Pre-illness changes in dietary habits and diet as a risk factor for inflammatory bowel disease: A case-control study

AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an age-matched healthy control group. METHODS: Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease) and 160 healthy controls were studied. Portions per week of 34 foods and beverages before onset of symptoms were recorded using a validated questionnaire. Duration of symptoms before IBD diagnosis, presence of specific symptoms and their impact on subjective changes in usual dietary habits were also recorded. The association between diet and IBD was investigated by multiple logistic regression and dietary patterns were assessed by factor analysis. RESULTS: Changes in dietary habits, due to the presence of symptoms, were reported by 38.6% of patients and were not significantly related to specific symptoms, rather to long duration of symptoms, only in Crohn's disease patients. In IBD patients who did not change dietary habits, moderate and high consumption of margarine (OR = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high consumption of red meat (OR = 7.8) and high intake of cheese were associated with Crohn's disease. CONCLUSION: More than one third of IBD patients change dietary habits before diagnosis. Margarine, red meat and cheese increase the risk of ulcerative colitis and Crohn's disease.

Comprehensive review on EUS-guided biliary drainage

Feasibility of endoscopic retrograde cholangiopancreatography(ERCP) for biliary drainage is not always applicable due to anatomical alterations or to inability to access the papilla. Percutaneous transhepatic biliary drainage has always been considered the only alternative for this indication. However,endoscopic ultrasonography-guided biliary drainage represents a valid option to replace percutaneous transhepatic biliary drainage when ERCP fails. According to the access site to the biliary tree,two kinds of approaches may be described: the intrahepatic and the extrahepatic. Endoscopic ultrasonography-guided rendezvous transpapillary drainage is performed where the second portion of the duodenum is easily reached but conventional ERCP fails. The recent introduction of self-expandable metal stents and lumen-apposing metal stents has improved this field. However,the role of the latter is still controversial. Echoendoscopic transmural biliary drainage can be challenging with potential severe adverse events. Therefore,trained endoscopists,in both ERCP and endoscopic ultrasonography are needed with surgical and radiological backup.

Role of the advanced glycation end products receptor in Crohn's disease inflammation

AIM:To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products(RAGE)in delayed apoptosis and tumor necrosis factor(TNF)-αproduction in Crohn’s disease(CD).METHODS:Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients,respectively,and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis.Normal tissues from 21 control subjects were used for comparison.The same polyclonal anti-human RAGE antibody(R and D System)was used in all experimental conditions.RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity;cellular pattern was also described.The effects of RAGE blocking on apoptotic rate and TNF-αproduction were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus.Statistical analysis was performed via the test for trend,with regression models to account for intra-patient correlations.A 2-sided P<0.05 was considered significant.RESULTS:In inflamed areas,RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues(P=0.001 and 0.021,respectively),and a cluster of positive cells were usually found in proximity of ulcerative lesions.Similar results were obtained in the lamina propria compartment of non-inflamed areas(P=0.025).The pattern of staining was membranous and granular cytosolic at the epithelial level,while in the lamina propria it was diffuse cytosolic.When evaluating the amount of protein expression by immunoblotting,a significant increase of both surface area and band intensity(P<0.0001 for both)was observed in CD inflamed areas compared to control tissue,while in non-inflamed areas a significant increase was found only for band intensity(P<0.005).Moreover,a significantly lower expression in noninflamed areas in comparison with inflamed areas was found for both surface area and band intensity(P<0.0006 for both).Finally,RAGE blocking largely affects both the apoptotic rate of mucosal cells(towards an increase in both non-inflamed and inflamed areas of P<0.001 and<0.0001,respectively)and TNF-αsecretion(towards a decrease in both non-inflamed and inflamed areas of P<0.05 and<0.01,respectively),mainly in the presence of antigenic stimulation.CONCLUSION:RAGE is up-regulated in CD,especially in inflamed areas,and it appears to play a role in the mechanisms involved in chronic inflammation.

Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy

AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.

Combined therapeutic approach:Inflammatory bowel diseases and peripheral or axial arthritis

Inflammatory bowel diseases(IBDs), particularly Crohn's disease(CD) and ulcerative colitis(UC), are associated with a variety of extra-intestinal manifestations(EIMs).About 36% of IBD patients have at least one EIM, which most frequently affect the joints, skin, eyes and the biliary tract.The EIMs associated with IBD have a negative impact on patients with UC and CD, and the resolution of most of them parallels that of the active IBD in terms of timing and required therapy;however, the clinical course of EIMs such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis is independent of IBD activity.The peripheral and axial arthritis associated with IBD have traditionally been treated with simple analgesics, non-steroidal anti-inflammatory drugs, steroids, sulfasalazine, methotrexate, local steroid injections and physiotherapy, but the introduction of biological response modifi ers such as tumor necrosis factor-α blockers, has led to further improvements.

Glucose intolerance and diabetes mellitus in ulcerative colitis: Pathogenetic and therapeutic implications

Diabetes mellitus is one of the most frequent co-morbidities of ulcerative colitis patients.The epidemiological association of these diseases suggested a genetic sharing and has challenged gene identification.Diabetes co-morbidity in ulcerative colitis has also relevant clinical and therapeutic implications,with potential clinical impact on the follow up and outcome of patients.These diseases share specific complications,such as neuropathy,hepatic steatosis,osteoporosis and venous thrombosis.It is still unknown whether the coexistence of these diseases may increase their occurrence.Diabetes and hyperglycaemia represent relevant risk factors for postoperative complications and pouch failure in ulcerative colitis.Medical treatment of ulcerative colitis in patients with diabetes mellitus may be particularly challenging.Corticosteroids are the treatment of choice of active ulcerative colitis.Their use may be associated with the onset of glucose intolerance and diabetes,with difficult control of glucose levels andwith complications in diabetic patients.Epidemiologic and genetic evidences about diabetes co-morbidity in ulcerative colitis patients and shared complications and treatment of patients with these diseases have been discussed in the present review.

Endoscopic retrograde cholangiopancreatography,lights and shadows:Handle with care

The role of endoscopic retrograde cholangiopancreatography(ERCP) has dramatically changed in the last years, mainly into that of a therapeutic procedure. The treatment of benign biliary disease, like "difficult"choledocolithiasis, with endoscopic papillary large balloon dilation combined with endoscopic sphinterotomy has proven an effective and safe technique.Moreover, safety in ERCP has improved as well, with the prevention of postERCP pancreatitis and patient-to-patient transmission of infections. The advent of self-expandable metal stenting has radically changed the management of biliopancreatic malignant strictures, while the role for therapy of benign strictures is still controversial. In addition, cholangioscopy(though the direct visualization of the biliopancreatic ductal system) has allowed for characterization of indeterminate biliary strictures and facilitated rescue therapy of large biliary stones deemed removable. Encouraging data from tissue ablation techniques, such as photodynamic therapy and radiofrequency ablation, need to be confirmed by large sample size clinical controlled trials. On the other hand, we have no drug-coated stents yet available to implant and evidence for the use of biodegradable stents is still weak. The competency and privileging of ERCP and endoscopic ultrasonography have been analyzed longer but the switch between the two procedures, at the same time, is becoming ordinary; as such, the endoscopist interested in this field should undergo parallel edification through training plans. Finally, the American Society for Gastrointestinal Endoscopy's statement on non-anesthesiologist administration of propofol for gastrointestinal endoscopy is not actually endorsed by the European Society of Anaesthesiology,having many medical-legal implications in some European countries.