iKNIFE NEAR REALITY

An "intelligent knife" that lets surgeons know immediately whether the tissue they are cutting is cancerous or not was 100% accurate in the first study to test the product in the operating theater.

The results of the study were published in the July 17 issue ofScience Translational Medicine.

The innovative tool, known as the "iKnife," couples electrosurgery with rapid evaporative ionization mass spectrometry.

When surgeons slice through tissue with an electrosurgical knife, rapid heat vaporizes the tissue, creating an aerosol that contains tissue fragments that are usually sucked away by extraction systems. With the iKnife, however, that aerosol is collected and analyzed in real time with mass spectrometry. Readings are compared with a reference database and the tissue fragments are identified immediately as being cancerous or not.

"In cancer surgery, you want to take out as little healthy tissue as possible, but you have to ensure that you remove all of the cancer. There is a real need for technology that can help the surgeon determine which tissue to cut out and which to leave in," said study coauthor Ara Darzi, PC, MD, KBE, FRS, FMedSci, HonFREng, professor of surgery at Imperial College London, Royal Marsden Hospital, and the Institute of Cancer Research in the United Kingdom.

This study "shows that the iKnife has the potential to do this, and the impact on cancer surgery could be enormous," he said in a statement.

Building Reference Library

The iKnife was invented by Zoltán Takáts, PhD, who previously worked at Semnelweiss University in Budapest, Hungary. He formed MediMass Ltd. to fund its development. Dr. Takáts is now a reader in medical mass spectrometry at the Department of Cancer and Surgery at Imperial College, and is senior author on the paper.

Dr. Takáts and colleagues first used the iKnife to analyze a variety of tissue samples collected from 302 patients. The samples included healthy tissue and tissue from brain, lung, breast, and liver tumors.

From that analysis, the researchers created a reference database of specific mass spectra for 1624 cancerous and 1309 noncancerous entries. "These spectra were unique for each cancer type, with lipids such as phosphatidylcholine and phosphatidylinositol showing different ratios," notes an accompanying Editor's Summary, and using these ratios even allowed the researchers to identify the origin of metastatic tumors.

First Use in Operating Theater

Next, the team used the iKnife during 91 resections. The tool matched the vaporized tissue removed during surgery to entries in the reference database and, within 3 seconds, could report whether or not the tissue was cancerous.

The usual scenario during cancer surgery is that if the surgeon is unsure where the tumor margins are, tissue is sent off to a pathologist for testing, which can take 20 to 30 minutes; often, additional tissue samples are required. During this time, the patient remains under anesthesia, according to the Editor's Summary.

If the surgeon fails to remove all the cancerous tissue, a second operation might be needed; the researchers point out that 20% of breast cancer patients who undergo a lumpectomy require further surgery to clear positive margins. However, re-excision is not always possible, such as in soft tissue tumors or colon cancer, and further adjuvant treatment can be required, they add.

When results from the 91 iKnife resections were compared with postoperative histologic diagnosis, they agreed in all cases, the researchers report.

"These results provide compelling evidence that the iKnife can be applied in a wide range of cancer surgery procedures," Dr. Takáts said in a statement. "It provides a result almost instantly, allowing surgeons to carry out procedures with a level of accuracy that hasn't been possible before. We believe it has the potential to reduce tumor recurrence rates and enable more patients to survive."

This initial study of the iKnife was carried out in 3 hospitals in Hungary; further studies with the tool are now underway at 3 hospitals in the United Kingdom.

The researchers acknowledge that more clinical testing is needed, and note that the product will not likely be commercially available for another year or so. Discussions about licensing the technology are underway.

Nevertheless, they are very enthusiastic about its potential.

"We are looking to completely transform the way that surgeons make sure they're cutting into exactly the right place," said Dr. Darzi. "This will make surgery safer and improve our success rate at removing cancers. Ultimately, we hope to apply this approach to less invasive types of surgery, such as endoscopy and keyhole surgery," he said in a statement.

More Research Needed

Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society, described the science behind the iKnife "fascinating," but he emphasized that more research is needed. He made the comments in a HealthDay News report.

"The real question everybody's going to ask is can this be translated directly to clinical practice," Dr. Lichtenfeld said. "The answer is possibly, but there's a lot of work that has to be done before that happens, and it would have to demonstrate a clear benefit to the patient and the healthcare system before it would happen. It's still quite a ways from actually showing up in an operating room at a local hospital."

Dr. Lichtenfeld cited the example of robotic surgery technology, which has become popular for prostate cancer surgery. Many hospitals purchased robots but the expected improvements have not panned out, he said. "People are only now asking if they make enough of a difference to justify the cost of the robot," he said. "We can't get into that situation again. We need to have scientific research before we have widespread adoption of new technology."

The study was funded by the National Institute for Health Research Imperial Biomedical Research Centre, the European Research Council, and the Hungarian National Office for Research and Technology. First author Julia Balog is an employee of MediMass Ltd.

Sci Transl Med. 2013;5:194ra93. Abstract, Editor's Summary