Advances in inflammatory bowel disease

Optimal management of patients with IBD requires a multidisciplinary approach involving primary care physicians, gastroenterologists, surgeons, radiologists, and nutritionists. The rapidly evolving medical armamentarium promises better quality of life for patients afflicted with these complex, chronic diseases. It is expected that future development of biologic agents will add to the therapeutic options, although it may complicate treatment algorithms. Surgical advancements, particularly in ileoanal anastomosis and bowel preservation by strictureplasty, have improved outcome dramatically. The focus on development of new therapies and refinement of older ones demands a constant attention to the latest peer-reviewed literature and that the clinician keep abreast of the various advancements that have been summarized here.     

Advances in clinical laboratory tests for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a generic term that refers to Crohn's disease and chronic ulcerative colitis (UC). The CD and UC are considered to be distinct forms of IBD; but there is a subgroup of CD with a UC-like presentation. The genetic factors play a significant role in IBD. IBD is associated with a strong familial pattern. Recent studies support the hypothesis that IBD patients have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract. The serologic responses seen in Crohn's disease include antibodies to Saccharomyces cerevisiae, mycobacteria, bacteroides and E. coli. The pANCA antibody seen in UC and CD has been demonstrated to react with epitopes of H1 histone, Bacteroides caccae (Ton-B linked outer membrane protein), Pseudomonas fluorescens-associated bacterial protein I-2, mycobacterial histone 1 homologue called Hup B. In recent years, several serologic markers have been found to be useful for the diagnosis and differentiation of CD and UC. These markers include the following antibodies: (a) pANCA, (b) ASCA, (c) anti-pancreatic antibody, (d) OmpC antibody and (e) I-2 antibody and antibodies to anaerobic coccoid rods. The application of a panel of markers with the use of an algorithm (i.e. IBD First Step) can identify specific subtypes of IBD that have different clinical courses and progression of the diseases. The serologic markers are useful for the diagnosis and management of CD and UC patients.     

Chemiluminescence in inflammatory bowel disease patients: a parameter of inflammatory activity

Background: Reactive oxygen species (ROS) are produced in excess in the inflamed mucosa and peripheral blood of patients with inflammatory bowel disease. These species have emerged as a common pathway of tissue injury in a wide variety of inflammatory and other disease processes. The present study was conducted to assess ROS production and to correlate this with parameters of inflammatory activity. Methods: In 25 patients with Crohn's disease (CD), 20 patients with ulcerative colitis (UC) and 65 age- and sex-matched healthy volunteers ROS production was measured using the whole blood luminol enhanced chemiluminescence assay (LECA). Disease activity was assessed using the Crohn's disease activity index and the Ulcerative Colitis Symptoms Score (UCSS) for CD and UC, respectively. Furthermore, the effect of various scavengers, enzymes and enzyme inhibitors on LECA was studied to assess the contribution of different ROS. Results: LECA was significantly higher in CD and UC patients compared with healthy controls (7.1±4.7 and 9.8±6 vs. 5.2±2.8×10³ counts per minute (cpm), p<0.05 and <0.001). In CD, relative LECA (patient/control) was correlated with the Crohn's disease activity index and C-reactive protein (CRP) (r=0.54, p=0.001 and r=0.51, p=0.01). In UC, CRP but not LECA was correlated with the Ulcerative Colitis Symptoms Score (C-reactive protein: r=0.42, p=0.01). Addition of azide, superoxide dismutase, deferoxamine and dimethylthiourea resulted in a decrease of LECA values. Conclusion: Whole blood LECA is increased in patients with CD and UC. This parameter is correlated with disease activity in CD. The observed chemiluminescence is probably due to generation of superoxide and the hydroxyl radical.     

Collagenase activity in colonic mucosa during inflammatory bowel disease

A simple test for collagenase activity was performed on colonic mucosa specimens of 35 patients with inflammatory bowel disease, 7 patients with carcinoma of the colon, 3 with benign polyps, and 34 normal subjects. Increased collagenase activity was present in 94.2% of the specimens taken from the inflamed mucosa and 71.4% of those obtained from colonic carcinoma, as compared to 8.8% of the control group.     

