A fluorescence guided steerable laser tool for precision resection of early stage cancers

In the UK 40,000 people are diagnosed every year with colorectal cancer which carries a life-time risk of 1:16 for men and 1:18 for women. The National Bowel Cancer Screening Programme is proving effective, with a 16% survival benefit for screened individuals. Importantly, there has been a shift in the detection to earlier disease with screening colonoscopy picking up polyps in 40% of cases and cancers in 10% of cases. There is therefore a growing demand to remove these early precancerous/cancerous tumours by endoscopic means. However, the shift away from conventional surgery to endoscopic techniques presents challenges. Existing procedures using relatively cumbersome electrical cutting devices to apply heat to the tissue are challenging to perform due to restricted access and a lack of fine control for the surgeon. In some cases it is not possible to remove colonic lesions due to them occupying sites inaccessible to "forward facing" endoscopic excision methods. This results in a non-ideal procedure sometimes resulting in serious complications such as bowel perforation.

Infrared lasers are attractive for surgery because the water in human tissue strongly absorbs this radiation. Additionally, "ultrafast" i.e. picosecond pulsed lasers deliver energy in such short pulses that thermal effects are minimal and tissue can be ablated with the resulting crater restricted only to the area on which the pulse was incident. Therefore, by precisely and flexibly delivering the energy to specific tumorous areas they can be cleanly removed minimising both damage to surrounding tissue and the risk of bowel perforation. Another advantage may come from improved haemostasis with laser ablation, reducing bleeding complications. Unfortunately, the use of lasers for endoscopic surgery has been severely limited due to the lack of a suitable flexible delivery system capable of handling the high intensities required.

Through EPSRC funding we developed a new family of optical fibres that are ideally suited for laser surgery. In particular these fibres deliver wavelengths and pulse energies previously unattainable. They have a small diameter (scale of a human hair) and are highly flexible and open up new routes for minimally invasive surgical therapies where the action of the laser is required within the body. The fibres were shown to deliver infrared and ultrafast lasers with adequate power for the ablation of hard and soft biological tissue and are mechanically and chemically robust. They can be bent to very small diameters (a few mm) and significantly outperform the current state-of-art technologies for laser delivery in surgery.

Additionally, new imaging techniques are emerging using molecules that specifically attach to, and mark, cancerous tissue. These marked tumours, when correctly illuminated, will fluoresce or "light-up" and stand out from healthy tissue. This is particularly useful for small, early stage, flat tumours that are not visible under standard illumination allowing them to be readily visualised aiding a precise surgical intervention. It will also facilitate complete eradication of the tumours, helping to avoid problems with tumour recurrence. Due to its precision (far exceeding that of thermal endoscopic tools) laser energy can exploit this function and accurately target tumours.

Through our Healthcare Partnership we will realise the full potential of these fibres and create a novel steerable surgical tool guided by the fluorescent marker. Our partnership consists of experts in high power laser applications and biophotonics at Heriot-Watt University and clinical expertise at the University of Leeds. Renishaw Plc have strong commercial activity in medical applications and can exploit the technology and Edinburgh Molecular Imaging Ltd developed the novel fluorescence marker. Together we will exploit this technology to develop a life-saving colorectal surgical procedure transferable to other life-threatening conditions.

Given the prevalence of colorectal cancer (40,000 people diagnosed in the UK every year), and the numbers of early polyps/cancers detected on national bowel cancer screening programmes, the societal impact of an improved and effective treatment at an earlier stage of the disease is clear. Our Healthcare Partnership is designed around impact and consists of a team of academics, clinicians and commercial partners. Specifically the following groups are expected to benefit directly form the impact of this programme:

Public and Society:
The public will directly benefit from this research through reduction in complications (bleeding and perforation) following endoscopic removal of polyps/cancers. This will help to eliminate the fear of the procedure, which is not negligible particularly in those individuals requiring repeat colonoscopy. Greater precision in polyp/cancer removal will also reduce recurrence rates. Additionally, the management of colorectal cancer, including population screening, is a significant burden on the NHS and any effective new procedures will have major benefits to our society from an economic standpoint.

Commercial sector:
This Healthcare partnership has been designed explicitly such that the commercial partners involved will directly benefit from exploitation of the technology. The industrial partners will benefit from the new relationships formed between the academic, clinicians and industrial partners that are expected to continue well after the project has completed.

Renishaw plc lead key technology areas that align with the proposed device and hence are well positioned to exploit commercially. If, as expected, this technology can be translated for other indications the market potential is significant. There is an opportunity for developing a theranostic tool by combining the laser device with bespoke diagnostic devices, currently under development by Renishaw, adding value to products already in the Renishaw's healthcare portfolio. The impact to EMI ltd is clearly of high commercial value, in the provision of experimental evidence that their proprietary molecule could be used in a diagnostic-therapy (theranostic) approach, allowing detection and treatment of a disease in a single clinical procedure.

More broadly our exploitation plan will explore pathways outside of the remit of the current partners, taking advantage of our partnership with the NIHR Healthcare Technologies Cooperative in Colorectal Therapies. This project will help maintain and develop the UK's lead in emerging healthcare technologies (i.e. theranostics via specific marking of polyps/cancers combined with a flexible laser scalpel). Thus, the project will enhance UK PLC's standing and position in these important areas and provide scope for future growth. The project will also importantly provide high-level training of the employed research staff and associated students to develop multi-skilled, cross-discipline scientists or engineers which is paramount to maintaining and growing a high-tech, high-value economy.

Clinical and medical:
Ultimately the provision of more effective procedures will give clinicians improved confidence and higher success rates when treating patients with precancerous or cancerous bowel pathology. A more flexible tool, with robust guidance and control, will impose less restriction on the surgeon's skills compared to existing techniques. From a medical perspective the specific molecules used to mark colorectal cancers may be translated to other diseases (e.g. pancreatic, head & neck, lung) and this study will provide vital evidence as to validity of such agents.

Academic:
The biophotonic community will benefit from knowledge and technology developed through this programme. However, the innovations and underpinning technologies will be transferable to the wider academic community with particular relevance in high value manufacturing, medicine, fibre optic communication and optical sensing.