Histological Healing In Ulcerative Colitis Research Articles

Comparison of diagnostic accuracy between linked color imaging and autofluorescence imaging in patients with ulcerative colitis: A prospective observational study.

Image enhancement endoscopy techniques, such as linked color imaging (LCI) and autofluorescence imaging (AFI), have shown promise in diagnosing mucosal inflammation in ulcerative colitis (UC). However, no studies have directly compared the diagnostic efficacy of LCI and AFI. This prospective observational study aimed to compare their diagnostic accuracy for histological healing in UC. This study included 81 UC patients, resulting in a total of 204 endoscopic images captured using LCI and AFI, respectively. Spearman's rank correlation coefficients assessed the correlation between LCI and AFI coloration and Geboes histopathology score (GHS). Six endoscopists, who were blinded to clinicopathological features, evaluated these images, and subsequently, the diagnostic accuracy was evaluated. Spearman's rank correlation coefficients between LCI index, AFI index (reverse gamma value), and GHS were 0.324 and -0.428, respectively (P<0.001), indicating a significant correlation between LCI and AFI coloration and histological healing. In LCI and AFI classifications, mean values for diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 76.3±2.2 versus 77.8±2.7, 91.8±4.0 versus 83.2±7.6, 53.4±10.0 versus 70.0±5.3, 74.0±3.5 versus 80.0±1.6, and 82.9±5.2 versus 75.5±7.5, respectively. No significant difference in diagnostic accuracy existed between LCI and AFI classifications. However, LCI displayed higher sensitivity than AFI while AFI showed higher specificity compared with LCI (P<0.05). LCI and AFI offer comparable diagnostic accuracy for histological healing. Clinically, it is necessary to recognize diagnostic features characterized by higher sensitivity in LCI and greater specificity in AFI.

STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD. Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale. In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth. STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.

Probe-based Confocal Laser Endomicroscopy for In Vivo Assessment of Histological Healing in Ulcerative Colitis: Development and Validation of the ENHANCE Index.

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]. 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. 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%]. 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.

Assessment of Endoscopic Healing by Using Advanced Technologies Reflects Histological Healing in Ulcerative Colitis.

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. 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. 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%. 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.

P148 Reproducibility of PICaSSO score by using narrow banding images (NBI) to assess mucosal and histological healing in ulcerative colitis (UC) patients

Abstract Background The endoscopic and histological healing are key therapeutic targets in ulcerative colitis(UC) patients. PICaSSO (Paddington International virtual ChromoendoScopy ScOre)1,2 is a new Virtual Chromoendoscopy Endoscopic (VCE) score to better define mucosal healing by mucosal and vascular features. Originally validated using iSCAN platform, the aim of this study was to evaluate the reproducibility of PICaSSO with NBI near focus platform and to assess if this could predict histological healing. Methods We prospectively studied 78 UC patients (mean age 43.4 years, 52.6% male) who underwent colonoscopy for colitis assessment or surveillance using NBI near focus (Olympus, Japan). Endoscopic activity was assessed by using ulcerative colitis Endoscopic Index of Severity (UCEIS) and PICaSSO; whilst histological activity was scored by the Robarts Histology Index (RHI). ROC curves were performed to evaluate sensitivity, specificity and accuracy of endoscopy scores to predict histological healing. Results Out of 78 patients, 47 (60.3%) were in clinical remission according to the partial Mayo score. 28(35.9%) and 32(41.0%) were in endoscopic remission according to UCEIS≤1 and PICaSSO≤3, respectively. The best cut-off of UCEIS to predict histological healing was less or equal to 1. Sensitivity, specificity and accuracy were 84.6% (95% CI 63.5, 96.4), 88.5% (95% CI 70.1, 97.8) and 87.2% (95% CI 75.6, 93.6), respectively. The Area Under the ROC curve (AUROC) was 93.3% (95% CI 88.2, 98.3). The best threshold of PICaSSO in the prediction of histological healing was less or equal to 3. PICaSSO ≤ 3 have sensitivity of 96.2% (95% CI 76.9, 100), specificity of 86.5% (95% CI 67.3, 96.2) and accuracy of 89.7% (95% CI 77.6, 96.2) to predict histological healing, estimated as RHI ≤ 3. The AUROC was 95.3% (95% CI 91.1, 99.5). Conclusion PICaSSO VCE score can be easily and accurately reproduced with NBI near focus platform and it has better operating characteristics than UCEIS to predict histological healing defined by RHI. Reference

P236 Evaluation of histological inflammation by a novel image enhanced endoscopy technique, dual red imaging, in patients with ulcerative colitis: Preliminary study

Abstract Background Endoscopic remission is the ideal treatment goal for patients with ulcerative colitis (UC) in clinical practice. However, several recent investigations tried to evaluate histological healing as a more optimal treatment goal. The assessment of histological healing, however, is usually inconvenient and time-consuming because of the requirement of a biopsy and pathological assessment. Dual red imaging (DRI; Olympus Corporation, Japan) is a novel image enhanced endoscopy technique that can visualise the inflammation, including that in the surface crypt, and vessel findings of the brownish surface or green-coloured deeper layer of the mucosa in contrast to narrow band imaging. We preliminarily evaluated the utility of DRI in the assessment of histological healing in UC as a practical approach. Methods We enrolled UC patients who provided consent from May 2018 to September 2019 in our hospital, and performed colonoscopy in the entire colon with white-light imaging and DRI, and then endoscopic pictures and biopsy samples were obtained. Central pathological assessment of histological inflammation based on the Nancy index with individual items was performed for each biopsy sample. We also assessed the clinical background, UC activity according to the Mayo score, white-light endoscopic activity according to the Mayo endoscopic subscore (MES), and DRI findings using a 5-point scale. Results We evaluated a total of 90 sets of DRI and pathological findings from 47 UC patients (20 females; median age, 42 [20–84] years; 25 with pancolitis, 17 left-sided colitis, 3 proctitis, and 2 others; median duration of disease, 83 [1–379] months; median Mayo score, 2 [0–11]). Participants were treated with 5-aminosalicylates (38 oral; 7 topical), steroid (4 systemic; 6 topical), immunomodulator (7), anti-TNF agents (5), tofacitinib (3), and tacrolimus (8). Both the MES (r = 0.70) and DRI scale (r = 0.65) correlated well with the Nancy index. Among individual pathological items with respect to inflammation, ulceration (r = 0.69), chronic inflammatory infiltrate (r = 0.66), neutrophils in the lamina propria (r = 0.65), and serrated architectural abnormalities (r = 0.60) correlated well with the Nancy index in contrast to other pathological items. DRI seemed to facilitate the visualisation of histological inflammation in deeper layers of the mucosa compared with white-light imaging or narrow-band imaging. Conclusion The novel DRI technique has potential in the evaluation of histological inflammation without the requirement of a biopsy in patients with UC as a practical approach. A further prospective multicenter study in this regard is needed.

P297 Novel serum soluble markers of histological healing in ulcerative colitis

Abstract Background The recent introduction of a commercial panel of soluble biomarkers, that can predict endoscopic healing, may support the monitoring and management of Crohn’s disease reducing the need of repeated endoscopy.1 Achieving histological remission (HR) is currently considered to be an important target in ulcerative colitis (UC).2 The aim of this study was to identify serological markers of HR in patients with UC and determine their diagnostic accuracy individually and in combination to predict HR. Methods We enrolled 40 UC patients referred to a tertiary academic centre for colonoscopy as part of standard of care. Demographic data and histologic data (RHI, Nancy) were collected. Concentrations of these biomarkers were compared with the histology at the time that the patients underwent colonoscopy with advanced enhancement technologies and targeted biopsies. Histological healing was defined as Nancy ≤1 and RHI ≤3. A total of 55 soluble analytes, relevant to inflammation or shown to be altered in IBD, were measured in serum using Procartaplex luminex assays (ThermoFisher). Finally, 24 analytes that were detected in more than 40% of patients were selected in downstream modelling and used to train a logistic regression model. Results We identified Brain-Derived Neurotrophic Factor (BDNF) and Macrophage Inflammatory Proteins (MIP-1 α) that, when combined together, showed the highest predictive power for predicting RHI≤3 and Nancy ≤ 1 with an area under the receiver operating characteristic curve (AUROC) of 0.82 (95% CI: 0.69–0.97). When we investigated analytes separately for predicting the same outcome, univariate logistic regression was significant for two other markers: Leukemia Inhibitory Factor (LIF) and Vascular Cell Adhesion Molecule 1 (sVCAM1) showing higher values associated with the lack of healing. The AUROC was 0.74 for LIF (95% CI: 0.591–0.89) and 0.72 for sVCAM1 (95% CI: 0.53–0.90). Conclusion BDNF, MIP-1α, LIF and sVCAM may be promising markers to assess histological healing in UC patients. Replication in larger cohorts of patients is now required. *OMN and LJ contributed equally. References

P227 Defining faecal calprotectin thresholds to predict endoscopic and histological healing in ulcerative colitis (UC) by using advanced optical enhancement techniques

