Between 20% and 30% of women having breast cancer surgery will have to go back for another operation. Why? Due to a lack of technology.

Mr Daniel Leff is a breast cancer surgeon at Imperial College London. Every day he takes women with breast cancer into surgery to remove their tumours. Before they go into theatre, they have to sign a consent form. At the bottom of every form sits a stat that out of 100 women having this type of surgery, on average between 20 and 30 will have to go back for another operation.

All this disruption is down to a lack of technology. Right now, surgeons don’t have a way to know for sure that they’ve removed every cancer cell from the body during the procedure, first time.

“Not only do patients not like being reoperated on,” says Leff, “but if you have to go back into surgery, the risk of problems after surgery also goes up.” “The risk of infection is greater and the cosmetic outcomes are certainly poorer.” Leff says the cost of reoperation is financial as well as physical. Reoperation means more time off work, longer recovery and hospital beds remaining occupied. In many cases, patients who need further treatment, such as chemotherapy or radiotherapy, can’t have it until their final surgery is finished and they’re fully recovered.

While the patient is in recovery, a tissue sample from the edge of where the surgeon has cut is already on its way to a pathology lab to be looked at under a microscope. If cancer cells are detected around the edge of where the surgeon has cut it’s called a ‘positive margin’.

“In that situation it’s 50:50, a flip of the coin, as to whether there’s more disease inside the patient,” says Leff. “The risk of leaving cancer inside them is too high, so we have to go back to theatre and check by removing more tissue.”

But all this could change thanks to an experimental surgical device called the intelligent knife that has the unique ability to sniff out cancer cells.

iknife smoke

The iKnife is a surgical knife, which tests tissue as it contacts it during an operation, and immediately gives information as to whether that tissue contains cancer cells.

During a surgery this information is given continuously to the surgeon, significantly accelerating biological tissue analysis and enabling removal of virtually all cancer cells.

The device was invented by Zoltán Takáts, Ph.D, a Hungarian research chemist associated with Semmelweis University, in Budapest. He currently is Professor of Analytical Chemistry at Imperial College London (UK).

How does the iKnife work?

When meat cooks on a barbecue the tissues heat up and start to smoke. Surgeons say this is no different in surgery.

When the surgeon’s knife heats up the tissue to break it apart, an aerosol is created containing a complex mix of all the molecules from the tissue that has just been cut. In theatre, this aerosol has a smoky appearance. Ever since electro-surgery began, this smoke has been thought of as an irritant, which is sucked out of the operating room and thrown away.

So, the idea was born: what if we could analyse the surgical smoke in greater detail?

Takats was already working on developing new tools that could analyse samples directly without any treatment.  “Tools that could tell you the composition of a sample in real time.” His project involved a piece of technology called a mass spectrometer. This rather chunky machine can be found in most chemistry labs around the world. It reveals the different molecules inside a sample by measuring them based on their size and charge, like a very accurate molecular weighing scale.

Takats knew that he had invented a way for the mass spectrometer to recognise different tissue types. He now had to find a medical need that could benefit from his research. After talking to various surgeons in Hungary, Takats suspected that the surgical smoke produced in theatre might be the perfect sample to play with.

“As we learnt more about cancer biology and cancer care we realised we could help. I was then gradually pulled into this world,” he says.

Takats proposed that the smoke made from the regular surgeon’s knife could be funnelled into his molecular weighing machine through a tube. After a few seconds of analysis, there was a chance the machine could work out the fingerprint profile of the tissue type that has just been cut.

This would mean the surgeon would know if they’re cutting through healthy tissue or cancer only a few seconds after their first cut. This would open the possibility of making decisions live in the operation based on this information.

Takats knew that if he could prove his machine was able to tell cancer tissue and healthy tissue apart in theatre, then it had the potential to boost the accuracy of cancer surgery. He started working with a group of surgeons in Hungary in 2008 to do the initial work and moved to Imperial College in 2012. And so, he took the now-trademarked iKnife with him to the UK.

In London, Takats and Leff started initial tests to ensure the iKnife could tell the difference between healthy tissue samples and breast cancer in the controlled setting of the lab.

“We had to teach the iKnife to recognise cancer,” says Takats. “We used machine learning algorithms, which need to be trained.” The team trained these computer programs by using the iKnife on hundreds of tumour samples taken from surgery. Slowly but surely, the team has built a molecular library that means the iKnife can accurately tell the difference between a tumour sample and a healthy one.

While Takats’ team is also studying the iKnife’s potential in other cancers, these stats have spurred their work with breast cancer on.

“Breast cancer was one of the ‘low-hanging fruits’ because of the high re-excision rates that women have to go through,” says Takats. “It was a place where we could really make a difference. Even if we just half the current re-excision rate then it’s already a big achievement.”

In 2017, Takats and Leff were awarded a Cancer Research UK grant to help them fund the REI-EXCISE trial.

The conclusion? With more testing and tinkering, the surgeons of the future could have something that the surgeons today don’t always have; certainty that every last cancer cell has been removed, and the confidence to tell their patients that surgery went well, and they won’t be seeing them again.

The iKnife pilot ex-vivo results will be presented in LIFE 4.0 Conference by Dr. Daniel Richard Leff.

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