Assessment of Disease Activity in Ulcerative Colitis by Endoscopic Ultrasound
Condition: Ulcerative Colitis; Inflammatory Bowel Disease
MeSH terms: Colitis; Colitis, Ulcerative; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer
Study type: Observational

Summary: 
      In this cross-sectional study patients with active or quiescent ulcerative colitis will be
      studied to determine the utility of endoscopic ultrasound measurements of rectal wall blood
      flow and thickness as reliable indices of disease severity and the degree of correlation that
      exists with validated clinical, endoscopic, and histological indices.
    

Detailed description: 
      Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown etiology
      characterized by diffuse mucosal inflammation limited to the colon. The basis of medical
      treatment is with agents that reduce the inflammatory process. Tailoring appropriate therapy
      will depend on disease severity, which can be difficult to identify. A response to therapy
      may also require months to determine. Medications for induction of remission and/or for
      maintenance in patients with mild to severe UC include 5-aminosalicylates (5'ASA),
      corticosteroids, azathioprine (AZA), cyclosporine, and infliximab (IFX). All medications have
      their own inherent side effect profile. Cost can be a major issue with some medications such
      as IFX, which can be tens of thousands of dollars annually. Medical management can still fail
      in those with severe disease necessitating surgical management with a colectomy.
      Identification of high-risk patients who are candidates for more intensive therapy early in
      the disease course might be a strategy to improve treatment outcomes and limit cost.

      This notion of "individualizing" therapy is attractive and a distinct departure from the
      current "step-care" paradigm in which treatments are added sequentially on the basis of
      symptom-defined treatment failure. However, for this paradigm to be implementable an
      objective means of accurately stratifying risk must be identified and validated. Accordingly,
      increased interest has evolved in the use of biomarkers as prognostic tools. Although fecal
      calprotectin and serum CRP are potential candidates for this role, these tests have
      limitations.

      Transabdominal ultrasound (US) has been used in the diagnostic workup of IBD. US was a good
      surrogate of disease activity when compared to colonoscopy, but is unable to reliably assess
      the rectal wall which tends to cause the most symptoms in UC. Endoscopic ultrasound (EUS) is
      a highly accurate diagnostic modality for the assessment of rectal pathology. However, the
      role of EUS in IBD is not well defined. Tsuga et al showed total wall thickness to be highly
      predictive for acute inflammation in patients with UC compared to healthy controls and that
      the degree of rectal wall involvement correlated with endoscopic severity. Higaki et al
      showed patients with quiescent UC who relapsed had initial sonographic evidence of "deep"
      disease activity shown by significantly greater baseline thickness of the first 3 layers of
      the rectal wall. Yoshizawa et al subsequently demonstrated that inflammation reaching the
      muscularis propria or deeper predicted the need for colectomy. Hurlstone et al correlated EUS
      scores with histopathology, endoscopic, and clinical scores and found good concordance to
      only exist with superficial EUS scores. In all of these studies the investigators who
      performed the EUS analysis did so with knowledge of the endoscopy scores. This questions the
      validity of these results due to the potential for bias. Another parameter that shows promise
      for evaluation of inflammatory burden is EUS evaluation of blood flow. Surprisingly, Doppler
      flow has not been used to assess bowel wall vascularity in UC with EUS. We believe that
      assessment of vascularity has the potential to differentiate with a high degree of accuracy
      active from quiescent disease.

      Although the existing literature indicates that EUS has potential as an evaluative and
      prognostic tool the investigators believe that a great deal of additional research is needed
      to further develop this technology. This study will correlate Doppler EUS and other EUS
      indices with validated clinical, endoscopic, and histological indices of UC inflammation to
      assess its utility as a diagnostic tool. It will assess the reproducibility of these indices
      by calculating inter and intra-observer agreement by blinded expert reviewers. This
      information may have prognostic importance and might ultimately be used to guide therapy in
      individual patients.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Consecutive adult patients with IBD attending outpatient IBD clinics at the University of
        Western Ontario teaching hospitals and patients admitted to hospital with severe UC will be
        included for endoscopic ultrasound assessment.
      
Keywords: endoscopic ultrasound; ulcerative colitis; inflammatory bowel disease