Background and aims Inflammatory bowel disease (IBD) is associated with a higher risk of developing colorectal cancer, according to the inflammation-dysplasia-cancer (IDC) sequence from inflammation to colitis-associated colorectal cancer (CAC). The objective of this study was to identify and generate a transcriptomic signature and score, related to the IDC sequence, that could ultimately classify dysplasia and cancer in IBD.Methods Demographics, clinical parameters, histological characteristics, and RNA-sequencing data were evaluated on 134 formalin-fixed paraffin-embedded lesions from 2 independent cohorts of IBD patients with low- or high-grade dysplasia (LGD, HGD) and/or CAC. An ordinal logistic regression screened for significant IDC sequence-associated genes that were computed in a transcriptomic signature score.Results Principal component analysis and unsupervised clustering on 1% of the most variable genes showed a good clustering between the 4 lesion groups (Normal Mucosa, Inflamed Mucosa, LGD/HGD, and CAC). A gene signature was identified on 27 genes that correlated with the lesion groups in the exploratory cohort. The most weighted gene in this transcriptomic signature was the long non-coding regulatory RNA KCNQ1OT1, a gatekeeper against genomic instability and transposon activation. Based on the expression of these 27 genes, we built and validated a transcriptomic signature score to classify dysplasia and CAC. The overall accuracy of the transcriptomic signature score was 85.71% in the exploratory cohort and 90.91% in the validation cohort.Conclusion We identified a tissue-based transcriptomic score to classify IDC lesions in IBD patients and uncovered some of the pivotal genes in carcinogenesis related to inflammation in IBD.

BACKGROUND AND AIMS:Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is the goal in managing Crohn's disease (CD). The role of histological remission (HR) remains unclear. This study aimed to examine the impact of histological inflammation on clinical relapse risk in CD and explore the relationship between histology, endoscopic scores, and biomarkers. METHODS:Patients from the prospective STORI (Stable Remission on Combined Therapy with Immunosuppressors) cohort underwent ileocolonoscopy with Crohn's Disease Endoscopic Index of Severity calculation and 2 biopsies from the most inflamed or previously inflamed areas. Histological scores (Robarts, Geboes, modified Geboes, Nancy, and IBD-DCA) were determined by 2 independent pathologists in a central reading process. Histological remission was defined by specific score thresholds. Clinical relapse, defined by Crohn's Disease Activity Index (CDAI) > 250 or a CDAI increase of 70 points over 2 weeks, was monitored for at least 1 year. RESULTS:Out of 115 patients included in STORI, 160 biopsies (44 ileal and 116 colonic) from 76 patients were analyzed. Histological remission rates were 46% (Nancy), 55% (Robarts), 61% (Geboes), and 41% (IBD-DCA). During follow-up, 35 patients (46%) experienced a clinical relapse: 37% with HR and 56% without, based on the Nancy score. Among the mucosal healing subgroup (45 patients), 34% with HR, and 44% without relapsed (p = 0.18). Histological scores did not predict clinical relapse. Only fecal calprotectin was a significant predictor in multivariate analysis (p = 0.029). CONCLUSIONS:Despite correlations with endoscopy and biomarkers, histological scores did not predict clinical relapse in CD patients in remission. Thus, these scores are not recommended for clinical practice to assess relapse risk in CD.