Fungal microbiome in inflammatory bowel disease: a critical assessment

The gut microbiome is at the center of inflammatory bowel disease (IBD) pathogenesis and disease activity. While this has mainly been studied in the context of the bacterial microbiome, recent advances have provided tools for the study of host genetics and metagenomics of host-fungal interaction. Through these tools, strong evidence has emerged linking certain fungal taxa, such as Candida and Malassezia, with cellular and molecular pathways of IBD disease biology. Mouse models and human fecal microbial transplant also suggest that some disease-participatory bacteria and fungi may act not via the host directly, but via their fungal-bacterial ecologic interactions. We hope that these insights, and the study design and multi-omics strategies used to develop them, will facilitate the inclusion of the fungal community in basic and translational IBD research.     

The role of diffusion-weighted MRI in assessment of inflammatory bowel disease

Aim

To evaluate the role of diffusion-weighted MRI (DW-MRI) in detecting and differentiating acute from chronic bowel inflammation in patients with Crohn’s disease (CD).

Materials and methods

MR-enteroclysis examinations with DW-MRI were reviewed from 24 patients with histologically proven CD. Segments of bowel were evaluated for acute and chronic inflammation in three different reviews of the MRI images: T2w alone, T2w + DWI, and T2w + CET1w. Mean ADC values of normal bowel segments, as well as bowel segments with acute and chronic inflammation were calculated and compared. Analyses of receiver-operating characteristic (ROC) curve were performed.

Results

Hundred and forty four bowel segments in total were reviewed. Inflammation was present in 45 segments. Acute inflammation was present in 31 segments, chronic inflammation in 14. 98 bowel segments showed no inflammatory activity. Sensitivity and specificity for differentiation between normal and inflamed bowel segments was 0.6, 0.67, and 0.80 on T2w, T2w + DWI, and T2w + CET1w datasets, respectively. Specificities for differentiation between normal and inflamed bowel segments were 0.96, 0.96, and 0.98. Sensitivities for differentiation between acute and chronically inflamed bowel segments were 0.85, 0.91, and 0.96, and specificities were 0.88, 0.89, and 1.0, respectively. The mean ADC value of normal bowel (2.18 ± 0.37 × 10^?3 mm²/s) was statistically significantly greater than the mean value of inflamed bowel segments (p < 0.001). The mean ADC value of acutely inflamed bowel segments was statistically significantly lower than that of chronically inflamed bowel segments (1.09 ± 0.18 × 10^?3 vs. 1.55 ± 0.21 × 10^?3 mm²/s) (p < 0.001). Estimated area under the ROC curve for the diagnosis of acute vs. chronic inflammation was 0.950. A threshold of ADC value of 1.41 × 10^?3 mm²/s was optimal for calculation of sensitivity and specificity.

Conclusion

DW-MRI improves detection and differentiation of acute vs. chronic inflammatory changes of the bowel in patients with CD compared to T2w-images alone.

     

Endoscopy of the small bowel in inflammatory bowel disease

With the heterogeneous clinical presentation of IBD, endoscopy plays an integral role in the initial diagnosis of Crohn's disease. Although radiographic tests are often supplemental in the evaluation of Crohn's disease, they previously had been the only modality available allowing for visualization of much of the small bowel. The advent of small bowel endoscopy allows for direct visualization, and often biopsy, of the small bowel, allowing for confirmation of diagnosing and extent of involvement. Currently, the only mode for obtaining biopsies from beyond the ligament of Treitz is via push enteroscopy or intraoperative enteroscopy. Knowing the extent of disease can also help explain recalcitrant symptoms or lack of response to certain therapies. With the advent of capsule endoscopy, endoscopic visualization of the entire small intestine is now possible with a relatively noninvasive test. Further advancements in capsule endoscopy may relegate push enteroscopy and intraoperative enteroscopy to those cases in which biopsies or therapy are required. In the future, total enteroscopy with new enteroscopes may become more widely available, allowing biopsies and therapy in all segments of the small intestine, without the need for operative intervention.     

Colonoscopy in inflammatory bowel disease

This article discusses the important role endoscopy plays in the diagnosis and management of inflammatory bowel disease and how the procedure adds crucial information to the constellation of history, physical examination, radiographic findings, and laboratory values. Differentiation between Crohn's disease and ulcerative colitis has important ramifications for medical therapy, surgical options, and prognosis. This distinction can be accurately made in at least 85% of patients.     

血小板相关参数对评估炎症性肠病活动性的临床意义

目的探讨血小板相关参数评估炎症性肠病(IBD)活动性的价值。方法回顾性收集2010年1月至2019年6月九江学院附属医院消化内科住院的溃疡性结肠炎(UC)及克罗恩病(CD)患者共206例,另选取于九江学院附属医院健康体检50例健康人员作为对照;收集研究对象临床资料,并依据病史、Myao活动指数、蒙特利尔分级及克罗恩病活动指数(CDAI)对患者进行分组及疾病严重程度分级。收集患者首次诊断时的血常规检测指标。结果IBD患者的血小板相关参数除P-LCR外与对照组比较均有明显差异(P<0.05);CD患者PCT及PLT显著高于UC(P分别0.007、<0.001);IBD活动期患者血小板参数与对照组存在显著差异(P<0.05);且UC患者病情与血小板参数存在相关性,重度患者PLT高于轻度患者(P<0.05)、MPV低于轻度患者(P=0.001);将MPV、PDW、P-LCR、PCT、PLT联合诊断IBD的活动性,得到AUC=0.857,95%CI 0.803~0.912,P<0.05。结论MPV、PDW在IBD活动期降低;PLT、PCT则增高;血小板相关参数联合诊断可较好反映IBD活动性。     

Angiogenesis in inflammatory bowel disease

Both ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel diseases, are recognized, at the moment, as perplexing and challenging clinical entities, in which several molecules and cell types are implicated. Recent molecular evidence proposes the intestinal microvascular remodelling or angiogenesis, as a phenomenon implicated in the pathogenesis of these chronic inflammatory disorders, together with other proposed theories involved in the pathogenesis of inflammatory bowel diseases, such as genetic, microbacterial and immune factors. Intestinal damage is followed by a physiological angiogenesis, but the abnormal expression of pro- and anti-angiogenic molecules and the changes of vascular cell types could reflect a pathological vascular remodelling. Thus, the inflammation may be favoured and maintained by a pathological angiogenesis. A better understanding of the angiogenic process may facilitate the design of more effective therapies for chronic intestinal inflammation.     

Immunotherapy in inflammatory bowel disease

Inflammatory bowel disease affects an increasing number of patients worldwide and is associated with significant morbidity. The dysregulation of the immune system with increased expression of proinflammatory cytokines and increased mucosal expression of vascular adhesion molecules play an important role in its pathogenesis. Strategies targeting TNF-alpha and alpha4-integrin have led to the development of novel therapies for treatment of patients with IBD. This article discusses the efficacy of immunologic agents currently approved for treating Crohn disease and ulcerative colitis and reviews the risks and challenges associated with their use.     

Diagnostic value of the serum platelet-activating factor acetylhydrolase activity in inflammatory bowel disease

Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme hydrolyzing platelet-activating factor (PAF), a potent inflammatory mediator, but the relationship between this enzyme and inflammatory bowel disease (IBD) is not fully elucidated. The aim of the present study was to examine the usefulness of the serum PAF-AH activity in order to differentiate ulcerative colitis (UC) from Crohn's disease (CD). The serum PAF-AH activity was measured in 57 patients with IBD (39 UC and 18 CD patients) and 13 control subjects by a spectrophotometric method. The serum PAF-AH activity was thus found to be significantly lower in patients with CD (median 265.5 U/l) than in those with UC (355 U/l) or control subjects (374 U/l). This marker at a cutoff level of 386 U/l demonstrated a sensitivity of 46%, a specificity of 100%, and a positive predictive value of 100% regarding its ability to distinguish UC from CD. Moreover, the marker responded inversely to the changes in the disease activity of IBD. These results suggest that measuring the serum PAF-AH activity is a useful diagnostic modality for making a differential diagnosis between UC and CD.     

炎症性肠病病情活动监测指标的临床价值

目的探讨髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)作为炎症性肠病(IBD)病情活动临床监测指标的价值。方法分别观察了IBD活动组患者15例[其中活动期溃疡性结肠炎(UC)10例,活动期克罗恩病(CD)5例],IBD非活动组患者15例(其中缓解期UC10例,缓解期CD5例)和12例对照组患者的结肠黏膜病理变化,按Oshitani评分标准和d'Haens评分标准进行UC和CD组织学评分,测定结肠黏膜MPO和SOD活性。结果IBD活动组、IBD非活动组病理组织评分均比对照组高(8±5 vs 3±1)、(5±2 vs 3±1)(P<0.01),IBD活动组病理组织评分亦较IBD非活动组高(8±5 vs 5±2)(P<0.01);IBD活动组、IBD非活动组肠黏膜MPO活性均较对照组高[(3.55±0.38)U/g vs(1.52±0.24)U/g、(2.28±0.30)U/g vs(1.52±0.24)U/g](P<0.01),IBD活动组MPO活性较IBD非活动组高[(3.55±0.38)U/g vs(2.28±0.30)U/g](P<0.01);IBD活动组、IBD非活动组肠黏膜SOD活性均较对照组低[(104.58±18.91)U/mg vs(212.44±14.22)U/mg、(170.91±13.57)U/mg vs(212.44±14.22)U/mg](P<0.01),IBD活动组SOD活性较IBD非活动组低[(104.58±18.91)U/mg vs(170.91±13.57)U/mg](P<0.01)。结论MPO活性与IBD病情活动程度呈正相关,SOD活性与IBD病情活动程度呈负相关,两者可作为IBD病情活动的临床监测指标。     

In vivo assessment of inflammatory bowel disease in rats with ultrahigh-resolution colonoscopic OCT

A technology capable of high-resolution, label-free imaging of subtle pathology in vivo during colonoscopy is imperative for the early detection of disease and the performance of accurate biopsies. While colonoscopic OCT has been developed to visualize colonic microstructures beyond the mucosal surface, its clinical potential remains limited by sub-optimal resolution (∼6.5 µm in tissue), inadequate imaging contrast, and a lack of high-resolution OCT criteria for lesion detection. In this study, we developed an ultrahigh-resolution (UHR) colonoscopic OCT and evaluated its ability to volumetrically visualize and identify the pathological features of inflammatory bowel disease (IBD) in a rat model. Owing to its improved resolution (∼1.7 µm in tissue) and enhanced contrast, UHR colonoscopic OCT can accurately delineate fine colonic microstructures and identify the pathophysiological characteristics of IBD in vivo. By using a quantitative optical attenuation map, UHR colonoscopic OCT is able to differentiate diseased tissue (such as crypt distortion and microabscess) from normal colonic mucosa over a large field of view in vivo. Our results suggest the clinical potential of UHR colonoscopic OCT for in vivo assessment of IBD pathology.     

Pathophysiology of inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) of unknown origin. Current data suggest that the interaction of genetic, immunologic and environmental factors leads to chronic inflammation. In UC, the inflammation is limited to the mucosa whereas in CD, the whole bowel wall may be affected. The concept of genetic background is supported by the increased prevalence of CD within certain populations and individual families and by the results of twin studies. It is believed that not only the phenotype (CD or UC), but also the clinical course are influenced by genetic factors. It is unknown which trigger induces chronic immune stimulation. It could be either a nutritional antigen, a self antigen, a component of the normal gut flora or certain bacteria such a mycobacteria. The chronic immune stimulation may be due to a dysbalance of pro-inflammatory and inhibitory cytokines. Besides cytokines, a variety of different inflammatory mediators have a crucial role for the inflammatory process. Smoking has a significant effect on occurrence and outcome of CD and UC.