Clinical Research in Luminal Gastroenterology
The ethos of Oxford Gastroenterology is for each Clinical Fellow to have their own project or to contribute to departmental research, leading to publications, even if they are in Oxford in the capacity of observer. This has resulted in >50 publications (excluding abstracts) from clinical fellows in the past 3yrs, including major contributions to international guidelines (eg OMED-ECCO Consensus on small bowel endoscopy and Opportunistic Infections in IBD) by young investigators from Oxford.
Clinical Trials in IBD
The unit currently has 8 Phase 2, 3 or 4 clinical trials in ulcerative colitis or Crohn's disease in progress, or about to start in the Gastroenterology Clinical Trials Facility.
These including proof of concept (Il-23 antagonists in ulcerative colitis) and novel molecular targets (CCR9 and SIP1 inhibition). Fellows are expected to have a Good Clinical Practice certificate (training is available) and contribute to the running of allocated studies. The Unit is contributing to an international initiative exploring the patient perspective in outcomes of clinical trials (PROACT, Marie Curie grant application), with Oxford taking the lead in IBD.
Predicting outcome
The Oxford index for acute severe colitis is internationally used and new predictive indices examining good (and poor) prognostic factors in Crohn's are under study. This links with biomarker studies and a Genome-based prediction of response to therapies for IBD (FP7 project, GENPRED-IBD). There are opportunities for projects evaluating the therapeutic response to treatment strategies in the Oxford IBD cohort.
Evaluating disease activity in IBD
Evaluation of activity indices and inter-observer variation is another focus of interest, especially in how it affects clinical trials and practice. This includes evaluating the outcome of different definitions of remission in ulcerative colitis, defining early IBD and validating the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), with a view to developing it as a training tool. Oxford is contributing to the development of the cumulative damage index in Crohn's disease (Lémann score, through IPNIC).
Endoscopy
A research endoscopy facility is being commissioned (2011), to enable confocal endomicroscopy and evaluation of narrowed spectrum endoscopy (NBI, i-Scan), especially comparing their value in assessment of inflammatory activity as much as the detection of dysplasia. This is lead by James East, assisted by consultants with an interest in endoscopy (Barbara Braden, Adam Bailey) and collaborating with the IBD specialists (Simon Travis, Satish Keshav, Alison Simmons). Current trials: BOSS (Barrett's oesophagus) and SPECTACLE (IBD dysplasia, with AMC Amsterdam).
Burden of disease in IBD
Oxford has a track record in evaluating the burden of disease in IBD through Oxford IBD patient cohort (Satish Keshav) and the Oxford Record Linkage System (Professor Michael Goldacre) and collaboration with the General Practice Research Database (Tim Card, Nottingham). Other areas of interest are response to vaccination against opportunistic infection sexual, function in IBD, the effect of smoking on mucosal function (combining clinical and laboratory-based studies) and extraintestinal manifestations - such as primary sclerosing cholangitis (Roger Chapman, with the largest cohort in the UK), neoplasia (molecular carcinogenesis, Simon Leedham), iron deficiency and ileal-pouch anal anastomosis. Surgical outcomes after colectomy, ileocaecal resection, combined medical and surgical management of fistulating Crohn's disease are also being examined or open for study.
Blood transfusion in GI bleeding
Oxford Gastroenterology, together with the National Blood Service (Professor Mike Murphy) lead the UK National audit on acute upper gastrointestinal bleeding, and we are now developing a clinical trial (RESTRAIN) comparing liberal and restrictive transfusion studies. Allied to this are studies on platelet function (thromboelastography) in variceal bleeding and acute inflammatory conditions.
Microscopic gut inflammation
Drug-induced microscopic colitis is open to study, collaborating with Professor Bryan Warren in histopathology, and we have recently redefined the novel entity of collagenous gastritis. Interaction between histopathology and luminal gastroenterology is well established, with studies on pouchitis, dysplasia and correlating histopathology with clinical and endoscopic disease activity in colitis.
Coeliac disease
There is a well established cohort of patients with coeliac disease in Oxford. Apart from contributing to genome wide association scanning with Professor David Van Heel, we have examined the impact of diet on fracture risk (through the FRAX index) and have work in progress with Kassim Javaid (Metabolic medicine).
Insights from clinical practice
Messages from clinical cases are not neglected. The first description of ulcerative colitis was a case report after all! However, publications need to have a dimension beyond clinical associations, to give an insight into the pathogenesis of the condition or management dilemmas. Recent examples include the gastrointestinal consequences of mitochondrial myopathy and rearrangements in mitochondrial DNA, patent foramen ovale and mesenteric infarction, the outcomes from intestinal transplantation, early gastric cancer, gastric cancer in common variable immunodeficiency and orbital myositis in Crohn's disease.
Outlook
The principal strength of clinical Gastroenterology in Oxford is the integration of basic science and clinical practice. The wards, laboratories, academic and clinical offices are co-located. There are regular joint meetings between clinical and academic gastroenterology. Opportunity beckons.