AMMF at Imperial College 11.02.15
This report on the research presentations and Q&A session at AMMF’s event at Imperial College London on 11 February, has been written by Rebecca Morement, who is currently working as an intern with the charity.
A philosophy graduate of the University of York, Rebecca has a keen interest in bioethics, and is gaining a real insight and understanding of the problems associated with cholangiocarcinoma.
AMMF’s Research Update Event at Imperial College London
Report by Rebecca Morement
In collaboration with Imperial College London, AMMF and its supporters held a day of presentations and discussions addressing the latest scientific developments in the detection and treatment of cholangiocarcinoma.
The day was hosted by Professor Simon Taylor-Robinson at the Medical School on Imperial’s St Mary’s Campus, and the topics discussed ranged from the current progress being made nationally, including the Cholangiocarcinoma Biomarker Bank, and internationally, including the Mayo Clinic in Minnesota and the trialling of new imaging equipment in Thailand.
The Cholangiocarcinoma Biomarker Bank – Presented by Larry Koomson
Treating cholangiocarcinoma is usually unsuccessful due to the late diagnosis of the condition, often once the cancer is at an advanced stage. Late diagnosis limits the course of treatment as patients may no longer be suitable for surgery, currently the only potentially curative treatment.. Early diagnosis is therefore essential for successful treatment of cholangiocarcinoma.
Imperial College London have been researching the use of biomarkers in early detection. Biomarkers are a gene or molecule that can identify a particular disease. If biomarkers for cholangiocarcinoma can be identified then it would be possible to create a standard test for the disease. Imperial are currently researching using test strips in urine samples that would change colour if the biomarker for cholangiocarcinoma is present. These tests could be used nationally by GPs and hospitals as a quick and inexpensive method of testing for cholangiocarcinoma. This is similar to the current method used for testing and diagnosing diabetes.
The current aim of Dr. Shahid Khan and Larry Koomson is to collect and test nationwide samples, in order for them to be stored for genetic research. The samples include urine, blood and bile, which together with information provided by the patient, such as lifestyle and medical history, can help to determine these biomarkers and could also suggest causal factors of cholangiocarcinoma.
Over the course of five years Imperial has catalogued 11,708 samples. Of this figure 2,362 samples have been collected from cholangiocarcinoma patients. Whilst many of the samples have come from the UK, there has also been collaboration with research labs in both Norway and the US.
To see Larry’s presentation slides, click here.
Collecting Samples – Presented by Mary Crossey
Samples are imperative for biomarkers research, as the more samples catalogued the more data will be available. To collect a sample, medical staff must first receive permission from the patient. If the patient declines then no sample can be taken. The three major reasons for not obtaining a sample are: the patient’s personal objections, public awareness and time.
Patients are usually approached whilst they are undergoing treatment, as samples are often taken at the same time as their treatment or during their diagnostic tests. Asking patients for samples during this time can be difficult, as they are often under a lot of stress and many patients feel that taking a sample is an added pressure. Another reason may be that whilst taking urine samples is a simple and non-intrusive procedure, taking blood and bile samples is more invasive. Although a patient can choose which samples they want to give, some believe that they do not have a choice. This often leads to them declining any sample to be taken. Alternatively some patients feel that by providing samples for research, their medical information may be used for other purposes aside from research. Although all samples and information is kept confidential, some feel that it is a breach of privacy.
The lack of awareness about samples and how they are used in medical research can also influence a patient’s decision. Many people are unaware that they can give samples due to the lack of publicity on the subject. By making the public aware about samples it normalises the procedure and makes it less objectionable for patients, just as blood and organ donations have become more accepted in society.
The process of collecting samples is time consuming and often medical staff do not have enough time to discuss and collect samples from patients. In order to obtain a sample, medical staff must get patients to read and sign several consent forms. Patients must also provide in-depth medical and lifestyle information under staff supervision. The questions asked range from medical history, use of prescription or over the counter drugs, diet, previous occupations and addresses. This information gives researchers a context to the sample and may provide evidence that some external factors may be linked to cholangiocarcinoma. Whilst this information is vital, the length of time needed for medical staff to supervise the process is not always possible. Once the consent forms and additional information are completed and the sample is taken, it can take up to two hours to process and freeze the sample.
An additional way to collect samples that is being considered is from friends and relatives of patients with cholangiocarcinoma. These samples could be incredibly useful for research, as friends and family have often lived a similar lifestyle in a similar area. Relatives’ samples also contain the same genetic information to the patient. Research shows that both our external and internal environment play a role in developing cholangiocarcinoma, which means that whilst external factors such as environment and lifestyle can be linked to cholangiocarcinoma, we may also have a genetic predisposition that reacts to these external factors in a way that becomes cancerous. By providing samples, relatives and friends can offer information about the patient and could link certain external factors to the disease.
Click below to see the documentation used with sample collection:
Urinary Biomarkers Research – Presented by Munirah Al Saleh
The use of biomarkers for early detection is incredibly important in tackling cholangiocarcinoma. The symptoms of cholangiocarcinoma often lead to a late diagnosis. Symptoms include: jaundice, urine or stool discolouration, itchiness, abdomen pain, weight loss, tiredness, loss of appetite and high temperature. The issue is that often these symptoms are not apparent until the later stages of the disease and can often be misdiagnosed. The research into which biomarkers are prevalent in cholangiocarcinoma samples could lead to a potential breakthrough in creating a standardised urine test for the disease, which in theory would then lead to earlier diagnoses.
To test for these biomarkers, researchers at Imperial College have been looking at metabolites in the samples of urine from the UK and comparing them to metabolites found in the urine of cholangiocarcinoma patients in Thailand. Metabolites are small molecules that are a by-product of metabolism. By looking at these molecules researchers can look at what percentage of the sample is made up of different metabolites. If a few types of metabolites are dominant in cholangiocarcinoma samples, compared to the control samples, then it would show a link between those metabolites and cholangiocarcinoma. If it is possible to single out these metabolites and create a test to detect them then it would be possible to create a test that detects cholangiocarcinoma.
Unfortunately, as this is an ongoing research project for eventual publication, we cannot provide Munirah’s presentation.
The Mayo Clinic – Presented by Dr. Abigail Zabron
The Mayo Clinic in Rochester, USA, is at the forefront of cholangiocarcinoma research, boasting an impressive liver transplant programme for cholangiocarcinoma. Last year Dr. Abigail Zabron, during her time as AMMF’s Research Fellow, received the prestigious ‘Sheila Sherlock Award’ which enabled her to visit the Mayo Clinic in order to develop research collaboration and to train staff in bile collection.
The Mayo Clinic receives on average 200-250 cholangiocarcinoma patients a year. A third of these patients have previously been diagnosed with PSC (Primary Sclerosing Cholangitis), which is a non-malignant inflammatory in the bile-duct or liver. Out of the 200-250 patients admitted to the clinic only 10% will be allowed on to the liver transplant programme. In order to be eligible for the programme patients must not have received any previous treatment for cholangiocarcinoma nor had any previous cancers. The patient’s physical and mental health is also assessed to make sure that they can cope with the treatment the programme requires. The treatment is intensive, with the patient undergoing local chemotherapy, radiotherapy and brachytherapy. Out of the 287 patients that have been enrolled on the transplant programme, 71 patients (roughly 25%) did not receive a transplant. For those who received a transplant the recurrence-free survival rate is 79% at two years and 66% at five years.
The Mayo Clinic’s liver transplant programme shows the benefits of transplant as a treatment for cholangiocarcinoma. However, currently in the UK, liver transplantation for cholangiocarcinoma is not a treatment option. With proven results overseas, it is hoped clinical trials may be considered in the near future.
To see Dr Abigail Zabron’s presentation, please click here. (Dr Zabron’s presentation slides are still awaited – as at 09.03.15)
Improving Liver Imaging: High Resolution Internal Magnetic Resonance Imaging of the Biliary Ductal System – Presented by Evdokia Kardoulaki
By improving internal imaging it would be possible to diagnose cholangiocarcinoma in its early stages. Current internal imagery of the bile duct can provide a lot of information, however due to the lower resolution the image does not give medical staff the entire story. If the resolution of the image of the bile duct was higher, the quality of the picture would improve. This would allow medical staff to see exactly the location and the severity of the cancerous tissue in the bile duct, which would lead to more accurate diagnoses. Also higher resolution imaging would be able to detect smaller tumours, leading to earlier diagnoses. Imperial College are now researching and testing new equipment that will provide higher resolution imaging of the bile duct.
Currently medical staff use Magnetic Resonance Cholangiopancreatography (MRCP) to capture images of the bile duct. MRCP is a non-invasive technique that is commonly used when testing for Cholangiocarcinoma; however the method produces images with poor resolution. As a result, Imperial has focused research into a catheter based device, which can be inserted via a duodenoscope at ERCP (Endoscopic Retrograde Cholangiopancreatography) or it can be used as an MR compatible duodenoscope. Both versions provide higher resolution images and present a more accurate picture of the bile duct.
To see Evdokia Kardoulaki’s presentation, click here.
Update: The team from Imperial College, Professor Richard Syms, Dr Chris Wadsworth and Dr Evdokia Kardoulaki, made a first collaborative research visit to Khon Kaen University, Thailand, 6 – 12 March 2015, to transfer equipment and technologies so that development of the internal MRI imaging work can continue in Thailand. To read their report and see photographs, click here
The Incidence of Cholangiocarcinoma in Thailand – Presented by Munirah Al Saleh
In Thailand there are approximately 30,000 known cases of cholangiocarcinoma each year. Out of the 30,000 people diagnosed, only 300 are successfully treated. This puts the survival rate of cholangiocarcinoma in Thailand at just 1%. Cases of cholangiocarcinoma in Thailand differ to that of the UK, as many of the cases are not sporadic but are a direct result of dietary factors.
