Electronic Noses: Sniffing out bowel cancer - Guts UKgutscharity.org.uk/wp-content/uploads/2016/12/Sniffing-out-bowel... · •Do not detect individual chemicals, rather the overall

Electronic Noses: Sniffing out bowel cancer

Dr Mike McFarlane

Gastroenterology Research Fellow UHCW, Coventry

6th December 2016

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

What causes bowel cancer

• Age

• Smoking

• Family history

• Obesity

• Diet (lots of red meat, not enough fibre)

• Alcohol

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

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.............

A quick history lesson.......

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

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

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

• 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

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

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?

E-nose

• 32 part sensor array • Sample presented to sensor • Each sensor detects different

chemicals • Overall chemical “smell print” is

unique

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

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?

• 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%

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

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……

What will results look like…… Spouses

Relatives

CRC

Relatives Spouses

CRC

or

Spouses

Relatives

CRC

Thanks

• Prof Nwokolo – for cracking the whip

• Prof Arasaradnam – for being a sounding board

• CORE – bursary award

Questions

• For now: please do the stool tests!!