Francesca Albano

Endothelial function and cardiovascular risk in active inflammatory bowel diseases

BACKGROUND Endothelial dysfunction has been already reported in inflammatory bowel diseases (IBD). However, case series so far examined were rather heterogeneous as for disease severity and subsets investigated. OBJECTIVE We evaluated endothelial dysfunction by brachial artery flow-mediated vasodilatation (FMD), and subclinical atherosclerosis by assessment of common carotid intima-media thickness (CCA-IMT) in a cohort of patients with Crohns disease (CD) or Ulcerative colitis (UC) in active phase compared to healthy control subjects. METHODS Forty-nine patients (mean age 41±16 years), 25 with CD and 23 with UC, and forty controls (mean age 45±15 years) were enrolled. Diagnosis was based on the standard clinical, endoscopic and histological criteria. Disease activity was assessed by Crohns Disease Activity Index or Disease Activity Index. All patients, were under medical treatment as appropriate. RESULTS FMD values were lower in IBD patients than controls (6.1±3.0 vs 8.2±3.4. p=0.003); no difference was seen between UC/CD groups (5.9±3.5 vs 6.3±2.6, p=0.67). No changes in statistical differences occurred after adjustment for age, gender, body mass index and family history of cardiovascular disease. Finally, no differences in IMT values were seen between IBD patients and controls. Disease duration and medical treatment did not affect endothelial function. CONCLUSIONS Our study showed a lower FMD in IBD patients. Inflammation and immune response could explain endothelial dysfunction, which is the earliest stage of atherosclerotic process. IBD patients in active phase might therefore be at higher risk for atherosclerosis progression.

Dietary, Endocrine, and Metabolic Factors in the Development of Colorectal Cancer

IntroductionColorectal cancer is the third cause of death in industrialized countries. Genetic susceptibility and diet are determinant of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual genome, will likely provide important clues about responders and non-responders to nutritional intervention.DiscussionEpidemiological and experimental studies suggest a protective role of some normal components of daily diet (fish oil, milk, and vegetables), estrogens, and phytoestrogens in colorectal cancer. The effect of estrogen seems to be mediated by their binding to estrogen receptor beta (ER-β), one of the two estrogen receptors with high affinity for these hormones. Very recently, the demonstration of an involvement of ER-β in the development of adenomatous polyps of the colon has also been documented, suggesting the use of selective ER-β agonists in primary colorectal cancer prevention. Phytoestrogens are plant-derived compounds that structurally and functionally act as estrogen agonists in mammals. They are characterized by a higher binding affinity to ER-β as compared to estrogen receptor alpha (ER-α), the other estrogen receptor subtype. These biological characteristics explain why the administration of phytoestrogens does not produce the classical side effects associated to estrogen administration (cerebro- and cardiovascular accidents, higher incidence of endometrial and breast cancer) and makes these substances potential candidates for colorectal cancer prevention.

Estrogen receptors expression in long-lasting ulcerative pancolitis with and without dysplasia: A preliminary report

Please check these proofs carefully. It is the responsibility of the corresponding author to check against the original manuscript and approve or amend these proofs. A second proof is not normally provided. Informa Healthcare cannot be held responsible for uncorrected errors, even if introduced during the composition process. The journal reserves the right to charge for excessive author alterations, or for changes requested after the proofing stage has concluded.

Gastroenterology: Video capsule endoscopy disclosure of unprecedented therapeutic effect of Eviendep on small bowel polyposis in Lynch syndrome

