Mariabeatrice Principi

Oral tacrolimus long-term therapy in patients with Crohn's disease and steroid resistance.

To report the results of a prospective, open‐label, uncontrolled study in 13 patients affected by Crohn’s disease with resistance to steroids.

Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease?

Inflammatory bowel diseases (IBDs), namely Crohns disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota (i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in the literature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.

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 lifestyle and colorectal cancer onset, recurrence, and survival: myth or reality?

Background and PurposeInterest in the possibility that diet might help to reduce the risk of colorectal cancer dates back to 1970 based on both the large variation in rates of specific cancers in different countries and the impressive changes observed in the incidence of cancer in migrants from low- to high-risk areas. Here, we report the state of art of literature data about this topic.MethodsThree sections have been separately considered: chemoprevention of first tumor onset, chemoprevention of recurrence after surgery, and chemoprevention of polyp recurrence in the course of the follow-up of subjects with elevated risk. A particular attention has been pointed to dietary factors and survival, whose relevance is showing a growing interest.ResultsThe relationship between diet and colorectal cancer has been extensively studied about the onset, sometimes with controversial results. Its influence on recurrence and survival has been examined in only few studies.ConclusionsLiterature data are convincing for a protective role on the onset of preneoplastic and neoplastic lesions for some foods such as fibers, vitamin A and D, folic acid, calcium, antioxidants, and promising perspectives for some substances such as phyto-estrogens. Less evidence-based data are available on the possibility to avoid the recurrence of the disease or to affect its mortality with dietary habits. Future perspectives will be directed be not only to identify new dietary style able to prevent the onset of neoplastic lesion of the colon but also to realize an effective chemoprevention.

Effect of probiotic or prebiotic supplementation on antibiotic therapy in the small intestinal bacterial overgrowth: A comparative evaluation

UNLABELLED Bacterial intestinal overgrowth syndrome (SIBO) treatment is based on antibiotics. Probiotics have been shown to give similar results, whilst no study is available about prebiotics. This study evaluated the addition of probiotics or prebiotics to antibiotics on SIBO symptoms in a 6-month follow-up. We enrolled 40 patients (14 males and 26 females) reporting abdominal compliant without gastrointestinal diseases/alarm symptoms. SIBO was diagnosed by the agreement of lactulose and glucose breath tests. Patients were randomly divided into two groups homogeneous for sex and age: group 1 received Rifaximin 400 mg/day for 7 days/month followed by Lactobacillus casei for 7 days more and group 2 antibiotic followed by short chain fructo-oligosaccharides. All patients recorded a questionnaire for subjective symptom evaluation according to Rome III criteria and Bristol scale for stool characters before the study and after 6 months. STATISTICS Students t and Fishers exact tests. In group 1, a significant improvement was obtained in 5 out of 6 symptoms, whilst in group 2 in 4 out of 6 symptoms (nausea and number of bowel movements failed to improve). Despite we observed a trend of probiotics to be more effective than prebiotics, the difference in the percentage of improved symptoms was not significant (83,3% vs 66.6%; p= 0.57). Our preliminary data show a good outcome with sequential antibioticprobiotic/ prebiotic administration in patients with SIBO.

Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage?

Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohns disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease. Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development. The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.

Epithelial Proliferation and ras p21 Oncoprotein Expression in Rectal Mucosa of Patients with Ulcerative Colitis

In ulcerative colitis (UC), epithelial proliferation plays a role in crypt repair and neoplastic evolution. Proliferative status is predominantly connoted in active disease, but not defined in remission. Histologically, remission is characterized by normalization of the picture or development of atrophy. Mutation of the ras oncogene is involved in intestinal carcinogenesis. Aim of this work was to assess the proliferative pattern of rectal epithelium in UC during disease activity and in remission and correlate it with ras oncoprotein p21. The study was performed retrospectively in rectal biopsies from four groups each of 10 patients: active ulcerative colitis (AUC), remission with a normal histology (RUC), remission with rectal atrophy (ARUC), and irritable bowel syndrome (C, control group). In all, immunohistostain was employed to evaluate the proliferation cell nuclear antigen labeling index (PCNA LI) and ras p21. Statistical analysis was performed by ANOVA and Student-Neumann-Keuls tests. %PCNA LI was significantly higher in AUC and ARUC than in RUC and C. Positive cells were predominant in the lower zone of crypts in RUC and C, while a significant expression of PCNA was also observed in the upper areas in AUC and ARUC. Oncoprotein p21 was expressed on the apical surface of the epithelium in 3/10 AUC patients, in all 10 ARUC patients and in none of RUC and C. %The persistently increased epithelial proliferation associated with ras p21 expression in ARUC may be due to the action of an abnormal, mutated ras gene that could play a role in UC-related tumorigenesis.

Chromoendoscopy for Surveillance in Ulcerative Colitis and Crohn’s Disease: A Systematic Review of Randomized Trials

BACKGROUND & AIMS: Key international guideline agencies recommend dysplasia surveillance in inflammatory bowel diseases with chromoendoscopy. We performed a systematic review of randomized trials comparing chromoendoscopy vs other endoscopic techniques for dysplasia surveillance in inflammatory bowel diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant studies published through September 2016. We estimated risk ratios (RRs) for dichotomous outcomes (all‐cause/colorectal cancer‐related mortality, time to interval cancer, patients with dysplasia, total/subtypes of dysplastic lesions, dysplasia detected by targeted biopsies, adverse events), mean differences for continuous outcomes (procedural time, costs, total/targeted biopsies), and their 95% confidence intervals (CIs) using a random‐effects model. Subgroup analyses included technique compared with chromoendoscopy, type of disease, and type of dye. We estimated sensitivity and specificity of the techniques with reference to histology. RESULTS: We identified 10 randomized trials (n = 1500 participants). There was a higher likelihood of detecting patients with dysplasia with chromoendoscopy compared with other techniques (RR, 1.37; 95% CI, 1.04–1.79). Subgroup analyses confirmed this effect only if chromoendoscopy was compared with standard‐definition white‐light endoscopy (RR, 2.12; 95% CI, 1.15–3.91). Chromoendoscopy required a significantly longer procedural time compared with other techniques (mean difference, 8.91 min; 95% CI, 1.37–16.45). There was no difference in the likelihood of detecting dysplastic subtypes and dysplasia by targeted biopsies between groups. Test sensitivity and specificity were similar between groups. CONCLUSIONS: In surveillance of inflammatory bowel diseases, chromoendoscopy identifies more patients with dysplasia only when compared with standard‐definition white‐light endoscopy. It is associated with longer procedural time with no direct evidence of effect on preventing all‐cause/cancer‐specific mortality or time to interval cancer.

phytoestrogens/insoluble fibers and colonic estrogen receptor β: randomized, double-blind, placebo-controlled study

AIM To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

The Italian Registry of Therapeutic Apheresis: granulocyte-monocyte apheresis in the treatment of inflammatory bowel disease. A multicentric study.

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte–monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohns disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohns disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered.