A Poullis

Bowel Inflammation as Measured by Fecal Calprotectin: A Link between Lifestyle Factors and Colorectal Cancer Risk

The mechanisms by which the lifestyle risk factors obesity, physical inactivity, and low fiber intake predispose to colorectal cancer (CRC) are unclear. Chronic bowel inflammation predisposes to malignancy in cases of inflammatory bowel disease. Many lifestyle risk factors for CRC are associated with evidence of systemic inflammation as indicated by circulating levels of C-reactive protein (CRP), but it is unknown how this relates to inflammation at tissue level. Little is known about the degree of bowel inflammation in general population and the factors that affect it. Therefore, we aimed to assess the relation of levels of bowel inflammation in the general population and lifestyle risk factors for CRC, and to additionally assess whether these associations, if present, were attenuated by controlling for evidence of systemic inflammation. Average CRC risk subjects (320) of either sex aged 50–70 were recruited in South London. A stool sample was provided for calprotectin measurement (a marker of bowel inflammation), serum for CRP, and a detailed dietary and lifestyle questionnaire completed. There was a significant positive relationship between fecal calprotectin and increasing age (P = 0.002), obesity (P = 0.04), physical inactivity (P = 0.01), and an inverse relationship with fiber intake (P = 0.02) and vegetable consumption (P = 0.04). The relationship with obesity was attenuated by controlling for serum CRP. Fecal calprotectin levels are associated with lifestyle risk factors for colorectal cancer. Low-level asymptomatic bowel inflammation may be the link between lifestyle and the pathogenesis of CRC, and circulating proinflammatory cytokines may be part of the mechanism for this link.

A new, highly sensitive assay for C-reactive protein can aid the differentiation of inflammatory bowel disorders from constipation- and diarrhoea-predominant functional bowel disorders.

Background Patients presenting to gastroenterology clinics with symptoms suggestive of lower-bowel disorders often require extensive investigation to differentiate functional from organic disease. C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Levels of CRP are frequently raised in cases of inflammatory bowel disease (IBD). However, using conventional assays, not all cases of IBD have a detectable level. Objective To determine whether a new highly sensitive CRP enzyme-linked immunosorbent assay (ELISA) can aid the differentiation between IBD and functional bowel disorders (FBDs) in gastroenterology outpatients presenting with lower-bowel symptoms. Methods Serum was taken from 224 subjects attending a gastroenterology outpatient clinic. Of these, 203 were new patients and 21 were follow-up patients with quiescent colitis. The serum was analysed using a sensitive in-house ELISA. All new patients had a rigid sigmoidoscopy and rectal biopsy. Patients were investigated as deemed appropriate by the attending physician. Notes were reviewed after at least 6 months to determine the final diagnosis. Results A cut-off value of 2.3 mg/l had a sensitivity of 100% and a specificity of 67% in differentiating FBD from new cases of IBD. The geometric mean CRP was 0.383 mg/l in the constipation-predominant FBD group, 1.435 mg/l in diarrhoea-predominant FBD, 1.455 mg/l in quiescent IBD, 8.892 mg/l in newly presenting cases of ulcerative colitis, and 13.123 mg/l in newly presenting cases of Crohns disease. Conclusion A new, highly sensitive assay for CRP may help to distinguish FBD from IBD.

Emerging role of calprotectin in gastroenterology

Abstract  Calprotectin is a calcium and zinc binding protein of the S100 family derived predominantly from neutrophils and monocytes. It is detectable in body fluids and tissue samples and is emerging as a valuable marker in the diagnosis, and the monitoring and determining of the prognosis of commonly encountered gastroenterological conditions. Fecal calprotectin, in particular, has for a long time been regarded as a promising marker of gastrointestinal pathology and has now been established as a routine test in Norway and at several centers in the UK.

Systematic review: does gastro‐oesophageal reflux disease progress?