Abstract Background Deep remission has become the target in the management of Crohn’s disease (CD). The role of histology in the management of CD has not yet been established. The aim of this work was to study the impact of histological inflammation on the risk of clinical relapse in patients with CD in clinical and endoscopic remission and to study the correlation between histology and endoscopic scores and biomarkers. Methods All patients included in STORI (1) were eligible for inclusion. Fecal calproptectin and colonoscopy with CDEIS calculation were performed at inclusion. Two biopsies, taken either from the most inflammed macroscopic area or from an area with previous inflammation in case of mucosal healing (MH) were prospectively performed. MH was defined by the absence of ulcers. Different histological scores were calculated by 2 independent pathologists: Robart, Geboes, modified Geboes, Nancy, and DCA-IBD scores. Histological remission was defined by Nancy=0 ; Geboes ≤2 ; modified Geboes of grade 0 ; Robarts ≤3, IBD-DCA of C≤1 and A=0. Clinical relapse was prospectively evaluated in the STORI trial as CDAI>250 or CDAI between 150 and 250 with an increase of 70 points during 2 successive weeks compared to the inclusion visit. (1) Louis E et al .Gastroenterology 2012 Results Eighty biopsies (22 ileal and 58 colonic) were available from 76/115 patients included in STORI. Among the 45 patients with MH, 30 had colonic biopsies, 11 had ileal biopsies and 4 had biopsies in both locations. Among colonic biopsies 68% had histological remission according to Nancy and modified Geboes scores, 65% according to DCA-IBD and Geboes scores and 71% according to Robarts score. Among ileal biopsies 53% had histological remission according to Nancy score, 47% according to Modified Geboes, Geboes and DCA-IBD scores, and 67% according to the Robarts score. Thirty-five patients (46%) experienced a clinical relapse during the follow-up including 16/45 (36%) and 19/31 (61%) in the group with MH and without MH respectively. Histological characteristics and histological scores were not predictive of clinical relapse. In the total cohort (n=76), the CDEIS score was correlated to Nancy (p<0,001, r=0,43), Geboes (p<0,001, r=0,47) and Robarts (p<0,001, r=0,45) scores. Fecal calprotectin was correlated to Nancy (p<0,001, r=0,48), Geboes (p<0,001, r=0,45) and Robarts (p<0,001, r=0,46) scores. The histological scores of Nancy, Robarts and Geboes were highly correlated (p<0,0001 ; r > 0,9). Conclusion Although correlated with endoscopy and biomarkers, histology was not predictive of clinical relapse in CD patients in clinical and endoscopic remission. These findings do not support the use of histology to predict clinical relapse in CD in clinical practice.

Objectives: Risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) complications have been extensively studied and are well established; most complications are mild and self-limiting. This study aims to identify patients at risk of severe early post-ERCP complications. Methods: We conducted a retrospective cohort study with data from 2810 ERCP procedures performed at Ghent University Hospital between 2016 and 2022. Patient records and a maintained ERCP registry were used to identify all ERCP-related complications and possible risk factors. The AGREE classification was used to determine the severity of the complication. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of severe complications. Results: Out of 2810 procedures, 223 cases (7.9%) had post-ERCP complications, with severe complications occurring in 20.3% of cases. The most common severe complication was haemorrhage (22/49 severe complications, 44.9%), with perforation having the highest probability of being severe (10/15 cases, 67%). Independent predictors of severe complications included anticoagulative therapy (OR 6.3, 95% CI 1.4-28.3, p = 0.016) and high procedural difficulty (Schutz category 3: OR 11.5, 95% CI 2.4-54.6, p = 0.002; category 4: OR 5.9, 95% CI 1.4-23.5, p = 0.012). Conclusions: Patients on anticoagulation and those undergoing complex ERCP procedures (Schutz 3 or 4) are at particular risk of severe procedure-related complications.

