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Background and Aims: We aimed to identify serum metabolites associated with mucosal and transmural inflammation in paediatric Crohn disease [pCD]., Methods: In all, 56 pCD patients were included through a pre-planned sub-study of the multicentre, prospective, ImageKids cohort, designed to develop the Paediatric Inflammatory Crohn magnetic resonance enterography [MRE] Index [PICMI]. Children were included throughout their disease course when undergoing ileocolonoscopy and MRE and were followed for 18 months, when MRE was repeated. Serum metabolites were identified using liquid chromatography/mass spectroscopy. Outcomes included: PICMI, the simple endoscopic score [SES], faecal calprotectin [FCP], and C-reactive protein [CRP], to assess transmural, mucosal, and systemic inflammation, respectively. Random forest models were built by outcome. Maximum relevance minimum redundancy [mRMR] feature selection with a j-fold cross-validation scheme identified the best subset of features and hyperparameter settings., Results: Tryptophan and glutarylcarnitine were the top common mRMR metabolites linked to pCD inflammation. Random forest models established that amino acids and amines were among the most influential metabolites for predicting transmural and mucosal inflammation. Predictive models performed well, each with an area under the curve [AUC] > 70%. In addition, serum metabolites linked with pCD inflammation mainly related to perturbations in the citrate cycle [TCA cycle], aminoacyl-tRNA biosynthesis, tryptophan metabolism, butanoate metabolism, and tyrosine metabolism., Conclusions: We extend on recent studies, observing differences in serum metabolites between healthy controls and Crohn disease patients, and suggest various associations of serum metabolites with transmural and mucosal inflammation. These metabolites could improve the understanding of pCD pathogenesis and assessment of disease severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Colonic fibrosis has important clinical implications in ulcerative colitis [UC]. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis., Methods: Consecutive UC patients who had proctocolectomy from July 2022 to September 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria [MUC] were calculated and bowel wall stiffness was determined using two mean strain ratios [MSRs]. Degree of colonic fibrosis and inflammation was measured upon histological analysis. Receiver operating characteristic [ROC] analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis., Results: In all, 56 patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 [0-4] and the median Geboes score was 5 [0-13] and these two scores were significantly correlated [p < 0.001]. The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis [p = 0.003] but bowel wall thickness was not [p = 0.082]. The strain ratios [p < 0.001] and MUC [p = 0.010] were significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score [p < 0.001] but not MUC [p = 0.387]. At ROC analysis, mean strain ratio 1 [MSR1] had an area under the curve [AUC] of 0.828 [cutoff value 3.07, 95% CI 0.746-0.893, p < 0.001] to predict moderate-severe fibrosis., Conclusion: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision making in UC patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: The Milan ultrasound criteria [MUC] is a validated score to assess endoscopic activity in ulcerative colitis [UC]. MUC > 6.2 detects Mayo endoscopic score [MES] > 1. In this study we evaluated the predictive value of MUC for biologic treatment response, using colonoscopy [CS] as a reference standard., Methods: Consecutive UC patients starting biologic therapy were included, and underwent CS, IUS, clinical assessment and faecal calprotectin [FC] measurement at baseline and within 1 year. In addition, IUS, clinical and FC assessments were performed at week 12. The primary objective was to evaluate whether ultrasound improvement [MUC ≤ 6.2] at week 12 predicted endoscopic improvement at reassessment [MES ≤ 1]. Endoscopic remission was defined as MES = 0., Results: Forty-nine patients were included [59% under infliximab, 29% under vedolizumab, 8% under adalimumab, 4% under ustekinumab]. MUC ≤ 6.2 at week 12 was the only independent predictor for MES ≤ 1 and MES = 0 at reassessment (odds ratio [OR] 5.80, p = 0.010; OR 10.41, p = 0.041; respectively). MUC ≤ 6.2 at week 12 showed a negative predictive value of 96% for detecting MES = 0. A ≥2 reduction of the MUC predicted MES = 0 (area under the curve [AUC] 0.816). MUC ≤ 4.3 was the most accurate cut-off value for MES = 0 [AUC 0.876]. Guyatt's responsiveness