Mo1688 Interobserver and Intraobserver Agreement of the Mayo Score of Endoscopic Activity in Ulcerative Colitis

Mo1687 Efficacy of Anti-TNF on Severe Postoperative Endoscopic Recurrence in Crohn's Disease

Infliximab treatment of postoperative ulcers in Crohn's disease: to inject or not to inject—that is the question

Sa1237 Long-Term Evaluation of Preoperative Wireless Capsule Endoscopy As a Predictor of Outcome After Ileal Pouch-Anal Anastomosis

To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1. UC patients with sustained clinical remission of 6 mo or more at the time of colonoscopy were examined for clinical outcomes and the hazard ratios of clinical relapse according to MES. Parameters, including blood tests, to identify predictive factors for MES 0 and slight endoscopic recurrence in clinically stable patients were assessed. Moreover, a receiver operating characteristic curve was generated, and the area under the curve was calculated to indicate the utility of the parameters for the division between complete and partial mucosal healing. All P values were two-sided and considered significant when less than 0.05. A total of 183 patients with clinical remission were examined. Patients with MES 0 (complete mucosal healing: n = 80, 44%) were much less likely to relapse than those with MES 1 (partial mucosal healing: n = 89, 48%) (P < 0.0001, log-rank test), and the hazard ratio of risk of relapse in patients with MES 1 vs MES 0 was 8.17 (95%CI: 4.19-17.96, P < 0.0001). The platelet count (PLT) < 26 × 10(4)/μL was an independent predictive factor for complete mucosal healing (OR = 4.1, 95%CI: 2.15-7.99). Among patients with MES 0 at the initial colonoscopy, patients of whom colonoscopy findings shifted to MES 1 showed significant increases in PLT compared to those who maintained MES 0 (3.8 × 10(4)/μL vs -0.6 × 10(4)/μL, P < 0.0001). The relapse rate differed greatly between patients with complete and partial mucosal healing. A shift from complete to partial healing in clinically stable UC patients can be predicted by monitoring PLT.

Postoperative Crohn's Disease Recurrence: Time to Adapt Endoscopic Recurrence Scores to the Leading Surgical Techniques

The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in ulcerative colitis. Patients with ulcerative colitis (n = 138) who had undergone blood tests and colonoscopy were included. Serum gelsolin was measured using enzyme-linked immunosorbent assay, and correlation between the gelsolin level and clinical and endoscopic activities was examined. The serum gelsolin level in patients with ulcerative colitis was significantly lower than that in healthy subjects, and it decreased in proportion to increasing Mayo score and Mayo endoscopic subscore. The area under the curve for correlation between clinical and endoscopic remission and serum gelsolin level was higher than that for C-reactive protein. Furthermore, in C-reactive protein-negative patients, the serum gelsolin level was lower in the active phase than in remission. Our findings indicate that the serum gelsolin level correlates with clinical and endoscopic activities in ulcerative colitis, has a higher sensitivity and specificity than C-reactive protein, and can detect mucosal healing, suggesting that gelsolin can be used as a biomarker for ulcerative colitis.

The Value of Myenteric Plexitis to Predict Early Postoperative Crohn’s Disease Recurrence

Issue Highlights

MUC1-glycoprotein is expressed at low levels and in fully glycosylated form on epithelial cells. Inflammation causes MUC1 overexpression and hypoglycosylation. We hypothesized that overexpression of hypoglycosylated MUC1 would be found in postoperative Crohn's disease (CD) recurrence and could be considered an additional biomarker of recurrence severity. We examined archived neo-terminal ileum biopsies from patients with prior ileocecal resection who had postoperative endoscopic assessment of CD recurrence and given a Rutgeerts ileal recurrence score. Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies, HMPV that recognizes all forms of MUC1 and 4H5 that recognizes only inflammation-associated hypoglycosylated MUC1. A total of 71 postoperative CD patients were evaluated. There was significant increase in MUC1 expression of both glycosylated/normal (P<0.0001) and hypoglycosylated/abnormal (P<0.0001) forms in patients with severe endoscopic CD recurrence (i3+i4), ileal score i2, compared with patients in endoscopic remission (i0+i1). Results were similar regardless of anti-TNF-α use. Although MUC1 expression and Rutgeerts scores were in agreement when characterizing the majority of cases, there were a few exceptions where MUC1 expression was characteristic of more severe recurrence than implied by Rutgeerts score. MUC1 is overexpressed and hypoglycosylated in neo-terminal ileum tissue of patients with postoperative CD recurrence. Increased levels are associated with more severe endoscopic recurrence scores, and this is not influenced by anti-TNF-α use. Discrepancies found between Rutgeerts scores and MUC1 expression suggest that addition of MUC1 as a biomarker of severity of postoperative CD recurrence may improve categorization of recurrence status and consequently treatment decisions.

Background Crohn’s disease (CD) has a significant impact on health status and quality of life, by affecting physical and emotional well-being and by impairment of social and functional abilities. In the era of treat to target concept, endoscopic healing has emerged to be the goal to achieve to prevent intestinal damage and disability. It is not clear what level of endoscopic healing is associated with CD disability. We, therefore, aimed to compare disability associated to complete endoscopic healing or partial endoscopic healing in patients with CD. Methods We conducted a multicentric prospective study, between September 2019 and November 2020, in one University Hospital, one general hospital and one private practice center including consecutive patients with CD in clinical remission and either complete mucosal healing (CDEIS =0) or partial mucosal healing (CDEIS &amp;gt; 0 and ≤ 4). The 10-item self-questionnaire IBD-disk was used to assess disability. Moderate-to-severe disability was defined as an overall IBD-disk score ≥ 40. Results A total of 82 patients were included. Forty-four (53%) were women, the median age and disease duration were respectively 35.3 years (Interquartile range (IQR 28.6–45.2) and 8.0 years (IQR, 3.0–17.0). The median overall IBD-disk score was 26.5 (IQR, 9 -45.0) and 30 (36.6%) had moderate-to-severe disability. Complete endoscopic healing was observed in 48 patients (57.3%). Median IBD-Disk score was respectively 24 (IQR, 9.0–40.5) and 34 (IQR, 9.5–51.5) for patients with complete and partial endoscopic healing (p=0.068). Respectively, 13/48 (27%) and 17/34 (50%) of patients with complete and partial endoscopic healing had moderate-to-severe disability (p=0.039). In multivariate analysis, partial mucosal healing (OR=3.04, CI95% [1.11, 8.94], p=0.03), female gender (OR=3.93, CI95% [1.43, 11.94], p=0.008) and smoking (OR= CI95% 5.88 [1.72, 25.0] p=0.039) were significantly associated with moderate-to-severe disability. Among the IBD-disk subscores, defecation score (median, IQR) (0.0 [0.0–3.0] vs 4.0 [0.0–7.5], p=0.028) and energy score (4.0 [0.0–6.0] vs 6.0 [2.5–8.0], p=0.023) were significantly lower in complete endoscopic healing. Conclusion One-third of patient with endoscopic healing reported moderate-to-severe disability. Complete endoscopic healing (CDEIS = 0) was associated with lower disability than partial endoscopic healing (CDEIS &amp;gt; 0 and ≤ 4) in CD. Deeper endoscopic healing may be needed to reduce the risk of disability in CD.

Risk Prediction and Comparative Efficacy of Anti-TNF vs Thiopurines, for Preventing Postoperative Recurrence in Crohn's Disease: A Pooled Analysis of 6 Trials

Introduction: Endoscopic recurrence of Crohn's disease (CD) after curative ileocecal resection, which is reported in up to 70% of patients within 1 year, precedes clinical relapse. Azathioprine (AZA) reduces the risk of both clinical and endoscopic recurrence. Aim: To evaluate the association between thiopurine metabolite levels and endoscopic improvement in CD patients with moderate to severe postoperative endoscopic recurrence. Methods: Patients treated with AZA within the AZT-2 study, a prospective double-blinded trial comparing 2.0–2.5mg/kg/d AZA versus 4.0g/d mesalamine for prevention of clinical relapse in patients with postoperative moderate to severe endoscopic recurrence, were included. Ileocolonoscopy was performed at baseline and at week 52 or at premature discontinuation (median 364 days, range: 176–381). Red blood cell concentrations (RBC) of 6-thioguanine nucleotides (6-TGN), 6-methyl-mercaptopurine ribonucleotides (6-MMPR), and 6-methyl-thioguanine nucleotides (6-MTGN) were measured by high-performance liquid chromatography assay. A cut-off value of 6-TGN of ≥235pmol/8×108 RBC was used as established in literature. 6-MMPR and 6-MTGN levels below and above the median were considered low and high, respectively. Endoscopic improvement was defined as a reduction of the endoscopic score according to Rutgeerts by at least one point, and mucosal healing as endoscopic score of i0 (=no lesions). Results: Endoscopic data were available on 31 patients treated with azathioprine (f/m=13/18, median age: 32 years, median AZA dose: 2.24mg/kg/d) for median 358 days. At last observation, the median levels of 6-TGN (n=26), 6-MMPR (n=27), and 6-MTGN (n=26) were 139.7, 1696.1 and 70.1pmol/8×108 RBC, respectively. Overall, endoscopic score improved from i3-i4 to i0-i2 (p=0.004). Mucosal healing was achieved in 6/31 (19.4%) of patients. High 6-TGN levels (n=8) were associated with a significantly higher drop in the Rutgeerts score than low 6-TGN (n=18) levels (median drop of 3 vs. 1, p=0.023). There was no difference concerning mucosal healing (p=0.33). Furthermore, there was no correlation between 6-MMPR and 6-MTGN levels and endoscopic improvement. Conclusion: Our data suggest that high 6-TGN levels may linked to endoscopic improvement in patients with postoperative endoscopic recurrence of CD.

