St. Mark’s research and the need for funding

FLEX Project – New Detection and Treatments of Early Bowel Cancer

St. Mark’s Hospital Foundation is currently raising money for new research which aims to develop a new, less invasive technique for the treatment of early colon cancer. Our Consultants Mr. Robin Kennedy and Dr. Chris Fraser are key collaborators in this project. It is their belief that if the research is successful, it will help to spare up to 2,400 patients from major surgery each year in the UK.

Cancer of the colon (large bowel) kills 655,000 people worldwide each year. It is the third most common form of cancer and the second leading cause of cancer-related death in the UK and the Western world. The tragedy is that the success rate for curing bowel cancer is extremely high providing it is detected early, but very low if it is detected late. Thus early screening and detection are essential to prevent unnecessary deaths.

However, due to the limitations of current surgical techniques there is no method of removing only the part of the bowel that has been affected by the cancer and it is impossible to determine conclusively whether the cancer has spread from the bowel wall to the surrounding lymphatic “basin” (this is made up of lymph glands or nodes which are part of the body’s drainage system and combat cancer by localising abnormal cells in the nodes).

These limitations mean that the only way the surgeon can be sure they have effectively removed any affected tissue and stopped the spread of the disease, is to remove a large section of the bowel as well as the attached large section of the surrounding lymph nodes. Major tissue removal has significant disadvantages such as intra-abdominal scarring, whilst resulting bowel shortening may increase the frequency of bowel movements and cause diarrhoea. There is also a risk of complications, some of which are life-threatening. These include post-operative pain, reduced mobility, delayed return to work and various surgical problems.

The Solution: A New Approach Combining Laparoscopy and Endoscopy

Our researchers believe that recent developments in endoscopic and laparoscopic technology will help to address the limitations and problems that have been highlighted. Using a technique called Full Thickness Laparoendoscopic Excision (FLEX) of the colon we will be able to remove early colon cancers by taking only a small portion of the colon, rather than a large section. Moreover, by incorporating the innovative method of sentinel lymph node biopsy (SLNB) combined with near-infrared spectral fluorescence laparoscopy and radioisotope tracing we will be able to assess the surrounding lymph nodes to determine whether or not they are affected by the cancer.

It is estimated that the successful combination of FLEX and SLNB would allow up to 2,400 patients to be spared major surgery each year in the UK, thus achieving faster healing and recovery times, as well as minimising abdominal scarring and the other disadvantages of a segmental colectomy. In fact, this research may eventually lead to surgery without any scars or a scar that is invisible. In addition, other patients will benefit as beds will be freed that would otherwise have been needed for major surgery and whilst the primary focus here is on lesions of the colon, a similar operative strategy could also pay dividends for early cancers of the stomach. Thus, in other institutions, work will also be possible in this organ.

Intestinal Tissue Engineering

Recently scientists and clinicians have replaced a patient’s diseased windpipe (trachea) with one which had been made in the laboratory. This tissue engineered trachea restored normal function to the patient’s lung thereby improving her quality of life. This impressive bio-engineered organ was achieved by taking a trachea from a patient who had recently died and removing all the cells. The remaining tissue (scaffold) was repopulated with stem cells taken from the recipient patient’s bone marrow. The re-populated trachea, when transplanted, convinced the patient’s body that it was a part of it thereby avoiding the danger of rejection which is a serious problem when undergoing normal organ transplantation.

At St Mark’s and Northwick Park Institute of Medical Research (NPIMR) we are aiming to do this for the intestine. However, the intestine is much more complicated than the trachea.  It has a blood supply, absorbs nutrients, has muscles to squeeze the fluid along and has nerves to coordinate the muscles and sense pain.

So far we have been able to make a novel scaffold suitable for growing a new intestine.  This scaffold is made from another piece of intestine and has had all the cells removed, in the same way as for the windpipe.  The way this is original is that we have been able to keep the blood supply to the scaffold.  This is important because when it is transplanted, the cells that will grow on this scaffold will need a blood supply to receive oxygen and nutrients.

Our theory is that repopulating scaffolds made from a biological material with the right stem cells will produce a working intestine. So far we have not used stem cells to generate the new intestine.  There are different types of stem cells and the ones that we will aim to use can be harvested from you or me.  They come from the bone marrow.  That way, if we are successful, we can use the cells from the patient needing more bowel and grow these into a new segment of bowel.  This transplanted bowel would not be rejected, like the trachea described above.

We have a research consortium for this research.  There are scientists, biologists, engineers and clinicians. This research is completely original and we hope to develop a model suitable for patients in 5 years time.

Intestinal Growth Factors

Patients with short bowel syndrome have not got enough remaining intestine to be able to absorb the nutrition that they need to survive.  These patients are dependent on intravenous nutrition as a form of life support.  A different approach to treating patients with this condition is to use naturally occurring hormones to help the remaining bowel grow larger.  This has been tried with growth hormone but it is not very successful and also not specific to the gut, so could have a number of unwanted side effects.

A hormone called GLP-2 is a growth hormone that just works on the gut and has been shown to increase the ability of the intestine to absorb fluid and nutrition.  We are undertaking research to find out if this hormone also affects the intestinal immune system.  The immune system in the intestine is very sophisticated and we are only beginning to understand how it works.  The effect of growth factors on the gut immune system is not known, but we have recently found out that patients with short bowel syndrome also lack a whole population of immune cells.  We also know that these patients can be more susceptible to infections.  It will therefore be interesting to find out if growth factors that affect the bowel itself also affect the bowel immune system. This could open up a lot of avenues for different approaches to treatments.

Dr Simon Gabe
Consultant Gastroenterologist & Honorary Senior Lecturer
Co-Chair of the Lennard-Jones Intestinal Failure Unit

Check out the St Mark’s website to learn more about their research projects and how they spend their funding.