ratio for the MUC was 1.73 [>0.8]., Conclusion: MUC ≤ 6.2 at week 12 predicts long-term endoscopic response. MUC is accurate in monitoring treatment response and may be used in both clinical trials and routine practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: This study examines colonic histological features in ulcerative colitis [UC] in endoscopic remission to determine which cell types and biopsy sites best predict a patient's likelihood of remaining in remission., Methods: This is a retrospective chart, endoscopy and histology review of 166 patients with UC in endoscopic remission followed in a single inflammatory bowel disease practice over a median of 6 years [range, 2-11 years]. Clinical remission was based on global physician assessment and colonoscopy reports, and clinical relapse on chart review. Histological features of previous injury and also number and location of plasma cells and eosinophils were assessed. We evaluated all of these features semi-quantitatively using a standard set of illustrations for the grade to maintain consistency. Multiple logistic regression and survival analyses were used to identify features associated with relapse., Results: Clinical relapse occurred in 44 patients. Ulceration, especially in the left colon, was highly predictive of relapse. In the absence of acute inflammation of ulceration, the variables most predictive of relapse were increased plasma cells in the basal 20% of the lamina propria, and eosinophils in the left colon. The variable most predictive of persistent remission was the presence of intra-epithelial eosinophils whether in the surface epithelium or within crypts, especially in the right colon. Lamina propria eosinophils [grade > 2] throughout the colon predicted relapse., Conclusion: In the absence of neutrophils or ulceration, left-sided plasmacytosis in the basal 20% of the lamina propria and increased lamina propria eosinophils provide the best indicators of relapse in UC in clinical and endoscopic remission., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Histological healing may represent the ultimate therapeutic goal in ulcerative colitis [UC], but it requires biopsies. Our aim was to develop a non-invasive index able to assess histological disease activity in ulcerative colitis, using probe-based confocal laser endomicroscopy [pCLE]., Methods: One hundred patients with quiescent UC were prospectively included in five French centres. After fluorescein intravenous injection, during colonoscopy, the colorectal mucosa was analysed by white light imaging and pCLE, and then biopsied in different locations. Five endoscopists performed central reading of pCLE images blinded to clinical, endoscopic, and histological data. One expert pathologist performed a central histological reading [Nancy index: gold standard]. Univariate and multivariate analyses were performed to identify the endomicroscopic items associated with the presence of histologically active disease., Results: Over 1000 pCLE videos sequences performed in 100 UC patients in endoscopic remission [Mayo 0 and 1] were evaluated. We observed that vessel diameter >20 µm, dilated crypt lumen, fluorescein leakage, and irregular crypt architecture were statistically associated with histologically proven inflammation according to the Nancy index. Hence, we built a pCLE index of mucosal inflammation with overall accuracy of 79.6% and overall sensitivity and specificity of, respectively, 57.8% and 82.8%. Negative predictive value, especially when a pCLE index ≤1 was observed, was high [93.1%]., Conclusions: Using a robust methodology, large vessel diameter, dilated crypt lumen, fluorescein leakage,and irregular crypt architecture are reliable endomicroscopic items defining the ENHANCE index for real-time assessment of histological disease activity in UC., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]., Aims: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage., Methods: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52., Results: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037)., Conclusion: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Several studies have reported that ulcerative colitis [UC] patients with endoscopic mucosal healing may still have histological inflammation. We investigated the relationship between mucosal healing defined by modified PICaSSO [Paddington International Virtual ChromoendoScopy ScOre], Mayo Endoscopic Score [MES] and probe-based confocal laser endomicroscopy [pCLE] with histological indices in UC., Methods: A prospective study enrolling 82 UC patients [male 66%] was conducted. High-definition colonoscopy was performed to evaluate the activity of the disease with MES assessed with High-Definition MES [HD-MES] and modified PICaSSO and targeted biopsies were taken; pCLE was then performed. Receiver operating characteristic [ROC] curves were plotted to determine the best thresholds for modified PICaSSO and pCLE scores that predicted histological healing according to the Robarts Histopathology Index [RHI] and ECAP 'Extension, Chronicity, Activity, Plus' histology score., Results: A modified PICaSSO of ≤ 4 predicted histological healing at RHI ≤ 3, with sensitivity, specificity, accuracy and area under the ROC curve [AUROC] of 89.8%, 95.7%, 91.5% and 95.9% respectively. The sensitivity, specificity, accuracy and AUROC of HD-MES to predict histological healing by RHI were 81.4%, 95.7%, 85.4% and 92.1%, respectively. A pCLE ≤ 10 predicted histological healing with sensitivity of 94.9%, specificity of 91.3%, accuracy of 93.9% and AUROC of 96.5%. An ECAP of ≤ 10 was predicted by modified PICaSSO ≤ 4 with accuracy of 91.5% and AUROC of 95.9%., Conclusion: Histological healing by RHI and ECAP is accurately predicted by HD-MES and modified virtual electronic chromoendoscopy PICaSSO, endoscopic score; and the use of pCLE did not improve the accuracy any further., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: The current goal of treatment for ulcerative colitis [UC] is endoscopic and ultimately histological mucosal healing. However, there is no consensus on the definition of histological mucosal healing. We evaluated histological risk factors for clinical relapse in UC patients with endoscopically normal mucosa to focus on the importance of histological evaluation., Methods: Patients with UC who underwent colonoscopy confirming Mayo endoscopic subscore [MES] ≤ 1 with biopsies were enrolled into this retrospective cohort. Three expert pathologists evaluated the presence or absence of chronic inflammatory cell infiltrate, breaches in the surface epithelium, crypt abscesses, mucin depletion, crypt architectural irregularities and basal plasmacytosis. Clinical relapse was defined as partial Mayo score ≥ 3 or modification of induction treatment. Prediction models of clinical relapse were generated, especially in patients with MES 0., Results: A total of 194 UC patients were enrolled. Histological abnormalities existed more frequently in patients with MES 1 than those with MES 0, while the vast majority of patients still possessed at least one abnormality. There was no significant difference in time to relapse between MES 0 and 1. Crypt architectural irregularities and mucin depletion were associated with time to relapse in patients with MES ≤ 1. In patients with MES 0, the presence of mucin depletion was the only factor significantly and independently associated with the risk of relapse (hazard ratio, 2.18 [1.16-5.82]; p = 0.03)., Conclusions: Mucin depletion was shown to be a histological risk factor for clinical relapse in UC patients with MES 0.

Background and Aims: The Nancy score is a luminal Crohn's disease [CD] activity index applied in diffusion-weighted magnetic resonance imaging [DW-MRI]. We assessed the accuracy of the Nancy score in detecting mucosal healing and treatment response, and in predicting surgery., Methods: This was a retrospective, single-centre study of all patients with active CD and serial DW-MRI before and after treatment initiation with a biologic drug, between January 2010 and September 2016. The gold standard was endoscopy. The association between the Nancy score and the cumulative probability of intestinal resection during follow-up was tested combining Kaplan-Meier curves and log-rank testing., Results: A total of 96 patients were included; 20 had concomitantly undergone endoscopy. The Nancy score correlated well with the Crohn's Disease Endoscopic Index of Severity [r = 0.60 for the total score and r = 0.63 for the segmental score]. A total Nancy score <6 and a segmental Nancy score <2 detected mucosal healing with an area under the receiver operating characteristic curve [AUROC] of 0.82 (95% confidence interval [CI] 0.69-0.94, p <0.0001) and 0.80 [95% CI 0.73-0.87, p <0.0001], respectively. The Nancy score was highly sensitive to changes [Guyatt's responsiveness indices: 1.18 for the total score and 0.85 for the segmental score]. Mucosal healing on DW-MRI after treatment initiation was associated with a lower cumulative probability of intestinal surgery (p = 0.0251, median [interquartile range: IQR] follow-up 2.2 [1.6-3.7] years)., Conclusions: In CD, the Nancy score accurately detects mucosal healing and treatment response, the latter associated with a lower likelihood of intestinal resection.

