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Electronic Noses: Sniffing out bowel cancer
Dr Mike McFarlane
Gastroenterology Research Fellow UHCW, Coventry
6th December 2016
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Bowel Cancer
• Also known as Colorectal cancer (CRC)
• Cancer affecting the large intestine
• 4th commonest in the UK
• ~41,000 new cases in UK in 2013
• ~16,000 deaths in UK in 2014 (2nd commonest)
• Survival improving, but still work to be done
• Better survival linked to earlier detection – before it has spread
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What causes bowel cancer
• Age
• Smoking
• Family history
• Obesity
• Diet (lots of red meat, not enough fibre)
• Alcohol
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Diagnosis • Emergency – usually due to cancer blocking the bowel
• 2 Week Wait – where people have symptoms e.g. new onset diarrhoea/ constipation, bleeding from bottom, weight loss
• Bowel Cancer Screening Programme – people without symptoms
• Available to everyone in UK aged 60-74
• Faecal Occult Blood Test (FOBT)/ Faecal Immunohistochemistry Testing (FIT)
• Essentially looking for small amounts of blood in stool
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Problems with BCSP
• Uptake is low ~50-60%
• Stool test based – puts a lot of people off!
• Only 8% of people with a positive FOBT have bowel cancer
• How to improve it.............
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A quick history lesson.......
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Sniffing Urine
• Ancient Greece – Hippocrates sniffed and tasted urine
• Carried on through ancient Rome, Byzantium and into middle ages
• Diseases linked historically to urine/smell:
• Diabetes - "pear drops"
• Liver Disease - "fetor hepaticus"
• Bladder cancer
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Modern world
• Initial interest began in 1970s
• Volatile organic compounds (VOCs) found in exhaled breath
• 1985 – exhaled breath of lung ca patients distinguished from healthy controls using Mass Spectrometry
• 1989 – a dog “diagnosed” a melanoma on its owners leg
• 1990s & 2000s – several studies showed that dogs could detect cancers (lung, breast, prostate, ovary and bladder) – sniffing either skin, urine or breath
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Rise of the machines
• Dogs need training
• What if the trainer/dog is unwell....
• Olfactory fatigue
• Dogs in clinic room…..
• Needed a reproducible, robust method for sample analysis
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• 1990s and 2000s:
• Hundreds of studies looking at the VOC composition of patients with malignant and non-malignant conditions in respiratory, gastro, metabolic, gynae, breast, urology conditions
• Analysing breath, urine, blood, stool samples
• Using Mass Spectrometry, Electronic nose (sensor based) and associated technology
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Smelling trouble
• Non-invasive detection of GI disease – BAM, Coeliac, IBD, CRC, Fatty liver disease
• E-nose or FAIMS machines (Field Asymmetric Ion Mobility Spectrometry)
• Do not detect individual chemicals, rather the overall pattern (tea vs coffee)
• The future: Point of care testing of bodily sample in clinic to screen for conditions
• ?Alternative screening tool to current stool tests for CRC
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VOC generation theories
• VOCs are present in everyone
• Altered VOC profile caused by:
• Diet/drugs
• Altered cell metabolism (due to disease)
• Altered composition of bacteria in our gut (microbiome) i.e. different metabolites due to different bacteria
• VOCs detected in studies represent the interaction between these 3 factors (diet/drugs, disease, micro-organisms)
• Which of the 3 factors has the biggest contribution?
• Lots of research into Microbiome at present
• Is it a phase?
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E-nose
• 32 part sensor array • Sample presented to sensor • Each sensor detects different
chemicals • Overall chemical “smell print” is
unique
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FAIMS • Samples are Ionised and their mobility (mass to
charge) affects their movement through an electric field (think a pinball)
• Overall chemical “smell print” is unique
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What to do with raw data…
• Statistical analysis allows identification of unique signals and signal patterns
• Allows generation of an analysis "pipeline”
• Generate sensitivities and specificities I.e. How good is it at detecting bowel cancer? how many time does it get it right? how many times does it get it wrong?
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• Previously:
• CRC from healthy controls using urine samples
1) FAIMS
• 83 patients, 50 controls
• Sensitivity 83%, Specificity 60%
2) Warwick Olfactory Device (WOLF)
• 39 patients, 35 IBS, 18 controls
• Sensitivity 78%, Specificity 79%
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What am I doing?
• Comparing the urinary VOC profile of patients with bowel cancer (pre treatment) with a first degree relative (genetic) and a spouse/co-habitor (environment)
• Try to understand how much of sporadic CRC is due to environmental factors and genetic factors
• Hypothesis: VOC profile of CRC patients will be different from relatives
and spouses/partners
• Also comparing pre treatment samples to post treatment (surgery, chemo) samples
• Try to determine if it could be used as a follow up tool for cancer
• Also looking at the bacteria in stool samples to understand the microbiome composition in all of the above groups
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Where am I up to?
• Sample collection:
• Pre treatment CRC: 30 historical, 70 new
• Post treatment CRC: 30 historical (2-3 years) and ~35 samples 3 months post surgery and ~20 samples 6 months post surgery
• Relatives: ~45
• Spouse ~50
• Sample analysis: Currently happening
• Statistics: January onwards……
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What will results look like…… Spouses
Relatives
CRC
Relatives Spouses
CRC
or
Spouses
Relatives
CRC
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Thanks
• Prof Nwokolo – for cracking the whip
• Prof Arasaradnam – for being a sounding board
• CORE – bursary award
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Questions
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• For now: please do the stool tests!!