High incidence of upper gastrointestinal tract involvement in Crohn’s disease

 A better definition of gastric mucosal histology in Crohn’s disease permits a more accurate estimation of the frequency of upper gastrointestinal tract involvement in Crohn’s disease. In a retrospective study of 792 patients with known Crohn’s disease the incidence of lesions associated with the disease was determined in the duodenum, duodenal bulb, and gastric antrum and body mucosa. Crohn’s disease was identified histologically in the antrum in 41.5%, in the body in 37.1%, in the duodenum in 12.1%, and in the duodenal bulb in 13%. In a further 15% and 17.4% of cases, Crohn’s disease of the duodenum and duodenal bulb, respectively, was suspected. The positive predictive value of focal gastritis in patients undergoing upper endoscopy and not yet known to have Crohn’s disease is as high as 94%. Thus, a high proportion of Crohn’s disease patients show upper gastrointestinal tract involvement, with the major involvement in the antrum. Focal gastritis suggesting Crohn’s disease turned out to have a high positive predictive value in patients not known to have Crohn’s disease at the time of gastroscopy. Received: 26 May 1997 / Accepted: 4 August 1997     

Heterotopic gastric mucosa of the gastrointestinal tract: a histopathologic study of 158 cases

The author retrieved and retrospectively investigated biopsy specimens of heterotopic gastric mucosa registered in our computer database. There were 1008 cases affecting the esophagus, 684 cases affecting the duodenum, and 1636 cases affecting the colorectum. A total of 158 cases of heterotopic gastric mucosa were identified (84 cases affecting the esophagus, 74 cases affecting the duodenum, and no case affecting the colorectum). The frequency amounted to 8% in the esophagus, 11% in the duodenum, and 0% in the colorectum. The male to female ratio was 112:46, and the mean age was 62.22 ± 14.29 years. Pathologically, two types of heterotopic gastric mucosa were identified. The first type consisted of gastric glands and foveolar epithelium, and the second type was composed only of foveolar epithelium. The first type was recognized in 69 of 84 cases (82%) in the esophagus, and in 54 of 74 cases (73%) in the duodenum. The second type was encountered in 15 of 84 cases (18%) in the esophagus, and in 20 of 74 cases (27%) in the duodenum. The first type appeared to be of congenital origin, while the second type was reminiscent of foveolar metaplasia. Foveolar hyperplasia and mild lymphocytic infiltration were frequent in the heterotopic gastric mucosa. Goblet cell metaplasia was recognized in 11 cases. The most frequent clinical diagnosis of heterotopic gastric mucosa of the esophagus was heterotopic gastric mucosa, followed in order by iodine-unstained area, reflux disease, flat elevation, polyp, carcinoma, ulcer, erosion, redness, submucosal tumor, esophagitis, adenoma, and tumor. The most frequent clinical diagnosis of heterotopic gastric mucosa in the duodenum was polyp, followed in order by ulcer, tumor, submucosal tumor, carcinoma, and duodenitis. The data suggest that esophageal gastric mucosa and duodenal heterotopic gastric mucosa are common lesions, with a frequency of about 9% in biopsy specimens in Japan.     

Endoscopic findings in upper gastrointestinal bleeding patients at Lacor hospital,northern Uganda

Background

Upper gastrointestinal bleeding (UGIB) is a common emergency medical condition that may require hospitalization and resuscitation, and results in high patient morbidity. Upper gastrointestinal endoscopy is the preferred investigative procedure for UGIB because of its accuracy, low rate of complication, and its potential for therapeutic interventions.

Objective

To determine the endoscopic findings in patients presenting with UGIB and its frequency among these patients according to gender and age in Lacor hospital, northern Uganda.

Methods

The study was carried out at Lacor hospital, located at northern part of Uganda. The record of 224 patients who underwent endoscopy for upper gastrointestinal bleeding over a period of 5 years between January 2006 and December 2010 were retrospectively analyzed.

Results

A total of 224 patients had endoscopy for UGIB which consisted of 113 (50.4%) males and 111 (49.6%) females, and the mean age was 42 years ± SD 15.88. The commonest cause of UGIB was esophagealvarices consisting of 40.6%, followed by esophagitis (14.7%), gastritis (12.6%) and peptic ulcer disease (duodenal and gastric ulcers) was 6.2%. The malignant conditions (gastric and esophageal cancers) contributed to 2.6%. Other less frequent causes of UGIB were hiatus hernia (1.8), duodenitis (0.9%), others-gastric polyp (0.4%). Normal endoscopic finding was 16.1% in patients who had UGIB

Conclusions

Esophageal varices are the commonest cause of upper gastrointestinal bleeding in this environment as compared to the west which is mainly peptic ulcer disease.     

