New Light on Deadly Liver Metastases

Metastasis. It’s the most deadly aspect of cancer, and a word that strikes fear in the hearts of cancer patients worldwide. Metastasis describes cancer’s ability to spread from the primary tumor. Once the tumor is formed, cells may begin to break off and travel to other more “distant” parts of the body. These disseminating cells are capable of establishing new tumors in locations remote from the site of the primary tumor. One of the most common sites is the liver—and this is especially common for cancers of the breast and colon. 

Using surgery to remove metastases in the liver is desirable yet often quite difficult, in part because it’s not always easy for the surgeon to discern where exactly the cancer exists within the liver. The surgeon’s ability to clearly visualize the cancerous “spots” is essential at the time of surgery, as it enables a more complete removal of the cancerous threat. This ability is of potentially life-saving importance for removing metastases in the liver and elsewhere.

To resolve this dilemma, scientists are increasingly interested in using substances that fluoresce, or “glow”, upon exposure to light. The best fluorescent agents or markers are selective for cancer cells, and they can enable cancer researchers to see where exactly the cancer is. Once they fluoresce (revealing themselves with the help of light), the metastasis can be either surgically removed or treated by other means, including photodynamic therapy.

Researchers from the University of California San Diego (USA) and Japan’s Yokohama City University recently teamed up to study the potential for using fluorescence-guided surgery (FGS) for liver metastasis. To carry out this study, 14 mice with a single liver metastasis were randomly assigned into either fluorescence-guided surgery (FGS) or bright-light surgery (BLS), the control group. These mice had liver metastases that were labeled with a green fluorescence protein that is found only in cancer cells.

The two treatments may be described as follows. BLS was performed under white light, while FGS was performed using a hand-held portable fluorescence imaging system. Whereas half the group underwent BLS, the other half was treated with FGS—again, with mice being randomly selected for each group. Both treatments happened three weeks after implanting the liver metastases.

After each surgery, the amount of fluorescence—again, an indication of the presence of residual cancer—was measured. The group receiving BLS showed a considerable amount of residual tumor fluorescence. “In contrast, residual tumor fluorescence after FGS was not detected even at high magnification…,” the authors write. “These results demonstrate the feasibility of FGS for liver metastasis”, as reported in the 1 October 2015 issue of PLoS One.

In this study, most if not all of the metastases were surgically removed by FGS but not by BLS. In other words, there was much more cancer left over after the usual way of doing surgery, in dramatic contrast with the fluorescence-guided way of doing surgery.

The San Diego research team observed that this advantage was sustained long after the surgery, as reflected by the fact that recurrence rates were greatly reduced by FGS in comparison to BLS. “The results of present study suggest that FGS has clinical potential of reducing residual cancer in patients who have liver metastasis resected,” the authors write. They go on to state that future studies should focus on using FGS as a curative strategy for liver metastases.

In a previous study by the same research team, mice with colon cancer and liver metastases were randomly assigned to ether FGS or BLS, using methods identical to those used in the above study.

Recurrences were found in multiple sites including the liver, lung, and other organs in the BLS-treated mice; however, such recurrences were significantly reduced in FGS-treated mice. Compared to the BLS-treated group, the FGS-treated group had significantly prolonged survival as well as lower recurrence rates. These findings would seem to suggest that FGS has “important clinical potential”, as reported in the August 2015 Journal of Surgical Oncology.



Murakami T, Hiroshima Y, Zhang Y, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM. Fluorescence-Guided Surgery of Liver Metastasis in Orthotopic Nude-Mouse Models. PLoS One. 2015 Oct 1;10(10):e0138752. eCollection 2015.

Murakami T, Hiroshima Y, Zhang Y, Bouvet M, Chishima T, Tanaka K, Endo I, Hoffman RM. Improved disease-free survival and overall survival after fluorescence-guided surgery of liver metastasis in an orthotopic nude mouse model. J Surg Oncol. 2015 Aug;112(2):119-24

Rovers JP, Saarnak AE, Molina A, Schuitmaker JJ, Sterenborg HJ, Terpstra OT. Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model. Br J Cancer. 1999 Oct;81(4):600-8.