To investigate the value of magnetization transfer (MT) MRI and texture analysis (TA) of T2-weighted MR images (T2WI) in the assessment of intestinal fibrosis in a mouse model. Chronic colitis was induced in mice by cyclic administration of dextran sodium sulphate (DSS) resulting in chronic inflammation and progressive bowel fibrosis. Mice underwent 7-T MR imaging at various time points. Bowel wall MT ratio (MTR) and textural features (skewness, kurtosis, entropy), extracted by a filtration histogram technique, were correlated with histopathology. Performance of both techniques were validated using antifibrotic therapy. Finally, a retrospective study was conducted in five patients with Crohn’s disease (CD) who underwent bowel surgery. MTR and texture entropy correlated with histopathological fibrosis (r = .85 and .81, respectively). Entropy was superior to MTR for monitoring bowel fibrosis in the presence of coexisting inflammation (linear regression R2 = .93 versus R2 = .01). Furthermore, texture entropy was able to assess antifibrotic therapy response (placebo mice versus treated mice at endpoint scan; Δmean = 0.128, p < .0001). An increase in entropy was indicative of fibrosis accumulation in human CD strictures (inflammation: 1.29; mixed strictures: 1.4 and 1.48; fibrosis: 1.73 and 1.9). MT imaging and TA of T2WI can both noninvasively detect established intestinal fibrosis in a mouse model. However, TA is especially useful for the longitudinal quantification of fibrosis in mixed inflammatory-fibrotic tissue, as well as for antifibrotic treatment response evaluation. This accessible post-processing technique merits further validation as the benefits for clinical practice as well as antifibrotic trial design would be numerous. • Magnetization transfer MRI and texture analysis of T2-weighted MR images can detect established bowel fibrosis in an animal model of gut fibrosis. • Texture entropy is able to identify and monitor bowel fibrosis progression in an inflammatory context and can assess the response to antifibrotic treatment. • A proof-of-concept study in five patients with Crohn’s disease suggests that texture entropy can detect and grade fibrosis in human intestinal strictures.

Objectives Gut inflammation commonly occurs in axial SpA (axSpA), and is linked to disease activity and outcome. Given the role of IgA in mucosal immunity, we explored the association between anti-CD74 IgA antibodies, gut inflammation and axSpA. Methods Anti-CD74 IgA was measured by ELISA in serum samples of axSpA patients, fulfilling the 2009 Assessment of SpondyloArthritis international Society classification criteria. A group of fibromyalgia (FM) and RA patients served as non-inflammatory and inflammatory controls. Newly diagnosed axSpA patients underwent ileocolonoscopy; mucosal biopsies were histopathologically assessed as normal, acute or chronically inflamed. Optimal anti-CD74 IgA cut-off values were determined with a receiver operating characteristics curve. Results axSpA patients (n = 281) showed higher anti-CD74 IgA levels [mean (s.d.) 18.8 (12.4) U/ml] compared with 100 FM patients [10.9 (5.0) U/ml, P < 0.001] and 34 RA patients [13.7 (9.6) U/ml, P = 0.02]. The area under the receiver operating characteristics curve for diagnosis (axSpA vs FM) was 0.70, providing a sensitivity of 60% and specificity of 87% (cut-off 15 U/ml). Antibody concentrations were not significantly different between axSpA patients with (n = 40) and without (n = 69) gut inflammation (P = 0.83), yielding an area under the receiver operating characteristics curve of 0.51. Anti-CD74 IgA levels were not associated with degree of bone marrow oedema on MRI of the sacroiliac joints, CRP or any other disease-specific feature such as the use of NSAIDs or biological treatment. Conclusion Serum anti-CD74 IgA is a potentially useful diagnostic biomarker for axSpA. However, antibody levels do not correlate with any phenotypical feature, including microscopic gut inflammation, suggesting this to be a disease-specific rather than an inflammatory marker.

Abstract Background and Aims Since there are no accurate methods for fibrosis identification or quantification, the purpose is to investigate the utility of magnetization transfer (MT) MRI and texture analysis (TA) of T2-weighted MR images for intestinal fibrosis assessment in a mouse model of gut fibrosis. Methods Chronic colitis was obtained in 16 C57BL/6 mice by cyclic administration of dextran sodium sulphate (DSS) inducing early phase inflammation and progressive bowel fibrosis. Mice underwent 7.0 T MR imaging at various timepoints. MT ratio (MTR) in the bowel wall was calculated. Textural features (skewness, kurtosis, entropy) were extracted by a filtration histogram technique. Resected colonic tissue was scored for inflammation and fibrosis. Performance of MT-MRI and TA was validated in a consecutive experiment in mice using antifibrotic therapy. Finally, a retrospective study was conducted in five CD patients who underwent bowel surgery. Results MTR and texture entropy both correlated with histopathological fibrosis (r = .85 and .81, respectively). Entropy was superior to MTR for monitoring bowel fibrosis in presence of coexisting inflammation (linear regression R² = .93 versus R2 = .01). Furthermore, texture entropy was able to assess antifibrotic therapy response (placebo mice versus treated mice at endpoint scan; Δ mean = 0.128, p < .0001). An increase in entropy was indicative of fibrosis accumulation in human CD strictures (1.29 in inflammation; 1.40 and 1.48 in mixed strictures; 1.73 and 1.90 in fibrosis). Conclusion Texture analysis of T2-weighted MR images outperforms magnetization transfer imaging in detecting the fibrotic component in mixed inflammatory-fibrotic bowel tissue and can be used for monitoring antifibrotic treatment response.

Abstract A common and untreatable complication of Crohn’s disease (CD) is the development of intestinal fibrosis for which no adequate noninvasive tools for fibrosis progression monitoring exist. For this purpose, we assessed the performance of magnetization transfer (MT) magnetic resonance imaging (MRI) and texture analysis (TA) on T2-weighted images by correlating them with histology in a fibrosis mouse model. MT-MRI and TA performance was validated during antifibrotic therapy in mice and on MR enterography images of CD patients undergoing bowel surgery. The MT-MRI and TA entropy correlated with histological fibrosis (r = .85 and .81, respectively). However, TA entropy was superior to MT-MRI for quantifying fibrosis progression during coexisting inflammation (linear regression R² = .93). TA entropy could efficiently monitor anti-fibrotic therapy efficacy and correlated with the grade of intestinal fibrosis in CD. In conclusion, MT-MRI and TA entropy are highly promising surrogate markers of intestinal fibrosis, but TA entropy performed better in the presence of concomitant inflammation.

Abstract Background Fatigue is highly prevalent in patients with IBD independent of the disease status but treatment options remain limited. A potential mediator in the pathophysiology of fatigue is tryptophan (Trp), a precursor of serotonin. Recently, reduced serum Trp levels have been linked to fatigue in patients with clinically and endoscopically inactive IBD. The aim of the current study was to determine the effect of oral 5-hydroxytryptophan (5-HTP), the direct precursor of serotonin, supplementation on fatigue in patients with inactive IBD. Methods This multicentre, randomized, double-blind, cross-over, placebo-controlled trial included fatigued patients with IBD in clinical and biochemical remission (CRP <10mg/L, calprotectin <250 mg/kg), treated with immunosuppressants and/or biologicals. Fatigue was assessed with the fatigue VAS (fVAS, range 0–10) and defined by a fVAS ≥5. Patients were treated in a cross-over manner with 100 mg 5-HTP or placebo bid for two consecutive periods of 8 weeks, without an intermediate washout period. The primary endpoint was the proportion of patients reaching a 20% reduction in fVAS after 8 weeks of intervention (week 8 versus week 0 and week 16 versus week 8). Secondary outcomes were changes in validated FACIT-F score, scores for depression and anxiety and changes in Trp metabolites. The effect of the intervention on the outcomes was evaluated by linear mixed modelling (LMM), with the intervention, period and intervention x period as fixed factors and study participant as random factor. Results A total of 166 patients were included in 13 Belgian centres between December 2018 and November 2020 (baseline characteristics: Table 1). The dropout rate was 10.8%. The evolution of the fVAS throughout the study was comparable between both study groups and no difference was observed in fVAS reduction between placebo and 5-HTP (Figure 1). The proportion of patients reaching ≥20% reduction in fVAS did not differ between placebo (37.6%) and 5-HTP (35.6%) (p=0.830). The evolution of the other scores for fatigue, depression, anxiety and stress were also similar between placebo and 5-HTP (Table 2). A significant increase in 5-HTP and serotonin serum levels was observed during 5-HTP treatment compared to placebo; whereas serum levels of Trp and kynurenine were comparable. Globally, changes in fVAS were not associated with changes in those metabolites (Figure 2). Adverse events (AEs) were seen in 29.2% and 34.8% of patients under treatment with placebo and 5-HTP respectively (p=0.282). Conclusion Despite a significant increase in serum 5-HTP and serotonin levels by oral treatment with 5-HTP, 5-HTP did not modulate IBD-related fatigue. Furthermore, treatment with 5-HTP had no impact on depression, anxiety and stress scores.

