ATG16L1 T300A polymorphism is associated with Crohn’s disease in a Northwest Greek cohort, but ECM1 T130M and G290s polymorphisms are not associated with ulcerative colitis

Background Crohn’s disease (CD) and ulcerative colitis (UC) are well-described disease entities with unknown etiopathogenesis. Environmental, genetic, gut microbiota, and host immune response correlations have been implicated. The role of susceptibility gene polymorphisms, such as ATG16L1 T300A and ECM1 T130M and G290S, is well-described, although controversial findings have been reported. Methods Two hundred five patients with inflammatory bowel disease (108 CD and 97 UC), and 223 healthy blood donors (control group) from the Northwest Greece region were genotyped for rs2241880 (T300A), rs3737240 (T130M) and rs13294 (G290S) single nucleotide polymorphisms. Genotyping was performed using the real-time polymerase chain reaction method. Results The frequency of G allele was significantly higher in CD patients compared to the control group (P=0.029; odds ratio [OR] 1.45, 95% confidence interval [CI] 1.04-2.03). Carriers of two G alleles (T300A), compared to those carrying only one, were 1.3 times more susceptible to CD (P=0.022; OR 2.45, 95%CI 1.14-5.27). In CD patients, the presence of the T300A polymorphism indicates a possible protective effect against developing a penetrating (B3) phenotype, while in UC patients, presence of the T300A polymorphism, indicates a possible protective effect against developing joint-involving extraintestinal manifestations. Conclusion Our study found a significant association of the T300A polymorphism with CD susceptibility, suggesting that CD occurrence in our population has a strong genetic background, with the T300A G allele having an additive effect. © 2020 Hellenic Society of Gastroenterology

The immunohistochemical expression of metallothionein in inflammatory bowel disease. Correlation with HLA-DR antigen expression, lymphocyte subpopulations and proliferation-associated indices

Metallothionein (MT) expression in intestinal resection specimens from 41 patients with ulcerative colitis (UC) and 10 patients with Crohn’s disease (CD ) was immunohistochemically studied by the avidin-biotin (ABC) method. In addition, the possible relationship of its expression with HLA-DR antigen expression, lymphocyte subpopulations and proliferation-associated indices was studied in order to elucidate the role of this molecule in inflammatory bowel disease (IBD). The MT immunoreactivity was recorded by staining and intensity-distribution scores. MT staining varied in and was mainly localized in the cytoplasm, although a combined nuclear/cytoplasmic reactive pattern was also seen in epithelial cells. MT expression was decreased in UC, and CD compared with normal mucosa. No difference in MT expression between UC and CD was noted. In UC, a gradually decreased expression from remission, to resolving and to active phase was observed. An inverse correlation of MT expression with HLA-DR antigen expression was detected (p=0.018) in the cases of UC. The data suggest that a low level of MT expression in inflammatory bowel disease and particularly in active phase of UC may indicate a decreased endogenous intestinal protection and it may be implicated in the pathogenesis of the disease

Bcl-2 expression in colorectal tumours. Correlation with p53, mdm-2, Rb proteins and proliferation indices

Immunostaining for bcl-2 protein was performed in 27 colorectal adenomas and 108 colorectal adenocarcinomas. The aim of the study was to determine bcl-2 expression in correlation with p53, mdm-2 and Rb expression, with proliferation indices (Ki-67-LI, PCNALI) as well as with conventional clinicopathological variables. A higher proportion of adenomas (30.8%) than carcinomas (16.7%) expressed bcl-2 and conversely, a lower proportion of adenomas (7.4%) than carcinomas expressed p53 (57.1 %), the difference being statistically significant (p<0.0001). No correlation of bcl-2 expression with p53 expression (parallel or inverse) as well as with the other parameters studied was observed in any tumour. The bcl-2+/p53- subgroup of cancers showed a trend for correlation with negative lymph node status. Our data suggest, that bcl-2 expression may be involved in the early phase of colorectal carcinogenesis regardless of p53 status, while p53 function may be involved in a late stage of the adenoma-carcinoma sequence. P53 is apparently not involved in the regulation of apoptosis in the colorectal neoplasias or perhaps bcl-2 expression, as an early event in colorectal tumours, may occur before changes of p53 take place. Tumours with bcl-2+/p53- immunophenotype are frequently associated with negative lymph node status and seem to have a less aggressive behavior