Introduction: Patients with inflammatory bowel disease (IBD) undergoing polypectomy are recommended by current guidelines to have biopsies taken from adjacent mucosa to determine whether there is dysplasia present. With improvements in endoscopic imaging, it is now possible to characterize colonic lesions with higher levels of confidence than previously. We have reviewed the diagnostic yield of polyp-adjacent biopsies in IBD., Materials and Methods: A systematic search of our histopathology database revealed cases in which polyps had been endoscopically resected or biopsied in patients with IBD. Endoscopy reports and medical records were reviewed, and patient demographic and disease-specific details were recorded, along with details of polyp characteristics and histopathology outcomes., Results: Three hundred and two polyps were biopsied or resected in 131 patients undergoing 178 colonoscopies. The median polyp size was 4 mm (range 1-45), and the predominant morphology was Paris 0-Is (n = 98, 32%). The histology was tubular adenoma in 76 (25%), tubulovillous adenoma in 14 (5%), hyperplastic in 112 (37%), post-inflammatory in 32 (11%), sessile serrated polyp in 31 (10%), traditional serrated adenoma in 2 (0.7%), flat high-grade dysplasia or cancer in 2 (0.7%) and other in 33 (11%). Dysplasia in adjacent biopsies was detected in 2 patients (0.7%), and was endoscopically visible in both cases. The proportion of endoscopically unsuspected dysplasia was 0/300 (0%, 95% CI 0-1.6%)., Conclusion: The diagnostic yield for polyp-adjacent biopsies in patients with IBD is negligible. With high-definition technology and chromoendoscopy, it may no longer be necessary to biopsy endoscopically normal adjacent tissue to detect invisible dysplasia.

Background and Aims: Mucosal healing is associated with improved long-term clinical outcomes in patients with ulcerative colitis. This population-based study assessed endoscopic and histological mucosal healing within the first year of diagnosis., Methods: Consecutive patients diagnosed with ulcerative colitis from six countries in Asia were prospectively enrolled. Clinical demographics, blood markers and inflammatory activity were assessed at baseline. Mayo score and Nancy index were used to assess endoscopic and histological activities, respectively. Clinical, endoscopic and histological evaluations were repeated at 1 year. Logistic regression was performed to identify predictors of mucosal healing., Results: Of 433 ulcerative colitis patients, 202 [46.7%] underwent colonoscopy at 1 year. In total, 68 [38.2%] achieved endoscopic mucosal healing and 35 [23.1%] achieved histological mucosal healing. On multivariate analysis, an elevated erythrocyte sedimentation rate [ESR] at diagnosis (odds ratio [OR], 0.332; 95% confidence interval (CI), 0.133-0.830; p = 0.018) was a significant negative predictor of endoscopic mucosal healing at 1 year, while histological features of ulceration [OR, 0.156; 95% CI, 0.028-0.862; p = 0.033] and being an ex-smoker [OR, 0.067; 95% CI, 0.005-0.965; p = 0.047] were significant negative predictors of histological healing at 1 year. Both endoscopic and histological mucosal healing were associated with less steroid use [p < 0.001 and p = 0.001, respectively] and hospitalization [p = 0.002 and p = 0.01, respectively]., Conclusions: Mucosal healing was achieved in fewer than half of patients with ulcerative colitis in the first year of diagnosis. An elevated ESR predicted less likelihood of endoscopic mucosal healing, while histological features of ulceration and being an ex-smoker at diagnosis predicted less likelihood of histological healing., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background and Aims: Endoscopic and histological healing are associated with improved clinical outcomes in ulcerative colitis [UC]. We aimed to investigate the predictive value of faecal immunochemical test [FIT] for endoscopic and histological healing in UC., Methods: We measured quantitative FIT and faecal calprotectin [FC] in 140 consecutive UC patients who underwent