title: Submillimeter-resolution fluorescence laparoscopy of pancreatic cancer in a carcinomatosis mouse model visualizes metastases not seen with standard laparoscopy.
abstract: BACKGROUND
  Staging laparoscopy can visualize peritoneal and liver metastases in pancreatic cancer otherwise undetectable by preoperative imaging. However, false-negative rates may be as high as 18%-26%. The aim of the present study was to improve detection of metastatic pancreatic cancer with the use of fluorescence laparoscopy (FL) in a nude-mouse model with the tumors expressing green fluorescent protein (GFP).
  
  
  METHODS
  The carcinomatosis mouse model of human pancreatic cancer was established by intraperitoneal injections of green fluorescent protein-expressing MiaPaca-2 human pancreatic cancer cells into 6-week-old female athymic mice. Two weeks later, mice underwent diagnostic laparoscopy. Laparoscopy was performed first under standard brightfield lighting, followed by fluorescent lighting. The number of metastatic foci identified within the four quadrants of the peritoneal cavity was recorded. After laparoscopy, the animals were sacrificed, opened, and imaged with the OV-100 Small Animal Imaging system as a positive control to identify metastasis. Tumors were collected and processed for histologic review.
  
  
  RESULTS
  FL enabled visualization of pancreatic cancer metastatic foci not visualized with standard brightfield laparoscopy (BL). Under FL, in 1 representative mouse, 26 separate micrometastatic lesions were identified. In contrast, only very large tumors were seen using BL. Use of the OV-100 images, as positive controls, confirmed the presence of tumor foci. FL thus allowed identification and exact localization of submillimeter tumor foci. Such small-sized tumor foci were not distinguished from surrounding tissue under BL. All malignant lesions were histologically confirmed.
  
  
  CONCLUSIONS
  The use of FL enables the identification of tumor foci that cannot be seen with standard laparoscopy. The technology described in this report has important potential for the clinical development of FL.
authors.affiliation: Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Hop S
authors.initials: HS
authors.lastname: Tran Cao
authors.forename: Sharmeela
authors.initials: S
authors.lastname: Kaushal
authors.forename: Rhiana S
authors.initials: RS
authors.lastname: Menen
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Metildi
authors.forename: Claudia
authors.initials: C
authors.lastname: Lee
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Snyder
authors.forename: Mark A
authors.initials: MA
authors.lastname: Talamini
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000556:secondary*; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D006801:Humans; D010535:Laparoscopy / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology*