Surgical mass spec: Intelligent knife finds tumour margins in real time

Tumour removal

Image: Imperial College London

Cancer surgery can only be considered successful when all of a tumour has been removed but this is not as easy as it sounds. It is often difficult to distinguish between cancerous and healthy tissue, especially at the margins of the tumour, so that excising all of it without removing excess healthy tissue is a tricky operation. This is borne out by success rates in the UK, where about 20% of all breast cancer patients who are subjected to lumpectomies require further surgery to clear the tumour margins.

The current test for complete tumour removal is cumbersome. Tissue sections are taken to the pathology lab and examined while the patient remains on the operating table under general anaesthetic. However, even though this is the best method available, it takes about 30 minutes and the results are not always conclusive.

Now, a new procedure promises to change all that by providing an instant analysis of the tissue while the patient is on the operating table. It is based on analysis of the smoke that is produced during electrosurgery, during which tissue is heated rapidly by an electrosurgical knife to minimise blood loss. This smoke can tell whether the tissue being cut is cancerous or healthy.

The method has been described by Jeremy Nicholson and Zoltán Takáts from Imperial College London and colleagues from the University of Debrecen and MediMass Ltd., Budapest. It relies on a modification to the electrosurgical knife which captures the smoke and directs it to a mass spectrometer for testing on the spot. This modified device, named the iKnife (intelligent knife) by its inventor Takáts, measures the phospholipids driven off in the smoke to characterise the tissue.

Phospholipid libraries from cancers and healthy tissue

The mass spectrometry measurements must be very fast to keep up with the surgical procedure, so the team employed rapid evaporative ionisation mass spectrometry (REIMS), a technique invented by Takats and reported in 2009. He discovered that rapid evaporation of tissues by an electric current produces ions which can be detected.

During subsequent testing of healthy and cancerous tissue that had been removed from patients, it was found that the spectra of the phospholipids that were given off during rapid evaporation could distinguish between clean tissue and tumours. Most of the different phospholipid types were found in all of the evaporated tissues, but their distributions marked out the tissue type.

A total of 1624 samples from gastric, colon, liver, breast, lung and brain tumours were analysed in the lab and compared to healthy samples from the same organs, plus some benign and inflammatory bowel disease samples. The results were used to construct a reference library with which to compare the spectra during surgery. Statistical analysis of the spectra showed that they could be used to identify cancerous or healthy tissue with a high level of success, so they applied the method to real operations in theatre.

The iKnife for surgical precision

While operating on 81 patients and collecting 864 mass spectra, the results from the iKnife agreed with those from the histology lab on the whole. In the 15 cases where they did not match, the iKnife was correct in 11 of those cases. Predicting healthy or cancerous tissue had a sensitivity of 97.7% and a specificity of 96.5%, with a very low rate of false positives and false negatives.

The level of success prompted Takáts to say “These results provide compelling evidence that the iKnife can be applied in a wide range of cancer surgery procedures. It provides a result almost instantly, allowing surgeons to carry out procedures with a level of accuracy that hasn’t been possible before.”

In practice, about 0.1 mm³ of tissue is sufficient to provide accurate mass spectrometric information and the complete cycle from sampling to audiovisual feedback takes up to 2.5 seconds. This speed will save a lot of time in the operating theatre, freeing up the table for more procedures, while providing a greater proportion of positive outcomes.

The next steps will involve integration into the clinical environment. To this end, a mass spectrometer that complies with current regulations is being developed and a lot more clinical testing will take place.

Away from cancer, Takáts says that the iKnife will not be limited to tumour recognition. It has the ability to perform other clinical tasks, like identifying tissue with an inadequate blood supply, or types of bacteria present in the tissue.