Abstract Background Faecal calprotectin (FC) is the most common surrogate marker of mucosal healing (MH) in UC. A number of endoscopic and histologic scoring systems in UC have been developed for defining MH. We report the optimum FC thresholds for defining MH using all the assessment methods. Methods In a prospective study we collected all clinical, endoscopic and histologic data and FC from 76 UC patients (mean age 44.2y, 50.0% male) who attended endoscopy unit for colitis assessment or surveillance. Endoscopic scores were determined by the same endoscopist (MI) and included Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and PICaSSO (Paddington International virtual ChromoendoScopy ScOre). Histological activity was scored by the Robarts Histology Index (RHI) and Nancy Index by the same pathologist (DZ). Faecal calprotectin was assayed using Buhlmann faecal turbo test, particle enhanced turbidimetric immunoassay. ROC curves were performed to evaluate sensitivity, specificity and accuracy of the optimum cut-off of FC to predict endoscopic and histological healing. Results The best cut-off for FC to predict endoscopic healing calculated as Picasso≤3 was 161 μg/g with Area Under ROC curve (AUROC) of 85.3% (95% CI 76.2, 94.4). Sensitivity, specificity and accuracy were 87.9% (95% CI 57.6, 100), 76.7% (95% CI 53.5, 90.7) and 81.6% (95% CI 68.4, 89.5), respectively. While, the best threshold of FC to predict UCEIS≤1 was 148 μg/g with AUROC of 89.2 (95% CI 81.9, 96.5). Sensitivity was 93.5% (95% CI 50.5, 100), specificity 82.2% (95% CI 53.3, 91.1) and accuracy 86.8% (95% CI 69.7, 92.1). The best threshold for FC to predict MES equal to 0, was 112 μg/g, with AUROC of 89.6 μg/g, (95% CI 82.5, 96.7). Sensitivity, specificity and accuracy were 89.7%ww (95% CI 39.2, 100), 85.1% (95% CI 55.3, 93.6) and 86.9% (95% CI 68.4, 92.1), respectively. The best value of FC to predict histological healing with RHI≤3 was 112μg/g with AUROC of 88.0% (95% CI 80.6, 95.4). Sensitivity, specificity and accuracy were 88.5% (95% CI 53.8, 100), 80.0% (95% CI 62.0, 90.0) and 82.9% (95% CI 72.5, 89.5), respectively. When used Nancy≤1 FC cut-off to predict healing was 172 μg/g with AUROC of 87.1% (95% CI 78.6, 95.6). Sensitivity was 96.4% (95% CI 60.7, 100), specificity 72.9% (54.2, 85.4) and accuracy 81.6% (69.7, 89.5). Conclusion Advanced enhancement technologies can accurately define the level of FC to predict endoscopic and histological healing in UC. The optimum FC threshold for MH by PICaSSO and by Nancy was similar (161 and 172 μg/g respectively), while the FC threshold for mucosal healing by MES and by RHI was 112 μg/g. The FC threshold for determining MH in clinical practice should be lower than at least 200 μg/g.

Fecal Calprotectin Levels Predict Histological Healing in Ulcerative Colitis

Introduction: Endoscopic healing (EH) is the therapeutic target for ulcerative colitis (UC). Recent data has suggested that patients who achieve histological healing (HH) may have even better outcomes. It has been shown that fecal calprotectin (FC) levels may be utilized as a proxy for assessment of endoscopic and histological remission. Our aim was to assess the clinical utility of FC levels to predict depth of remission in UC in a real-world military population. Methods: We performed a retrospective cohort study of UC patients who underwent a full colonoscopy and had FC measured within 6 weeks prior to colonoscopy at a large military treatment facility. Clinical, endoscopic, and histologic disease activity was assessed by Patient Reported Outcomes (PRO2), Mayo Endoscopic Score (0-3), and Nancy score (0-4), respectively. Outcomes of interest included 1) Deep remission (PRO2 remission and Mayo score 0) and 2) deeper remission (deep remission plus Nancy score 0 or 1). Median FC levels were expressed in μg/g. The association of FC with outcomes of interest were compared using Mann-Whitney U tests. The diagnostic ability of FC for endoscopic and mucosal healing was analyzed using receiver operating curve (ROC) analysis. Results: In 104 patients (median age 34 years), 24% had proctitis (E1), 23% left-sided (E2), and 53% pan-colitis (E3). Higher FC levels significantly correlated with Mayo score (p<0.001) and Nancy scores (p<0.001). FC levels werelower in Mayo 0 compared to Mayo 1, 2, and 3 (20 vs. 111, 362, and 915; p<0.001). FC levels were significantly lower in Nancy 0/1 compared to Nancy 2, 3, and 4 (20/68 vs. 429, 420, and 1250, respectively; p<0.001). Patients with endoscopic remission and Nancy score ≤1 (n=22) had significantly lower FC lovels compared to those with endoscopic remission and Nancy ≥2 (48 vs. 499, p<0.0001). FC levels of ≤45 predicted deep and deeper remission (AUC = 0.87, sensitivity 85%, specificity 78%). Conclusion: FC levels significantly correlated with endoscopic mucosal and histologic activity, and reflect microscopic disease activity even in the face of macroscopic healing. We validated an FC level of ≤ 45 μg/g robustly predicted depth of remission. We suggest that FC can be used instead of colonoscopy in a treat-to-target paradigm in patients with UC.

