Lesions In Inflammatory Bowel Disease Patients Research Articles

Hyper Mucinous Proliferations in the Mucosa of Patients with Inflammatory Bowel Disease: Histological Lesions with a Real Potential for Neoplastic Evolution?

Mucin disfunction is a critical event in the pathogenesis of inflammatory bowel disease (IBD). Although hyper mucinous conditions have a still debated implication in the clinical evolution of this disorder, hyper mucinous villous proliferations were found to have a preneoplastic biologic potential. We studied morphologic and immunophenotypic characteristics of these lesions in ileocolonic resections for IBD to add evidence about the evolutive potential of these lesions in samples with well oriented wall structures. Morphologic characteristics of bowel samples from 20 patients resected for IBD and with raised lesions at gross examination were studied and sections from cases with hyper mucinous lesions were stained with the following antibodies: Ki 67, p21, and p27, which were employed to evaluate the characteristics of the proliferative and differentiative activity of the epithelial structures; mismatch repair proteins and p53 have been studied as proteins implicated in carcinogenesis in IBD-affected mucosa; mucins subtypes in hyper mucinous structures were evaluated with MUC-2 and MUC-6. The results in 11 cases of saplings were that they harbored hyper mucinous proliferations. The occurrence of hyper mucinous structures was not related to dysplastic lesions, pseudo pyloric metaplasia, subtype of disease, or activity. In only one of our cases, mild cytologic atypia in the proliferative compartment was detected. Proliferation markers (Ki 67, p53) were expressed in the proliferative compartments of mucosal crypts and antiproliferative proteins p21 and p27 were expressed in differentiated epithelium. MMR proteins expression was limited to the proliferative compartment of the hyper mucinous projections. Mucin subtypes distribution was regular in the epithelium of hyper mucinous proliferations. The present monocentric retrospective study was conducted on surgical samplings with well oriented crypts. Collected data show that hyper mucinous features are frequent occurrences in raised lesions in IBD patients. In hyper mucinous proliferations of the selected cases, the status of the proliferative cycle, the expression of the proteins most frequently involved in carcinogenetic pathways of mucosa affected by IBD, and the mucins subtypes expression have no evident anomalies. Findings are not consistent with the increased risk of neoplastic evolution observed in other studies; rather, they suggest a hyperplastic nature. However, the capacity of hyper mucinous raised lesions for neoplastic evolution should be ruled out with more extensive prospective studies to identify functional defects that could explain the hypothesized neoplastic potential.

Dermal lesions associated with anti-tumor necrosis factor α therapy in patients with inflammatory bowel disease (IBD): findings from a tertiary IBD center in Poland.

There are scarce data on the occurrence of dermal lesions in patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor α (anti-TNF‑α) antibodies. Characteristics of the skin lesions, their clinical course, and impact on treatment are of high importance. The aim of this study was to assess the prevalence, risk factors, and clinical sequelae of dermal lesions in IBD patients treated with anti-TNF‑α antibodies. This retrospective, single‑center study evaluated 541 IBD patients treated with anti-TNF‑α drugs and 688 IBD individuals with no history of anti-TNF‑α treatment. Higher prevalence of dermal lesions was noted in the patients on anti-TNF‑α therapy than in the individuals not receiving such treatment (30.9% vs 16.4%; P <0.001). Risk factors for dermal lesions included higher body mass index (BMI), Crohn disease located in the small intestine, and longer duration of therapy. Some types of dermal lesions were associated with anti-TNF‑α therapy; these included infusion reactions and injection site reactions, cutaneous infection, psorasiform reactions, and lupus‑like symptoms. Overall, 5.9% of the patients on anti-TNF‑α therapy required treatment change or discontinuation due to dermal lesions (alopecia, lupus‑like symptoms, melanoma, and psoriasis). We observed a higher prevalence of dermal lesions in patients with IBD undergoing anti-TNF‑α therapy than in the treatment-naive group, although development of such lesions rarely necessitated a change in or discontinuation of treatment. Patients with IBD should regularly undergo follow-up dermatologic evaluation, which may improve detection of dermal lesions. Moreover, biologic therapy in IBD patients requires close collaboration with an experienced dermatologist.

The Feasibility, Safety, and Long-term Outcomes of Endoscopic Submucosal Dissection for Colorectal Neoplasia in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Evidence regarding the utility of endoscopic submucosal dissection (ESD) for neoplasia in patients with inflammatory bowel disease (IBD) is limited. This meta-analysis aims to understand the feasibility, safety, and long-term outcomes of ESD in IBD patients. Electronic databases were searched for observational and case-controlled studies. Primary endpoints were en bloc resection and margin-negative resection of neoplastic lesions. Secondary endpoints included procedure-related bleeding and perforation, local recurrence, and metachronous neoplasia. We analyzed 25 studies with a total of 585 neoplastic lesions in 552 patients. The rates of en bloc resection and margin-negative resection were 0.88 [95% confidence interval (CI) 0.82-0.92] and 0.78 (95% CI 0.72-0.83), respectively. Meta-regression analysis showed longer disease duration was significantly associated with the higher rate of en bloc resection. The rates of procedure-related bleeding and perforation were 0.080 (95% CI 0.057-0.11) and 0.055 (95% CI 0.038-0.081), respectively. The rates of local recurrence and metachronous neoplasia were 0.008 events/person-year (95% CI 0.002-0.013) and 0.031 event/person-year (95% CI 0.016-0.046), respectively. Meta-analysis of case-controlled studies found no significant differences in the endpoints between IBD patients treated by ESD and those treated by endoscopic mucosal resection, or non-IBD patients treated by ESD. ESD is a feasible and safe procedure to remove neoplastic lesions in IBD patients. Given there is a considerable risk of metachronous neoplasia development, postoperative surveillance colonoscopy with an appropriate consultation with surgeons is essential to monitor not only local recurrence but also neoplastic changes in the remaining colon.

Incidence of and Risk Factors for Paradoxical Psoriasis or Psoriasiform Lesions in Inflammatory Bowel Disease Patients Receiving Anti-TNF Therapy: Systematic Review With Meta-Analysis.

BackgroundParadoxical psoriasis or psoriasiform lesions induced by anti-tumor necrosis factor (anti-TNF) therapies receive increasing attention worldwide. However, no comprehensive meta-analysis investigating the incidence estimates and risk factors for anti-TNF-induced psoriasis is currently available. We aimed to precisely quantify its incidence as well as risk factors in patients with inflammatory bowel disease (IBD).MethodsThis study was registered on PROSPERO database under review registration number CRD42021233695. The electronic databases PubMed, EMBASE, and the Cochrane library were comprehensively searched for observational studies published as full-length papers in English and reporting the incidence and/or predictors for psoriasis or psoriasiform lesions in IBD patients. A random-effects meta-analysis was performed to calculate the pooled incidence. Pooled odds ratio (OR) and 95% confidence interval for potential predictors were combined using a fixed-effects or random-effects model.ResultsIn total, 30 articles comprising 24,547 IBD patients treated by anti-TNF were finally included. The overall pooled incidence of psoriasis and/or psoriasiform lesions following anti-TNF therapy was 6.0% (5.0–7.0%; I 2 = 93.9%), with 6.9% (5.1–8.7%; I 2 = 92.4%) for psoriasiform lesions and 4.6% (3.6–5.6%; I 2 = 93.9%) for psoriasis. Multivariable meta-regression analysis indicated regions and populations that significantly contributed to the heterogeneity. A statistically higher risk for psoriasis or psoriasiform lesions during anti-TNF therapy was observed in female patients (OR 1.46, 1.23–1.73), those who are at a younger age at anti-TNF initiation (OR 1.03, 1.00–1.05), smokers (OR 1.97, 1.56–2.48), ileocolonic Crohn’s disease patients (OR 1.48, 1.03–2.13), and those who are using adalimumab or certolizumab (vs. infliximab) (OR: 1.48 and 2.87 respectively).ConclusionsThe incidence of psoriasis or psoriasiform lesions was not uncommon in IBD patients following anti-TNF therapy. Female, younger age, smoker, ileocolonic Crohn’s disease, and the types of anti-TNF were significantly associated with such risk. These findings may help gastroenterologists to make more individualized decisions and understand the mechanisms of this paradoxical phenomenon.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=233695, identifier CRD42021233695.

The association of the quality of sleep with proinflammatory cytokine profile in inflammatory bowel disease patients

BackgroundThe role of circadian rhythm abnormalities in patients with inflammatory bowel disease (IBD) remains relatively unknown. The aim of this study was to identify the inflammatory cytokine profile in the IBD patients and its relationship with the quality of sleep.MethodsProspective, single-center observational cohort study was performed. In all enrolled adult IBD patients, the disease activity was assessed using Crohn’s Disease Activity Index (CDAI) for Crohn’s disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. To assess the quality of sleep, all patients were asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all enrolled patients, 15 ml venous blood was taken to determine serum inflammatory cytokine levels and perform standard laboratory tests.ResultsFifty-two IBD patients were enrolled in the study: 32 with CD and 20 with UC. The poor sleep was noted in 69.4% of patients with clinically active and in 6.3% of patients with inactive disease. In the group of IBD patients with poor sleep, the significantly higher level of serum IL-6, IL-17, and IL-23 were observed. In IBD patients with exacerbation, the significantly higher level of serum IL-6, IL-17, and IL-23 were recorded.ConclusionsThe relationship between quality of sleep and proinflammatory cytokine profile may show us a predisposition for the development of inflammatory intestinal lesions in IBD patients with sleep disturbances. This knowledge may allow the pharmacological and behavioral therapies of circadian rhythm abnormalities to become new significant targets in IBD patients.

Chromoendoscopy With Indigo Carmine vs Virtual Chromoendoscopy (iSCAN 1) for Neoplasia Screening in Patients With Inflammatory Bowel Disease: A Prospective Randomized Study.

The risk of colon cancer is greater in patients with inflammatory bowel disease (IBD) than in the general population. Chromoendoscopy with dye (CE) is the currently recommended method for detecting dysplasia in screening colonoscopies in IBD patients; however, the role of virtual chromoendoscopy (VC) is not yet well defined. The object of this study was to compare CE and VC with the iSCAN 1 system in the detection of neoplastic lesions in IBD patients. We conducted a prospective, single-center, randomized study in IBD patients who underwent a colonoscopy for colon cancer screening. A total of 129 patients were included and were randomized to undergo a CE (n = 67) or a VC (n = 62). The rates of detection of neoplastic lesions by the 2 endoscopic techniques were compared. A total of 19 neoplastic lesions (9 adenomas and 10 low-grade dysplasias [LGD]) was detected in 16 patients, 12 lesions in the CE group (17.9%), and 7 lesions in the VC group (11.3%; P = 0.2); no differences were found in the overall rate of detection of lesions (neoplastic or nonneoplastic; P = 1). The median of the total examination time and endoscope withdrawal time (minutes) was significantly lower in the VC group than in the CE group (15 vs 20 and 10 vs 14, respectively; P < 0.001). No differences occurred in the rate of detection of neoplastic lesions between CE and VC with iSCAN 1. The time spent on the technique with VC is significantly less than that with CE.

Serrated Lesions in Inflammatory Bowel Disease: Genotype-Phenotype Correlation.

Patients with inflammatory bowel disease (IBD) and hyperplastic/serrated polyposis have an increased risk of colorectal cancer. The aim of our study was to elucidate the nature of serrated lesions in IBD patients. Sixty-five lesions with serrated morphology were analyzed in 39 adult IBD patients. Lesions were classified according to the WHO 2019 criteria or regarded as reactive, and molecular analysis was performed. 82.1% of patients had ulcerative colitis, 17.9% had Crohn's disease; 51.3% were female, and the mean age was 54.5 years. The duration of IBD varied significantly (16.7 ± 11.4 years). Endoscopy showed polypoid lesions in 80.3%; the size ranged from 2 to 20 mm. A total of 21.6% of the lesions were located in the right colon. Five lesions were classified as inflammatory pseudopolyps, 28 as hyperplastic polyp, 21 and 2 as sessile serrated lesion without and with dysplasia, respectively, and 9 as traditional serrated adenoma with low-grade dysplasia. Analysis of all true serrated lesions revealed 31 mutations in KRAS and 32 in BRAF gene. No mutations were identified in inflammatory pseudopolyps. In the right colon BRAF mutations were more frequent than KRAS (16 vs 3), while KRAS mutations prevailed on the left side (28 vs 16, P < .001). One patient with traditional serrated adenomas progressed to an adenocarcinoma after 61 months. The molecular analysis could help discriminate true serrated lesions (IBD-associated or not) from reactive pseudopolyps with serrated/hyperplastic epithelial change. These should help in more accurate classification of serrated lesions.

