A computer-aided detection system in the everyday setting of diagnostic, screening, and surveillance colonoscopy: an international, randomized trial.

BACKGROUND: Computer-aided detection (CADe) has been developed to improve detection during colonoscopy. After initial reports of high efficacy, there has been an increasing recognition of variability in the effectiveness of CADe systems. The aim of this study was to evaluate a CADe system in a varied colonoscopy population. METHODS: A multicenter, randomized trial was conducted at seven hospitals (both university and non-university) in Europe and Canada. Participants referred for diagnostic, non-immunochemical fecal occult blood test (iFOBT) screening, or surveillance colonoscopy were randomized (1:1) to undergo CADe-assisted or conventional colonoscopy by experienced endoscopists. Participants with insufficient bowel preparation were excluded from the analysis. The primary outcome was adenoma detection rate (ADR). Secondary outcomes included adenomas per colonoscopy (APC) and sessile serrated lesions (SSLs) per colonoscopy. RESULTS: 581 participants were enrolled, of whom 497 were included in the final analysis: 250 in the CADe arm and 247 in the conventional colonoscopy arm. The indication was surveillance in 202/497 colonoscopies (40.6 %), diagnostic in 199/497 (40.0 %), and non-iFOBT screening in 96/497 (19.3 %). Overall, ADR (38.4 % vs. 37.7 %; P = 0.43) and APC (0.66 vs. 0.66; P = 0.97) were similar between CADe and conventional colonoscopy. SSLs per colonoscopy was increased (0.30 vs. 0.19; P = 0.049) in the CADe arm vs. the conventional colonoscopy arm. CONCLUSIONS: In this study conducted by experienced endoscopists, CADe did not result in a statistically significant increase in ADR. However, the ADR of our control group substantially surpassed our sample size assumptions, increasing the risk of an underpowered trial.

Endoscopic powered resection device for residual colonic lesions: the first multicenter, prospective, international clinical study.

BACKGROUND AND AIMS: Endoscopic resection is standard treatment for adenomatous colorectal lesions. Depending on lesion morphology and resection technique, recurrence can occur. Scarred adenomas are challenging to resect and may require surgical management. This study evaluated the safety and effectiveness of an endoscopic powered resection (EPR) system for scarred adenomatous colorectal lesions. METHODS: This single-arm, prospective, multicenter study was conducted from January 2018 to January 2021 at 12 sites. Patients with persistent flat or sessile colorectal lesions were enrolled. Primary end points were technical success (the ability of the device to resect the lesion[s] without use of other resection devices without device-related serious adverse events [AEs]) and safety (the occurrence of AEs through 90 days). Secondary end points included endoscopic confirmation of resection completeness, occurrence of colon stenosis, disease persistence, and diagnostic value of resected specimens. RESULTS: Sixty-five patients were in the intention-to-treat/safety analysis population. Primary analysis was performed on 45 per-protocol (PP) patients with 48 lesions. All PP patients were solely treated by using the EPR device. Technical success was achieved in 44 (98%) patients. Three (5%) serious AEs occurred: 2 delayed self-limited bleeds and 1 perforation. Nonserious AEs included 4 (6%) cases of mild intraprocedural bleeding. Completeness of resection and histopathologic diagnosis of tissue specimens were achieved in all patients. Twenty-one (46.7%) patients had disease persistence after the first treatment, and there was no colon stenosis. CONCLUSIONS: EPR is safe and effective for benign, persistent, large (>20 mm), scarred colorectal adenomas and should be considered as an alternative treatment in lieu of surgery. A persistence rate of 46.7% indicates that >1 treatment is necessary for effective endoscopic treatment. (Clinical trial registration number: NCT04203667.).

Factors influencing the presence of potentially explosive gases during colonoscopy: Results of the SATISFACTION study.

This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4 . Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel-group phase II-III study investigated this issue. The phase II dose-finding part of the study evaluated H2 , CH4 , and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split-dose 2 L polyethylene glycol (PEG)-Asc preparation (2 L PEG-Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG-Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019-002856-18).

Oral mannitol for bowel preparation: a dose-finding phase II study.

BACKGROUND: Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety. AIMS: The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study. METHODS: The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH4, H2, O2), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study. RESULTS: The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations. CONCLUSIONS: The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study.

Pharmacokinetics of oral mannitol for bowel preparation for colonoscopy.

This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose-finding, international, multicenter, randomized, parallel-group, endoscopist-blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T0), 1 h (T1), 2 h (T2), 4 h (T4), and 8 h (T8) after completion of mannitol self-administration. The mean mannitol plasma concentrations (mg/ml) were dose-dependent with a consistent difference among doses. The mean maximum concentration (Cmax) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC0-∞) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in Cmax, AUC0-t8, and AUC0-∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects.

The Colon Endoscopic Bubble Scale (CEBuS): a two-phase evaluation study.

BACKGROUND: To date, no scale has been validated to assess bubbles associated with bowel preparation. This study aimed to develop and assess the reliability of a novel scale - the Colon Endoscopic Bubble Scale (CEBuS). METHODS: This was a multicenter, prospective, observational study with two online evaluation phases of 45 randomly distributed still colonoscopy images (15 per scale grade). Observers assessed images twice, 2 weeks apart, using CEBuS (CEBuS-0 - no or minimal bubbles, covering < 5 % of the surface; CEBuS-1 - bubbles covering 5 %-50 %; CEBuS-2 - bubbles covering > 50 %) and reporting the clinical action (do nothing; wash with water; wash with simethicone). RESULTS: CEBuS provided high levels of agreement both in evaluation Phase 1 (4 experts) and Phase 2 (6 experts and 13 non-experts), with almost perfect intraobserver reliability: kappa 0.82 (95 % confidence interval 0.75-0.88) and 0.86 (0.85-0.88); interobserver agreement - intraclass correlation coefficient (ICC) 0.83 (0.73-0.89) and 0.90 (0.86-0.94). Previous endoscopic experience had no influence on agreement among experts vs. non-experts: kappa 0.86 (0.80-0.91) vs. 0.87 (0.84-0.89) and ICC 0.91 (0.87-0.94) vs. 0.90 (0.86-0.94), respectively. Interobserver agreement on clinical action was ICC 0.63 (0.43-0.78) in Phase 1 and 0.77 (0.68-0.84) in Phase 2. Absolute agreement on clinical action per scale grade was 85 % (82-88) for CEBuS-0, 21 % (16-26) for CEBuS-1, and 74 % (70-78) for CEBuS-2. CONCLUSION: CEBuS proved to be a reliable instrument to standardize the evaluation of colonic bubbles during colonoscopy. Assessment in daily practice is warranted.

Novel 1-L polyethylene glycol + ascorbate versus high-volume polyethylene glycol regimen for colonoscopy cleansing: a multicenter, randomized, phase IV study.

BACKGROUND AND AIMS: Adequate bowel cleansing is critical to ensure quality and safety of a colonoscopy. A novel 1-L polyethylene glycol plus ascorbate (1L-PEG+ASC) regimen was previously validated against low-volume regimens but was never compared with high-volume regimens. METHODS: In a phase IV study, patients undergoing colonoscopy were randomized 1:1 to receive split-dose 1L PEG+ASC or a split-dose 4-L PEG-based regimen (4L-PEG) in 5 Italian centers. Preparation was assessed with the Boston Bowel Preparation Scale (BBPS) by local endoscopists and centralized reading, both blinded to the randomization arm. The primary endpoint was noninferiority of 1L-PEG+ASC in colon cleansing. Secondary endpoints were superiority of 1L-PEG+ASC, patient compliance, segmental colon cleansing, adenoma detection rate, tolerability, and safety. RESULTS: Three hundred eighty-eight patients (median age, 59.8 years) were randomized between January 2019 and October 2019: 195 to 1L-PEG+ASC and 193 to 4L-PEG. Noninferiority of 1L-PEG+ASC was demonstrated for cleansing in both the entire colon (BBPS ≥ 6: 97.9% vs 93%; relative risk [RR], 1.03; 95% confidence interval [CI], 1.001-1.04; P superiority = .027) and in the right-sided colon segment (98.4% vs 96.0%; RR, 1.02; 95% CI, .99-1.02; P noninferiority = .013). Compliance was higher with 1L-PEG+ASC than with 4L-PEG (178/192 [92.7%] vs 154/190 patients [81.1%]; RR, 1.10; 95% CI, 1.05-1.12), whereas no difference was found regarding safety (moderate/severe side effects: 20.8% vs 25.8%; P = .253). No difference in adenoma detection rate (38.8% vs 43.0%) was found. CONCLUSIONS: One-liter PEG+ASC showed noninferiority compared with 4L-PEG in achieving adequate colon cleansing and provided a higher patient compliance. No differences in tolerability and safety were detected. (Clinical trial registration number: NCT03742232.).

Leukocytes and creatinine may predict severity and guide management of ischemic colitis.

BACKGROUND: Ischemic colitis (IC) is caused by a transient hypo-perfusion of the colon leading to mucosal ulcerations, inflammation, and hemorrhage. The primary aim was to identify predictive factors of endoscopic severity of IC. Secondary endpoints were to show epidemiology, clinical presentation, endoscopic findings, and outcomes of IC. METHODS: In this single-center retrospective analysis, IC was scored according to endoscopy as: grade 1 (hyperemia, <1 cm erosions and non-confluent ulcers); grade 2 (>1 cm superficial, partially confluent ulcers); and grade 3 (deep or diffuse ulcers or necrosis). Then, IC was grouped into low- (grade 1) and high-grade (grades 2 and 3). Significant (P≤0.1) independent factor of severe IC at univariate analysis were entered into multivariate analysis and considered significant at P<0.05. RESULTS: 227 patients (male:female 60:167; mean age 72.7±16.2 years) were included. IC was scored as grade 1 in 137/227 (60.4%), grade 2 in 62/227 (27.3%), and grade 3 in 28/227 (12.3%) patients. At univariate analysis, age (74.9 vs. 71.3 years; P=0.09), diabetes (14.4% vs. 12.4%; P=0.09), and leukocytosis or creatinine elevation (74.4% vs. 60.6%; P=0.032) were associated with endoscopic high-grade IC. At multivariate analysis, leukocytosis and creatinine levels remained associated with high-grade IC (44.7% vs. 29.9%; odds ratio 1.92, 95% confidence interval 1.07-3.52; P=0.030). CONCLUSIONS: Although confounding factors cannot be excluded due to study design and patients' characteristics, leukocytosis and/or creatinine elevation at hospital admission were significantly related with endoscopic high-grade IC and might be used to stratify patients for the need of endoscopy.

Artificial Intelligence in Lower Gastrointestinal Endoscopy: The Current Status and Future Perspective.

The present manuscript aims to review the history, recent advances, evidence, and challenges of artificial intelligence (AI) in colonoscopy. Although it is mainly focused on polyp detection and characterization, it also considers other potential applications (i.e., inflammatory bowel disease) and future perspectives. Some of the most recent algorithms show promising results that are similar to human expert performance. The integration of AI in routine clinical practice will be challenging, with significant issues to overcome (i.e., regulatory, reimbursement). Medico-legal issues will also need to be addressed. With the exception of an AI system that is already available in selected countries (GI Genius; Medtronic, Minneapolis, MN, USA), the majority of the technology is still in its infancy and has not yet been proven to reach a sufficient diagnostic performance to be adopted in the clinical practice. However, larger players will enter the arena of AI in the next few months.

Endoscopic submucosal dissection: Italian national survey on current practices, training and outcomes.

BACKGROUND AND AIMS: Most of the evidence supporting endoscopic submucosal dissection (ESD) comes from Asia. European data are primarily reported by specialized referral centers and thus may not be representative of common European ESD practice. The aim of this study is to understand the current state of ESD practice across Italian endoscopy centers. METHODS: All Italian endoscopists who were known to perform ESD were invited to complete a structured questionnaire including: operator features and competencies, ESD training details and clinical outcomes over a 2-year period. RESULTS: Twenty-nine operators from 23 centers (69% response rate) completed the questionnaire: 18 (62%) were <50 years old; 7 (24%) were female; 16 (70%) were located in Northern Italy. Overall ESD volume was <40 cases in 9 (31%) operators, 40-80 in 8 (27.5%), 80-150 in 4 (13.8%) and >150 in 8 (27.5%). Colorectal ESD was predominant for operators with an experience >80 cases. En-bloc resection rates ranged from 77.2 to 97.2% depending on the anatomic location with an R0 resection rate range of 75.3-93.6%. ESD perforation rates in the colon and rectum were significantly lower when experience was >150 compared to 80-150 cases (p < 0.0001 and p = 0.006 for colon and rectum, respectively). CONCLUSION: ESD in Italy is performed by a significant number of operators. Overall, Italian endoscopists performing ESD have achieved a good competence level. However, there is much variability in training protocols, initial supervision of procedures, practice settings, case mix and procedural volume/year that are likely responsible for some of the suboptimal resectional outcomes and increased perforation risk, mainly in the colon. Standardized training programs, practice parameters and auditing of outcomes are required.

How to identify patients who are less likely to have metachronous neoplasms after a colon cancer: a predictive model.

BACKGROUND: Patients with prior colon cancer have increased risk of metachronous colorectal neoplasms; therefore, endoscopic surveillance is indicated. Current recommendations are not risk-stratified. We investigated predictive factors for colorectal neoplasms to build a model to spare colonoscopies for low-risk patients. METHODS: This was a multicenter, retrospective study including patients who underwent surgery for colon cancer in 2001 - 2008 (derivation cohort) and 2009 - 2013 (validation cohort). A predictive model for neoplasm occurrence at second surveillance colonoscopy was developed and validated. RESULTS: 421 and 203 patients were included in derivation and validation cohort, respectively. At second surveillance colonoscopy, 112 (26.6 %) and 55 (27.1 %) patients had metachronous neoplasms in derivation and validation groups; three cancers were detected in the latter. History of left-sided colon cancer (OR 1.64, 95 %CI 1.02 - 2.64), ≥ 1 advanced adenoma at index colonoscopy (OR 1.90, 95 %CI 1.05 - 3.43), and ≥ 1 adenoma at first surveillance colonoscopy (OR 2.06, 95 %CI 1.29 - 3.27) were independently predictive of metachronous colorectal neoplasms at second surveillance colonoscopy. For patients without such risk factors, diagnostic accuracy parameters were: 89.3 % (95 %CI 82.0 %-94.3 %) and 78.2 % (95 %CI 65.0 %-88.2 %) sensitivity, and 28.5 % (95 %CI 23.5 %-33.9 %) and 33.8 % (95 %CI 26.2 %-42.0 %) specificity in derivation and validation group, respectively. No cancer would be missed. CONCLUSIONS: Patients with prior left-sided colon cancer or ≥ 1 advanced adenoma at index colonoscopy or ≥ 1 adenoma at first surveillance colonoscopy had a significantly higher risk of neoplasms at second surveillance colonoscopy; patients without such factors had much lower risk and could safely skip the second surveillance colonoscopy. A prospective, multicenter validation study is needed.

Chronic atrophic gastritis: Natural history, diagnosis and therapeutic management. A position paper by the Italian Society of Hospital Gastroenterologists and Digestive Endoscopists [AIGO], the Italian Society of Digestive Endoscopy [SIED], the Italian Society of Gastroenterology [SIGE], and the Italian Society of Internal Medicine [SIMI].

Chronic atrophic gastritis (CAG) is an underdiagnosed condition characterised by translational features going beyond the strict field of gastroenterology as it may manifest itself by a variable spectrum of gastric and extra-gastric symptoms and signs. It is relatively common among older adults in different parts of the world, but large variations exist. Helicobacter pylori-related CAG [multifocal] and autoimmune CAG (corpus-restricted) are apparently two different diseases, but they display overlapping features. Patients with cobalamin and/or iron deficiency anaemia or autoimmune disorders, including autoimmune thyroiditis and type 1 diabetes mellitus, should be offered screening for CAG. Pepsinogens, gastrin-17, and anti-H. pylori antibodies serum assays seem to be reliable non-invasive screening tools for the presence of CAG, helpful to identify individuals to refer to gastroscopy with five standard gastric biopsies in order to obtain histological confirmation of diagnosis. Patients with CAG are at increased risk of developing gastric cancer, and they should be estimated with histological staging systems (OLGA or OLGIM). H. pylori eradication may be beneficial by modifying the natural history of atrophy, but not that of intestinal metaplasia. Patients with advanced stages of CAG (Stage III/IV OLGA or OLGIM) should undergo endoscopic surveillance every three years, those with autoimmune CAG every three-five years. In patients with CAG, a screening for autoimmune thyroid disease and micronutrient deficiencies, including iron and vitamin B12, should be performed. The optimal treatment for dyspeptic symptoms in patients with CAG remains to be defined. Proton pump inhibitors are not indicated in hypochlorhydric CAG patients.

Colon capsule endoscopy and its effectiveness in the diagnosis and management of colorectal neoplastic lesions.

Introduction: Colorectal cancer (CRC) represents a major cause of morbidity and mortality in Western countries. Though colonoscopy is the benchmark for CRC diagnosis and management, other alternatives have been proposed. Colon capsule endoscopy (CCE) was first introduced in 2006 as a non-invasive painless technology that utilizes an ingestible, wireless, and disposable capsule to explore the colon, without sedation or air insufflation. Areas covered: To date, the European Society of Gastrointestinal Endoscopy (ESGE) guidelines consider CCE as an option for average-risk colorectal cancer screening patients and in patients with contraindications or unwilling to undergo colonoscopy and/or with an incomplete colonoscopy. Furthermore, Japan's Pharmaceuticals and Medical Devices Agency (JPMDA) and Food and Drug Administration (FDA) approved the use of CCE in patients unwilling or unable to undergo colonoscopy. Expert commentary: CCE accuracy is nearly comparable to conventional colonoscopy for CRC and significant polyps. Moreover, in the setting of incomplete colonoscopy, CCE was demonstrated to have a higher diagnostic yield for significant polyps and to be better tolerated than CTC. However, the use of CCE is still limited. The lesson coming out is that we should explore new populations that are suitable for colon capsules and for which the colon capsule can be an advantage.

Evaluation of Clensia®, a new low-volume PEG bowel preparation in colonoscopy: Multicentre randomized controlled trial versus 4L PEG.

BACKGROUND: Success of colonoscopy is linked to the adequacy of bowel cleansing. Polyethylene glycol 4L (PEG 4L) solutions are widely used for colonic cleansing but with limitations concerning tolerability and acceptability. AIM: To demonstrate the equivalence of a new low-volume PEG containing citrates and simeticone (Clensia) versus a standard PEG 4L. METHODS: In this, multicentre, randomised, observer-blind trial, patients received either Clensia 2L or PEG 4L solution. Primary endpoint was the proportion of patients with colon cleansing evaluated as excellent or good. RESULTS: 422 patients received Clensia (n=213) or PEG 4L (n=209). Rate of excellent/good bowel cleansing was 73.6% and 72.3% in Clensia and PEG 4L group respectively. Clensia was demonstrated to be equivalent to PEG 4L. No SAEs were observed. Clensia showed better gastrointestinal tolerability (37.0% vs 25.4%). The acceptability was significantly better with Clensia in terms of proportion of subjects who felt no distress (Clensia 72.8% vs PEG 4L 63%, P=0.0314) and willingness-to-repeat (93.9% vs 82.2%, P=0.0002). The rate of optimal compliance was similar with both formulations (91.1% for Clensia vs 90.9% for PEG 4L, P=0.9388). CONCLUSIONS: The low-volume Clensia is equally effective and safe in bowel cleansing compared to the standard PEG 4L, with better gastrointestinal tolerability and acceptability.

Pre- and post-procedural quality indicators for colonoscopy: A nationwide survey.

BACKGROUND: The provision of high-quality colonoscopy can be assessed by evaluating technical aspects of the procedure and, at individual center level, by comparing structural indicators and institutional policies for managing peri-procedural issues with guideline recommendations. AIM: To assess the colonoscopy quality (CQ) in Italy at center level. METHODS: Gastroenterologists participating in a nationwide colonoscopy education initiative provided information on structural indicators of their centers and on institutional policies by answering 10 multiple-choice clinical scenarios. Practice variation across centers and compliance with guidelines were analyzed. RESULTS: Data from 282 Italian centers were evaluated. Overall, a significant proportion of centers did not meet CQ standards as concerns endoscopy facilities and equipments (e.g., dedicated recovery room, dirty-to-clean path, reporting software). CQ assurance programs were implemented in only 25% of centers. Concerning peri-procedural issues, main discrepancies with guidelines were recorded in the underuse of split-dose preparation (routinely adopted by 18% of centers), the routine request of coagulation tests prior to colonoscopy (30%), the routine interruption of aspirin for polypectomy (18%), and the adoption of 3-year surveillance for low-risk adenoma (49%). CONCLUSIONS: Present survey shows a significant variation in the CQ of endoscopy centers in Italy on many items of colonoscopy practice that should be targeted for future interventions.

Linking estrogen receptor ß expression with inflammatory bowel disease activity.

Crohn disease (CD) and ulcerative colitis (UC) are chronic forms of inflammatory bowel disease (IBD) whose pathogenesis is only poorly understood. Estrogens have a complex role in inflammation and growing evidence suggests that these hormones may impact IBD pathogenesis. Here, we demonstrated a significant reduction (p < 0.05) of estrogen receptor (ER)ß expression in peripheral blood T lymphocytes from CD/UC patients with active disease (n = 27) as compared to those in remission (n = 21) and healthy controls (n = 29). Accordingly, in a subgroup of CD/UC patients undergoing to anti-TNF-α therapy and responsive to treatment, ERß expression was higher (p < 0.01) than that observed in not responsive patients and comparable to that of control subjects. Notably, ERß expression was markedly decreased in colonic mucosa of CD/UC patients with active disease, reflecting the alterations observed in peripheral blood T cells. ERß expression inversely correlated with interleukin (IL)-6 serum levels and exogenous exposure of both T lymphocytes and intestinal epithelial cells to this cytokine resulted in ERß downregulation. These results demonstrate that the ER profile is altered in active IBD patients at both mucosal and systemic levels, at least in part due to IL-6 dysregulation, and highlight the potential exploitation of T cell-associated ERß as a biomarker of endoscopic disease activity.