Submillimeter-Resolution Fluorescence Laparoscopy of Pancreatic Cancer in a Carcinomatosis Mouse Model Visualizes Metastases Not Seen with Standard Laparoscopy

被引:17
作者
Cao, Hop S. Tran [2 ]
Kaushal, Sharmeela [1 ]
Menen, Rhiana S. [2 ]
Metildi, Cristina A. [2 ]
Lee, Claudia [3 ]
Snyder, Cynthia S. [1 ]
Talamini, Mark A. [2 ]
Hoffman, Robert M. [1 ,2 ,4 ]
Bouvet, Michael [1 ,2 ]
机构
[1] UCSD Moores Canc Ctr, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA
[3] UVP LLC, Upland, CA USA
[4] AntiCanc Inc, San Diego, CA USA
来源
JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES | 2011年 / 21卷 / 06期
关键词
SURGICAL NAVIGATION; STAGING LAPAROSCOPY; DIAGNOSIS; ANTIBODY; SURGERY;
D O I
10.1089/lap.2011.0181
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
引用
收藏
页码:485 / 489
页数:5
相关论文
共 15 条
[1]  
Arnold JC, 1999, Z GASTROENTEROL, V37, P483
[2]  
Bouvet M, 2002, CANCER RES, V62, P1534
[3]   Fluorescence laparoscopy imaging of pancreatic tumor progression in an orthotopic mouse model [J].
Cao, Hop S. Tran ;
Kaushal, Sharmeela ;
Lee, Claudia ;
Snyder, Cynthia S. ;
Thompson, Kari J. ;
Horgan, Santiago ;
Talamini, Mark A. ;
Hoffman, Robert M. ;
Bouvet, Michael .
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, 2011, 25 (01) :48-54
[4]   Laparoscopic photodynamic diagnosis of ovarian cancer peritoneal micro metastasis: An experimental study [J].
Collinet, Pierre ;
Sabban, Frederic ;
Cosson, Michel ;
Farine, Marie Odile ;
Villet, Richard ;
Vinatier, Denis ;
Mordon, Serge .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 2007, 83 (03) :647-651
[5]   Staging Laparoscopy Enhances the Detection of Occult Metastases in Patients With Pancreatic Adenocarcinoma [J].
Contreras, Carlo M. ;
Stanelle, Eric J. ;
Mansour, John ;
Hinshaw, J. Louis ;
Rikkers, Layton F. ;
Rettammel, Robert ;
Mahvi, David M. ;
Cho, Clifford S. ;
Weber, Sharon M. .
JOURNAL OF SURGICAL ONCOLOGY, 2009, 100 (08) :663-669
[6]   Improving diagnostic staging laparoscopy using intraperitoneal lavage of δ-aminolevulinic acid (ALA) for laparoscopic fluorescence diagnosis [J].
Gahlen, J ;
Stern, J ;
Laubach, HH ;
Pietschmann, M ;
Herfarth, C .
SURGERY, 1999, 126 (03) :469-473
[7]   A novel red fluorescent protein orthotopic pancreatic cancer model for the preclinical evaluation of chemotherapeutics [J].
Katz, MH ;
Takimoto, S ;
Spivack, D ;
Moossa, AR ;
Hoffman, RM ;
Bouvet, M .
JOURNAL OF SURGICAL RESEARCH, 2003, 113 (01) :151-160
[8]   Fluorophore-conjugated anti-CEA Antibody for the Intraoperative Imaging of Pancreatic and Colorectal Cancer [J].
Kaushal, Sharmeela ;
McElroy, Michele K. ;
Luiken, George A. ;
Talamini, Mark A. ;
Moossa, A. R. ;
Hoffman, Robert M. ;
Bouvet, Michael .
JOURNAL OF GASTROINTESTINAL SURGERY, 2008, 12 (11) :1938-1950
[9]   Intraoperative near-infrared image-guided surgery for peritoneal carcinomatosis in a preclinical experimental model [J].
Keramidas, M. ;
Josserand, V. ;
Righini, C. A. ;
Wenk, C. ;
Faure, C. ;
Coll, J. L. .
BRITISH JOURNAL OF SURGERY, 2010, 97 (05) :737-743
[10]   In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation [J].
Kishimoto, Hiroyuki ;
Zhao, Ming ;
Hayashi, Katsuhiro ;
Urata, Yasuo ;
Tanaka, Noriaki ;
Fujiwara, Toshiyoshi ;
Penman, Sheldon ;
Hoffman, Robert M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (34) :14514-14517