Deep Learning Algorithm for Diagnose Endoscopic and Histological Images With Ulcerative Colitis

The goal of treatment for ulcerative colitis is to achieve histological and endoscopic remission. Aiming at the problem that the observer will be affected by subjective factors in the endoscopic evaluation of ulcerative colitis and the cumbersome diagnosis process of histological images, this paper aims to develop a computer-assisted diagnosis system for real-time, objective diagnosis of endoscopic images and use the trained CNN model to predict histological images of patients with ulcerative colitis. Diagnosing endoscopic remission of ulcerative colitis, the accuracy of the CNN is 97.04% (95% CI,96.26%:97.62%). Diagnosing the severity of endoscopic inflammation in patients with ulcerative colitis, the accuracy of the CNN is 90.15% (95% CI, 89.49%:90.82%). The accuracy of predicting histological remission was 91.28%. The kappa coefficient between the CNN model and the biopsy results was 82.56%. The proposed computer-aided diagnosis system can effectively evaluate the inflammation of endoscopic images of patients with ulcerative colitis and predict the remission of histological images with high accuracy and consistency.

Treatment Targets in Ulcerative Colitis: Is It Time for All In, including Histology?

The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.

Pediatric eosinophilic esophagitis: a review for the clinician

Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms.EoE can occur at any age and has different clinical manifestations depending on the age onset.To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis.According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis.A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment.This review will provide a practical guide to assist pediatricians treating children with EoE.Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.

Analysis of Endoscopic Evaluation Reliability for Ulcerative Colitis in Histological Remission

The Mayo endoscopic subscore (MES) is a major endoscopic scoring system used to assign a status of mucosal inflammation and disease activity to patients with ulcerative colitis (UC). Using interobserver reliability (IOR), this study clarified the difficulties for endoscopic observers imposed by MES parameters used for the endoscopic evaluation of UC in histological remission. First, 42 endoscopists of four observer groups examined each MES parameter, which were evaluated from endoscopically obtained images of 100 cases as Grade 0 or 1 of the Nancy histological index of histopathological inflammation. Then, IOR was assessed using multiple κ statistics for each finding of MES. The results showed that IOR among all the observers was slight or fair for all the parameters, indicating a low IOR. The experts of the UC practice group had “moderate” or higher IOR for seven of the nine parameters, whereas “slight” or “fair” results were found for all parameters by the trainee group. The IOR for each MES parameter was calculated separately for the observer groups. All the groups showed “slight” or “fair” for “Erythema” and “Decreased vascular pattern”. Large differences between the endoscopists were found in the IOR for the MES parameters in UC in histological remission. Even among UC practice experts, the IOR was low for “Erythema” and “Decreased vascular pattern”.

Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls

Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.

Is histological remission of ulcerative colitis achievable?

Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.

Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis—An Exploratory Study to Define Deep Remission

Background Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores. Methods Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI). Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways. Results Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51–0.98) and NHI (r = 0.86; 95% CI, 0.42–0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27–0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa. Conclusions Endocytoscopy represents an interesting tool that may sit between endoscopy and histology—but closer to the latter—identifying gene expression markers and pathways that are also identified by histology.

P151 Validation of the MaRIA Score in pediatric patients

Background To validate the Magnetic Resonance Index of Activity (MaRIA Score) in the pediatric population and determine if it would be possible to monitor inflammatory bowel disease (IBD) without invasive tests in some cases. Methods A cross-sectional and descriptive study of paediatric patients with previously diagnosed or suspected IBD who underwent upper endoscopy (EGD) and colonoscopy, blood tests, stool analysis and MR Enterography (MRE) in a 15 days range, from October 2018 to February 2020. The clinical and endoscopic situation were assessed with the activity indices PUCAI/PCDAI/shPCDAI and the activity scores UCEIS/Mayo/SES-CD respectively, according to the underlying pathologies. We considered analytical remission as FC< 250 mcg/g, ERS< 20 mm and CRP< 1 mg/dl. The MRE results were assessed with the MaRIA Score, that is validated for adults. Results Amongst 21 patients, 12 (57%) were males. 12 patients had Crohn ́s disease (CD) (57%), 3 had ulcerative colitis (UC) (14%), 6 had IBD unclassified (IBDu) (28%). The mean age at diagnosis was 14.2 ± 0.7 and the progression time of the disease was 3.9 ± 0.6 years. A total of 16 patients showed clinical remission (76%), 6 of them (28%) also had endoscopic and histological remission. Eight patients were receiving biological treatment (38%). The measured acute phase reactants (APR) were: CRP 0.9 ± 0.5 mg/dl, ESR 13.7 ± 2.6 mm, α1 acid glycoprotein 95.5 ± 1.1 mg/dl and fecal calprotectin (FC) of 1154.3 ± 254.8 mcg/g. Rotavirus, adenovirus, Clostridium difficile toxin analysis and stool culture were performed in 14 patients, all of them negative. The MaRIA Score values were 54.3 ± 53.3, being 0 in 11 cases. We found no differences between the MaRIA Score and the analytical remission. We found a significant correlation between the MaRIA Score and the PUCAI value (p < 0.05), but not with other clinical scores. Patients in clinical remission showed a tendency to have a lower MaRIA Scores, but these differences were not statistically significant (p = 0.09). The MaRIA Score showed lower values for those with endoscopic and histological remission (p < 0.05), All the patients with MaRIA Score> 0 were CD except one, diagnosed with UC. Out of the 15 patients with endoscopic/histological involvement, 10 presented a MaRIA Score> 0. Five of the 11 patients (45%) in whom the MaRIA Score was 0 did not have endoscopic and histological remission, only one of them had a diagnosis of CD. Conclusion The MaRIA Score was significantly correlated with endoscopic scores in pediatric IBD patients, especially in CD. However, based on the results of this study, the MRE should not replace the EGD and colonoscopy in order to thoroughly evaluate the disease activity.