Cerebral arterial infarction in inflammatory bowel diseases

It has been estimated that up to 10% of hypercoagulable state manifestations in patients with inflammatory bowel disease (IBD) are ischemic strokes. The literature search through MEDLINE and EMBASE highlighted 33 case reports of IBD patients complicated with cerebral arterial infarction during the course of their disease. Most of these patients presented with either left or right sided hemiparesis on admission, while the most common site of arterial infarction was either the right or the left middle cerebral artery. Thrombocytosis and anemia were the most commonly observed potential risk factors for stroke in the laboratory analysis. Other coagulation abnormalities, hereditary thrombotic mutations, hyperhomocysteinemia, hyperlipidemia, structural cardiac abnormalities, endocarditis and cerebral artery vasculitis have also been reported in some of the cases that were reviewed. Even though many of these findings are commonly observed in IBD patients, literature data is still controversial about their causal relationship to ischemic stroke. Similarly, there is also lack of steady evidence and official guidelines for stroke management in both children and adults with IBD comorbidity. Finally, an algorithm based on both the American Heart Association and European Stroke Organization guidelines for stroke management and prevention in the general population, is presented as a reference point for the treatment of IBD patients who are complicated by an ischemic cerebral event. © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

Disease outcome in inflammatory bowel disease: mortality, morbidity and therapeutic management of a 796-person inception cohort in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).

Background: the course of inflammatory bowel diseases (ibd) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of ibd patients over a 4-year period in multiple centres across europe. Methods: a total of 796 patients with ibd diagnosed in 10 centres between october 1991 and october 1993, registered at the ec ibd study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physician's global assessment of disease activity. Results: complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (uc), 9 (50%) with indeterminate colitis (ic), but only in 87 (35%) of patients with crohn disease (cd). Improvement was reported in 195 (37%) patients with uc, 113 (45%) with cd and 6 (33%) with ic. During the 4-year follow-up period, 23 patients died (14 uc, 8 cd, and 1 ic). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to ibd. Conclusions: with the present approach to therapeutic management the short-term outcome of patients with ibd seems to be favourable in 10 medical centres in the north and south of europe. However, more detailed studies including both objective and subjective measures are necessary

Cancer in inflammatory bowel disease 15 years after diagnosis in a population-based European Collaborative follow-up study

AIM OF THE STUDY: To determine the occurrence of intestinal and extraintestinal cancers in the 1993-2009 prospective European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS-METHODS: A physician per patient form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from 9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year follow up period, rates of detection of intestinal and extraintestinal cancers were computed. RESULTS: Patient follow-up time was fifteen years. In total 62/681 patients (9.1%) [41 with ulcerative colitis/21 with Crohn's disease, 36 males/26 females] were diagnosed with sixty-six cancers (four patients with double cancers). Colorectal cancer was diagnosed in 9/681 patients [1.3%] (1 Crohn's disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal. There was a higher prevalence of intestinal cancer in the Northern centers compared to Southern centers [p=NS]. Southern centers had more cases of extraintestinal cancer compared to Northern centers [p=NS]. The frequency of all observed types of cancers in Northern and in Southern centers did not differ compared to the expected one in the background population. CONCLUSIONS: In the fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer was 9.1% with most patients having a single neoplasm and an extraintestinal neoplasm. In Northern centers there were more intestinal cancers while in Southern centers there were more extraintestinal cancers compared to Northern centers. In this IBD cohort the frequency of observed cancers was not different from that expected in the background population