Influence of environmental factors on the onset and courseof inflammatory bowel disease

Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn's disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn's disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course.

Emerging role of narrow band imaging in duodenum

Endoscopy using magnification narrow band imaging(m NBI) allows detailed assessment of mucosal surface and vascular pattern. This may help in better identification and prediction of the nature of the lesion. The role of this technology in duodenum is still evolving. Studies have shown that m NBI has high accuracy in predicting villous atrophy in the duodenum. Limited data suggests that this technique can provide additional information on duodenal polyps,nodules and ampullary tumour which can help guide their management. In this paper we describe the technique for duodenal assessment using NBI and review the existing literature evaluating its role in diagnosis of various duodenal pathologies.

Concise review on the comparative efficacy of endoscopic ultrasound-guided fine-needle aspiration vs core biopsy in pancreatic masses, upper and lower gastrointestinal submucosal tumors

Endoscopic ultrasound(EUS)-guided fine needle aspiration with or without biopsy(FNA/FNB) are the primary diagnostic tools for gastrointestinal submucosal tumors. EUS-guided fine needle aspiration(EUS-FNA) is considered a first line diagnostic method for the characterization of pancreatic and upper gastrointestinal lesions, since it allows for the direct visualization of the collection of specimens for cytopathologic analysis. EUSFNA is most effective and accurate when immediate cytologic assessment is permitted by the presence of a cytopathologist on site. Unfortunately, the accuracy and thus the diagnostic yield of collected specimens suffer without this immediate analysis. Recently, a EUS-FNB needle capable of obtaining core samples(fine needle biopsy, FNB) has been developed and has shown promising results. This new tool adds a new dimension to the diagnostic and therapeutic utility of this technique. The aim of the present review is to compare the efficacy of EUS-FNA to that afforded by EUS-FNB in the characterization of pancreatic masses and of upper and lower gastrointestinal submucosal tumors.

Inflammatory bowel disease patient profiles are related to specific information needs: A nationwide survey

BACKGROUND Inflammatory bowel diseases(IBD) is a heterogenous, lifelong disease, with an unpredictable and potentially progressive course, that may impose negative psychosocial impact on patients.While informed patients with chronic illness have improved adherence and outcomes, previous research showed that the majority of IBD patients receive insufficient information regarding their disease.The large heterogeneity of IBD and the wide range of information topics makes a one-size fits all knowledge resource overwhelming and cumbersome.We hypothesized that different patient profiles may have different and specific information needs, the identification of which will allow building personalized computer-based information resources in the future.AIM To evaluate the scope of disease-related knowledge among IBD patients and determine whether different patient profiles drive unique information needs.METHODS We conducted a nationwide survey addressing hospital-based IBD clinics.A Total of 571 patients completed a 28-item questionnaire, rating the amount of information received at time of diagnosis and the importance of information, as perceived by participants, for a newly diagnosed patient, and for the participants themselves, at current time.We performed an exploratory factor analysis of the crude responses aiming to create a number of representative knowledge domains(factors), and analyzed the responses of a set of 15 real-life patient profiles generated by the study team.RESULTS Participants gave low ratings for the amount of information received at disease onset(averaging 0.9/5) and high ratings for importance, both for the newly diagnosed patients(mean 4.2/5) and for the participants themselves at current time(mean 3.5/5).Factor analysis grouped responses into six informationdomains.The responses of selected profiles, compared with the rest of the participants, yielded significant associations(defined as a difference in rating of >0.5 points with a P < 0.05).Patients with active disease showed a higher interest in work-disability, stress-coping, and therapy-complications.Patients newly diagnosed at age > 50, and patients with long-standing disease(> 10 years)showed less interest in work-disability.Patients in remission with mesalamine or no therapy showed less interest in all domains except for nutrition and long-term complications.CONCLUSION We demonstrate unmet patient information needs.Analysis of various patient profiles revealed associations with specific information topics, paving the way for building patient-tailored information resources.

Targeting late SV40 factor: Is the achilles heel of hepatocarcinogenesis revealed?

Hepatocellular carcinoma (HCC) is a dreadful cancer and a major cause of death among patients with chronic liver disease and cirrhosis. The apparent alterations in a diversity of intracellular pathways found in HCC has set the rational for developing molecular-directed drugs that simultaneously inhibit multiple pathways, such as the multi-kinase inhibitor Sorafenib. However, recently this concept has been challenged by showing that HCC is heavily dependent on a single oncogene designated late SV-40 factor (LSF), a transcription factor that is over-expressed in liver cancer cells and that its expression is strongly correlated with tumor grade and aggressiveness. Furthermore, using an intensive screening for drugs that inhibit LSF activity, Grant et al have found a molecule designated factor quinolinone inhibitor 1 that can specifically block the ability of LSF to bind its target promoters, resulting in a massive death of HCC cells both in vitro and in vivo. The innovative findings of HCC representing "oncogene addiction" to LSF and the ability of a single molecule to block the activity of this oncogene resulting in tumor abolishment are encouraging and provide us with the hope that the "Achilles heel" of HCC has been found.

Do inflammatory bowel disease patient preferences from treatment outcomes differ by ethnicity and gender?A cross-sectional observational study

BACKGROUND Inflammatory bowel disease(IBD)patients’expectations of treatment outcomes may differ by ethnicity.AIM To investigate treatment preferences of Jewish and Arabs patients.METHODS This prospective survey ranked outcomes treatment preferences among Arab IBD patients,based on the 10 IBD-disk items compared to historical data of Jews.An anonymous questionnaire in either Arabic or Hebrew was distributed among IBD patients.Patients were required to rank 10 statements describing different aspects of IBD according to their importance to the patients as treatment goals.Answers were compared to the answers of a historical group of Jewish patients.RESULTS IBD-disk items of 121 Arabs were compared to 240 Jewish patients.The Jewish patients included more females,[151(62.9%)vs 52(43.3%);P<0.001],higher education level(P=0.02),more urban residence[188(78.3%)vs 54(45.4%);P<0.001],less unemployment[52(21.7%)vs 41(33.9%);P=0.012],higher income level(P<0.001),and more in a partnership[162(67.8%)vs 55(45.4%);P<0.001].Expectations regarding disease symptoms:abdominal pain,energy,and regular defecation ranked highest for both groups.Arabs gave significantly lower rankings(range 4.29-6.69)than Jewish patients(range 6.25-9.03)regarding all items,except for body image.Compared to Arab women,Jewish women attached higher priority to abdominal pain,energy,education/work,sleep,and joint pain.Multivariable regression analysis revealed that higher patient preferences were associated with Jewish ethnicity(OR 4.77;95%CI 2.36-9.61,P<0.001)and disease activity.The more active the disease,the greater the odds ratio for higher ranking of the questionnaire items(1-2 attacks per year:OR 2.13;95%CI 1.02-4.45,P=0.043;and primarily active disease:OR 5.29;95%CI 2.30-12.18,P<0.001).Factors inversely associated with higher patient preference were male gender(OR 0.5;95%CI 0.271-0.935,P=0.030),UC(OR 0.444;95%CI 0.241-0.819,P=0.009),and above average income level(OR 0.267;95%CI:0.124-0.577,P=0.001).CONCLUSION The highest priority for treatment outcomes was symptom relief.,Patients preferences were impacted by ethnicity,gender,and socio-economic disparity.Understanding patients'priorities may improve communication and enable a personalized approach.

Prior abdominal surgery as a potential risk factor for colonic diverticulosis or diverticulitis

BACKGROUND Abnormal colonic pressure profiles have been associated with an increased risk of colonic diverticulosis.A surgical history is a known risk factor for abdominal adhesions and these may lead to increased intraluminal colonic pressure.AIM To assess whether previous abdominal surgery is associated with colonic divertic-ulosis or diverticulitis.METHODS We analyzed data from a study of patients undergoing colonoscopy for different indications from 2020 through 2021.Patients completed a structured question-naire concerning previous abdominal surgeries,dietary and lifestyle exposures including smoking,alcohol use and co-morbidities.RESULTS Three hundred and fifty-nine patients were included in the study.The mean age was 67.6 and 46%were females.Diabetes mellitus,hypertension,ischemic heart disease,chronic obstructive pulmonary disease,chronic renal failure,and body mass index were similar in the diverticulosis and control groups.The overall prevalence of colonic diverticulosis was 25%(91/359)and 48%of the patients had previous abdominal surgery.As expected,the prevalence of diverticulosis increased with age.There was no difference in the rate of previous abdominal surgery between patients with or without diverticulosis(49%vs 47%,P=0.78).In regards to specific surgeries,inguinal hernia repair was significantly associated with diverticulosis(52%vs 20%,P=0.001),but not diverticulitis.In contrast,appendectomy was not associated with diverticulosis(6%vs 14%,P=0.048).CONCLUSION These findings suggest that post-operative abdominal adhesions inducing high colonic intraluminal pressures do not appear to be the mechanism for diverticula formation.Rather,inguinal hernia and diverticulosis may share similar connective tissue pathologies with no causative relationship between them.

