Surgical Technique Spots Cancer Invasion with Fluorescence

One of the greatest challenges faced by cancer surgeons is to know exactly which tissue to remove, or not, while the patient is under anesthesia. A team of surgeons and scientists at University of California, San Diego School of Medicine have developed a new technique that will allow surgeons to identify during surgery which lymph nodes are cancerous so that healthy tissue can be saved. The findings will be published in the January 15 print edition of Cancer Research.

“This research is significant because it shows real-time intraoperative detection of cancer metastases in mice,” said Quyen T. Nguyen, MD, PhD, associate professor of Head and Neck Surgery at UC San Diego School of Medicine. “In the future, surgeons will be better able to detect and stage cancer that has spread to the patient’s lymph nodes using molecules that were designed and developed at UC San Diego.”

Lymph nodes, located throughout the body, serve as filters that contain immune cells to fight infection and clean the blood. When cancer cells break away from a tumor, the cells can travel through the lymph system and hide in these tiny organs. Surgeons remove the nodes to determine if a cancer has spread. However, human nodes, only half a centimeter in size, are difficult to discern among the surrounding tissue during surgery. Furthermore, even when surgeons are able to map the location of the nodes, there is no current technique that indicates whether or not the lymph nodes contain cancer, requiring removal of more lymph nodes than necessary.

“With molecular-targeted imaging, surgeons can avoid unnecessary removal of healthy lymph nodes which is better long-term for patients,” said Nguyen, director of the facial nerve clinic at UC San Diego Health System. “The range of the surgeon’s visual field is greatly enhanced by a molecular tool that can help achieve accurate surgical margins and detection of metastases so that no tumor is left behind.”

The fluorescently labeled molecules, known as ratiometric activatable cell-penetrating peptides (RACPP), are injectable. When used in mouse models, surgeons could see where the cancer had spread with high sensitivity and specificity even when the metastatic sites were only a few millimeters in size.

This form of instant pathology is an improvement over traditional sentinel node mapping, whereby only the location of the lymph node is detected without gleaning any information on actual cancer involvement.

Current methods for managing prostate cancer and neck squamous cell carcinoma only reveal the extent of cancer involvement after the patient has undergone surgical removal of all susceptible lymph nodes.

This new technique will decrease OR time because the surgical team need not wait for pathology reports, decrease time under anesthesia, and decrease unnecessary surgery on noncancerous lymph nodes.

Nyguyen’s earlier research with Nobel Prize winner Roger Tsien, PhD, professor of pharmacology at UC San Diego School of Medicine, showed in animal models how injectable fluorescent peptides could be used to highlight hard-to-see peripheral nerves, allowing surgeons to avoid them when removing or repairing other tissues.

Cheniere's stock may continue to rise on news events, or macroeconomic trends that intimate that the price of gas in Asia and Europe will stay higher than the price of gas in the U.S., but this is a speculative play I'm happy to avoid. Energy markets are incredibly volatile, and the future of the world gas market is far from certain. Heck, Cheniere's own company history tells us that.

Let's explore, for a minute, what would happen if a country in one of the big LNG importing regions suddenly tapped into a vast amount of gas. I'll use China, as it is a very real possibility right now.

The Energy Information Administration estimates that China's technically recoverable shale gas resources are 50% larger than what the U.S. has . For a country that's expected to quadruple its LNG consumption over the next seven years, an ability to exploit that resource is game-changing on a global scale . China is trying to move from zero to 60, given that it produced no shale gas in 2011, and hopes to produce 230 billion cubic feet by 2015. The goal is nothing if not ambitious, given the industry expertise and manpower that China currently lacks.

Critics of China's shale future are quick to point out that the country doesn't have the pipeline system we do, nor does it have the water resources to scale up technologies, like hydraulic fracturing, that are necessary in shale gas production. But, where there's a will, there's a way, and China's shale gas reserves proved willful enough to send ConocoPhillips overseas to join forces with Sinopec to figure out how to get that gas out of the ground.

In an effort to kick-start production, China put 20 shale blocks up for auction in September and October of last year. Eighty-three companies made 152 bids for the blocks, so the game is officially afoot . That being said, even Chinese energy analysts doubt there will be much to note in this sector before 2015 .

But remember, the first well was drilled in the U.S.' Marcellus Shale in 2004 , and it only took four years for the price of natural gas to begin collapsing, finally bottoming out (hopefully) around the halfway point of last year. Though part of that drop can be blamed on the recession, most of it is because of a huge increase in production.

If -- and that is definitely an "if" -- this precedent were to hold true in China, it could change the U.S. LNG export story dramatically. A price collapse in Asia would decimate Cheniere's ability to make money. The long-term contracts the company has in place lock-in sales volumes, not prices. Margins are what make LNG export attractive, and Cheniere's future is more or less dependent on arbitrage. In order for it to be worthwhile for Cheniere to export LNG, the company needs to beat what it estimates are break-even delivery costs of $7.70 and $9.45 per mmbtu in Europe and Asia, respectively .

That model is built on several assumptions, however, including the price of the U.S.-produced gas that Cheniere must purchase, and shipping costs, not to mention the price gas is selling for in target markets. The import price of natural gas in Europe has ranged from a low of $9.36 to a high of $11.97 per mmbtu over the past two years, while Japan has seen prices hit a low of $11.45 and a high of $18.11 per mmbtu over the same period. The price of gas in the U.S. has ranged from $2.00 to around $3.50 in 2012.

The opportunity is obvious, but markets are unpredictable beasts; if the global price of natural gas drops too low, or the domestic price of natural gas climbs too high, Cheniere's margins will suffer.