Gastro‐oesophageal reflux disease affects approximately 20% of western populations. Barretts oesophagus, associated with severe gastro‐oesophageal reflux disease, is premalignant and regular endoscopic surveillance is generally performed. In contrast, mild gastro‐oesophageal reflux disease is thought not to progress and is not generally subjected to endoscopic follow‐up.

Proton pump inhibitors are associated with elevation of faecal calprotectin and may affect specificity.

As part of a study to assess the normal range of faecal calprotectin in a late middle-aged population (that would be the target population for any colorectal cancer screening) [5], we assessed the effect of a number of commonly prescribed drugs. We found that patients using proton pump inhibitors (PPIs) had a significantly elevated faecal calprotectin level compared to those not on PPIs (geometric mean 78.16 g/g vs 30.9 g/g; P , 0.0001) (Fig. 1). The effect of the PPIs appeared to be independent from the dyspepsia for which they were prescribed; in patients not taking a PPI, the geometric mean faecal calprotectin of those with no dyspepsia was not significantly different to the faecal calprotectin of those with dyspepsia (29.99 g/g vs 31.26 g/g).

Apoptosis in the Colonic Crypt, Colorectal Adenomata, and Manipulation by Chemoprevention

This review discusses the biology and the methods of assessment of apoptosis, of which, the monoclonal antibody M30 would seem to be the most useful; the role of apoptosis in the etiology of colorectal cancer; and its use as a marker to monitor the beneficial effects of chemopreventative interventions to reduce the development of colorectal cancer within the context of clinical trials. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1680–7)

Chronic subclinical bowel inflammation may explain increased risk of colorectal cancer in obese people

We read with interest the recent articles on obesity, inflammation and colorectal cancer (CRC).1–3 Although insulin resistance is the most widely accepted underlying mechanism explaining the association between obesity and CRC, recent evidence suggests that the effects of obesity on the immune system in general and on the gut in particular may play a role. We propose that obesity predisposes to CRC through its effects on innate immune activation (IIA) and consequent subclinical bowel inflammation. We further propose that the role of insulin resistance is either complementary or might merely represent an epiphenomenon. The justification of our argument is explained below. Recently, we studied the determinants of whole gut inflammation in a normal middle-aged population by determining levels of calprotectin in faeces. Calprotectin is a calcium-binding protein found only in neutrophils and monocytes. Levels in faeces correlate well with faecal levels of indium-labelled white cells and inflammatory bowel disease activity. It is well established that many risk factors for CRC influence levels of IIA in a healthy individual. Lack of physical exercise, for instance, is associated with increased serum levels of C reactive protein, as are body mass index, smoking and increasing age.4 We confirmed that faecal levels of calprotectin also correlated directly with increasing age, obesity, …

The NHS Bowel Cancer Screening Programme – a realistic approach with additional benefits

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer death in the UK with 36 100 new cases diagnosed each year in England and Wales and 55% of all patients presenting with lymph node metastases at the time of diagnosis. Early detection, before the development of symptoms, may be an effective way of reducing mortality and it is this which a screening programme seeks to address. The NHS Bowel Cancer Screening Programme (NHS BCSP) commenced in April 2006 and invites men and women aged 60–69 to participate via submission of a faecal occult blood test every 2 years; those with a positive result will be offered colonoscopy as the next investigation of choice. This article will explore the background to the programme, including the financial considerations behind it and the implication that this has had on colonoscopy standards and training in the UK. The chosen programme is not the most effective neither in terms of survival benefit nor cost effectiveness but is a compromise within a financially strained health care system. Endoscopy standards because of its introduction have, however, considerably improved in terms of patient experience, safety and improved practice.

Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease.

There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohns disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohns. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.

Uncomplicated diverticular disease is not a common cause of colonic symptoms

Background  Colonic diverticular disease is common among older individuals whereas colonic symptoms, such as those of irritable bowel syndrome, are frequent in the general population.