胶囊结肠镜的临床应用

胶囊结肠镜（CCE）是一种检查结肠黏膜病变的新型胶囊内镜。最初用于结肠癌的筛查,目前逐渐用于炎症性肠病,尤其是溃疡性结肠炎的诊断和病情评估。CCE在临床应用方面与传统结肠镜相比各有优劣。本文就CCE的临床应用现状作一综述。     

白细胞介素-25在炎症性肠病患者中的表达及临床意义

目的 通过检测白细胞介素(IL)-25在炎症性肠病(IBD)患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义.方法 收集12例溃疡性结肠炎(UC)患者、16例克罗恩病(CD)患者及13例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-25 mRNA的表达情况,免疫组化技术分析IL-25在肠黏膜中的原位表达;同期收集20例UC、24例CD患者及20名健康对照者血清标本,采用酶联免疫吸附测定(ELISA)检测血清中IL-25水平.结果 与健康对照组相比,UC及CD患者肠黏膜组织内IL-25 mRNA表达显著降低(P＜0.05),UC及CD组间的表达量差异无统计学意义(P＞0.05).免疫组化分析显示IL-25阳性细胞在正常肠黏膜固有层内有较多表达,同时黏膜内的肠上皮细胞也存在IL-25低表达,UC及CD患者肠黏膜IL-25蛋白表达量显著降低(P＜0.05),UC及CD组间的表达量差异无统计学意义(P＞0.05).ELISA显示UC及CD患者血清中IL-25表达量显著低于健康对照组(P＜0.05).结论 IL-25在IBD患者肠黏膜及血清中表达显著降低,提示IL-25表达缺陷与IBD的发生发展密切相关,IL-25有可能成为IBD治疗的新靶点.     

骨桥蛋白在炎症性肠病患者结肠组织中的表达

背景：骨桥蛋白（OPN）是一种分泌型磷酸化糖蛋白,参与细胞信号转导,促进细胞黏附和迁移。近年研究发现炎症性肠病（IBD）患者血浆OPN水平升高,患者结肠黏膜中可检出OPN表达。目的：了解OPN在IBD患者结肠黏膜组织中的表达情况,探讨其在IBD发病机制中的作用。方法：以免疫组化半定量方法检测53例溃疡性结肠炎（UC）、62例克罗恩病（CD）和15例源自结肠腺瘤患者的正常结肠组织标本中OPN的表达。结果：OPN广泛表达于结肠黏膜上皮细胞和固有层渗出细胞。UC组和CD组结肠上皮细胞的OPN平均光密度值显著低于对照组（11．84±0．98和10．04±1．37对12．64±1．45,P〈0．05）,结肠黏膜固有层渗出细胞的OPN阳性细胞百分率则显著高于对照组（20．31％±4．50％和12．69％±3．06％对3．85％±0．66％,P〈0．001）。UC和CD患者的病情严重程度与结肠上皮细胞和固有层渗出细胞中的OPN表达量均无相关性。结论：OPN在IBD患者结肠黏膜上皮和同有层中的表达不一致,结肠上皮细胞中OPN表达下调可能与肠黏膜屏障功能受损有关,而黏膜固有层渗出细胞中OPN表达上调可能与免疫反应有关。     

Applications of Colon Capsule Endoscopy

Purpose of Review

This is a review of colon capsule endoscopy (CCE) with a focus on its recent developments, technological improvements, and current and potential future indications.

Recent Findings

Based on the current literature, CCE II demonstrates comparable polyp detection rates as optical colonoscopy and CT colonography, and improved cost-effectiveness. The main limitation to patient acceptance is the requirement of a rigorous bowel preparation. Preliminary studies show good correlation between CCE and optical colonoscopy for assessment of colonic disease activity in inflammatory bowel disease (IBD).

Summary

CCE II is currently FDA, approved as an adjunctive test in patients with prior incomplete colonoscopy, and in the evaluation of patients with suspected lower gastrointestinal bleeding. The test is approved in Europe as one of the options for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy. CCE has a potential role in the evaluation and monitoring of colonic disease activity in IBD. Future technological advances should focus on minimizing bowel preparation, improvement in reading times, and development of therapeutic capabilities.? With technological improvements, the second-generation colon capsule has a significantly higher sensitivity than the first-generation capsule for detection of colon polyps.? Colon capsule endoscopy has been approved in Europe as an option for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy.? Colon capsule endoscopy has received FDA approval as an option for colorectal cancer screening in patients with prior incomplete colonoscopy, and in evaluation of patients with suspected lower gastrointestinal bleeding.? Colon capsule endoscopy may have a role in evaluation and monitoring of inflammatory bowel disease.? Colon capsule endoscopy currently requires a bowel preparation that is more rigorous than colonoscopy.

     

Reduced hydrophobicity of the colonic mucosal surface in ulcerative colitis as a hint at a physicochemical barrier defect

Purpose

There is increasing evidence that a defect of the gastrointestinal mucosal barrier is important for the development of inflammatory bowel diseases (IBD). The hydrophobicity of the colonic mucosal surface is a measure of its resistance to luminal antigens, e.g. of bacterial origin. Therefore, the purpose of this study was to determine this parameter in patients suffering from IBD.

Methods

Nineteen patients with ulcerative colitis (UC), ten patients with Crohn??s disease (CD) and 20 controls were examined. All underwent colonic surgery at the University Hospital Heidelberg. Clinical disease activity was determined. From every subject, colonic tissue specimens were obtained, and hydrophobicity of the mucosal surface was determined with a goniometer by multiple plateau contact angle measurements. Histological evaluation of disease activity was performed in directly adjacent tissue specimens.

Results

Hydrophobicity of the colonic mucosal surface, expressed as plateau contact angles, was significantly reduced in patients with UC (mean?±?SEM, 47.8°?±?3.4°) compared to those with CD (72.0°?±?5.2°) and controls (72.5°?±?5.6°; over-all P?=?0.0004; UC versus controls, P?P?P?>?0.05). Between mucosal hydrophobicity and clinical disease activity, as well as mucosal hydrophobicity and histological disease activity, no significant correlation was found.

Conclusions

The results suggest a defective physicochemical barrier as an essential factor in the pathogenesis of UC, but not CD. The fact that no correlation was found between mucosal hydrophobicity and disease activity may indicate that the loss of mucosal hydrophobicity in UC is not exclusively a secondary effect due to inflammation.     

Endoscopy in inflammatory bowel disease when and why

Endoscopy plays an important role in the diagnosis and management of inflammatory bowel disease(IBD).It is useful to exclude other aetiologies,differentiate between ulcerative colitis(UC) and Crohn’s disease(CD),and define the extent and activity of inflammation.Ileocolonoscopy is used for monitoring of the disease,which in turn helps to optimize the management.It plays a key role in the surveillance of UC for dysplasia or neoplasia and assessment of post operative CD.Capsule endoscopy and double balloon enteroscopy are increasingly used in patients with CD.Therapeutic applications relate to stricture dilatation and dysplasia resection.The endoscopist’s role is vital in the overall management of IBD.     

Mucosal and Invading Bacteria in Patients with Inflammatory Bowel Disease Compared with Controls

Background: Endogenous intestinal bacteria and/or specific bacterial pathogens are suspected of being involved in the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was to investigate IBD tissues for different bacterial population groups harbouring the mucosal surface and/or invading the mucosa. Methods: Tissue sections from surgical resections from the terminal ileum and/or the colon from 24 IBD patients (12 active ulcerative colitis (UC), 12 active Crohn disease (CD)) and 14 non-IBD controls were studied by fluorescent in situ hybridization on a quantifiable basis. Results: More bacteria were detected on the mucosal surface of IBD patients than on those of non-IBD controls ( P < 0.05). Bacterial invasion of the mucosa was evident in 83.3% of colonic specimens from the UC patients, in 55.6% of the ileal and in 25% of the colonic specimens from the CD patients, but no bacteria were detected in the tissues of the controls. Colonic UC specimens were colonized by a variety of organisms, such as bacteria belonging to the gamma subdivision of Proteobacteria , the Enterobacteriaceae , the Bacteroides/Prevotella cluster, the Clostridium histolyticum/Clostridium lituseburense group, the Clostridium coccoides/Eubacterium rectale group, high G + C Gram-positive bacteria, or sulphate-reducing bacteria, while CD samples harboured mainly bacteria belonging to the former three groups. Conclusion: Pathogenic events in CD and UC may be associated with different alterations in the mucosal flora of the ileum and colon.     

Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls

BACKGROUND: Endogenous intestinal bacteria and/or specific bacterial pathogens are suspected of being involved in the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was to investigate IBD tissues for different bacterial population groups harbouring the mucosal surface and/or invading the mucosa. METHODS: Tissue sections from surgical resections from the terminal ileum and/or the colon from 24 IBD patients (12 active ulcerative colitis (UC), 12 active Crohn disease (CD)) and 14 non-IBD controls were studied by fluorescent in situ hybridization on a quantifiable basis. RESULTS: More bacteria were detected on the mucosal surface of IBD patients than on those of non-IBD controls (P < 0.05). Bacterial invasion of the mucosa was evident in 83.3% of colonic specimens from the UC patients, in 55.6% of the ileal and in 25% of the colonic specimens from the CD patients, but no bacteria were detected in the tissues of the controls. Colonic UC specimens were colonized by a variety of organisms, such as bacteria belonging to the gamma subdivision of Proteobacteria, the Enterobacteriaceae, the Bacteroides/Prevotella cluster, the Clostridium histolyticum/Clostridium lituseburense group, the Clostridium coccoides/Eubacterium rectale group, high G + C Gram-positive bacteria, or sulphate-reducing bacteria, while CD samples harboured mainly bacteria belonging to the former three groups. CONCLUSION: Pathogenic events in CD and UC may be associated with different alterations in the mucosal flora of the ileum and colon.     

Neurologic manifestations in inflammatory bowel diseases: Current knowledge and novel insights

BackgroundCrohn's disease (CD) and ulcerative colitis (UC), widely known as inflammatory bowel diseases (IBD), are thought to result from an inappropriate activation of the mucosal immune system driven by intestinal bacterial flora.MethodsAlthough the extraintestinal manifestations of IBD are well documented, the association of IBD with neurologic and neuromuscular involvement is rare and often controversial, with sporadic and conflicting data on its prevalence and spectrum. In addition, a serious number of the latter manifestations may become life-threatening, playing a very important role in disease morbidity. To define the pattern of neurologic involvement in IBD, the most important manifestations in these patients have been reviewed, exploring also their clinical significance.ResultsThere is evidence that UC and CD can manifest both in the PNS and CNS. Thrombotic complications are common in IBD patients, but cerebral vascular involvement is rare.ConclusionsNeurologic manifestations in IBD patients are more common than previously estimated and may follow a different pattern of involvement in CD and UC. Small numbers of patients currently preclude a better characterization of the clinical spectrum and a better understanding of pathogenesis.     

TNF-α在IBD发病机制中的调节

炎症性肠病（inflammatory bowel disease,IBD）是一种病因不明的肠道非特异性炎症性疾病,包括溃疡性结肠炎和克罗恩病,它们有各自的临床特征,内镜表现和组织学可区分;有学者认为它们是同一疾病的两个不同的阶段。在免疫应答中,TNF-α（TNF核心家族成员之一）作为细胞增殖和凋亡的主要促炎因子,在IBD的发病机制中起重要的调节作用。     

G protein-coupled receptor 55 (GPR55) expresses differently in patients with Crohn’s disease and ulcerative colitis

Aim: To investigate the levels of G protein-coupled receptor 55 (GPR55) expression in colonic tissue of inflammatory bowel disease (IBD) patients and healthy controls, and its potential implication in IBD treatment.

Methods: Fifty patients were enrolled in our prospective study: n?=?21 with Crohn’s disease (CD) and n?=?16 with ulcerative colitis (UC); 19 women and 18 men. Control consisted of 13 non-IBD patients. In each subject, two biopsies were taken from different colonic locations. In IBD patients, biopsies both from endoscopically inflamed and non-inflamed areas were drawn and the development of inflammation confirmed in histopathological examination. GPR55 mRNA and protein expression were measured using real-time PCR and Western blot, respectively.

Results: GPR55 expression at mRNA and protein level was detected in all samples tested. The level of GPR55 mRNA expression in non-inflamed colonic areas was comparable in all analyzed groups (p?=?.2438). However, in the inflamed tissues GPR55 mRNA expression was statistically significantly (p?<?.0001) higher (6.9 fold) in CD patients compared to UC. Moreover, CD patients manifested higher (12.5 fold) GPR55 mRNA expression in inflamed compared with non-inflamed colonic tissues (p?<?.0001). Although no significant differences were stated, GPR55 protein level tends to decrease in IBD as compared to control.