colonoscopy. We assessed the diagnostic accuracy of FIT for predicting endoscopic healing using the Mayo endoscopic subscore [MES 0/1] and for histological healing using the Geboes score [< 2.0] and Nancy index [grade ≤ 1]. The predictive abilities of FIT were compared with those of FC., Results: FIT had an area under the curve [AUC] of 0.77 (95% confidence interval [CI] 0.67-0.86, p < 0.001) for endoscopic healing, an AUC of 0.77 [95% CI 0.67-0.86, p < 0.001] using the Geboes score, and 0.77 [95% CI 0.66-0.85, p < 0.001] using the Nancy Index for histological healing. The AUC of FIT was comparable to that of FC for endoscopic healing [p = 0.773] and histological healing [p = 0.767-0.960], and was comparable to colonoscopy for histological healing [p = 0.384-0.673]. FIT < 50 ng/ml predicted endoscopic healing with a sensitivity, specificity, and positive predictive value [PPV] of 72%, 68%, and 82%, respectively, and for histological healing with a sensitivity, specificity, and PPV of 73-75%, 67%, and 78-80%, respectively. Combining FIT with FC led to a higher specificity [90%] for histological healing. Over 85% of patients with FIT < 50 ng/ml and FC < 50 μg/g achieved histological healing., Conclusions: FIT is highly sensitive and accurate to predict endoscopic and histological healing in UC. It represents a promising non-invasive tool for monitoring mucosal healing in UC., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Introduction: Vedolizumab has proven efficacy in inflammatory bowel disease [IBD], but long-term mucosal healing in Crohn's disease [CD], as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy., Methods: Surveillance colonoscopy was prospectively scheduled for patients with longstanding ulcerative coltis [UC] or CD at a tertiary referral centre, in the open-label extension phase (vedolizumab 300 mg intravenously [IV] every 4 weeks) of the Gemini studies [GEMINI LTS, study number NCT00790933]. Mayo score ≤ 1 or ulcer disappearance [in CD] was defined as mucosal healing. Targeted biopsies were graded for inflammation and dysplasia., Results: Of 68 patients [29 CD/39 UC] treated for ≥ 1 year [median 3.2 years, range 1.1-6.1], 58 [24 CD/34 UC] were endoscopically monitored. Durable endoscopic healing corrected by non-responder imputation was found in 7/24, 29% [CD] and 17/34, 50% [UC]. Combined histological and mucosal healing was observed in 5/24 [CD] and 11/34 [UC] of those with endoscopic healing. Low-grade dysplasia was detected in 10% of patients and high-grade dysplasia in the resection specimen of one patient with biopsy-proven low-grade dysplasia., Conclusions: Long-term endoscopic and histological healing was observed in a proportion of patients treated with vedolizumab long-term. The dysplasia risk with vedolizumab deserves further study., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background and Aims: Mucosal healing and control of intestinal mucosal inflammation are important treatment goals for maintaining clinical remission in ulcerative colitis [UC] patients. Here, we investigated the efficacy of linked colour imaging [LCI], a novel endoscopic enhancement system, for diagnosing mucosal inflammation in UC patients., Methods: All examinations were carried out with a LASEREO endoscopic system [FUJIFILM Co., Tokyo, Japan]. Fifty-two patients with UC were enrolled, and 193 areas assessed by LCI were examined. LCI patterns were classified as; A, no redness; B, redness with visible vessels; and C, redness without visible vessels. Regions of interest [ROIs] were set at biopsy sites, and the red colour in the ROI was calculated from the Commission internationale de l'éclairage [CIE] color space and digitized [LCI-index]. Biopsy specimens were taken at each ROI and evaluated with Matts histopathological grade. Thirty months was defined as the time interval between endoscopic diagnosis and relapse of UC., Results: Interobserver agreement for LCI classification was excellent between an expert and non-experts. Among areas with a Mayo endoscopic subscore of 0, 41.8% and 4.6% were classified