Addenbrooke s NHS Trust IBD What s in it for you? Dr Miles Parkes Consultant Gastroenterologist Cambridge
What is IBD? - inflammatory bowel disease Ulcerative colitis + Crohn s disease = main forms Incidence 2-4 per 1000 in Europe; Cause unknown genetic susceptibility environmental trigger + microbiota immune dysregulation smoking increases CD; smoking cessation increases UC
What is UC? A relapsing / remitting form of IBD Classic symptoms = bloody diarrhoea with urgency +/- incont colon only involved 44% 36% 18% continuous inflammation from rectum to any extent north Langholtz et al Gastro 1994 Can usually be diagnosed in clinic with rigid sigmoidoscope
UC Endoscopic appearances
What is Crohn s disease? A relapsing / remitting form IBD Patchy, deep ulceration, with tendency to stricture and fistulate commonly ileal, colonic can be anywhere Symptoms a site involvement abdo pain, wt loss = ileal diarrhoea (non-bloody) - colonic perianal disease woody tags / abscess / fistulae etc.
Crohn s disease patchy, pleiomorphic ulcers
Ileal inflammation with stenosis
Perianal Crohn s Tags Fistulae Abscess
What do you need in a career? Depends on your personality! But some blend of Clinical challenges Patient variety Procedural activity Therapeutic evolution Interaction with colleagues Research interest
IBD has it all!
Clinical challenges New diagnosis / diagnostic modality Known IBD new symptoms clinical assessment + Ix Inflammation? IBD complication? Abscess? Stricture? Cancer? Kidney stone? Malabsorption? Incidental problem? Therapy selection efficacy vs safety Choices to be made++ an art and a science no 2 patients the same! Diet, oral vs topical, steroids, immunosuppressants, biologics, surgery
Patient variety All races all ages - Childhood to old age But most patients are people like you Young, focused on careers, education, relationships, family life Their priorities are your priorities!
Procedural activity Lots of endoscopy, esp colonoscopy Small bowel endoscopy Stricture dilatation, dysplasia management
Evolving Therapeutic Landscape
Interaction with colleagues Truly multi-disciplinary Gastroenterologists IBD Nurses Dieticians Radiologists Histopathologists Paediatricians Surgeons Colorectal, upper GI And patients are key to all decisions!
Research interest Basic Science Genetics IBD leads the world in complex disease! Microbiota massive expansion Immunology Clinical / translational science Stratified medicine New therapies
Summary It s the best part of gastro Why wouldn t you?!
Introduction Clinical course / prognosis varies ++ between Crohn s patients Often greater impact on patients lives than the diagnosis of CD itself Jess et al IBD 2007
Anti-TNF induction Conventional D Haens et al. Lancet (2008) Enhanced efficacy of early anti-tnf therapy vs late usage Schreiber et al. NEJM (2007) Feagan et al. Gastro (2008)
Tuberculosis Solid tumours Lymphoma Demyelination Other opportunistic infections
Right time, right drug, right strategy The success of personalised medicine depends on having accurate diagnostic tests that identify patients who can benefit from targeted therapies Dr Margaret Hamburg (Commissioner FDA) Dr Francis Collins (Director NIH) Aggressive disease Receive aggressive therapy as early as possible (ideally at diagnosis) Quiescent disease Protected from risks of unnecessary immunosuppression Hamburg and Collins. NEJM (2010)
Genes CD8 Transcriptomics to predict prognosis Patients IBD1 IBD2 Lee JC et al. JCI 2011
Genes Clinical translation? Patients
Biomarker validation Independent cohort of 85 samples from newly-diagnosed patients (Cambridge, St Mark s, Exeter, Nottingham) Bayesian Information Criterion method applied used to identify genes and this gene list taken forward to realtime qpcr assay development Optimised to 18 genes: 16 informative genes, 2 reference genes Hazard ratio = 3.52 (95% CI 1.84-6.76)
First ever biomarker stratified trial in inflammatory disease 4.2M translational fund award
Trial outline Large Small
Research Pathogenesis Genetics Microbiota Immunology stratified medcine Tim McGraw Me and Tennessee
Social aspects! It s a team approach Physicians + surgeons + radiol + histopath +/- ID etc MDT - incl (patients they are often experts in their own disease
Disease management Outline current Mx? Highlight scope for research Eg risk prediction / pathogenesi Predict dis course New therapies