Conclusions: Different patterns of GPR55 expression at mRNA level were observed in IBD patients. We speculate that GPR55 is crucial for the mucosal inflammatory processes in IBD, particularly in CD and its expression may affect disease severity, and response to treatment. The GPR55 receptors may become an attractive target for novel therapeutic strategies in IBD.     

Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria.

In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown. To investigate the specificities of these antibodies mucosal immunoglobulins were isolated from washings taken at endoscopy from 21 control patients with irritable bowel syndrome, 10 control patients with intestinal inflammation due to infection or ischaemia, and 51 patients with IBD: 24 Crohn's disease (CD, 15 active, nine quiescent), 27 ulcerative colitis (UC, 20 active, seven inactive). Total mucosal IgG was much higher (p < 0.001) in active UC (median 512 micrograms/ml) and active CD (256 micrograms/ml) than in irritable bowel syndrome controls (1.43 micrograms/ml), but not significantly different from controls with non-IBD intestinal inflammation (224 micrograms/ml). Mucosal IgG bound to proteins of a range of non-pathogenic commensal faecal bacteria in active CD; this was higher than in UC (p < 0.01); and both were significantly greater than controls with non-IBD intestinal inflammation (CD p < 0.001, UC p < 0.01) or IBS (p < 0.001 CD and UC). This mucosal IgG binding was shown on western blots and by enzyme linked immunosorbent assay (ELISA) to be principally directed against the bacterial cytoplasmic rather than the membrane proteins. Total mucosal IgA concentrations did not differ between IBD and controls, but the IgA titres against faecal bacteria were lower in UC than controls (p < 0.01). These experiments show that there is an exaggerated mucosal immune response particularly in active CD but also in UC directed against cytoplasmic proteins of bacteria within the intestinal lumen; this implies that in relapse of IBD there is a breakdown of tolerance to the normal commensal flora of the gut.     

Effect of Follow-Up Endoscopy on the Outcomes of Patients with Inflammatory Bowel Disease

Background

Little is known about the role of follow-up endoscopy in patients with inflammatory bowel disease (IBD).

Aim

The present study aimed to evaluate whether repeated endoscopies would be beneficial in improving outcomes of patients with IBD.

Methods

Patients who had been initially confirmed to have IBD at two tertiary hospitals in Korea were regularly followed and included in this study. The clinical impact as assessed by the presence or absence of a change in management after endoscopy and cumulative hospitalization rate was compared between two groups classified according to the presence or absence of indications.

Results

A total of 188 patients with IBD were enrolled [69 patients with Crohn’s disease (CD) and 119 with ulcerative colitis (UC)]. Of these patients, 130 underwent follow-up endoscopy (48 with CD and 82 with UC). The rate of management change was significantly higher in the group with indications for follow-up endoscopy (p = 0.001 in CD and <0.001 in UC). The presence of any indications for follow-up endoscopy was found to be a significant predictor of hospitalization risk in patients with UC (p = 0.015), but not in those with CD. However, there was no significant difference in cumulative hospitalization hazard with respect to treatment change in patients without any endoscopic indications (p = 0.561 in CD and 0.423 in UC).

Conclusions

Follow-up endoscopy might not have a significant impact on the overall clinical course and outcomes in patients with IBD. However, the presence of endoscopic indications predicts a poor clinical outcome in UC.     

Comparison of magnetic resonance imaging colonography with conventional colonoscopy for the assessment of intestinal inflammation in patients with inflammatory bowel disease: a feasibility study

AIM: Magnetic resonance imaging (MRI) based colonography represents a new imaging tool which has mainly been investigated for polyp screening. To evaluate this approach for patients with inflammatory bowel disease (IBD), we compared MRI based colonography with conventional colonoscopy for assessing the presence and extent of colonic inflammation. PATIENTS AND METHODS: In 22 consecutive patients with suspected or known IBD, MRI colonography was performed immediately before conventional colonoscopy. After bowel cleansing, a T1 positive contrast agent was applied rectally. In addition to T2 weighted sequences, T1 weighted two dimensional and three dimensional Flash acquisitions as well as volume rendered virtual endoscopy were performed. All images were evaluated with regard to typical MRI features of inflammation. The results were compared with colonoscopy findings. RESULTS: Distension and image quality was assessed as good to fair in 97.4% of all colonic segments. Only four of 154 segments were considered non-diagnostic. With colonoscopy serving as the gold standard, the sensitivity for correctly identifying inflammation on a per segment analysis of the colon was 31.6% for Crohn's disease (CD) and 58.8% for ulcerative colitis (UC). In CD, in most cases mild inflammation was not diagnosed by MRI while in UC even severe inflammation was not always depicted by MRI. Virtual endoscopy did not add any relevant information. CONCLUSION: MRI based colonography is not suitable for adequately assessing the extent of colonic inflammation in patients with IBD. Only severe colonic inflammation in patients with CD can be sufficiently visualised.     