Introduction: Differentiation between inflammatory and fibrotic bowel strictures remains a holy grail in Crohn’s disease (CD) management, primarily because of the therapeutic implications. Stricture characterisation in CD patients is further hampered by the co-occurrence of inflammation and fibrosis in various degrees. Currently, there are no validated imaging tools to differentiate fibrotic from inflammatory or mixed strictures, but several new techniques, such as magnetization transfer magnetic resonance imaging (MT-MRI) and magnetic resonance texture analysis (MR-TA), seem promising. Aim: We investigated whether MT-MRI and MR-TA can detect and quantify intestinal fibrosis in an established mouse model of fibrosis-inducing chronic colitis. Methods: Chronic colitis was induced in C57BL/6 (n=16) mice by three consecutive cycles of administration of the colitis inducing agent dextran sodium sulphate (DSS) for 7 days, followed by a 14-day recovery period. Using a 7.0 Tesla scanner, MT and T2-weighted MR images were recorded for each mouse at baseline and weeks (wk) 1, 3, 4, 6, 7, and 9. Regions of interest were created over the bowel wall on both MT and T2-weighted images. The bowel wall to spine muscle normalized MT ratio was calculated using ImageJ. Textural features, including skewness, kurtosis and entropy, were extracted by a filtration histogram technique, enclosed in the TexRAD software. Masson’s trichrome stained colon sections were used as golden standard for the quantification of fibrosis. Multivariate mixed model analysis and receiver operating characteristic (ROC) curves were applied to statistically assess the MR parameters for evaluating intestinal fibrosis. Results: Conducting mixed model analysis, significant differences in MT-ratio between mixed strictures and pure fibrotic strictures were observed at wk4 vs. wk6 (p=0,012) and at wk7 vs. wk9 (p<0,0001), whereas the significance for TA-entropy was lower at these compared timepoints (p= 0,108 and p=0,012, respectively). Nonetheless, TA-entropy performed better when monitoring the increasing proportion of fibrotic tissue in mixed strictures between first and second (wk1 vs. wk4, p=0,001) and second and third DSS-cycle (wk4 vs. wk7, p=0,004), compared to the MT-ratio. ROC-curve analysis using histopathology as reference score, generated a sensitivity, specificity and area under the curve (AUC) for TA-entropy of 83%, 80% and 0,93 (p=0,018) respectively, while MT-ratio outperformed with a sensitivity and specificity of 100% and an AUC of 1 (p=0,006). Conclusions: To our knowledge, we have shown for the first time that MT-MRI and MR-TA can both accurately detect fibrosis in a fibrosis-induced chronic colitis mouse model. Where TA-entropy excels in detecting fibrosis build-up in an inflammatory environment, MT-ratio has higher sensitivity and specificity to detect fibrotic tissue as such. MT-ratio and TA-entropy should be seen as complementing techniques prompting comprehensive fibrosis detection.

Introduction: Crohn’s disease (CD) patients are at high risk of developing fibrotic strictures, which significantly affects the patient’s quality of life. The accumulation of fibrotic tissue and progression of stricture formation is difficult to assess, leading to late awareness of stricture formation and surgical resection. Therefore, fibrostenosis-specific biomarker profiles are highly needed. Aim: Given the increasing evidence of metabolic alterations in activated fibroblasts, we aimed to identify discriminating metabolic markers in the serum of CD patients with and without fibrostenosis. Methods: In this retrospective study, samples of 66 CD patients with (n=28) and without (n=38) ileal fibrotic strictures at the time of sampling were selected from a local biobank (UZ Gent, BB190100). Fibrostenosis was defined as a narrowing of lumen and prestenotic dilation on CT/MRI at the time of serum collection. Both groups included an equal number of patients in remission or with active disease, based on imaging and/or CRP levels (cut-off at 10mg/L) and were age- and gender-matched. Metabolomics analysis was performed applying UHPLC-Q-Orbitrap-HRMS. The in-house method for metabolite extraction and mass spectrometry analysis was validated for serum compatibility. Statistical analysis of the untargeted MS data was performed using SIMCA 15.0 and MetaboAnalyst 4.0, allowing multivariate statistical modelling through, amongst others, Principal Component Analysis (PCA) and sparse Partial Least-Squares Discriminant Analysis (sPLS-DA). Results: Age at diagnosis, exposure to anti-TNF drugs, disease location and disease activity were similar between both groups. Validation of metabolomics analysis of serum samples, including instrumental precision, intra-assay, and inter-day analyses, showed excellent coverage of the measured metabolites with respective coefficients of variance 75% of metabolites complied) and <30% for untargeted analysis (compound compliance rate of 80% in positive and 90% in negative ionisation mode). The extraction and analysis of the serum samples yielded a total of 5,959 features. sPLS-DA models were used to determine which features were most discriminating between groups, and 1,000 features were retained. A valid Orthogonal PLS-DA model based on these 1,000 features had R2Y of 0.99 and Q2 of 0.83, suggesting excellent predictivity and fitting of the existent data. The top differentiating features, 47 in total, were retained after further filtering, based on a Variable Influence on Projection score higher than 1, Jack-knifed confidence interval higher than 0 and S-plot with p(corr)-values lower than -0.3 or higher than 0.3. Conclusions: To our knowledge, this is the first study using a comprehensive metabolomics approach by which we unveiled a discriminative metabolic fingerprint in the serum of fibrostenotic CD patients. Further MS2 measurements to allow the identification of these metabolites and validation are on-going and will allow to prove biomarker potential and gain insight in the functional pathways involved.

Abstract Background Patients with inflammatory bowel diseases (IBD) are at increased risk of dysplasia and colitis-associated cancer (CAC). The presentation of (pre)neoplastic lesions (low-grade dysplasia (LGD), high-grade dysplasia (HGD) or colorectal cancer (CRC) is reported to vary depending if the lesions are located inside disease area (IDA) or outside diseased area (ODA). The primary aim was to analyse the characteristics and prognostic of IDA compared with ODA neoplastic lesions in a large cohort of IBD patients. Methods We performed a multicentre retrospective pathological data collection from 7 tertiary referral regional or academic IBD centres in Belgium. Clinical, endoscopic and pathological data were retrieved through retrospective electronic chart review. From the IBD pathology databases, 1183 colorectal lesions were identified in 541 IBD patients: 415 developed dysplasia (77%) and 126 CRC (23%) during their follow-up. Biopsies and surgical specimen were centrally reviewed by an expert IBD pathologist to confirm the diagnosis of dysplasia and/or CRC. Results Demographic and clinical variables of the study population are summarised in Table 1. More patients with IDA lesions had HGD (9%) or CAC (27%) during their follow-up compared with the group of patients with ODA lesions (3% of HGD and 11% of CRC) (p < 0,0001). Mortality was higher in patients with IDA than in those with ODA lesions (p < 0.05). When comparing IBD patients with IDA lesions and CAC (=111) to those with ODA lesions and sporadic CRC (n = 15), median age at IBD diagnosis was lower (29 (IQR:22–49) vs. 41(IQR:28–54) years; p = 0.0001). Characteristics of the 1183 neoplastic lesions are summarised in Table 2. IDA lesions were more frequently non-visible, non-polypoid and ≥ 1 cm than ODA lesions (p < 0.0001). ODA sporadic CRC was more frequently located in the right colon compared with IDA CAC (5/16 (31%) vs. 21/133 (16%), p < 0.01). Conclusion Neoplastic lesions outside the diseased area were more likely to be visible, polypoid, < 1cm, in the right colon and diagnosed at endoscopy than inside disease area lesions. A lower prevalence of HGD and Cancer were reported with neoplastic lesions outside the diseased area.

Background: Ustekinumab [UST] was recently approved in Europe for the treatment of moderate to severe Crohn's disease [CD]. Long-term real-world data are currently scarce for CD patients previously exposed to several biologics. Methods: This is an observational, national, retrospective multicentre study. Patients received intravenous UST ~6 mg/kg at baseline, with 90 mg subcutaneously thereafter every 8 weeks. Response and remission rates were assessed at Weeks 8, 16, and 52. Results: Data from 152 patients were analysed. All patients were exposed to at least one antiTNFα agent, with 69.7% were exposed to even two anti-TNFα and vedolizumab. After 1 year, 42.1% and 25.7% of patients had experienced clinical response and clinical remission, respectively, and 38.8% and 24.3% had achieved steroid-free clinical response and remission, respectively; 38.8% of patients discontinued therapy during the 12 months of follow-up. Colonic location was predictive of clinical response at 1 year, and low body mass index [BMI] at baseline was a negative predictor of clinical remission. Resolution of arthralgia was associated with clinical response over time. De novo arthralgia was reported by 17.9% of patients at Week 8 and 13.5% of patients at Week 52. No impact of UST on arthralgia was observed in patients with concomitant ankylosing spondylitis [n = 17]. Others adverse events were reported in 7.2% of patients. Conclusions: This real-world cohort study confirms the effectiveness of UST in CD patients previously exposed to several biologics. Ustekinumab was well tolerated with respect to adverse events.

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBD) have increased risks of dysplasia and colitis-associated cancer (CAC). We evaluated the risk of development of high-grade dysplasia (HGD) or CAC after diagnosis of dysplasia using data from a national cohort of patients with IBD. METHODS: We performed a multicenter retrospective analysis of data collected from 7 tertiary referral regional or academic centers in Belgium. In searches of IBD pathology databases, we identified 813 lesions (616 low-grade dysplasias [LGDs], 64 high-grade dysplasias [HGDs], and 133 CACs) in 410 patients with IBD: 299 had dysplasia (73%) and 111 had CAC (27%). The primary aim was to determine the risk of more-advanced lesions after diagnosis of LGD or HGD. RESULTS: Of the 287 patients with LGD, 21 (7%) developed more-advanced lesions (HGD or CAC) after a median time period of 86 months (interquartile range, 34-214). Of the 28 patients with HGD, 4 (14%) developed CAC after a median time period of 180 months (interquartile range, 23-444). The overall cumulative incidence of CAC at 10 years after an initial diagnosis of HGD was 24.3% and after an initial diagnosis of LGD was 8.5% (P <.05). Metachronous lesions, non-polypoid lesions, and colonic stricture were associated with risk of occurrence of more-advanced lesions after LGD(P <.05). Of the 630 dysplastic lesions identified during endoscopy, 545 (86%) were removed during the same procedure or during a follow-up endoscopy or by surgery. Of 111 patients with CAC, 95 (86%) did not have prior detection of dysplasia and 64 of these 95 patients (67%) developed CAC outside of the screening or surveillance period recommended by the European Crohn's and Colitis Organisation. CONCLUSIONS: In an analysis of pathology data from 7 medical centers in Belgium, we found a low rate of detection of more-advanced lesions following detection of LGD or HGD-taking into account that most of the lesions were removed. Main risk factors for development of more-advanced lesions after LGD were metachronous lesions, non-polypoid lesions, and colon strictures.

BACKGROUND/AIMS:Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS:Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS:Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS ≥6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p = .004 and p=.04), for bleeding and ulceration/erosion than for vascular pattern at day 42 [63% and 65% vs. 33% (n=54); p<.001 for both] and at day 98 [78% and 92% vs. 56% (n = 50); p = .007 and p < .001]. Global endoscopic remission rates at day 98 were higher in patients treated with infliximab than with cyclosporine [73% vs. 25% (n = 26 and 24); p < .001]. CONCLUSION:In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial. METHODS: Patients with refractory IBS, defined as failure of >= 3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial. RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse. CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment.