Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission

BackgroundIt has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission.MethodsPatients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005–2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated.ResultsOne hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15–56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P = 0.048) or together with a past flare within the previous 12 months (P = 0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR = 7.5; IC95%; 1.8–29.9; P = 0.005).ConclusionsIn UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse.     

Correlation of endoscopic disease severity with pediatric ulcerative colitis activity index score in children and young adults with ulcerative colitis

AIM To investigate of pediatric ulcerative colitis activity index(PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity(Mayo endoscopic score).METHODS We reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d(either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions(such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayoendoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo score was assessed.RESULTS We identified 99 patients(53% female, 74% pancolitis) that met inclusion criteria. The indications for colonoscopy included ongoing disease activity(62%), consideration of medication change(10%), assessment of medication efficacy(14%), and cancer screening(14%). Based on PUCAI scores, 33% of patients were in remission, 39% had mild disease, 23% had moderate disease, and 4% had severe disease. There was "moderate-substantial" agreement between the two reviewers in assessing rectal Mayo scores(kappa = 0.54, 95%CI: 0.41-0.68). CONCLUSION Endoscopic disease severity(Mayo score) assessed by reviewing photographs of pediatric colonoscopy has moderate inter-rater reliability, and agreement was less robust in assessing patients with mild disease activity. Endoscopic disease severity generally correlates with clinical disease severity as measured by PUCAI score. However, children with inflamed colons can have significant variation in their reported clinical symptoms. Thus, assessment of both clinical symptoms and endoscopic disease severity may be required in future clinical studies.     

Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis

Proinflammatory cytokines are believed to be involved in the pathogenesis of ulcerative colitis (UC). The aim of this study was to clarify the profiles of proinflammatory cytokine production in patients with UC in terms of disease intractability, endoscopic findings, and host response to lipopolysaccharide (LPS) stimulation. Colonic mucosal tissues were obtained from patients with active UC (n = 15, including 4 patients with intractable disease) and inactive UC (n = 7), non-inflammatory bowel disease (IBD) colitis (n = 11), and controls (n = 20). Organ culture was performed, and the amounts of four cytokines (described below) in the culture media were determined by enzyme-linked immunosorbent assay (ELISA). LPS stimulation enhanced interleukin (IL)-1β, IL-8, and IL-6 production in colonic specimens from all groups, but enhanced tumor necrosis factor (TNF)-α production only in active UC specimens. Levels of IL-6, IL-8, and TNF-α were significantly higher in active UC than in non-IBD colitis, and the production of all three of these cytokines was correlated to the endoscopic grade of inflammation. The production of these cytokines was also significantly higher in patients with intractable disease receiving corticosteroids than in patients with non-intractable disease receiving corticosteroids. These results suggest that enhanced production of mucosal proinflammatory cytokines may be implicated in the pathogenesis of UC. (Received Jan. 30, 1998; accepted Aug. 28, 1998)     

Health-related quality of life correlates with clinical and endoscopic activity indexes but not with demographic features in patients with ulcerative colitis

BACKGROUND: Inflammatory bowel disease (IBD) impairs health-related quality of life (HRQOL). Our aim was to investigate whether the improvement in the Clinical Activity Index (CAI) and Endoscopic Activity Index (EAI) is significantly correlated with the advancement of HRQOL and its dimensions in ulcerative colitis (UC) and to assess whether demographic and disease-related factors influence patients' experience of HRQOL. This examination was performed in the context of our recently published study of the anti-inflammatory effect of phosphatidylcholine in UC. METHODS: Sixty patients with chronic active UC were treated with phosphatidylcholine or placebo over 3 months. They were asked to complete the Inflammatory Bowel Disease Questionnaire-Deutschland (IBDQ-D) before and after the study. The correlations between CAI and EAI and IBDQ-D scores were calculated. Demographic and disease-related factors were obtained. RESULTS: A statistically significant lowering of CAI and EAI after treatment in the phosphatidylcholine group led to a statistically significant improvement in HRQOL (r = -0.623, P = 0.0003 for CAI; r = -0.511, P = 0.005 for EAI). Constant disease activity indexes in the placebo group accompanied constant HRQOL (r = -0.747, P < 0.0001 for CAI; r = -0.634, P = 0.0002 for EAI). Furthermore, besides a few exceptions, significant correlations between CAI and EAI and the 4 dimensions of the IBDQ-D could be shown. Demographic parameters did not significantly influence the IBDQ-D scores. CONCLUSIONS: This study points out the strong relationship between CAI and EAI and all domains of HRQOL in patients with UC. Therefore, the IBDQ-D is a valid and reliable assessment tool that reflects changes in the health status of UC patients. It is a useful measure of therapeutic efficacy and should be used in clinical trials in IBD.     

Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity

Interaction of the receptor for advanced glycation endproducts (RAGE) with its ligands results in expression of inflammatory mediators, activation of NF-κB, and induction of oxidative stress, all of which have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Soluble receptor for advanced glycation endproducts (sRAGE) has recently emerged as a reliable biomarker of inflammation in numerous RAGE-mediated disorders.

Objective

To assess sRAGE levels in adult patients with IBD.

Method

Serum was collected from adult patients with Crohn's disease (CD, 56 patients), ulcerative colitis (UC, 60 patients), and healthy controls (HC, 113 subjects). Levels of sRAGE were determined by enzyme-linked immunosorbent assay.

Results

Serum sRAGE levels were elevated in IBD compared to HC and were higher in UC patients compared to CD and HC. Levels of sRAGE were significantly higher in the serum of UC patients with active disease compared to patients with inactive disease, but no association with the Montreal Classification was evident. Serum sRAGE was lower in CD patients with biological therapies.

Conclusions

These findings suggest that serum levels of sRAGE are altered in patients with intestinal inflammation and may reflect distinct immunoinflammatory pathogenesis of UC and CD.     

118例溃疡性结肠炎临床、内镜与直肠动力分析

目的了解溃疡性结肠炎(UC)的临床、内镜和直肠动力特点。方法分析1982年2002年我院确诊118倒UC的临床、内镜、直肠动力特点。结果①UC症状以腹泻、粘液、粘液血便、腹痛为主,肠外表现少见;病程通常较短;病变范围以左半结肠为主;IgG、IgM升高;②肠镜下充血水肿最多见,其次是糜烂、溃疡;③腹压增加时肛门内外括约肌净增压降低(P<0.05),直肠最低敏感量、最大耐受性、最大顺应性明显降低(P<0.01);④大多数患者以柳氮磺胺吡啶治疗有效。结论了解UC的临床、内镜和直肠动力特点,有助于理解UC的发病规律、病理生理和更有效地治疗该病。     

Diagnosis of ulcerative colitis in endoscopic biopsies

Accurate diagnosis of "colitis", and hence the appropriate therapy, can be a big problem. Routine microscopy of endoscopic biopsies remains very important. Yet a biopsy diagnosis may also be difficult, and its accuracy depends upon the criteria used. The major parameters for the diagnosis of ulcerative colitis are reviewed.     

Factors affecting clinical and endoscopic efficacies of selective leucocytapheresis for ulcerative colitis

BackgroundGranulocyte, monocyte/macrophage adsorptive apheresis is a novel treatment for active ulcerative colitis. However, as yet no study has reported on a subset of patients who might respond well to granulocyte, monocyte/macrophage adsorptive apheresis therapy.AimTo identify factors affecting clinical and endoscopic efficacies of granulocyte, monocyte/macrophage in patients with ulcerative colitis.MethodsFifty consecutive patients with active ulcerative colitis initially received five granulocyte, monocyte/macrophage adsorptive apheresis sessions with the Adacolumn over five consecutive weeks. Patients who improved without achieving remission received five additional granulocyte, monocyte/macrophage adsorptive apheresis sessions.ResultsOne week after the last granulocyte, monocyte/macrophage adsorptive apheresis session, 26 (52%) and 17 patients (34%) achieved clinical and endoscopic remission, respectively. In the multivariate analysis, the dose of prednisolone administered at entry and the cumulative dose of prednisolone administered before entry were independent significant factors for both clinical and endoscopic remission, negatively impacted the efficacy of granulocyte, monocyte/macrophage adsorptive apheresis. Age, gender, duration of ulcerative colitis, number of prior relapses, duration of current exacerbation, extent and severity of ulcerative colitis, extra-intestinal manifestations, entry haematology values and C-reactive protein did not affect the outcome.ConclusionsBased on the outcomes of this study, it appears that steroid-naïve patients and patients on low dose steroid and short duration of exposure respond to granulocyte, monocyte/macrophage adsorptive apheresis. Further studies in larger cohorts of patients should strengthen our findings.     

Infliximab induces clinical, endoscopic and histological responses in refractory ulcerative colitis.

BACKGROUND: infliximab is a monoclonal antiTNF-ct antibody that has repeatedly shown to be effective in the management of Crohn's disease. However, data are scarce about its efficacy in ulcerative colitis. AIM: to describe the joint experience of three Spanish hospitals in the use of infliximab in patients with active refractory ulcerative colitis. PATIENTS AND METHODS: we present seven cases of ulcerative colitis (6 with chronic active disease despite immunosuppressive therapy, and one with acute steroid-refractory ulcerative colitis) treated with infliximab 5 mg/kg of body weight. Clinical response was evaluated by means of the Clinical Activity Index at 2, 4 and 8 weeks after initial infusion. Biochemical (erythrocyte sedimentation rate and C-reactive protein), endoscopic, and histological changes were also assessed. RESULTS: mean age of patients was 45.8 +/- 17 years (range 23-77); 4 were female. No adverse effects were recorded. Inflammatory activity diminished significantly in 6 of 7 patients (85.7%; CI 95%: 42-99%) both from a clinical (p = 0.01) and biochemical (p <0.05) point of view. Five out of six patients (83.3%; 36-99%) with corticosteroid-dependent disease could be successfully weaned off these drugs. Five patients were endoscopicly controlled both before and after therapy, and a positive endoscopic and histological response could be recorded in all of them. CONCLUSION: infliximab may be an effective and safe therapy for some patients with ulcerative colitis refractory to other forms of therapy, although controlled studies are needed to assess its role in the general management of this disease.     

Reticulated platelet levels in patients with ulcerative colitis

Background and aims In this study, we investigated whether reticulated platelets (RP) would be useful markers in the evaluation of ulcerative colitis (UC) activity and also aimed to gain indirect information about the platelet kinetics. Materials and methods Complete blood count, C-reactive protein, erythrocyte sedimentation rate, and proportion of RP were measured in 16 active, 21 inactive UC patients, and 20 healthy blood donors. UC activity was assessed by Truelove–Witts criteria. Results Mean platelet count was increased in patients with active compared to inactive UC (p = 0.008) or healthy donors (p = 0.000). Mean platelet volume (MPV) was significantly decreased in patients with active compared to inactive (p = 0.015) and healthy donors (p = 0.001). RP values was significantly decreased in active and inactive UC groups compared to healthy donors (p = 0.000, p = 0.000, respectively), while there was no significant difference between active and inactive UC patients (p = 0.980). Significant negative correlation between platelet count and MPV in patients with active UC (r = −0.542, p = 0.030) was observed. Conclusions RP values is reduced in active and inactive UC patients compared to healthy donors. To our knowledge, this is the first study about proportion of RP with UC in literature. However, the role of low RP values have not been determined clinically. Further studies are needed to evaluate the role of platelet abnormalities and changes in megakaryopoiesis caused by inflammatory state on low MPV and RP values during the course of UC.     

Serum proinflammatory cytokines and adhesion molecules in ulcerative colitis

BACKGROUND/AIMS: The aim of this study was to define the correlation between serum markers, such as proinflammatory cytokines and adhesion molecules, and disease activity in ulcerative colitis (UC). METHODOLOGY: Nineteen patients with UC treated in our hospital from April 2003 to June 2004, were enrolled into this study. We measured serum interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule (VCAM-1) from a blood sample. We investigated the correlation between these cytokine molecules and clinical activity. RESULTS: Serum levels of IL-6 after treatment were significantly decreased proportionately as disease activity improved. Serum levels of IL-8 also significantly correlated with disease activity. On the other hand, serum levels of TNF-alpha were within the normal range in most of cases despite being in the active phase. There were also no significant differences between before and after treatment in serum levels of ICAM-1 or VCAM-1. CONCLUSIONS: Serum IL-6 and IL-8 significantly reflected disease activity in patients with UC.