Publisher
WILEY
DOI: 10.1002/lsm.22617
Keywords
liver metastases; confocal laser endomicroscopy; virtual histology; fluorescence microscopy; indocyanine green; fluorescein
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Funding
- Health Innovation Challenge Fund, Department of Health [HICF-T4-317, WT100247MA]
- Wellcome Trust [HICF-T4-317, WT100247MA]
- Cancer Research UK [16463] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/H046410/1, EP/M020533/1] Funding Source: researchfish
- National Institute for Health Research [10/4001/11, NF-SI-0509-10143] Funding Source: researchfish
- EPSRC [EP/M020533/1, EP/H046410/1] Funding Source: UKRI
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BackgroundMetastasis of colorectal cancer to the liver is the most common indication for hepatic resection in a western population. Incomplete excision of malignancy due to residual microscopic disease normally results in worse patient outcome. Therefore, a method aiding in the real time discrimination of normal and malignant tissue on a microscopic level would be of benefit. Material and MethodsThe ability of fluorescent probe-based confocal laser endomicroscopy (pCLE) to identify normal and malignant liver tissue was evaluated in an orthotopic murine model of colorectal cancer liver metastasis (CRLM). To maximise information yield, two clinical fluorophores, fluorescein and indocyanine green (ICG) were injected and imaged in a dual wavelength approach (488 and 660nm, respectively). Visual tissue characteristics on pCLE examination were compared with histological features. Fluorescence intensity in both tissues was statistically analysed to elucidate if this can be used to differentiate between normal and malignant tissue. ResultsFluorescein (488nm) enabled good visualisation of normal and CRLM tissue, whereas ICG (660nm) visualisation was limited to normal liver tissue only. Fluorescence intensity in areas of CRLM was typically 53-100% lower than normal hepatic parenchyma. Using general linear mixed modelling and receiver operating characteristic analysis, high fluorescence intensity was found to be statistically more likely in normal hepatic tissue. ConclusionReal time discrimination between normal liver parenchyma and metastatic tissue with pCLE examination of fluorescein and ICG is feasible. Employing two (rather than a single) fluorophores allows a combination of qualitative and quantitative characteristics to be used to distinguish between hepatic parenchyma and CRLM. (C) 2016 Wiley Periodicals, Inc.
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