Pantelis Karatzas

DNA methylation profile of genes involved in inflammation and autoimmunity in inflammatory bowel disease.

AbstractThe contribution of epigenetic alterations to disease pathogenesis is emerging as a research priority. In this study, we aimed to seek DNA methylation changes in peripheral blood and tissue biopsies from patients with inflammatory bowel disease.The promoter methylation status of genes involved in inflammation and autoimmunity was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. Methylation was considered to be hypermethylated if >20% according to the instructions of the manufacturer. The microarrays were validated with Quantitative Real-time PCR.Regarding Crohn disease (CD) no gene appeared hypermethylated compared to healthy controls. In ulcerative colitis (UC) 5 genes (CXCL14, CXCL5, GATA3, IL17C, and IL4R) were hypermethylated compared to healthy controls. Some of the examined genes show different methylation patterns between CD and UC. Concerning tissue samples we found that all hypermethylated genes appear the same methylation pattern and confirmed a moderate–strong correlation between methylation levels in colon biopsies and peripheral blood (Pearson coefficients r = 0.089–0.779, and r = 0.023–0.353, respectively).The epigenetic changes observed in this study indicate that CD and UC exhibit specific DNA methylation signatures with potential clinical applications in IBD non-invasive diagnosis and prognosis.

Prevalence and Characteristics of Extra-intestinal Manifestations in a Large Cohort of Greek Patients with Inflammatory Bowel Disease

BACKGROUND AND AIMS Extraintestinal manifestations [EIMs] are common in inflammatory bowel disease [IBD]. Data on epidemiology and risk factors of EIMs in IBD patients are limited. The aim of this study was to investigate the prevalence of EIMs in a large cohort of Greek IBD patients and identify risk factors for their development. METHODS The study population consisted of IBD patients, who were followed in eight tertiary Greek hospitals. Demographic and clinical characteristics of patients were analysed. The diagnosis of EIMs was based on standard criteria and on specialist consultation. RESULTS In total, 1860 IBD patients (1001 with Crohns disease [CD], 859 with ulcerative colitis [UC]) were registered. Among them 615 [33.1%] exhibited at least one EIM; 238 patients [38.6%] developed an EIM before IBD diagnosis. An association between active IBD and presence of an EIM was established in 61.1% of the patients. Arthritic [peripheral arthritis], mucocutaneous [erythema nodosum], and ocular [episcleritis] were the most common manifestations. EIMs were more prevalent in females, patients with CD, smokers [for all p <0.0001], patients with extensive UC [p = 0.007], and patients with a previous appendectomy [p < 0.0001] or a major IBD-related surgery [p = 0.012]. CONCLUSIONS About one-third of Greek IBD patients developed at least one EIM. Of those, more than one-third had their EIM diagnosed before IBD, and in about two-thirds it was related to disease activity. EIMs were more frequently present in females and patients with extensive UC in multivariate analysis.

Addition of an Immunomodulator as a Rescue Therapy for Loss of Response to Adalimumab Dose Escalation in Patients With Crohn’s Disease

Adalimumab is an effective therapy for Crohn’s disease [CD]. However, 20–60% of initial responders will need dose escalation, whereas 30–40% will eventually discontinue treatment for loss of response [LR].1,2 Treating these patients is often challenging, as they may have already failed all available immunomodulators [IMM] and anti-tumour necrosis factor alpha [anti-TNFα] agents, remaining with very few alternative therapeutic options. Moreover, options such as dose intensification, switching to another anti-TNFα agent, or changing drug class, may be circumvented by regulatory barriers, limited availability, no access to therapeutic drug monitoring [TDM], and/or lower efficacy, such as when switching between TNFα inhibitors.3 Consequently, many physicians would rightly attempt to maximise the benefit of any currently used TNFα inhibitor before drug discontinuation. Preliminary data show …

Faecal calprotectin but not C-Reactive Protein (CRP) or Crohn's Disease Activity Index (CDAI) may predict post-operative endoscopic recurrence of Crohn’ s Disease

Dear Sir, There are scarce and rather conflicting data regarding the value of faecal calprotectin (FC) as a surrogate marker for post-operative endoscopic recurrence (PER) of Crohns disease (CD).1,2 In this respect, we read with interest the article by Lobaton et al.3 suggesting that FC, measured by two different techniques, is a more accurate and better surrogate marker of endoscopic activity and PER of CD than markers of clinical and/or serological activity. We share similar experience based on retrospective analysis of prospectively acquired data between 2005 and 2009 from 59 patients [30 males, median age 28.5 years …

European Crohn’s and Colitis Organisation Topical Review on IBD in the Elderly

This ECCO topical review of the European Crohns and Colitis Organisation [ECCO] focuses on the epidemiology, pathophysiology, diagnosis, management and outcome of the two most common forms of inflammatory bowel disease, Crohns disease and ulcerative colitis, in elderly patients. The objective was to reach expert consensus to provide evidence-based guidance for clinical practice.

The impact of immunosuppressive therapy on QuantiFERON and tuberculin skin test for screening of latent tuberculosis in patients with inflammatory bowel disease scheduled for anti-TNF therapy

Abstract Objective. Patients with inflammatory bowel disease (IBD) should be routinely screened for latent tuberculosis (LTB) before starting anti-TNF therapy in order to prevent reactivation of LTB. Besides tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube (QFT-G-IT) has gained wide acceptance as a screening strategy for LTB in IBD, although it may be negatively influenced by the prior use of immunomodulators (IMM) such as azathioprine or methotrexate. This study aimed to assess the impact of IMM on the TST and the QFT-G-IT for LTB screening in IBD patients scheduled for anti-TNF therapy. Material and methods. This observational, prospective, single-center study included consecutive IBD patients scheduled for anti-TNF therapy undergoing on the same day both TST and QFT-G-IT for screening of LTB, between 2008 and 2010. Patients with a prior history of known or suspicious (L)TB receiving (prophylactic) anti-TB therapy were excluded. Results. Seventy-five patients were finally included; 28 were treated with thiopurines (IMM group), while 47 (control group) received either 5-aminosalicylic acid (n = 41) or no therapy (newly diagnosed patients, n = 6). Overall, TST and QFT-G-IT were positive in 14 (18.7%) and 16 (21.3%) patients, respectively. There was no statistically significant difference between the two groups regarding the TST (p = 0.761) and QFT-G-IT (0.572) positivity. The overall concordance between the two tests was moderate (kappa = 0.584), being substantial in the IMM group (kappa = 0.700) and moderate in the control group (kappa = 0.498). Conclusion. These preliminary results suggest that IMM may not have a significant impact on either QFT-G-IT or TST, although larger, prospective studies are certainly warranted.

De-escalation of Infliximab Maintenance Therapy from 8- to 10-week Dosing Interval Based on Faecal Calprotectin in Patients with Crohn's Disease.

Dear Sir, Anti-tumour necrosis factor (TNF) therapy, such as infliximab, is an effective treatment for Crohn’s disease (CD). However, based on potential cost and safety concerns, de-escalation strategies for anti-TNF therapy may be considered, especially in inflammatory bowel disease (IBD) patients with low relapse risk.1 It was recently shown that de-escalation of infliximab maintenance therapy, based on therapeutic drug monitoring, may be feasible in IBD patients who are in deep remission or who have a stable clinical response and supra-therapeutic infliximab trough concentrations, as the risk of relapse is relatively low.2,3 Faecal calprotectin (FC) may also potentially guide therapeutic decisions in IBD patients on stable maintenance infliximab therapy, although data are limited.4,5 Thus, based on serial …

LFA-1 Expression in a Series of Colorectal Adenocarcinomas

IntroductionLFA-1 is an adhesion molecule which belongs to the β2-integrin family. Overexpression of LFA-1 in hepatic natural killer cells has been associated with increased apoptosis of neoplastic cells in colorectal cancer (CRC); moreover, studies in CRC have linked LFA-1 overexpression in neoplastic cells with vascular intrusion through adhesion to endothelial cells, thus implying a possible role in creation of metastases.Aims and MethodsWe studied the expression of LFA-1 in a series of 82 patients with CRC. A standard three-step immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded tissue sections. An IgG2a anti-CD11a monoclonal antibody was used. Cases were characterized according to clinicopathological variables including sex, age, tumor localization, size, grade, Dukes stage, wall invasion, and presence of metastatic lymph nodes (mLNs) or distal metastases.ResultsLFA-1 was expressed at the primary tumor site in 51 cases and 6/33 cases with metastatic lymphnodes. In Dukes D cases (n = 4), only one case was LFA-1(+). LFA-1 expression at the primary tumor site was associated with the absence of metastatic disease and with Dukes B stage. However, in those cases with LFA-1 expression in cancer cells in mLNs, this was associated with its expression at the primary tumor site.ConclusionThe positive association of LFA-1 expression in mLNs when the primary tumor site is also LFA-1(+) could imply an adaptation advantage of this specific cellular clone to its micro-environment, predisposing it to creation of mLNs, pointing to a role for LFA-1 in creation of mLNs in CRC.

Role of pancreatic endoscopic ultrasonography in 2010

Endoscopic ultrasonography (EUS) was introduced 25 years ago aiming at better visualization of the pancreas compared to transabdominal ultrasonography. This update discusses the current evidence in 2010 concerning the role of EUS in the clinical management of patients with pancreatic disease. Major indications of EUS are: (1) Detection of common bile duct stones (e.g. in acute pancreatitis); (2) Detection of small exo- and endocrine pancreatic tumours; and (3) Performance of fine needle aspiration in pancreatic masses depending on therapeutic consequences. EUS seems to be less useful in cases of chronic pancreatitis and cystic pancreatic lesions. Moreover the constant improvement of computed tomography has limited the role of EUS in pancreatic cancer staging. On the other hand, new therapeutic options are available due to EUS, such as pancreatic cyst drainage and celiac plexus neurolysis, offering a new field in which new techniques may arise. So the main goal of this review is to determine the exact role of EUS in a number of pancreatic and biliary diseases.

Small bowel enteropathy associated with olmesartan medoxomil treatment

Sprue-like enteropathy associated with treatment with olmesartan medoxomil, an angiotensin II receptor blocker, has been described recently. Herein, we report two patients who developed chronic severe non-bloody diarrhea, weight loss, and muscle wasting after prolonged use of olmesartan. Histologic and immunohistochemical examination of multiple duodenal biopsies revealed severe villous atrophy. Clinical signs ceased upon drug discontinuation. Physicians should be aware of this enteropathy even if olmesartan has been taken for months or years. Whether this adverse event is specific for olmesartan or is a class effect of angiotensin II receptor blockers is currently unknown. To the best of our knowledge, these case reports are the first reported in Greece.