These cases of cholangiocarcinoma appear in poorer regions alongside the Mekong River, in areas where their diet consists of raw fish. The fish are often infected with a parasite known as liver fluke (Opisthorchis vivverini) which if eaten raw can cause inflammation within the liver or bile duct, which can lead cholangiocarcinoma. On average 6,000,000 people have liver fluke infections a year, meaning that only 0.5% develop cholangiocarcinoma as a result of the infection.
In order tackle the high level of cholangiocarcinoma cases in these areas, the Thai government has introduced health education classes to teach the community about the importance of food preparation and cooking and to bring awareness to the issue. They have also introduced targeted food and health programmes in schools in order to teach the future generation about the dangers of liver fluke. From a medical stance, the use of ultrasound screening tests is being implemented, as well as trialling the new imaging equipment that has been developed at Imperial.
Question and Answer Session
Following a guided visit to the Fleming museum and a tour of the labs, guests took part in a question and answer session with the team at Imperial. The following answers are solely the opinions of the participants and staff at Imperial. These opinions do not necessarily represent those of AMMF.
Q Regarding surgery, does the success or failure of the procedure depend on the team?
A. Multi-disciplinary teams sometimes make decisions about surgery without meeting the patient in person – and this can make some some patients feel that they were being treated not as a person but as a statistic. 1
A potential solution to this issue might be to have patient advocates – medical staff (either part of or independent of the practice) who work on behalf of the patient.
Q. Is it OK to seek a second opinion? Will this affect my treatment?
A. Sometimes patients may wish to seek a second opinion about possible treatment for cholangiocarcinoma. Patients and relatives are well within their rights to seek another opinion, especially considering the rareness of the condition. AMMF provides information and support for anyone who wishes to speak to a cholangiocarcinoma specialist.
If patients do seek a second opinion it should have no effect on their treatment by their current doctor. If for any reason patients feel like their choice has affected their treatment there are governing medical bodies that they can report to.
Q. Is there an element of chance involved with successfully treating cholangiocarcinoma? Does your doctor or location make a difference?
A. Unfortunately in the UK there is no set standard of treatment across all hospitals. This means that treatment patients receive in one hospital is not equal to treatment patient’s receive in another.
There are doctors who have experience in treating cholangiocarcinoma, along with several specialist treatment centres that have good statistics for the treatment of the disease.
(There are published UK Guidelines for the Diagnosis and Treatment of Cholangiocarcinoma, and these are available from AMMF’s website.2 And for more information on experienced medics and centres, please check the resources made available on AMMF’s website or contact AMMF via email.)
Q. How are medical staff and Thailand’s government tackling the rise of cholangiocarcinoma due to environmental factors?
A. Firstly by using both environmental and health education to teach the public in the rural areas most affected not to eat raw river fish, and if they do the importance of food preparation and cooking in killing off the parasite.
Secondly the use of ultrasound screenings in order to detect cholangiocarcinoma sooner. This includes trialling the new imaging equipment developed at Imperial College.
Q. If developed, how early would a urine test be able to diagnose cholangiocarcinoma?
A. Within the early stages of the condition in order to provide effective treatment.
The urine test could be a form of generalised testing for other cancers and something that could be requested if the patient or doctor has any concerns.
There is currently funding from the EU for liver testing and equipment used for Olympic drug testing is also being used.
Q. Is more needed to be done in regard to the Corporate Responsibility Program?
A. The Corporate Responsibility Program or Corporate Social Responsibility (CSR) is defined as:
“A company’s sense of responsibility towards the community and environment (both ecological and social) in which it operates. Companies express this citizenship (1) through their waste and pollution reduction processes, (2) by contributing educational and social programs and (3) by earning adequate returns on the employed resources.” 3
Within the UK there is not a set law that requires companies to engage in CSR, rather several acts, codes and guidance that emphasise a company’s responsibility to have a positive impact on society. This means that whilst no company has to comply with CSR, there is pressure for them to do so. 4
Therefore there is no set way in which companies engage with CSR, some provide aid to communities, donations to non-profit organisations or promote environmental or ethical practices within their own corporation.
The issue of CSR is one that requires public engagement and publicity in order to increase pressure on organisations to adopt CSR practices, although companies’ engagement with CSR is on the rise.5
Q. What industrial pollutants have been linked to cholangiocarcinoma?
A. Batteries, industrial paint, environmental toxins have been linked to cholangiocarcinoma, although there is no evidence to suggest they are a direct cause. 7
1. For more information see: https://ammf.org.uk/article-7-demystifying-mdt/
3. Definition obtained at: http://www.businessdictionary.com/definition/corporate-social-responsibility.html
4. For more information see: http://www.out-law.com/page-8221
5. For more information see Business In The Community’s website at: http://www.bitc.org.uk/
6. For a list of members currently registered by Business In The Community see: http://www.bitc.org.uk/our-network/members-directory
7. For risk factors for cholangiocarcinoma, see: https://ammf.org.uk/2011/09/23/risk-factors-for-cholangiocarcinoma/