Cholangiocarcinoma: The cancer you’ve never heard of
In her runner-up article for the 2016 Max Perutz Science Writing Award, Katie Ember, a PhD student at the MRC Centre for Regenerative Medicine, explains how she is using light to improve detection of a rare cancer.
It’s just as vital to our survival as our hearts. But the first time I watched a human liver being dissected, I realised how little I knew about this incredible organ.
Wei – the post-doc carrying out the procedure – was sitting in front of a sterile cabinet, a scalpel in one purple-gloved hand and forceps in the other. Unfortunately, I’m not a biologist by training and was about to make this painfully obvious.
“How many livers have you got there?” I asked. From what I could see, he was working on about three livers all piled together on a stainless steel tray. He looked momentarily confused. “Half,” he replied. “This is half a liver.”
I was astonished. Admittedly, this liver wasn’t surrounded by bones, muscles, fat and other organs to keep it compact, so it had expanded. Even so, I couldn’t imagine how the half-a-liver could fit inside a body along with heart, lungs, intestines, pancreas and stomach. Let alone a full liver. “Yeah, it’s actually the largest internal organ,” Wei explained. “It takes up most of the middle of your torso.”
Weighing approximately 1.5kg with a diameter of 14cm, the liver is responsible for detoxification of harmful substances in your body; including alcohol, drugs and toxic by-products of normal biological processes. It assists blood clotting, synthesises hormones and stores energy. It’s a fascinating, complex organ and we can’t live without it, but what I’m interested in is something inside the liver that can put the rest of it at risk.
Wei indicated a tiny pale vessel, running like a string through the surrounding rustcoloured tissue. “Here’s a branch of the bile duct.” This small tubule is the focus of my research. The bile duct carries bile from the gall bladder, where it’s stored, through the liver to the small intestine. Here, bile is critical for the digestion of fats.
All the thread-like branches of the bile duct connect to a main ‘trunk’ in the liver, the common bile duct, which is about 1.5cm wide. But compared to the size of the liver, it is minuscule and this is the challenge I’m facing. This seemingly innocuous vessel is the source of a rare but incredibly lethal form of cancer – cholangiocarcinoma.
In general, cancer survival rates are improving dramatically: now half of those diagnosed with cancer survive at least ten years after diagnosis. However, if you’re diagnosed with cholangiocarcinoma, your chance of still being alive in five years is 5 per cent. That’s one of the worst prognoses for any cancer out there and it hasn’t changed in decades.
One of the main problems is that conventional medical imaging techniques such as magnetic resonance imaging (MRI), X-ray and positron emission tomography (PET) scanning all rely on detecting rays of light or radiation passing through the patient – whether these are radio waves, X-rays or gamma radiation.
These methods are brilliant for imaging large organs or diseases that cause significant internal changes, such as coronary heart disease. But light is absorbed by tissue: if there is a lot of tissue between the source and the detector, the resolution of the images produced is much lower. As the bile duct is embedded in our enormous liver which is in turn surrounded by more tissue, tumours arising from this area are only detected when they’re about 2cm in diameter. And by then, it’s almost always too late.
Although considered a ‘rare cancer’ thousands die annually from cholangiocarcinoma and research is hampered by a lack of awareness and funding. We need early diagnosis. Bile duct biopsies are possible, but they’re painful for the patient and there’s the danger that samples could be taken from the unaffected area alone.
The aim of my research is to develop a way of detecting cholangiocarcinoma as early, accurately and non-invasively as possible, and to do this I’m also using light. But unlike standard scanning methods, I’m going to be detecting as much light as possible by both shining it and collecting it inside the bile duct via endoscopy.
Endoscopes are formed of bundles of optical fibres – glass cables that can transmit light with incredible accuracy. These are identical to the cables used to channel internet data at high speeds, except I’ll be using them to shine light into the bile duct and then collect light scattered back by the same bundle. Light scattered by cells tells us about their chemistry, because different molecules absorb and scatter light to different extents.
Cancer cells are chemically very distinct from healthy cells: they direct their chemical reactions into growing and dividing rapidly, rather than carrying out normal cellular functions. My hope is that we can sense these molecular changes using endoscopy.
Maybe then we will be able to diagnose this most lethal of cancers in time to do something about it.