title: Clinical translation of ex vivo sentinel lymph node mapping for colorectal cancer using invisible near-infrared fluorescence light.
abstract: BACKGROUND
  Sentinel lymph node (SLN) mapping in colorectal cancer may have prognostic and therapeutic significance; however, currently available techniques are not optimal. We hypothesized that the combination of invisible near-infrared (NIR) fluorescent light and ex vivo injection could solve remaining problems of SLN mapping in colorectal cancer.
  
  
  METHODS
  The FLARE imaging system was used for real-time identification of SLNs after injection of the NIR lymphatic tracer HSA800 in the colon and rectum of (n = 4) pigs. A total of 32 SLN mappings were performed in vivo and ex vivo after oncologic resection using an identical injection technique. Guided by these results, SLN mappings were performed in ex vivo tissue specimens of 24 consecutive colorectal cancer patients undergoing resection.
  
  
  RESULTS
  Lymph flow could be followed in real-time from the injection site to the SLN using NIR fluorescence. In pigs, the SLN was identified in 32 of 32 (100%) of SLN mappings under both in vivo and ex vivo conditions. Clinically, SLNs were identified in all patients (n = 24) using the ex vivo strategy within 5 min after injection of fluorescent tracer. Also, 9 patients showed lymph node involvement (N1 disease). In 1 patient, a 3-mm mesenteric metastasis was found adjacent to a tumor-negative SLN.
  
  
  CONCLUSIONS
  The current pilot study shows proof of principle that ex vivo NIR fluorescence-guided SLN mapping can provide high-sensitivity, rapid, and accurate identification of SLNs in colon and rectum. This creates an experimental platform to test optimized, non-FDA-approved NIR fluorescent lymphatic tracers in a clinical setting.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Merlijn
authors.initials: M
authors.lastname: Hutteman
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: J Sven D
authors.initials: JS
authors.lastname: Mieog
authors.forename: Joost R
authors.initials: JR
authors.lastname: van der Vorst
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Ashitate
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: Marian C
authors.initials: MC
authors.lastname: van Groningen
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D003952:Diagnostic Imaging; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes; D006801:Humans; D008027:Light; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D021701:Sentinel Lymph Node Biopsy; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods*; D013552:Swine
chemical_list: D005456:Fluorescent Dyes