iKnife cutting through liver

The iKnife and iEndoscope

Currently, surgeons have to wait on histopathology results to determine the cancerous margins during surgery and the results are often unclear. The iKnife and iEndoscope have been designed to allow real-time identification of cancerous margins so surgeons can immediately determine what tissue needs to be removed.  The technology also allows a real-time diagnosis of abnormal tissue, allowing surgeons to differentiate malignant from healthy tissue.

How they work

Electrosurgical knives use electricity to provide a high heat at the tip of the instrument; this cuts and vaporises tissue whilst sealing blood vessels to stop bleeding.  The iKnife was created by adapting such knives to allow the vapour created during heating to be channelled to a mass spectrometer for REIMS analysis.  The spectral profile observed, mainly comprising lipids, is characteristic of the tissue type; thus malignant tissue results in a spectral profile that differs from healthy cells. A real time comparison to a spectral database provides tissue type identification immediately which can assist the surgeon in identifying cancer margins.  The iKnife has shown promising results in the detection of breast, ovarian, breast and gastrointestinal cancers.

The iEndoscope employs a bespoke modified polypectomy snare (developed in collaboration with Medwork) to allow collection of electrosurgical aerosol from the bowel lumen (inside the bowel). During hot snare polypectomy, the aerosol is collected through small fenestrations in the snare outer sheath and suctioned back through the endoscope to the mass spectrometer, via a side port in the handle of the snare.  The lipidomic signal is then processed in the same fashion as the surgical iKnife.

When patients will benefit

The iKnife, was first described in 2009 and initial studies show promising results for the diagnostic accuracy of REIMS technology in distinguishing tissues of different compositions. Since this time the iKnife has been translated across many clinical disciplines, the most notable of which is in cancer detection during surgery. The iKnife is currently being trialled as a research tool in multiple studies in breast, colon, brain and ovarian cancer surgery at Imperial College London and across the global iKnife network. Before the iKnife can become a regular device in operating theatres all over the world it has to follow the same approval pathway as all new medical technology, with clinical trials and licensing to ensure safe use, but we are well on the way to patients and surgeons benefiting from this ground-breaking research in the near future.

Improving diagnostics in cancer

Breast

Breast cancer is the most common cancer affecting females in the United Kingdom. In 2011, 41,523 women in the UK were diagnosed with invasive breast cancer the vast majority of whom received surgery with curative intent. Although this can be done by a variety of methods surgery, that conserves as much “normal” breast tissue as possible, is often the treatment of choice.

A wide local excision involves cutting out the breast cancer with a healthy rim (margin) of tissue. Unfortunately, there is currently no perfect way for the surgeon to know if they have cut away all of the breast cancer or if there is any cancer remaining. As a result of this approximately one in five (20%) of patients undergoing this surgery require another operation to take more breast tissue away as the first sample showed evidence of cancer at the edges (margins) of the tissue removed. 

Gastrointestinal

Bowel cancer is the fourth most common cancer in the UK, and causes over 15,000 deaths per year. Certain genetic mutations and lifestyle factors such as smoking and alcohol consumption have been linked to bowel cancer. Current treatments include surgery, chemotherapy and radiotherapy, but unfortunately not all patients benefit. The bowel is host to billions of bacteria, which outnumber the body’s own cells.

We are trying to better understand the role of bacteria in the development of bowel cancer. By studying the metabolic interactions of these bacteria with their host using mass spectrometry, we are identifying new targets for cancer treatment and prevention. We have also developed an intelligent endoscope ‘iEndoscope’, which allows us to gather key diagnostic information about cancers during a colonoscopy procedure, in real time. The aim of this work is to make bowel cancer treatment more efficient and targeted to each individual patient

Ovarian

Ovarian cancer is the 6th most common cancer in women in the UK, with over 7400 cases diagnosed each year. Women with early stage ovarian cancer commonly will not have any symptoms and therefore by the time symptoms present in a patient with this cancer, there has already been spread of tumour deposits throughout the abdomen and pelvis.

When women present with a pelvic mass, the diagnosis is often not determined pre-operatively by either clinical examination or imaging. Currently the diagnosis of a mass is not made until after it has been removed and once the histopathology reporting is complete. Ovarian cancer survival is significantly improved by surgical reduction of disease but as many pelvic masses are of a benign or borderline nature, they should not require such extensive surgery as ovarian cancer. This inevitably results in some women having more radical surgery than is necessary if the intraoperative assumption is they have a cancer but are ultimately diagnosed with a non-malignant tumour. Other women will have inappropriately conservative surgery if their tumour is thought to be benign or borderline and subsequently turns out to be invasive cancer.

Along with this, if a patient has undergone neoadjuvant (upfront) chemotherapy difficult for the surgeon to detect tumour deposits visually or by touch, as this process causes scarring and fibrosis. Surgeons therefore cannot confidently identify scarred deposits which may contain residual tumour and this raises the possibility that deposits of tumour are left behind. Conversely it could result in a radical “de-bulking” operation which risks disease-free scar tissue being removed unnecessarily because it cannot easily be identified as such. Both of these possible outcomes show that there is a need for a rapid, intraoperative cancer detection tool for the identification of diseased tissue during ovarian cancer surgery. The iKnife is able to diagnose tissue histology intraoperatively, and in real-time, enabling gynaecology surgeons to tailor their surgery precisely for the needs of each patient.