炎症性肠病内镜活检标本的诊断及鉴别诊断

目的探讨炎症性肠病(inflammatory bowel disease,IBD)内镜活检标本的病理诊断及鉴别诊断。方法对209例内镜下活检诊断为IBD的HE切片重新阅片,按照系统性诊断步骤,即组织结构、上皮及固有层的改变综合评估,进行病理形态分析。结果溃疡性结肠炎(ulcerative colitis,UC)108例,克罗恩病(Crohn disease,CD)19例,不能排除CD 20例,不能确定为UC或CD 27例,按系统性诊断方法,其中35例不能诊断为IBD。结论按照系统性诊断步骤,IBD不易漏诊,也不会过诊断。内镜活检标本诊断UC较容易,诊断CD较难,除非看到非干酪样上皮样肉芽肿,CD内镜活检的主要目的是排除淋巴瘤和肠结核。     

Budesonide in the treatment of inflammatory bowel disease

Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, features recurrent episodes of inflammation of the GI tract. The treatment of inflammatory bowel disease is aimed at breaking the cycle of relapsing and remitting inflammation by inducing and maintaining remission. Systemically active conventional corticosteroids have long played a role in the induction of remission in both Crohn’s disease and ulcerative colitis, however, their long-term use can lead to adverse systemic effects. Budesonide, a synthetic steroid, has potent local anti-inflammatory effects and limited systemic bioavailability making it an appealing therapeutic option. Ulcerative colitis with predominantly distal disease may be treated with topical budesonide, however, novel oral controlled-release formulations have also been developed to allow for treatment of the entire colon. This article summarizes the use of budesonide in the management of inflammatory bowel disease.     

Coeliac disease and other intraepithelial lymphocytic disorders of the upper gastrointestinal tract

The finding of increased intraepithelial lymphocytes (IEL) in the upper gastrointestinal tract is common to a wide variety of disorders that involve mucosal injury. Coeliac disease or gluten-sensitive enteropathy is perhaps the first entity in pathologists' differential diagnosis when asked to identify disorders with increased IEL, but it is far from the only condition that can result in such a finding. The numerous causes that can result in this histological feature can be easily organized into three categories. Inflammatory and immune causes include coeliac disease and other autoimmune conditions, as well as relatively rare hematolymphoid neoplasms. Infectious causes include numerous conditions that often have subtle histological findings, such as giardiasis and bacterial overgrowth. Finally, “ingested” causes range from pharmacological agents to morbid obesity, which has also been associated with the isolated finding of increase IEL in the upper gastrointestinal tract. This contribution reviews selected entities from each of these categories, with special attention to coeliac disease.     

Autoinflammatory disease with focus on NOD2-associated disease in the era of genomic medicine

Systemic autoinflammatory diseases (SAIDs) represent a spectrum of genetically heterogeneous inflammatory disorders. Some SAID-associated genes are located in chromosome 16, including familial Mediterranean fever gene (MEFV) and nucleotide-binding oligomerization domain 2 [NOD2] gene that are linked to Crohn’s disease, Blau syndrome, and Yao syndrome. These disorders share overlapping clinical phenotypes, and genotyping is diagnostically helpful and distinctive. Using next generation sequencing in SAIDs, digenic variants or combinations of more genetic variants in different genes can be detected, and they may be related to the MEFV and NOD2 genes. These variants may contribute to heterogeneous phenotypes in an individual, complicating the diagnosis and therapy. An awareness of the clinical significance of the digenic or combined gene variants is important in the era of genomic medicine.     