Presence of intestinal Mycobacterium avium subspecies paratuberculosis (MAP) DNA is not associated with altered MMP expression in ulcerative colitis

Background

Mycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in human Crohn's disease (CD). Recent evidence suggests that pathogenic mycobacteria and MAP can induce the expression of Matrix Metalloproteinases (MMP), which are the main proteases in the pathogenesis of mucosal ulcerations in inflammatory bowel disease (IBD). Within this study we assessed the prevalence of intestinal MAP specific DNA in patients with Crohn's disease, ulcerative colitis (UC), and healthy controls. We further analysed regulation patterns of MMPs in mucosal tissues of UC patients with and without intestinal MAP DNA detection.

Methods

Colonic biopsy samples were obtained from 63 Norwegian and German IBD patients and 21 healthy controls. RNA was quantified by quantitative real-time polymerase chain reaction (PCR) to study MMP gene expression in both pathological and healthy mucosal specimens. The presence of MAP DNA in colonic mucosa was examined using MAP specific PCR.

Results

MAP DNA was detected in 20% of UC patients and 33% of healthy controls but only in 7% of patients with CD. UC patients treated with corticosteroids exhibited a significantly increased frequency of intestinal MAP DNA compared to those not receiving corticosteroids. Expression of MMP-1, -2, -7, -9, -13, -19, -28 and TNF-α did not differ between UC patients with presence of intestinal MAP DNA compared to those without. MMP-2, MMP-9 and MMP-13 were significantly decreased in UC patients receiving corticosteroids.

Conclusions

The presence of intestinal MAP specific DNA is not associated with altered MMP expression in UC in vivo. Corticosteroids are associated with increased detection of intestinal MAP DNA and decreased expression of certain MMPs. Frequent detection of MAP DNA in healthy controls might be attributable to the wide environmental distribution of MAP and its presence in the food-chain.     

T-cell co-stimulatory molecules are upregulated on intestinal macrophages from inflammatory bowel disease mucosa.

BACKGROUND AND AIMS: Macrophages play an important role during mucosal inflammation in inflammatory bowel disease (IBD). As the co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) play an integral role in the activation of T cells by antigen-presenting cells (APC) we investigated the surface expression of B7-1 and B7-2 on colonic macrophages from normal and IBD mucosa. METHODS: Intestinal macrophages were isolated from biopsies of 13 control persons and 14 patients with IBD (seven with Crohn's disease (CD); and seven with ulcerative colitis (UC)). Cells were characterized by triple fluorescence flow cytometrical analysis using CD33 as macrophage marker. RESULTS: The expression of B7-1 (CD80) (9.2% +/- 4.2%) and B7-2 (CD86) (15.1% +/- 7.3%) was low on colonic macrophages from normal mucosa, indicating only a low antigen presenting potential. However, on macrophages from IBD colon there was a significant increase in the expression of co-stimulatory molecules (CD80, 33.8% +/- 8.9%, P = 0.00005 vs. control; CD86, 39.9% +/- 8.8%, P = 0.00002). There was no significant difference between CD and UC in the expression of CD80 (CD, 31.3% +/- 6.7%; UC, 34.4% +/- 13.3%) and CD86 (CD, 41.9% +/- 3.8%; UC, 35.6% +/- 13.8%). While in normal mucosa only 10.6% +/- 4.9% of the macrophages expressed CD14, more than 90% of the CD86/CD80 positive cells of the inflamed mucosa were positive for CD14. CONCLUSION: Colonic macrophages from normal mucosa rarely express the co-stimulatory molecules CD80 and CD86. In IBD a new macrophage population is found with high expression of co-stimulatory molecules presumably responsible for the perpetuated immune response.