as LCI-B and LCI-C, respectively. Among areas with a Mayo endoscopic subscore of 1, 60.5% and 34.6% were classified as LCI-C and LCI-B, respectively. The LCI index strongly correlated with the histopathological Matts score. Non-relapse rates significantly correlated with LCI classification [p = 0.0055], but not with Mayo endoscopic subscore [p = 0.0632]., Conclusion: Endoscopic LCI classification and LCI index can subdivide samples with the same Mayo endoscopic subscore. LCI may be a novel approach for evaluating colonic mucosal inflammation and for predicting outcome in UC patients., (Copyright © 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background and Aims: Using sigmoidoscopy as the gold standard, we assessed the accuracy, and the responsiveness to change, of diffusion-weighted magnetic resonance colonography in ulcerative colitis, using the Nancy score., Methods: A total of 29 ulcerative colitis patients, having undergone at least two diffusion-weighted magnetic resonance colonographies, were included. Disease activity was evaluated using the Mayo endoscopic subscore and the Nancy score. We determined the accuracy of the Nancy score in the diagnosis of mucosal healing. We also assessed its responsiveness to change in 17 patients with a Mayo endoscopic subscore of 2 or 3 at treatment initiation., Results: A total Nancy score < 7 had a sensitivity of 0.75 and a specificity of 0.67 (area under the curve: 0.72; 95% confidence interval: [0.56-0.88]; p = 0.0063) in the diagnosis of mucosal healing. The total Nancy score was sensitive to change in ulcerative colitis [Guyatt's responsiveness index: 1.8; standardised effect size ratio: 1.36]. The Nancy score was reliable [intra-class correlation coefficient: 0.63; p = 0.01]. The mean Mayo endoscopic subscore and the mean Nancy score both fell significantly in patients who achieved mucosal healing (mean ± standard deviation [SD] Mayo endoscopic subscore: 2.4 ± 0.55 at baseline and 0.6 ± 0.55 at reassessment, p = 0.02; mean Nancy score: 18.2 ± 9.1 at baseline and 3 ± 1.6 at reassessment, p = 0.006). No significant changes in Nancy score were observed in active patients at reassessment., Conclusions: The Nancy score is a highly responsive, reliable tool for assessing treatment response in patients with ulcerative colitis. The Nancy score accurately detects mucosal healing., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background and Aims: The original Geboes Score [OGS] is the most commonly used histological score in ulcerative colitis [UC], but rather complicated to use in daily clinical practice. The aim of this study was to develop a Simplified Geboes Score [SGS] and to compare it with the OGS in patients newly diagnosed with UC., Methods: All patients diagnosed with UC at a tertiary referral centre between 2005 and 2010, who had serial colonoscopies with biopsies, were retrospectively included. The 5-year endoscopic/histological evolution after diagnosis was recorded. Histological activity was scored by an experienced inflammatory bowel disease pathologist and three trained readers using the OGS and also the new SGS that only includes variables linked to active inflammatory disease. The correlation between endoscopic and histological activity and the histological inter-observer agreement were measured., Results: A total of 528 slides from 339 colonoscopies of 103 UC patients were reviewed. Forty [12%] colonoscopies presented Mayo 0, 74 [22%] Mayo 1, 107 [31%] Mayo 2 and 118 [35%] Mayo 3. Active microscopic disease [≥ 3.1 in both scores] was described in 10/40 [25%] patients who were in complete endoscopic remission [Mayo 0], and 62/74 [84%] with mild endoscopic lesions [Mayo 1]. The correlation analysis between endoscopy and OGS/SGS did not show significant differences between the histological scores. The inter-observer agreement was moderate for all the grades of the SGS., Conclusions: The assessments of histological activity based on the OGS and the SGS were comparable in newly diagnosed active UC patients. Further prospective validation should now be