Lynch syndrome (LS) is an autosomal dominant condition featuring defects in mismatch repair genes (MLH1, MSH2, PMS2 and MSH6). LS accounts for 2–5 % of colorectal cancers (CRC), characterized by early onset, predominantly right-sided, synchronous and metachronous, and extracolonic malignancies. In LS patients the small-bowel carcinoma risk is >100-fold that of the general population, affecting the entire small bowel (proximal: 43%, jejunum: 33%, ileum: 7%); prognosis is poor. Epidemiological and experimental studies demonstrate a protective role of estrogens against CRC, mediated by binding to beta receptors (ER-β). A mixture of phytoestrogens and insoluble fibers (Eviendep®, CMD Pharma Limited, London, UK) selectively increased ER-β expression. In adenomatous polyposis mouse models (ApcMin/+), Eviendep® reduced polyp size, number, and dysplasia. In Familial Adenomatous Polyposis with recurrent duodenal adenomas, 90-day supplementation with Eviendep® markedly reduced polyp number and size. We report the case of a 55-year-old man, who underwent right hemicolectomy for CRC when he was 28. After 24 years, a subtotal colectomy and 15 cm-ileum resection were performed for carcinoma recurrence; a mutation in gene hMSH1 was detected (LS diagnosis). Video capsule endoscopy (VCE) (PillCam SB2 CE system, Given Imaging Ltd., Israel) demonstrated few small gastric polyps and multiple polyps covering the intestinal mucosa (Fig. 1). Sigmoidoscopy showed a normal ileocolic anastomosis. Magnetic Resonance enteroclysis (MRE) confirmed VCE findings: multiple intraluminal sessile and pedunculated protrusions at the jejunum and ileum (size: 5–15 mm) (Fig. 2). After giving informed consent, the patient started dietary supplementation with Eviendep® (2 sachets/day/3 months). Subsequently, MRE showed a significant reduction of polyp number and size (Fig. 3). Therefore, Eviendep® was continued for a further 6 months, and VCE showed a further reduction in number and size of small bowel polyps. After 9 months VCE showed no abnormality in the esophagus and stomach. A small polyp (0.2 cm) in the duodenal bulb and two small polyps (0.1 cm) in the jejunum were detected; rare polyps (about 5) measuring 0.1 cm were seen in the proximal ileum and a few (5–6), mean size 0.2, in the distal ileum (Fig. 4). Our report confirms the promise of Eviendep® as a chemopreventive agent for intestinal polyps.

Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors

Background Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Methods Crohns disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. Results For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). Conclusions NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.

Sa1260 Non Invasive Evaluation of Endothelial Function in Inflammatory Bowel Diseases

In the last decades an ever-growing body of evidence has suggested the involvement of intestinal microvascular endothelial cells in development and maintenance of inflammatory bowel diseases (IBD). Changes in structure and function of endothelium, mediated by a multifaceted network of chemokines, cytokines and inflammatory growth factors, are a distinctive feature of active disease. In addition, human intestinal microvessels taken from inflamed mucosa exhibit consistent degrees of endothelial dysfunction, with significant impairment of acetylcholine-induced vasodilation based on decreased endothelial nitric oxide (NO) synthase (eNOS) activity. By “endothelial dysfunction” is comprehensively meant a condition in which the varied homeostatic functions of endothelium are impaired. Endothelial function can be measured through the flow-mediated dilation (FMD) technique, a wellestablished non invasive procedure in which changes in the calibre of the brachial artery induced by an increased vessel wall shear stress are measured ultrasonographically. AIM: The present study was designed to evaluate whether FMD at the brachial artery was impaired in a sample of patients with Crohns disease (CD) and ulcerative colitis (UC) in comparison to healthy control subjects. As a secondary measure of interest, intima-media thickness at the common carotid artery (ccIMT) was also calculated. MATERIALS AND METHOD: 49 patients (25 males; mean age, 41 yrs ± 16) with CD (26) and UC (23) in moderate-severe activity phase were included. Endothelial function was assessed through FMD and shear stress reactive hyperemia determination; moreover, ccIMT was measured ultrasonographically. Statistical analyses were made by using Statistica 6.1 software (StatSoft Inc.. Tulsa. OK. USA). RESULTS: In IBD patients FMD% values were significantly lower than in controls (6.3±3.3 vs 8.1±3.4, p=0.013). Such difference was not related to age, sex, disease duration, or comorbidity (such as, hypertension or diabetes). On the contrary, ccIMT measurements did not differ consistently between cases and controls. CONCLUSIONS: IBD group showed significant levels of endothelium dysfunction compared with controls. In our view, this result was more likely related to systemic inflammation than to traditional risk factors. By contrast, the lack of significant differences in ccIMT was possibly related to the low mean age and disease duration in our study population. Future studies of endothelial function are warranted comparing case series before and after remission obtained under elective treatments.