Tu1969 - Simultaneous PET/MRI Enterography with 18F-FDG PET/MRI in Predicting Histological Healing in Ulcerative Colitis: A Prospective Segment-Based Study Using the Riley and the Nancy Index

Tu1969 - Simultaneous PET/MRI Enterography with 18F-FDG PET/MRI in Predicting Histological Healing in Ulcerative Colitis: A Prospective Segment-Based Study Using the Riley and the Nancy Index

Endocytoscopy can be used to assess histological healing in ulcerative colitis.

Background and study aim Endocytoscopy (ECS) is used in the in vivo microscopic inspection of microstructural mucosal features and enables endoscopists to assess the histological severity of ulcerative colitis (UC). The aim of this study was to assess histological healing in UC patients by using ECS. Patients and methods A total of 64 patients in clinical and endoscopic remission who underwent ECS were selected. The correlation between the ECS score and Geboes score at the rectum was evaluated in patients with a Mayo endoscopic score (MES) of 0. The diagnostic accuracy of the ECS score for histological remission (Geboes score ≤ 2) was also assessed. Results The ECS score ranged from 0 to 5 in patients with endoscopic remission on conventional white-light images (MES of 0). The agreement between histological remission regarding the ECS score and the Geboes score had a κ value of 0.72, and the ECS score showed high accuracy for histological remission, with a sensitivity of 0.77, a specificity of 0.97, and a diagnostic accuracy of 0.86. Conclusion ECS can be used to assess histological healing in patients with UC without the need for biopsy specimens.

1124 - Fecal Immunochemical Test Predicts Histological Healing in Ulcerative Colitis: A Prospective Study Using the Geboes Score and Nancy Index

1124 - Fecal Immunochemical Test Predicts Histological Healing in Ulcerative Colitis: A Prospective Study Using the Geboes Score and Nancy Index

Fecal Calprotectin Levels Predict Histological Healing in Ulcerative Colitis

Fecal Calprotectin Levels Predict Histological Healing in Ulcerative Colitis

P606. Histological healing in ulcerative colitis with mesalazine and its prognostic role

P606. Histological healing in ulcerative colitis with mesalazine and its prognostic role

P184 Mucosal healing does not correspond to histological healing in ulcerative colitis

P184 Mucosal healing does not correspond to histological healing in ulcerative colitis L. Laterza1 *, I. Scoleri1, S. Bibbo1, E. Gaetani1, G. Bruno1, L. Larosa2, A. Poscia3, A. Amato4, L.M. Minordi2, L. Bonomo2, G. Cammarota1, A. Gasbarrini1, V. Gerardi1. 1Gastroenterology Division, Catholic University of the Sacred Hearth, Rome, Italy, 2Radiology Department, Catholic University of the Sacred Hearth, Rome, Italy, 3Institute of Hygiene, Catholic University of the Sacred Hearth, Rome, Italy, 4Institute of Anestesiology, Catholic University of the Sacred Hearth, Rome, Italy

P185 Mucin 16 (MUC16) and mucin 20 (MUC20) over-expression in colonic mucosa is associated with histological remission in patients with ulcerative colitis

P184 Mucosal healing does not correspond to histological healing in ulcerative colitis L. Laterza1 *, I. Scoleri1, S. Bibbo1, E. Gaetani1, G. Bruno1, L. Larosa2, A. Poscia3, A. Amato4, L.M. Minordi2, L. Bonomo2, G. Cammarota1, A. Gasbarrini1, V. Gerardi1. 1Gastroenterology Division, Catholic University of the Sacred Hearth, Rome, Italy, 2Radiology Department, Catholic University of the Sacred Hearth, Rome, Italy, 3Institute of Hygiene, Catholic University of the Sacred Hearth, Rome, Italy, 4Institute of Anestesiology, Catholic University of the Sacred Hearth, Rome, Italy