Head mass in chronic pancreatitis: Inflammatory or malignant

Chronic pancreatitis increases the risk of developing pancreatic cancer. This often presents as a mass lesion in the head of pancreas. Mass lesion in the head of pancreas can also occur secondary to an inflammatory lesion. Recognising this is crucial to avoid unnecessary surgery. This is sometimes difficult as there is an overlap in clinical presentation and conventional computed tomography(CT) abdomen findings in inflammatory andmalignant mass. Advances in imaging technologies like endoscopic ultrasound in conjunction with techniques like fine needle aspiration, contrast enhancement and elastography as well as multidetector row CT, magnetic resonance imaging and positron emission tomography scanning have been shown to help in distinguishing inflammatory and malignant mass. Research is ongoing to develop molecular techniques to help characterise focal pancreatic mass lesions. This paper reviews the current status of imaging and molecular techniques in differentiating a benign mass lesion in chronic pancreatitis and from malignancy.

Factors associated with surgery in patients with intra-abdominal fistulizing Crohn's disease

AIM To characterize radiological and clinical factors associated with subsequent surgical intervention in Crohn's disease(CD) patients with intra-abdominal fistulae.METHODS From a cohort of 1244 CD patients seen over an eight year period(2006 to 2014), 126 patients were identified as having intra-abdominal fistulae, and included in the study. Baseline patient information was collected from the medical records. Imaging studies were assessed for: anatomic type and number of fistulae; diameter of the inflammatory conglomerate; length of diseased bowel; presence of a stricture with pre-stenotic dilatation; presence of an abscess; lymphadenopathy; and the degree of bowel enhancement. Multivariate analysis for the prediction of abdominal surgery was calculated via Generalized Linear Models.RESULTS In total, there were 193 fistulae in 132 patients, the majority(52%) being entero-enteric. Fifty-nine(47%) patients underwent surgery within one year of the imaging study, of which 36(29%) underwent surgery within one month. Radiologic features that were associated with subsequent surgery included: multiple fistulae(P = 0.009), presence of stricture(P = 0.02), and an entero-vesical fistula(P = 0.01). Evidence of an abscess, lymphadenopathy, or intense bowel enhancement as well as C-reactive protein levels was not associated with an increased rate of surgery. Patients who were treated after the imaging study with combination immunomodulatory and anti-TNF therapy had significantly lower rates of surgery(P = 0.01). In the multivariate analysis, presence of a stricture [RR 4.5(1.23-16.3), P = 0.02] was the only factor that increased surgery rate.CONCLUSION A bowel stricture is the only factor predicting an increased rate of surgery. Radiological parameters may guide in selecting treatment options in patients with fistulizing CD.

Human microbiome: From the bathroom to the bedside

The human gut contains trillions of bacteria, the major phylae of which include Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. Fecal microbial transplantation(FMT) has been known of for manyyears but only recently has been subjected to rigorous examination. We review the evidence regarding FMT for recurrent Clostridium difficile infection which has resulted in it being an approved treatment. In addition there is some evidence for its use in both irritable bowel syndrome and inflammatory bowel disease. Further research is needed in order to define the indications for FMT and the most appropriate method of administration.

Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease

Background:Family studies support a genetic predisposition to inflammatory bowel diseases(IBD),but known genetic variants only partially explain the disease heritability.Families withmultiple affected individuals potentially harbour rare and highimpact causal variants.Long regions of homozygosity due to recent inbreedingmay increase the risk of individuals bearing homozygous loss-of-function variants.This study aimed to identify rare and homozygous genetic variants contributing to IBD.Methods:Four families with known consanguinity and multiple cases of IBD were recruited.In a family-specific analysis,we utilised homozygosity mapping complemented by whole-exome sequencing.Results:We detected a single region of homozygosity shared by Crohn’s disease cases from a family of Druze ancestry,spanning 2.6Mb containing the NOD2 gene.Whole-exome sequencing did not identify any potentially damaging variants within the region,suggesting that non-coding variation may be involved.In addition,affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1,WHAMM,DENND3,and C5.Conclusion:This study examined the potential contribution of rare,high-impact homozygous variants in consanguineous families with IBD.While the analysis was not designed to achieve statistical significance,our findings highlight genes or loci that warrant further research.Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn’s disease.