Endoscopic and histological changes in upper gastrointestinal tract of patients with chronic renal failure

To evaluate the endoscopic and histological changes in upper gastrointestinal tract of patients with chronic renal failure 50 patients and 50 controls were studied. Upper gastrointestinal endoscopy was done and 2 biopsies each were taken from oesophagus, corpus and antrum of the stomach and duodenum. Sections were stained with haematoxylin & eosin, Alcian blue--Periodic acid Schiff's (pH 2.5), and Loeffler's methylene blue stains. Oesophagus was endoscopically normal in most of the patients. Predominant histological finding was chronic oesophagitis which was significantly higher in patients than controls (47.1% Vs 26%; p<0.05). Significantly higher (p<0.001) number of patients had gastritis, oedema and pale mucosa on endoscopic examination of stomach. Predominant histological changes were mucosal oedema (82.35%), gastritis (23.5%) and increase in number of bi- and multinucleated parietal cells with vacuolation and fragmentation of the cytoplasm (29%). Prevalence of H. pylori was less in patients as controls (35.2% Vs 54%; p< 0.01). Endoscopic examination of duodenum mainly showed duodenitis, pale mucosa, oedema and nodularity. Brunner's gland hyperplasia (82.4%), duodenitis (70.6%) and gastric metaplasia (29.4%) were the main histological features. H. pylori was seen in 5.9% cases of gastric metaplasia in duodenum. Patients with CRF have significant upper gastrointestinal tract abnormalities which mainly occur due to metabolic changes in response to high urea concentration in gastric juice and are not related to H. pylori infection.     

Genetic dissection of inflammatory bowel disease: unravelling etiology and improving diagnostics

Over the past 10 years, remarkable advances in the mapping and identification of genes involved in susceptibility to inflammatory bowel disease have been witnessed. Most notable among these advances has been the discovery of variants in the CARD15, DLG5, SLC22A4 and SLC22A5 genes, which are associated with increased risk of inflammatory bowel disease or specifically Crohn’s disease. These discoveries have provided critical new insights into the molecular pathophysiology of inflammatory bowel disease and the pathways wherein genetic and environmental factors such as enteric bacterial flora may interact to trigger immune dysregulation and intestinal inflammation. This review will outline the discovery of these inflammatory bowel disease-related genes, describe future prospects for further inflammatory bowel disease gene identification, and consider the impact of a genetic understanding of inflammatory bowel disease on future clinical practice.     

Escherichia coli isolates from patients with inflammatory bowel disease: ExPEC virulence- and colicin-determinants are more frequent compared to healthy controls

A set of 178 Escherichia coli isolates taken from patients with inflammatory bowel disease (IBD) was analyzed for bacteriocin production and tested for the prevalence of 30 bacteriocin and 22 virulence factor determinants. Additionally, E. coli phylogenetic groups were also determined. Pulsed-field gel electrophoresis (PFGE) was used for exclusion of clonal character of isolates. Results were compared to data from a previously published analysis of 1283 fecal commensal E. coli isolates.The frequency of bacteriocinogenic isolates (66.9%) was significantly higher in IBD E. coli compared to fecal commensal E. coli isolates (54.2%, p < 0.01). In the group of IBD E. coli isolates, a higher prevalence of determinants for group B colicins (i.e., colicins B, D, Ia, Ib, M, and 5/10) (p < 0.01), including a higher prevalence of the colicin B determinant (p < 0.01) was found. Virulence factor determinants encoding fimbriae (fimA, 91.0%; pap, 27.5%), cytotoxic necrotizing factor (cnf1, 11.2%), aerobactin synthesis (aer, 43.3%), and the locus associated with invasivity (ial, 9.0%) were more prevalent in IBD E. coli (p < 0.05 for all five determinants). E. coli isolates from IBD mucosal biopsies were more frequently bacteriocinogenic (84.6%, p < 0.01) compared to fecal IBD isolates and fecal commensal E. coli. PFGE analysis revealed clusters specific for IBD E. coli isolates (n = 11), for fecal isolates (n = 13), and clusters containing both IBD and fecal isolates (n = 10).ExPEC (Extraintestinal Pathogenic E. coli) virulence and colicin determinants appear to be important characteristics of IBD E. coli isolates, especially the E. coli isolates obtained directly from biopsy samples.     

Optimising use of thiopurines in inflammatory bowel disease

Introduction: Thiopurines are central to inflammatory bowel disease (IBD) therapeutics, either as monotherapy or in combination with newer biologic therapies, however it is only recently that focus has increased on improving effectiveness and tolerability through optimisation.

Areas covered: We review the role of thiopurines in IBD and the importance of the timing of initiation of therapy. Drug metabolism and pharmacogenetics have increasingly played a role in determining dosing and dose optimisation and we review the rationale for this in both thiopurine monotherapy and in combination with biologic agents. We also discuss allopurinol co-therapy as a strategy for enhancing both efficacy and tolerability of thiopurine therapy. Although immunomodulators carry safety considerations, we discuss methods of optimisation to minimise side-effects and maximise safety to ensure the broadest number of patients can benefit.

Expert commentary: We provide a practical guide to drug initiation and dose optimisation in a clinical setting, and address potential treatment duration. The forward view considers the place for thiopurines in the treatment of IBD, and how the application of the plethora of genetic data may help inform thopurine therapy in the future.     

胆固醇在阿尔茨海默病发病机制中的作用

阿尔茨海默病是一种进行性的神经退行性病变，其病理特点是细胞外β-淀粉样蛋白沉积和细胞内神经元纤维缠结。近几年的研究发现胆固醇在AD的发病机制中有重要作用，β-淀粉样蛋白的沉积和神经元纤维缠结的形成都受脑中胆固醇水平的影响。载脂蛋白E在阿尔茨海默病发病中的重要作用也已经为大家所认同。     

Mannose-binding lectin (MBL) in adult patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) refers to disorders associated with progressive inflammatory processes in the gastrointestinal system. IBD consists of two major forms, Crohn’s disease (CD), and ulcerative colitis (UC). IBD became a global disease in the 21^st century. Its pathogenesis is still not fully understood. Mannose-binding lectin (MBL) is a pattern-recognising molecule, involved in anti-microbial and anti-cancer immunity. It is able to opsonize microorganisms and abnormal host cells, and to initiate complement activation. The aim of this study was to investigate possible involvement of MBL in inflammatory bowel disease in adults. Forty persons diagnosed with CD and 28 with ulcerative colitis were recruited. The control group consisted of 136 healthy persons. Single nucleotide polymorphisms of the MBL2 gene (localised to both promoter and exon 1) were determined as were serum MBL concentrations. The exon 1 variant alleles and MBL deficiency-associated genotypes were more frequent among patients compared with controls, although this difference was not statistically significant. No differences of MBL levels were found between the major groups. However in MBL2 A/A homozygous IBD patients, the median was significantly higher than in corresponding healthy subjects. That was particularly evident in the case of active Crohn’s disease (1493 ng/ml vs. 800 ng/ml, p = 0.021). It may suggest that MBL and MBL-dependent complement activation contributes to excessive inflammation and its adverse effects in the course of CD. It cannot also be excluded that high MBL activity constitutes in some cases part of a multifactorial network conducing to development of CD.     

The granuloma in Crohn's disease. A bioptical study

Serial sections of 1434 colonic and rectal biopsies of 347 patients with Crohn's disease were performed. The relationship between the incidence of granulomas and the inflammatory alterations of the mucosa and some clinical parameters was studied. The presence of granulomas depends on the severity of inflammatory alterations and not on the site of the biopsy. The number of granulomas per mm3 increases from caecum to rectum. The incidence of granulomas decreases with age, duration of illness and under a conservative therapy. If several biopsies, taken at the same or at different times, are studied, granulomas can be found in 40-50% of these patients.     

IL-23 Blockade for Crohn s disease: next generation of anti-cytokine therapy

Introduction: Adaptive immunity in intestinal inflammation may play a key role in the pathogenesis of Crohn’s disease. In particular, interleukin (IL)-23 may be a key mediator in chronic intestinal inflammation by inducing the differentiation of naïve CD4 + T cells into Th17, with the production of several pro-inflammatory cytokines. Furthermore, IL-23 induces interferon-γ (IFN- γ) production from activated T cells, a critical cytokine in innate and adaptive immunity against infections.

Areas covered: We aim to review the available data from literature regarding the role of IL-23, with a more specific focus on the recent progresses in the therapeutic modulation of this cytokine.

Expert commentary: Increased knowledge regarding the role of IL-23 has allowed for the development of effective therapeutic progresses by blocking the IL-23 mediated pathways. Primary or secondary loss of response to anti-TNF therapies in Crohn’s disease patients during the first year is widely described in literature: the development of new drugs, with alternative mechanisms of action, is thus a key point to consider for the optimal management of these subjects. Drugs blocking the IL-12/23 pathway showed a good efficacy and safety profile in immune-mediated diseases Further studies are necessary regarding the role of the single blockade of IL-23.