done to replace the OGS with the SGS., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: Exclusive Enteral Nutrition (EEN) induction in children with luminal Crohn's disease (CD) gives early mucosal healing (MH), but the long-term benefits of EEN-induced MH are just emerging., Aims & Methods: We prospectively followed an Australian cohort of newly diagnosed children with predominantly luminal CD who completed at least six weeks EEN and with paired clinical Pediatric Crohn's Disease Activity Index (PCDAI), biochemical (C-reactive protein; CRP) and endoscopic assessment at diagnosis and post EEN. All commenced immunomodulators (IMs) early (<3 months from diagnosis) and had a minimum of 1 year follow-up. Complete MH was a simple endoscopic score for Crohn's disease (SES-CD) of 0, and SES-CD≥1 was ascribed to active endoscopic disease (aED) and further divided into near complete MH (SES 1-3), mild active disease (SES-CD 4-10) and moderate to severe disease (SES-CD>10). The primary outcome was long-term supervised sustained remission (SR) on IMs alone without need for corticosteroids, infliximab (IFX) or surgery., Results: A total of 54 eligible children (33 males) completing EEN induction were analysed. The median duration between pre and post EEN assessments was 60.5 days [interquartile range (IQR), 56-69.5]. Post EEN: clinical remission (PCDAI < 10) was observed in 45/54 (83%), and biochemical remission (PCDAI < 10 and CRP < 5 mg/dl) was observed in 39/54 (72%). Complete MH was observed in 18/54 (33%), near complete in 10/54(19%). SR was superior in those with complete MH vs. aED; 13/18, (72%) vs. 10/36 (28%), p = 0.003 at 1 year, 8/16, (50%) vs. 3/24, (8%), p = 0.008 at 2 years and (8/16, (50%) vs. 1/19, (6%), p = 0.005) at 3 years. Near-complete MH did not lead to superior SR., Conclusions: Only complete MH post EEN induction predicts more favourable SR for up to 3 years., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Mucosal healing is an important therapeutic goal for ulcerative colitis. Once-daily administration of budesonide 2-mg foam is widely used for inducing clinical remission. No study has assessed the usefulness of twice-daily budesonide 2mg foam on mucosal healing in ulcerative colitis patients. We explored the efficacy for mucosal healing of once- or twice-daily budesonide foam in distal ulcerative colitis patients., Methods: This study was a multicentre, randomised, double-blind, placebo-controlled trial. In all, 165 patients with active, mild to moderate distal ulcerative colitis were randomised to three groups: once- or twice-daily budesonide 2mg/25ml foam, or placebo foam, for 6 weeks. Complete mucosal healing [endoscopic subscore = 0] and the safety profile were assessed at Week 6. Prespecified and post hoc analyses were used., Results: The percentages of complete mucosal healing in the twice-daily budesonide foam group were 46.4% compared with 23.6% in the once-daily group [p = 0.0097], or 5.6% in the placebo group [p < 0.0001]. The percentages of clinical remission and the percentages of endoscopic subscore ≤ 1 in the twice-daily budesonide foam group were 48.2% and 76.8%, compared with 50.9% and 69.1% in the once-daily group [no difference], or 20.4% and 46.3% in the placebo group [p = 0.0029 and p = 0.0007], respectively. In the subgroup of patients with previous use of a 5-aminosalicylic acid suppository or enema, there was a greater percentage of complete mucosal healing in the twice-daily budesonide foam group [32.0%] compared with that in the once-daily [8.7%, p = 0.0774] or placebo groups [4.8%, p = 0.0763], though there was no significant difference. No serious adverse event occurred., Conclusions: A significantly greater percentage of patients receiving twice-daily administration of budesonide foam compared with once-daily administration/placebo achieved complete mucosal healing. This is the first study to evaluate the endoscopic efficacy of twice-daily administration of 6-week budesonide foam treatment for ulcerative colitis., (© European Crohn’s and Colitis Organisation 2015.)