Correlation between serological biomarkers and endoscopic activity in patients with inflammatory bowel disease

Background Recently, a new antimesenteric, functional, end-to-end, hand-sewn ileocolic anastomosis (Kono-S) has shown a significant reduction in endoscopic recurrence (ER) and surgical recurrence (SR) rate in Crohn’s disease (CD). This trial aimed to provide randomized controlled data comparing Kono-S anastomosis and conventional stapled ileocolic side-to-side anastomosis. Methods Randomized controlled trial (RCT) at a tertiary referral centre. The primary endpoint is ER rate (Rutgeerts score ≥ i2) after 6 months and surgical recurrence at 60 months. Secondary endpoints are clinical recurrence (CR) rate after 24 and 36 months, and SR after 24 and 36 months. Statistics was performed by using standard analyses. Furthermore, a sample size able to consent the detection of a reduction &amp;gt;30% in total endoscopic recurrence (when assuming a 60% to 65% ER expected rate in the control group and a 30% in the case group) was calculated; to allow a 10% drop-out of patients, 36 patients per group were needed (72 patients in the entire population). Results A total of 119 CD patients were included in the study. In all, 51 ileocolic CD patients were randomized in the Kono group and 68 in the conventional side-to-side group. At 6 months, 17 (33.3%) patients in the Kono group and 51 (75%) patients in the conventional group presented an ER (Rutgeerts score≥i2) at colonoscopy (p&amp;lt;0.001). A severe post-operative ER (Rutgeerts score≥i3) was found in 8 (15.7%) patients in the Kono group versus 23 (33.8%) patients in the conventional group (p=0.03). At 24 months, CR rate was 19.6% in the Kono group versus 30.9% in the conventional group (p=0.2), while SR rate was 0% in the Kono group versus 4.4% (3 patients) in the standard group (p=0.2). At 36 months, CR rate was 19.6% in the Kono-s group versus 33.8% in the conventional group (p=0.1). At 36 months, no patients (0%) in the Kono group experienced SR, while 6 patients (8.8%) in the conventional group did (p=0.03). Furthermore, when considering a median follow-up of 54 (42-60) months at interim analysis of SR, the difference between the two groups was confirmed to be significant (0% vs 8.8%; p=0.02). Conclusion This is the first RCT comparing Kono-S anastomosis and conventional side-to-side anastomosis in CD. The results demonstrate a significant reduction in postoperative endoscopic and surgical recurrence rates, no safety issues, and a favourable trend for lower clinical recurrence rate in patients who underwent Kono-S anastomosis compared to the conventional side-to-side anastomosis.

There is growing evidence that in Crohn's disease the achievement and maintenance of mucosal healing (MH) through anti-TNFα antibodies may change the natural history of the disease. Few studies evaluating such outcome as a therapeutic goal are available in paediatrics. The primary aim of the study was to assess the efficacy of biologics in obtaining MH in a paediatric Crohn's disease cohort. The secondary aims were: (1) to assess response based on early or late treatment introduction and on combination therapy with immunomodulators versus biologics alone; and (2) to evaluate clinical outcome 2 years after the second endoscopy. Biologic-naive paediatric Crohn's disease patients starting anti-tumour necrosis factor α (TNFα) treatment were enrolled. Patients' demographic and treatment data were recorded. Clinical [Pediatric Crohn's Disease Activity Index (PCDAI)] and endoscopic [Simple Endoscopic Score for Crohn's Disease (SES-CD)] evaluations were performed at time 0 (T0) and after 9-12 months (follow-up). Appropriate induction and maintenance therapeutic schemes were applied. Thirty-seven patients were enrolled. At enrolment, mean age was 12.3 ± 3.4 years and mean disease duration was 13.0 ± 16 months. At follow-up there was a significant decrease in PCDAI and SES-CD compared with T0 (p < 0.01). No statistical difference in frequency of MH between the early and late treatment introduction groups was found. Combination therapy was superior in obtaining complete plus partial MH (p < 0.01). One and 2 years after the second endoscopy, all and 79% of patients with complete MH and 75 and 67% of those with partial MH were still in clinical remission, respectively. Biologics improve mucosal lesions, apparently more effectively if given in combination with immunomodulators. MH appears to sustain a better disease course.