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Fluorescence-Guided Surgery of Liver Metastasis in Orthotopic Nude-Mouse Models.

Murakami T, Hiroshima Y, Zhang Y, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM - PLoS ONE (2015)

Bottom Line: Post-surgical residual tumor fluorescence was visualized with the OV100 Small Animal Imaging System.Residual tumor fluorescence after BLS was clearly visualized at high magnification with the OV100.In contrast, residual tumor fluorescence after FGS was not detected even at high magnification with the OV100.

View Article: PubMed Central - PubMed

Affiliation: AntiCancer, Inc., San Diego, California, United States of America; Department of Surgery, University of California San Diego, San Diego, California, United States of America; Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

ABSTRACT
We report here the development of fluorescence-guided surgery of liver metastasis. HT29 human colon cancer cells expressing green fluorescent protein (GFP) were initially injected in the spleen of nude mice. Three weeks later, established liver metastases were harvested and implanted on the left lobe of the liver in other nude mice in order to make an orthotopic liver metastasis model. Fourteen mice with a single liver metastasis were randomized into bright-light surgery (BLS) or fluorescence-guided surgery (FGS) groups. Seven mice were treated with BLS, seven were treated with FGS. Three weeks after implantation, the left lobe of the liver with a single metastasis was exposed through a median abdominal incision. BLS was performed under white light. FGS was performed using a hand-held portable fluorescence imaging system (Dino-Lite). Post-surgical residual tumor fluorescence was visualized with the OV100 Small Animal Imaging System. Residual tumor fluorescence after BLS was clearly visualized at high magnification with the OV100. In contrast, residual tumor fluorescence after FGS was not detected even at high magnification with the OV100. These results demonstrate the feasibility of FGS for liver metastasis.

No MeSH data available.


Related in: MedlinePlus

Pre-operative and post-operative images from the orthotopic liver metastasis model treated with FGS.(A)—(C) Upper panels show bright field images, and lower panels are images of tumor fluorescence obtained with the OV100. Residual tumor fluorescence could not be detected even at high magnification (C). (D,F,H) Pre-FGS tumor fluorescence was clearly visualized with the Dino-Lite imaging system. (E,G,I) Dino-Lite imaging showed no evidence of tumor after FGS. (J-K) Dino-Lite settings. (J) After exposing the left lobe of the liver, the mouse was put under the Dino-Lite. (K) Connection between the Dino-Lite and computer. Tumor fluorescence was imaged on the monitor during FGS. Magnifications are indicated above the columns.
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pone.0138752.g004: Pre-operative and post-operative images from the orthotopic liver metastasis model treated with FGS.(A)—(C) Upper panels show bright field images, and lower panels are images of tumor fluorescence obtained with the OV100. Residual tumor fluorescence could not be detected even at high magnification (C). (D,F,H) Pre-FGS tumor fluorescence was clearly visualized with the Dino-Lite imaging system. (E,G,I) Dino-Lite imaging showed no evidence of tumor after FGS. (J-K) Dino-Lite settings. (J) After exposing the left lobe of the liver, the mouse was put under the Dino-Lite. (K) Connection between the Dino-Lite and computer. Tumor fluorescence was imaged on the monitor during FGS. Magnifications are indicated above the columns.

Mentions: Single liver metastases were clearly detected preoperatively with the OV100 (Figs 3A and 4A). In the BLS group, residual tumor fluorescence was marginally detected at a magnification of 0.14×. However, at a magnification of 0.56×, residual cancer was clearly visualized (Fig 3B and 3C). By contrast, residual tumor fluorescence could not be detected even at a magnification of 0.56× in the FGS group (Fig 4B and 4C). Tumor fluorescence was also clearly visualized before FGS with the Dino-Lite at a magnification of 30× (Fig 4D). Dino-Lite imaging showed no evidence of residual cancer after FGS (Fig 4E). All resected specimens exhibited strong GFP expression (Fig 3D). Histologically, viable cancer was detected on the resection line in the BLS group, but not in the FGS group which had clear margins (Fig 5), which is consistent with the fluorescence data. Residual tumor area after BLS was significantly larger than after FGS (0.34 ± 0.28 mm2 and 0 mm2, respectively; P = 0.003; Fig 6).


Fluorescence-Guided Surgery of Liver Metastasis in Orthotopic Nude-Mouse Models.

Murakami T, Hiroshima Y, Zhang Y, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM - PLoS ONE (2015)

Pre-operative and post-operative images from the orthotopic liver metastasis model treated with FGS.(A)—(C) Upper panels show bright field images, and lower panels are images of tumor fluorescence obtained with the OV100. Residual tumor fluorescence could not be detected even at high magnification (C). (D,F,H) Pre-FGS tumor fluorescence was clearly visualized with the Dino-Lite imaging system. (E,G,I) Dino-Lite imaging showed no evidence of tumor after FGS. (J-K) Dino-Lite settings. (J) After exposing the left lobe of the liver, the mouse was put under the Dino-Lite. (K) Connection between the Dino-Lite and computer. Tumor fluorescence was imaged on the monitor during FGS. Magnifications are indicated above the columns.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591295&req=5

pone.0138752.g004: Pre-operative and post-operative images from the orthotopic liver metastasis model treated with FGS.(A)—(C) Upper panels show bright field images, and lower panels are images of tumor fluorescence obtained with the OV100. Residual tumor fluorescence could not be detected even at high magnification (C). (D,F,H) Pre-FGS tumor fluorescence was clearly visualized with the Dino-Lite imaging system. (E,G,I) Dino-Lite imaging showed no evidence of tumor after FGS. (J-K) Dino-Lite settings. (J) After exposing the left lobe of the liver, the mouse was put under the Dino-Lite. (K) Connection between the Dino-Lite and computer. Tumor fluorescence was imaged on the monitor during FGS. Magnifications are indicated above the columns.
Mentions: Single liver metastases were clearly detected preoperatively with the OV100 (Figs 3A and 4A). In the BLS group, residual tumor fluorescence was marginally detected at a magnification of 0.14×. However, at a magnification of 0.56×, residual cancer was clearly visualized (Fig 3B and 3C). By contrast, residual tumor fluorescence could not be detected even at a magnification of 0.56× in the FGS group (Fig 4B and 4C). Tumor fluorescence was also clearly visualized before FGS with the Dino-Lite at a magnification of 30× (Fig 4D). Dino-Lite imaging showed no evidence of residual cancer after FGS (Fig 4E). All resected specimens exhibited strong GFP expression (Fig 3D). Histologically, viable cancer was detected on the resection line in the BLS group, but not in the FGS group which had clear margins (Fig 5), which is consistent with the fluorescence data. Residual tumor area after BLS was significantly larger than after FGS (0.34 ± 0.28 mm2 and 0 mm2, respectively; P = 0.003; Fig 6).

Bottom Line: Post-surgical residual tumor fluorescence was visualized with the OV100 Small Animal Imaging System.Residual tumor fluorescence after BLS was clearly visualized at high magnification with the OV100.In contrast, residual tumor fluorescence after FGS was not detected even at high magnification with the OV100.

View Article: PubMed Central - PubMed

Affiliation: AntiCancer, Inc., San Diego, California, United States of America; Department of Surgery, University of California San Diego, San Diego, California, United States of America; Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

ABSTRACT
We report here the development of fluorescence-guided surgery of liver metastasis. HT29 human colon cancer cells expressing green fluorescent protein (GFP) were initially injected in the spleen of nude mice. Three weeks later, established liver metastases were harvested and implanted on the left lobe of the liver in other nude mice in order to make an orthotopic liver metastasis model. Fourteen mice with a single liver metastasis were randomized into bright-light surgery (BLS) or fluorescence-guided surgery (FGS) groups. Seven mice were treated with BLS, seven were treated with FGS. Three weeks after implantation, the left lobe of the liver with a single metastasis was exposed through a median abdominal incision. BLS was performed under white light. FGS was performed using a hand-held portable fluorescence imaging system (Dino-Lite). Post-surgical residual tumor fluorescence was visualized with the OV100 Small Animal Imaging System. Residual tumor fluorescence after BLS was clearly visualized at high magnification with the OV100. In contrast, residual tumor fluorescence after FGS was not detected even at high magnification with the OV100. These results demonstrate the feasibility of FGS for liver metastasis.

No MeSH data available.


Related in: MedlinePlus