Objectives: We evaluated the performance of blood and faecal biomarkers for differentiating between endoscopic inflammation and mucosal healing, and clinically active disease and sustained clinical remission, and determined the predictive value for a flare in patients with ulcerative colitis [UC]., Methods: Clinical Activity Index [CAI], faecal lactoferrin [FLA], calprotectin [CAL], PMN-elastase [PMN-e], C-reactive protein [CRP], white blood cells [WBC], Endoscopic Index [EI], and UC-Disease Activity Index [DAI] were determined repeatedly during 12 months and at acute flares., Results: Of 91 patients [45 female; mean age 48.1±13.4 years] entering in remission, 42 [46%] patients developed a clinical flare. A total of 529 CAI and 179 EI assessments were performed. Median levels for active disease confirmed by EI [n = 35] vs clinical remission with endoscopic inflammation [n = 37] vs mucosal healing [n = 107] for FLA were 44/37/4 µg/g, CAL 25/20/10 µg/g [both p < 0.0001], PMN-e 0.06/0.03/0.02 µg/g, CRP 0.7/0.2/0.2mg/dl [both p < 0.001], and WBC 7.0/6.5/6.4/nl [p = 0.1]. There was no difference for any of the markers for defining mucosal healing by EI = 0 vs EI = 1 with the exception of PMN-e [p = 0.03], where the difference was very small and with questionable clinical relevance. Using manufacturers' cut-offs, only FLA at baseline was associated with a significant higher relative risk [RR] of flaring [RR 1.69; p = 0.018]. Using optimised cut-offs, CAL, PMN-e, and CRP were also predictive of a flare., Conclusions: Faecal biomarkers FLA, CAL, and PMN-e were able to distinguish between UC patients with mucosal healing from clinical remission and mild disease, showed significant correlations with endoscopy, and were predictive of a flare., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: The current approach to managing the loss of response to anti-tumour necrosis factor (TNF) agents is generally empirical. Prior studies have suggested that adalimumab levels of >4.9 µg/mL are required to achieve clinical remission. Our aim was to identify an optimal adalimumab level to achieve endoscopic healing in Crohn's disease (CD)., Methods: A cohort of 60 CD patients treated with adalimumab between 2005 and 2013 were reviewed for the study. Demographic and clinical information was obtained from chart review and patient interview. Disease activity was determined using the Harvey-Bradshaw index (HBI), ileocolonoscopy reports and C-reactive protein (CRP) levels. Clinical remission was defined as HBI <5. Endoscopic remission/mucosal healing (MH) was defined as the absence of any ulceration in all ileocolonic segments. Trough adalimumab levels and adalimumab antibody levels were tested using a liquid-phase mobility shift assay., Results: Lower median CRP was significantly associated with MH 1.2mg/dl vs no MH 14.4mg/dl (p = 6.93×10(-6)). Higher adalimumab trough level was significantly associated with MH (median 14.7 µg/mL in those with MH vs 3.4 µg/mL in those without, p = 6.25×10(-5)). Higher adalimumab trough level was also significantly associated with the combined outcome of clinical and endoscopic remission (median 13.0 vs 4.8 µg/mL, p = 5.36×10(-3)). A cut-off of 8.14 µg/ml best discriminated subjects with MH from those without MH, with sensitivity and specificity of 91.4 and 76.0%, respectively (positive and negative predictive values 84.2 and 86.4%, respectively)., Conclusions: Higher adalimumab levels were significantly associated with MH. This study suggests that attaining MH alone or a combined outcome of clinical and endoscopic remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 8.14 μg/mL., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)