Body mass index and the risk for Crohn's disease and ulcerative colitis: data from a European Prospective Cohort Study (The IBD in EPIC Study).

OBJECTIVES: Obesity is associated with a proinflammatory state that may be involved in the etiology of inflammatory bowel disease (IBD), for which there are plausible biological mechanisms. Our aim was to perform the first prospective cohort study investigating if there is an association between obesity and the development of incident IBD. METHODS: A total of 300,724 participants were recruited into the European Prospective Investigation into Cancer and Nutrition study. At recruitment, anthropometric measurements of height and weight plus physical activity and total energy intake from validated questionnaires were recorded. The cohort was monitored identifying participants who developed either Crohn's disease (CD) or ulcerative colitis (UC). Each case was matched with four controls and conditional logistic regression used to calculate odds ratios (ORs) for body mass index (BMI) adjusted for smoking, energy intake, and physical activity. RESULTS: In the cohort, 177 participants developed incident UC and 75 participants developed incident CD. There were no associations with the four higher categories of BMI compared with a normal BMI for UC (Ptrend=0.36) or CD (Ptrend=0.83). The lack of associations was consistent when BMI was analyzed as a continuous or binary variable (BMI 18.5<25.0 vs. ≥25 kg/m(2)). Physical activity and total energy intake, factors that influence BMI, did not show any association with UC (physical activity, Ptrend=0.79; total energy intake, Ptrend=0.18) or CD (physical activity, Ptrend=0.42; total energy, Ptrend=0.11). CONCLUSIONS: Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD.

Pneumatosis intestinalis as the initial presentation of systemic sclerosis: a case report and review of the literature.

Introduction. Pneumatosis intestinalis (PI) is an uncommon pathology characterised by the presence of gas within the intestinal wall. It has been associated with various conditions, including connective tissue diseases. This is the first report of PI being the initial presentation of systemic sclerosis. Case Presentation. The patient, a 75-year-old female, presented with an 8-month history of worsening dysphagia and epigastric pain, as well as other nonspecific symptoms. Initial investigations with an oesophagogastroduodenoscopy diagnosed Candida oesophagitis and also identified an extrinsic compression of the gastric antrum. Subsequently a CT scan of the abdomen and pelvis showed moderately dilated small bowel loops and PI. Due to the patient's stability, non-critical clinical condition, conservative management was instituted. More detailed investigations confirmed the diagnosis of systemic sclerosis with positive anticentromeric and antinuclear antibodies. The patient improved on methotrexate and was discharged with appropriate outpatient follow-up. Discussion. PI is a rare but well-documented pathology associated with connective tissue diseases, such as systemic sclerosis. In most cases, conservative management is preferable to surgical intervention, depending on the patient's clinical presentation and progress. This is the first report of PI being the initial presentation of a patient with systemic sclerosis responsive to conservative management.

The reasons for discontinuation of infliximab treatment in patients with Crohn's disease: a review of practice at NHS teaching hospital.

Introduction. There is little information on the reasons for discontinuing infliximab treatment in patients with Crohn's disease. The aim of this study was to document these reasons to determine if any were preventable which would allow patients to continue the therapy. Aims & Methods. A review of the medical notes was conducted at the Norfolk and Norwich University Hospital on patients with Crohn's disease treated with infliximab between 2002-2008 to determine the reasons for stopping it. Results. A total of 65 patients were identified who had treatment with infliximab, of whom 23 (35.3%) had their therapy stopped. The reasons for discontinuation of infliximab in the 23 patients were: 47.8% side effects, 17.4% refractory disease, 13.0% achieved remission and did not receive long-term maintenance treatment, 4.34% pregnancy, 4.34% death, and unknown 13.0%. Conclusions. The main reasons for the discontinuation of infliximab were side effects rather than a lack of clinical response.

Preventing bowel cancer: an insight for clinicians.

Worldwide, colorectal cancer causes 610,000 deaths annually with 38,000 new cases diagnosed in the UK and 16,000 deaths each year. The prognosis is directly related to the staging of the cancer at diagnosis, with an overall 5-year survival rate of approximately 50%. However, for localized disease the figure is much higher at 90%, although unfortunately many cancers present at an advanced stage. Importantly, there is the potential to reduce the incidence because most tumours arise from premalignant adenomatous polyps, which if detected and removed interrupts the adenoma-adenocarcinoma sequence. In addition, identifying colorectal cancer at an early stage can impact on the mortality rates for this neoplasm. The current screening options for bowel cancer include analysis of stool for occult blood and endoscopic assessments of the colorectum, including flexible sigmoidoscopy and full colonoscopy. The aim of this review is to present information on the natural history of colorectal cancer, the evaluation of the different screening modalities and the current faecal occult blood screening program within the UK National Health Service, and to discuss how dietary factors and aspirin may affect aetiology.

Ulcerative colitis: current medical therapy and strategies for improving medication adherence.

Ulcerative colitis (UC) is chronic inflammation of large intestine and often requires lifelong medication. Medical therapy aims to induce and maintain a clinical remission, reduce the risk of colorectal cancer and improve quality of life. Aminosalicylates are currently the first choice therapy both for the induction and the maintenance of remission in the patients with mild-to-moderate UC. For moderate-to-severe cases or those who do not respond to aminosalicylate therapy, additional treatment options including corticosteroids, immunomodulators, biological agents, cyclosporin, tacrolimus and surgery are available. Poor adherence to medication has been an important barrier to successful management of UC. Nonadherence has been associated with increased relapse rates, higher risk of colorectal cancer, poor quality of life and significantly increased healthcare costs. Therefore, improving adherence to medication is an important approach for a better care of the patients with UC. Definitive strategies are required to help the patients effectively self manage their disease and improve adherence. This review examines current medical therapy for UC, research progresses on medication adherence and the possible strategies for improving adherence in these patients.

Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control.

BACKGROUND: Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. METHODS: We examined telomere length (by flow fluorescent in situ hybridization) and oxidative DNA damage (flow cytometry of 8 - oxoguanosine) in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9%) and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. RESULTS: Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5). Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7). There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1). CONCLUSION: Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism.

Diet in the aetiology of ulcerative colitis: a European prospective cohort study.

BACKGROUND/AIMS: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study. METHODS: The study population was 260,686 men and women aged 20-80 years, participating in a large European prospective cohort study (EPIC). Participants were residents in the UK, Sweden, Denmark, Germany or Italy. Information on diet was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles. RESULTS: A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99-1.43) p = 0.07). CONCLUSIONS: No associations between ulcerative colitis and diet were detected, apart from a possible increased risk with a higher total polyunsaturated fatty acid intake. A biological mechanism exists in that polyunsaturated fatty acids are metabolised to pro-inflammatory mediators.

Pancreatic cancer: a review of the evidence on causation.

Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.

Hepatology outpatient service provision in secondary care: a study of liver disease incidence and resource costs.

This paper discusses the annual incidence of liver disease and resource costs in providing a hepatology service for all new outpatient referrals to a secondary care setting. In a retrospective study, we found that 200 patients (1 in 1,000 of the West Suffolk population) with a mean age of 52 years were referred per year. One-third of patients had cirrhosis (almost half due to alcohol). Annual incidence (per 100,000 population) were as follows: non-alcoholic fatty liver disease (29: of which 23.5 non-cirrhotic and 5.5 cirrhotic), hepatitis C (25), hepatitis B (3), alcohol-related cirrhosis (12.5), primary biliary cirrhosis (3.5), autoimmune hepatitis (3), primary sclerosing cholangitis (2), haemochromatosis (2), hepatocellular carcinoma (1.5) and oesophageal variceal haemorrhage (6.5). Using national indicative tariffs, the total annual hepatology budget was 130K pounds (58K pounds for resources and 72K pounds for clinic attendances). The greatest resource expenditure was on endoscopy (almost half for oesophageal varices) and radiological imaging (one-third of the total budget). These findings will help inform commissioners in hepatology service funding.