Daniel Burger

Comparing disease activity indices in ulcerative colitis

BACKGROUND Comparisons between disease activity indices for ulcerative colitis (UC) are few. This study evaluates three indices, to determine the potential impact of inter-observer variation on clinical trial recruitment or outcome as well as their clinical relevance. METHODS One hundred patients with UC were prospectively evaluated, each by four specialists, followed by videosigmoidoscopy, which was later scored by each specialist. The Simple Clinical Colitis Activity (SCCAI), Mayo Clinic and Seo indices were compared by assigning a disease activity category from published thresholds for remission, mild, moderate and severe activity. Inter-observer variation was evaluated using Kappa statistics and its effect for each patient on recruitment and outcome measures for representative clinical trials calculated. Clinical relevance was assessed by comparing an independently assigned clinical category, taking all information into account as if in clinic, with the disease activity assigned by the indices. RESULTS Inter-observer agreement for SCCAI (κ=0.75, 95% CI 0.70-0.81), Mayo Clinic (κ=0.72, 95% CI 0.67-0.78) and Seo (κ=0.89, 95% CI 0.83-0.95) indices was good or very good as was the agreement for rectal bleeding (κ=0.77) and stool frequency (κ=0.90). Endoscopy in the Mayo Clinic index had the greatest variation (κ=0.38). Inter-observer variation alone would have excluded up to 1 in 5 patients from recruitment or remission criteria in representative trials. Categorisation by the SCCAI, Mayo Clinic and Seo indices agreed with the independently assigned clinical category in 61%, 67% and 47% of cases respectively. CONCLUSIONS Trial recruitment and outcome measures are affected by inter-observer variation in UC activity indices, and endoscopic scoring was the component most susceptible to variation.

Association between the ulcerative colitis endoscopic index of severity (UCEIS) and outcomes in acute severe ulcerative colitis.

BACKGROUND The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) accounts for 86% of the variance between observers in the overall assessment of endoscopic severity, but has not been correlated with outcomes. METHODS Consecutive cases of acute severe colitis (ASC) defined by Truelove and Witts (TW) criteria were retrospectively evaluated. Demographic details, number of TW criteria, prior medical therapy, UCEIS and inpatient medical therapy were recorded. Pre-specified (adverse) endpoints included rescue therapy, colectomy and readmission. RESULTS Eighty-nine patients, 48 (54%) male, mean age 38 years, all received intravenous hydrocortisone 400mg/d (median 5 days [range 1-11]). Median follow-up was 14 months (2-33). Forty-eight (54%) were diagnosed the year prior to or at the time of admission. Thirty-six (40%) required rescue therapy (infliximab 25/36, ciclosporin 12/36, one receiving both). Twenty-one (24%) underwent colectomy on the index admission (9/21) or during follow-up (12/21). Median UCEIS score (possible range 0-8) was 5 (3-8). UCEIS was higher in patients requiring rescue therapy or colectomy (median score 6 [range 4-8] versus 5/8 [3-8], both p < 0.005). For UCEIS ≥5, 27/54 (50%) required rescue therapy, compared with 9/33 (27%) for UCEIS ≤4 (p = 0.037). When UCEIS was ≥5, 18/54 (33%) came to colectomy during follow-up, compared with 3/33 (9%) with UCEIS ≤4. Of 14 patients with UCEIS 7 or 8, 11/14 needed rescue therapy and 13/14 met any adverse endpoint. CONCLUSION Endoscopic severity is associated with a worse outcome in ASC. When the UCEIS is ≥7 on admission, almost all patients will need treatment with infliximab or ciclosporin beyond steroids. This may mark a threshold for an early decision to use infliximab or ciclosporin.

Colon salvage therapy for acute severe colitis: cyclosporine or infliximab?

Purpose of review Steroid-refractory acute severe colitis (ASC) poses a significant clinical challenge to both physicians and surgeons alike. This review highlights advances in management of these patients and the role of cyclosporine compared to infliximab. Recent findings ASC affects 25% of patients with ulcerative colitis and is associated with measurable morbidity and mortality. Simple clinical and laboratory measures predict steroid refractoriness (such as stool frequency 3–8/day and C-reactive protein > 45 mg/l on day 3) and salvage therapy is appropriate at this stage. Preliminary data from randomized controlled trials suggest that early (7 and 98 day) response to cyclosporine and infliximab are comparable. Serum trough infliximab concentrations may correlate with outcome. Sequential therapy cannot usually be recommended due to limited response (70% colectomy at 3 years) and high rate of serious adverse events. Summary Optimal salvage therapy will depend on detailed results of randomized controlled trials. Meanwhile, patients with ASC should receive either cyclosporine or infliximab before surgery as long as there is specialist expertise that allows early decision-making.

Tu1196 Gastrointestinal (GI) Symptoms in Patients With Dysphagia Referred for High Resolution Manometry: Presence of Lower GI Symptoms Is a Negative Predictor for Achalasia

Background: High Resolutions Manometry (HRM) is the gold standard for the categorisation of motility disorders of the oesophagus, with achalasia as one of the most distinct manometric conditions. We aimed to compare the gastrointestinal symptom pattern and intensity in patients referred for HRM with and without a final diagnosis of achalasia utilising the recently developed SAGIS (Structured Assessment of Gastrointestinal Symptoms) instrument. Methods: Data from 50 consecutive patients referred for HRM for dysphagia were included in this study, mean age 56 years, range 17-84, 28 female. All patients had a negative upper GI endoscopy and other tests required to exclude structural abnormalities. Gastrointestinal symptoms were assessed prior to the HRM utilising the SAGIS questionnaire. Results: Based upon the Chicago Classification, 9 out of the 50 patients were diagnosed as having achalasia (6 males, 3 females). Overall, neither dysphagia nor the cumulated upper GI symptom score or scores for retrosternal discomfort were different for patients with or without achalasia (table 1). In contrast, patients with non-specific motor abnormalities had increased scores for IBS-type lower gut symptoms. Conclusions: Utilising the recently developed SAGIS instrument, patients with achalasia are not different from dysphagia patients with no/unspecific motor abnormalities of the oesophagus with regard to upper gastrointestinal symptoms. In particular, there are no differences in relation to the dysphagia or the retrosternal discomfort score. In contrast, patients with no/unspecific motor abnormalities, scored much higher for lower gastrointestinal symptoms than achalasia patients. In addition, IBS-type symptoms such as urgency to defecate are significantly increased. In patients with dysphagia, the presence of lower gut symptoms is a negative predictor for achalasia. Table 1