Circadian rhythm abnormalities in patients with inflammatory bowel disease – association with adipokine profile

Background: The role of sleep disturbances in patients with inflammatory bowel disease (IBD) remained relatively unknown. The aim of this study was to identify the adipokine profile in the patients with IBD and its relationship with the circadian rhythm disorders.Methods: Prospective, observational cohort study was performed. In all the enrolled adult IBD patients, the disease activity was assessed by using Crohn’s Disease Activity Index (CDAI) for Crohn’s disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all the enrolled patients, 15 mL venous blood was taken to determine adipokine levels and perform standard laboratory tests.Results: Sixty-five IBD patients were enrolled in our study: 30 with CD and 35 with UC. Poor sleep was noted in 69.2% patients with clinically active and in 7.7% patients with inactive disease (p = .0023). In the group of IBD patients with poor sleep, the significantly higher level of serum resistin (p = .0458), and lower level of serum adiponectin and leptin (p = .0215, p = .0201; respectively) were observed. In the IBD patients with exacerbation, the significantly higher level of serum resistin (p = .0396), significantly lower serum level of leptin (p = .0453) and tendency to lower serum level of adiponectin (p = .1214) were recorded.Conclusions: The relationship between circadian rhythm abnormalities and specific adipokine profile may show us a risk factor of developing inflammatory intestinal lesions in IBD patients. This knowledge may allow the treatment of sleep disturbances, body weight-control and dietary habits become new targets in IBD therapy.

A41 LOSS OF SATB2 EXPRESSION IN COLORECTAL CANCER IS ASSOCIATED WITH DURATION OF INFLAMMATORY BOWEL DISEASE

Abstract Background Patients with inflammatory bowel disease (IBD) are at higher risk for developing colitis-associated colorectal cancer (CAC). Clinical and endoscopic features are used to stratify the risk of CAC, but new biomarkers are necessary to improve this stratification. Recent studies have shown that loss of expression of special AT-rich sequence binding protein 2 (SATB2) is frequent in CAC compared to sporadic colorectal cancer and this SATB2 status is found in pre-cancerous dysplastic lesions as well. However, the relationship of known clinical risk factors for CAC and loss of SATB2 has not been explored. Aims To assess the association of loss of SATB2 expression in CAC with clinical characteristics of IBD. Methods Patients with a known diagnosis of ileocolonic or colonic Crohn’s disease (CD), ulcerative colitis (UC), or IBD unclassified (IBDU) who underwent colectomy between October 2010 and December 2017 for CAC were included. SATB2 expression in neoplastic tissue was evaluated using immunohistochemistry (IHC), where less than 5% of tumor cells showing staining was considered loss of SATB2. Tumor grade, P53 and mismatch repair (MMR) status were assessed as well. Available clinical data such as sex, smoking status, IBD diagnosis (CD, UC or IBDU), age at IBD diagnosis, duration of IBD, extent of colitis and previous medications were collected. We used a generalized linear model to assess the association between these biomarkers and clinical data. Results A total of 58 patients with mean age at CAC diagnosis of 50.3 ±13 years, 27 (46%) females were analyzed. Mean IBD duration was 17.6 ±10 years and 22 (37.9%), 34 (58.6%) and 2 (3.4%) were CD, UC and IBDU, respectively. Thirty-two (55.2%) CACs had loss of SATB2 expression. There was no association between age at CAC diagnosis or grade of the tumor and loss of SATB2. However, longer duration of IBD (21.2 ± 9 years vs 13.7 ± 9 years, p = 0.01) was significantly associated with loss of SATB2. There was no association between SATB2 status and other explored clinical or endoscopic variables. Tumors with P53 mutation were associated with a younger age at diagnosis of CAC (47.2 ±13 vs 55.0 ±12 years, p = 0.03), but no other associations of this marker or MMR with clinical or endoscopic variables of IBD were found. Conclusions Loss of SATB2 expression is significantly associated with IBD duration, a well-known risk factor for CAC. This association with duration of IBD could denote an effect of longer chronic inflammation on SATB2 status. Given the previously reported association of loss of expression of SATB2 with pre-cancerous lesions in IBD patients, this could be a potential biomarker for risk of CAC. Funding Agencies National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

P299 A prospective randomised trial comparing dye-based chromoendoscopy with electronic virtual chromoendoscopy for detection of colonic neoplastic lesions during IBD surveillance colonoscopy

Abstract Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. Dye-based chromoendoscopy (CE) is the currently recommended method for the detection of dysplasia in IBD surveillance colonoscopy; the role of virtual chromoendoscopy (VCE) is not yet well defined. To compare CE with VCE using iSCAN1 digital image enhanced colonoscopy in the detection of colonic neoplastic lesions in IBD patients. Methods Randomised, single-centre trial to assess the detection rate of colonic neoplastic lesions in patients with long-standing IBD. Patients were randomised in two arms: dye-spraying CE using indigo carmine and electronic VCE using iSCAN1 digital image. Detection rates of dysplasia or any neoplastic lesion were compared by the two endoscopic techniques. Results A total of 129 patients were studied (67 by CE and 62 by VCE). Demographic and clinical characteristics were homogeneous in the two groups; 26 Crohn′s disease and 103 ulcerative colitis, 52% women, mean age 50 years, median duration of IBD 204 months, family history of colorectal cancer in 10 (8%), associated primary sclerosing cholangitis in 8 (6%), personal history of colorectal dysplastic lesions in 12 (9%), and more than 50% colonic involvement in 72 (56%). In total, 27 lesions (9 hyperplastic, 8 adenomatous and 10 low-grade dysplasia) were detected in 23 patients, without differences between CE and VCE arms (15 [22%] and 12 [19%] lesions, respectively; p = 0.98); on the other hand, neoplastic lesion (dysplasia or adenoma) detection rates was similar (12 [18%] in CE and 6 [10%] in VCE arms, p = 0.2). The duration of the withdrawal time of colonoscopy in minutes for patients in the CE group was median 14 min and in the VCE group was median 10 min (p &amp;lt; 0.001). Conclusion There is no statistical difference between CE and VCE using iSCAN1 in the detection rate of colonic neoplastic lesions in IBD patients. Surveillance colonoscopy with VCE (iSCAN1) spends less time than conventional CE.

A Randomized Trial Comparing High Definition Colonoscopy Alone With High Definition Dye Spraying and Electronic Virtual Chromoendoscopy for Detection of Colonic Neoplastic Lesions During IBD Surveillance Colonoscopy.

Dye spraying chromoendoscopy (DCE) is recommended for the detection of colonic neoplastic lesions in inflammatory bowel disease (IBD). The majority of neoplastic lesions are visible endoscopically and therefore targeted biopsies are appropriate for surveillance colonoscopy. To compare three different techniques for surveillance colonoscopy to detect colonic neoplastic lesions in IBD patients: high definition (HD), (DCE), or virtual chromoendoscopy (VCE) using iSCAN image enhanced colonoscopy. A randomized non-inferiority trial was conducted to determine the detection rates of neoplastic lesions in IBD patients with longstanding colitis. Patients with inactive disease were enrolled into three arms of the study. Endoscopic neoplastic lesions were classified by the Paris classification and Kudo pit pattern, then histologically classified by the Vienna classification. A total of 270 patients (55% men; age range 20-77 years, median age 49 years) were assessed by HD (n=90), VCE (n=90), or DCE (n=90). Neoplastic lesion detection rates in the VCE arm was non-inferior to the DCE arm. HD was non-inferior to either DCE or VCE for detection of all neoplastic lesions. In the lesions detected, location at right colon and the Kudo pit pattern were predictive of neoplastic lesions (OR 6.52 (1.98-22.5 and OR 21.50 (8.65-60.10), respectively). In this randomized trial, VCE or HD-WLE is not inferior to dye spraying colonoscopy for detection of colonic neoplastic lesions during surveillance colonoscopy. In fact, in this study HD-WLE alone was sufficient for detection of dysplasia, adenocarcinoma or all neoplastic lesions.

The Significance of Sessile Serrated Polyps in Inflammatory Bowel Disease.

The significance of serrated lesions in inflammatory bowel disease (IBD) remains unclear. We aim to characterize synchronous and metachronous lesions in IBD patients with an index serrated polyp and compare them to sporadic subjects with SSP. Serrated lesions in patients with IBD were identified from a pathology database and, after review, were reclassified as hyperplastic (HP), sessile serrated (SSPs), or serrated polyps unclassifiable (SPU). One hundred thirty-four IBD patients were found to have 147 serrated polyps at index colonoscopy. SSPs were more likely to be located in the right colon: SSP (76.0%), SPU (41.7%) and HP (27.8%); P = 0.002. Synchronous multifocal visible dysplasia occurred more frequently in the SSP or SPU groups (44.5% and 66%) compared to the HP group (12%); P = 0.031. Among 13 IBD patients with index SSP followed over a median of 6 years, 61.5% developed metachronous visible dysplasia or additional SSPs. Larger index SSP size was associated with higher risk of developing subsequent visible dysplasia with a 10% increase for every 1 mm increase in size (HR = 1.1; P = 0.028), but was not associated with developing subsequent SSP (P = 0.50). The risk of subsequent SSP or visible dysplasia was no different between the IBD and non-IBD groups, but there was a trend suggesting SSP may be a marker of increased early risk of metachronous visible dysplasia in IBD patients. IBD patients with an index SSP and SPU have a heightened risk of synchronous multifocal visible dysplasia. Additionally, IBD patients with SSP may be at risk of early metachronous visible dysplasia.

Serrated adenoma prevalence in inflammatory bowel disease surveillance colonoscopy, and characteristics revealed by chromoendoscopy and virtual chromoendoscopy.

Sessile or nonpolypoid neoplastic lesions, including sessile serrated adenomas (SSAs), are difficult to detect in patients with inflammatory bowel disease (IBD). To assess the prevalence and endoscopic features of SSA in IBD patients undergoing surveillance colonoscopy using novel endoscopic techniques. Histology results of biopsies from a cohort of 87 patients (47 men; median age 51.4 years; median duration of disease 16.9 years; ulcerative colitis [n=40], Crohn disease [n=43], ischemic colitis [n=4]) with longstanding colonic IBD undergoing surveillance colonoscopy were reviewed. Lesions of dysplasia (adenoma-like mass, or dysplasia-associated lesion or mass), SSAs, adenoma-like polyps, hyperplastic polyps and inflammatory polyps were identified. Surveillance colonoscopy using high-definition alone, or with iScan (Pentax, USA) dye-sprayed or virtual chromoendoscopy was performed. Lesion characteristics were described before histological diagnosis. Fourteen SSAs were detected in 87 (11%) IBD patients. The endoscopic characteristics of SSA lesions were: nonpolypoid appearance (86%), predominant localization in the proximal colon (79%), >6 mm in size (79%), cloudy cover (64%), Kudo pit pattern modified type IIO (86%) and irregular spiral vascular pattern (79%). Among the 44 SSAs and hyperplastic polyps found in the present study, the above characteristics of SSA at colonoscopy had a sensitivity of 92.86% (95% CI 66.06% to 98.8%) and specificity of 93.33% (95% CI 77.89% to 98.99%) in predicting a histological diagnosis of SSA (positive predictive value 86.67%, negative predictive value 96.55%). SSAs are a common finding at surveillance colonoscopy in IBD and have several characteristic features. Further studies are needed to evaluate the natural history of these lesions in IBD patients.

Met-enkephalins in patients with inflammatory bowel diseases

Opioid peptides provide a link between the neuroendocrine and immune systems. They modify the inflammatory process through their effect on the synthesis and secretion of cytokines and on the proliferation of leukocytes to the inflammatory lesion. The evaluation analyzed changes in free met-enkephalin concentration values in the serum and colon mucosal biopsy specimens of patients with inflammatory bowel disease (IBD). In serum and colon mucosal biopsy specimens, free met-enkephalin levels were determined in 43 patients with ulcerative colitis (UC) and 38 individuals with Crohn's disease (CD). The evaluation analyzed the effect of disease activity, inflammatory lesions of the colon and laboratory parameters, on the level of the investigated marker. The control group consisted of 45 healthy volunteers. Serum free met-enkephalin levels were depressed in patients with CD (85.4pg/ml) and UC (101.5pg/ml) as compared to the controls (119.4pg/ml). Met-enkephalin levels in colonic biopsies collected from inflammatory lesions in IBD patients were significantly higher as compared to sections without inflammatory lesions (6.59pg/mg vs. 2.89pg/mg, p < 0.01 in the CD group and 6.12pg/mg vs. 3.47pg/mg, p < 0.05 in the UC group) and their level correlated with disease activity. The present investigation is the first study that demonstrates changes in free met-enkephalin levels in IBD that may play a role in the pathogenesis and course of the disease. Further studies are necessary to assess the anti-inflammatory effect of opioid peptides.

Faecal chitinase 3-like-1: a novel biomarker of disease activity in paediatric inflammatory bowel disease

Chitinase 3-like-1 (CHI3L1) is up-regulated in the inflamed mucosa of inflammatory bowel disease (IBD). To evaluate the usefulness of a faecal CHI3L1 assay, as a reliable marker for predicting the severity of paediatric IBD. Faecal samples were obtained from ulcerative colitis (UC, n = 94), Crohn's disease (CD, n = 87), and healthy individuals (n = 56). The faecal CHI3L1 and calprotectin levels were determined by ELISA. For endoscopic evaluation, the sum of the Matts' score for UC and the simple endoscopic score for CD (SES-CD) were used. Ileal lesions were evaluated by ultrasonography. Faecal CHI3L1 levels were significantly elevated in active UC (median 366.6 ng/g, n = 44) and active CD (median 632.7 ng/g, n = 48) patients, as compared with healthy individuals (median 2.2 ng/g, n = 56). In UC patients, the faecal CHI3L1 levels were positively correlated with the sum of the Matts' score (r = 0.73, P < 0.01, n = 42). In CD patients, there was a significant correlation between faecal CHI3L1 levels and endoscopic activity as determined by the SES-CD scoring system (r = 0.61, P < 0.01, n = 25). The faecal CHI3L1 levels of patients with wall thickening of their small intestine were significantly higher than those of healthy controls or patients without wall thickening. The cutoff value of 13.7 ng/g for fecal CHI3L1(the 95th percentile of the control value) predicted active lesions in IBD patients with a sensitivity of 84.7% and a specificity of 88.9%. Faecal CHI3L1 assays may be useful for predicting the severity and activity of mucosal inflammation in IBD.

The role of the selenoprotein S (SELS) gene −105G&gt;A promoter polymorphism in inflammatory bowel disease and regulation of SELS gene expression in intestinal inflammation

Recently, a -105G>A promoter polymorphism coding for selenoprotein S (SELS) has been shown to increase proinflammatory cytokine expression. We, therefore, analyzed SELS expression and potential phenotypic consequences of the -105G>A polymorphism in patients with inflammatory bowel disease (IBD). SELS mRNA was measured by quantitative polymerase chain reaction (PCR) in intestinal epithelial cells (IEC) after stimulation with proinflammatory cytokines and in human colonic biopsies of IBD patients as well as in murine models of ileitis and murine cytomegalovirus (MCMV) colitis. Genomic DNA from 563 individuals (Crohn's disease: n = 205; ulcerative colitis: n = 154; controls: n = 204) was analyzed for the presence of the SELS-105G>A polymorphism and the three nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/caspase recruitment domain-containing protein 15 (CARD15) variants p.Arg702Trp, p.Gly908Arg and p.Leu1007fsX1008. SELS mRNA expression was increased in IEC after stimulation with proinflammatory cytokines, while its expression was not significantly altered in murine ileitis and MCMV colitis and in inflamed ileal and colonic lesions in IBD patients compared with normal controls. The SELS-105G>A polymorphism was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype or serum tumor necrosis factor alpha (TNF-alpha) levels in these patients. Medium serum TNF-alpha was 1.27 pg/ml in IBD patients, while none of the controls had TNF-alpha concentrations above the detection threshold (P < 0.0001). SELS mRNA expression is upregulated by proinflammatory cytokines in IECs but the SELS-105G>A polymorphism is not associated with IBD susceptibility and does not contribute to a certain disease phenotype or increased TNF-alpha levels in IBD patients.