Investigating the use of fluorescent proteins to identify dysplasia during endoscopy and surgery

Lead Research Organisation: University of Oxford
Department Name: Surgical Sciences


The purpose of this research project is to look at a promising new way of guiding doctors when they perform endoscopic procedures (colonoscopy/flexible sigmoidoscopy) or surgery on patients.

Our previous work using fresh tissue has shown that specially labelled proteins, called lectins, can make abnormal areas of tissue easier to see.
The aim of this study is to test lectins in patients undergoing endoscopic examination to see if they can identify these abnormal areas specifically, compared to the current gold standard, that is using white light during endoscopy. It is hoped that these lectins will make the abnormal tissue easier to see and remove during endoscopy and surgery. This is important because the accurate identification of abnormal tissue will allow doctors to remove all abnormal areas preventing the disease from recurring in future. It is also hoped that these lectins can help identify abnormal tissue (dysplasia or cancer) at an earlier stage, allowing more treatment options for patients that are less invasive and with a higher curative rate. If this study is successful, it could lead to the development of a simple tool than can identify abnormal tissue at the time of colonoscopy and surgery, with significant benefits for patients.

Lectins are proteins that are derived from plants. Lectins bind differently to the bowel wall, depending on whether or not the tissue is abnormal. Lectins can be labelled with a special dye that shines brightly when viewed under light of a certain colour. This is called fluorescence and can be captured using special cameras, which are built into colonoscopes. We would be using these lectins at very low doses so any side effects, if any, will be very small. Furthermore, we will only be applying it to the large bowel and not the small bowel, where most of the nutrients are absorbed. We therefore expect very little lectin, if any, will be absorbed by the digestive system.

Technical Summary

We have identified a fluorescent protein that is able to distinguish between normal and pre- cancerous tissue, which can be applied topically and assist visualisation of dysplasia that might otherwise be missed using white light endoscopy alone. Treatment at this early stage can be achieved less invasively, often at endoscopy and is associated with higher survival rates. This technique therefore has the potential to improve patient quality of life, reduce mortality and overall costs to the NHS.

The protein probe is naturally derived and can be applied topically as a spray during colonoscopy or transanal endoscopic microsurgery (TEMS). We have validated the use of this protein on simulated endoscopic examinations using freshly resected specimens.

We are now in a position to undertake a "first in man" feasibility study using this tool to see if it can help identify flat lesions that might otherwise be missed by white light endoscopy and in clarifying the borders of lesions for complete resection. Suspicious lesions will be characterized with white light and compared with fluorescence after application with the protein. Signal to background ratios will be calculated. Specimens of tissue from normal and abnormal fluorescent staining will be taken and compared with subsequent histology. This will allow calculation of sensitivity and specificity, and allow sufficient data for a power calculation for a subsequent clinical trial. We will also record any complications that arise, including side effects associated with the use of this probe.

This feasibility study will aim to recruit 50 patients. Inclusion criteria are patients aged over 18 undergoing endoscopic examination (colonoscopy/flexible sigmoidoscopy) or TEMS surgery. We will enrich our patient population for the presence of dysplasia by recruiting those with known flat lesions, colorectal cancer and ulcerative colitis with dysplasia. Exclusion criteria will include pregnancy and vulnerable patient groups.

Planned Impact

Olympus (the maker of the ETMI colonoscope) would be interested in this research as if it is successful, it could potentially lead to an increase in the popularity and therefore sales of their ETMI colonoscopes.

Manufacturers of NIR dyes and NIR capable endoscopes would also be interested in the results of our study, as our lectin could be conjugated to NIR dyes, which may be an alternative way to visualise fluorescent lectins in future.

The Department of Health and the NHS is keen on early diagnosis, as highlighted by their recent "Be Clear on Bowel Cancer" campaigns. They would be very interested in knowing about the results of our study, given that lectins could potentially be a useful endoscopic tool in identifying dysplasia and early cancer.

Early diagnosis can lead to more treatment options for patients which are less invasive and which are associated with a higher chance of cure. This in turn could lead to significant reductions in patient morbidity and mortality, and have a beneficial effect on society with reduced social costs and burden on patients' families if curative intent could be achieved in the first procedure.

This project would cement the UK's position as one of the leading countries in translational medicine and innovation. Fluorescence image guided surgery is a new and exciting technology, which has the potential to significantly improve patient outcomes in the next few years. Up until now, most of the research in this field has been done using non-specific fluorescent dyes, and in patients undergoing open surgery, not using minimally invasive endoscopes.

If this feasibility study is successful, we will be one of the first units in the world that will be using specific molecular probes in vivo that can be detected under fluorescent endoscopic imaging. This would have a significant impact on highlighting the creative and health output of the UK, and if demonstrated to be cost-effective, it would enhance the economic competitiveness of the UK.

The timescales in order for these benefits to be realised will be relatively short, as this study is due to be completed within 3 years and the results of this study would help set up a larger prospective clinical trial examining efficacy, which may be suitable for support from NIHR EME.

Staff working on this project will develop unique but transferable skills as they will be working at the interface between basic sciences and clinical medicine i.e. true translational research. As there in increasing emphasis on translational research studies, the staff will be very well suited to lead other projects this area.


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