title: Near-infrared fluorescence-guided resection of colorectal liver metastases.
abstract: BACKGROUND
  The fundamental principle of oncologic surgery is the complete resection of malignant cells. However, small tumors are often difficult to find during surgery using conventional techniques. The objectives of this study were to determine if optical imaging, using a contrast agent already approved for other indications, could improve hepatic metastasectomy with curative intent, to optimize dose and timing, and to determine the mechanism of contrast agent accumulation.
  
  
  METHODS
  The high tissue penetration of near-infrared (NIR) light was exploited by use of the FLARE (Fluorescence-Assisted Resection and Exploration) image-guided surgery system and the NIR fluorophore indocyanine green in a clinical trial of 40 patients undergoing hepatic resection for colorectal cancer metastases.
  
  
  RESULTS
  A total of 71 superficially located (< 6.2 mm beneath the liver capsule) colorectal liver metastases were identified and resected using NIR fluorescence imaging. Median tumor-to-liver ratio was 7.0 (range, 1.9-18.7) and no significant differences between time points or doses were found. Indocyanine green fluorescence was seen as a rim around the tumor, which is shown to be entrapment around cytokeratin 7-positive hepatocytes compressed by the tumor. Importantly, in 5 of 40 patients (12.5%, 95% confidence interval = 5.0-26.6), additional small and superficially located lesions were detected using NIR fluorescence, and were otherwise undetectable by preoperative computed tomography, intraoperative ultrasound, visual inspection, and palpation.
  
  
  CONCLUSIONS
  NIR fluorescence imaging, even when used with a nontargeted, clinically available NIR fluorophore, is complementary to conventional imaging and able to identify missed lesions by other modalities.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Joost R
authors.initials: JR
authors.lastname: van der Vorst
authors.forename: Boudewijn E
authors.initials: BE
authors.lastname: Schaafsma
authors.forename: Merlijn
authors.initials: M
authors.lastname: Hutteman
authors.forename: Floris P R
authors.initials: FP
authors.lastname: Verbeek
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Liefers
authors.forename: Henk H
authors.initials: HH
authors.lastname: Hartgrink
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Vahrmeijer
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery*; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D007208:Indocyanine Green; D008113:Liver Neoplasms / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D025321:Surgery, Computer-Assisted / Q000379:methods*; D016019:Survival Analysis
chemical_list: D005456:Fluorescent Dyes; D007208:Indocyanine Green
keywords: colorectal cancer; fluorescence; image-guided surgery; indocyanine green; liver neoplasms; near-infrared