Organic Bowel Disease Research Articles

Newer Fecal Tests: Opportunities for Professionals in Laboratory Medicine

There are differences in practice between the US, Europe, and other countries in screening for colorectal neoplasia (1) and investigation of other common lower gastrointestinal tract problems. Colonoscopy is often considered the gold standard for detection of colorectal neoplasia, and deaths from colorectal cancer can undoubtedly be reduced through removal of adenomatous polyps (2, 3). Colonoscopy is a scarce resource in many countries, however, and it may be limited to those with comprehensive health insurance. Consequently, there is much interest in using fecal tests to decide who will truly benefit from colonoscopy, particularly because the symptoms reported for colorectal diseases overlap considerably, making clinical decision-making about whom to refer difficult. In this issue of the Journal, Kok and colleagues (4) report a study on the diagnostic accuracy of point-of-care tests (POCTs)6 for fecal calprotectin and occult blood in primary care and assessing what they term “organic bowel disease.” A qualitative immunochemical fecal occult blood test was used. We have recommended (5) that tests that use antibodies to detect fecal hemoglobin be termed “fecal immunochemical tests for hemoglobin” and that the abbreviation “FIT” be used, because guaiac-based fecal occult blood tests (gFOBTs) and FITs are very different tests. As the authors mention, FITs are rapidly superseding traditional gFOBTs because of their many advantages, including that only a single sample is generally collected, the available collection devices encourage adoption of the test, the test is more specific for lower gastrointestinal bleeding, and dietary restriction is definitely not required. Indeed, the many disadvantages of gFOBTs with respect to sample collection and handling, analysis, and interpretation of results (6) have led to the general consensus that their use is obsolete because of the much better performance characteristics of FITs. We strongly advocate that professionals in laboratory medicine (PLMs) encourage current users of …

PMO-243 Faecal calprotectin analysis: does the method matter?

IntroductionFaecal calprotectin (FC) is a sensitive marker of intestinal inflammation and is useful to help distinguish between organic and non-organic (functional) disease. The increasing popularity of this test, with various...

P087 Comparative study of the Quantum Blue rapid test for point of care quantification of faecal calprotectin with an established ELISA method

Background: Faecal calprotectin (FC) has proven its utility as a non-invasive marker for neutrophilic intestinal inflammation. It can be used in the differential diagnosis between functional and organic bowel disease. In Crohn’s disease and ulcerative colitis, FC is a very useful biomarker as it correlates with endoscopic disease activity. The objective of this study is to evaluate the recently launched quantitative immunochromatographic point of care tests (POCT) (Quantum Blue Calprotectin, Buhlmann Laboratories AG) to the currently used ELISA method (Buhlmann Laboratories AG) both numerically and regarding its reliability in distinguishing functional from organic bowel disease. Methods: 142 samples were analysed both with the ELISA and the POCT (normal range (30 300mg/g faeces) or high range (10

Faecal calprotectin as a reliable screening biomarker in the patients with organic bowel diseases

Calprotectin is a calcium and zinc binding protein released from leucocytes, markedly elevated in organic bowel diseases (OBD). Faecal calprotectin (FC) is supposed to be a reliable biomarker to screen the suspected patients with OBD. This study was aimed to determine the role of FC level in screening the suspected OBD patients. It was carried out by measurement of FC using a commercially available ELISA kit among 50 patients with chronic diarrhoea for ? 6 weeks with or without other GIT symptoms who underwent colonoscopic evaluation (35 OBD patients and 15 disease control) and 12 healthy control. Significantly higher value (P<0.001) of FC level were observed among OBD patients (n=35) (479.5+133µg/g) than those in disease control (n=15) (82.17+75.64µg/g) and healthy control (n=12) (27+18.2µg/g). Measurement of FC in diagnosing OBD revealed the sensitivity 100%, specificity 67%, PPV 88% and NPV 100%. FC can be used as a reliable biomarker in screening of suspected OBD by selecting the patients who need colonoscopy.DOI: http://dx.doi.org/10.3329/bjmm.v6i1.19353 Bangladesh J Med Microbiol 2012; 06(01): 7-10

Radiation Exposure From Diagnostic Imaging Among Patients With Gastrointestinal Disorders

There are concerns about levels of radiation exposure among patients who undergo diagnostic imaging for inflammatory bowel disease (IBD), compared with other gastrointestinal (GI) disorders. We quantified imaging studies and estimated the cumulative effective dose (CED) of radiation received by patients with organic and functional GI disorders. We also identified factors and diagnoses associated with high CEDs. We analyzed data from 2590 patients who were diagnosed with GI disorders at a tertiary gastroenterology center from January 1999-January 2009 on the basis of International Statistical Classification of Diseases and Health-related Problems, 10th revision and Rome III criteria. High annual CED and high total CED were defined as figures exceeding the 90th percentile for the population. Diagnostic imaging was performed on 57% of the patients (1429 of 2509). High annual CEDs (>9.6 millisieverts/annum) were independently associated with Crohn's disease (odds ratio [OR], 5.3; P < .0001), organic small bowel disease (OR, 2.6; P < .005), and functional disorders of childhood and adolescence (OR, 9.8; P < .005). High total CEDs (>30.8 millisieverts) were independently associated with Crohn's disease (OR, 81.9; P < .0001), ulcerative colitis (OR, 19.0; P < .0001), indeterminate colitis (OR, 7.5; P < .0005), and the following non-IBD diagnoses: organic small bowel disorders (OR, 12.5; P < .0001), organic hepatic disorders (OR, 3.6; P < .01), and functional disorders of childhood and adolescence (OR, 13.8; P = .02). Higher levels of annual and total diagnostic radiation exposure are associated with IBD and with other organic and functional GI disorders. Evidence-based guidelines for image analysis of patients with organic and functional gastrointestinal disorders, especially those that reduce radiation exposure, are needed.

COMPARATIVE EVALUATION IDENTIFICATION OF INFLAMMATORY BOWEL DISEASE AND TUMOR ON THE BASIS OF LACTOFERRIN AND CALPROTECTIN

The study was a comparative evaluation of the identification of inflammatory bowel disease and tumor on the basis of fecal lactoferrin and fecal calprotectin. 40 patients with colorectal cancer, 52 patients with ulcerative colitis, 45 patients with irritable bowel syndrome and 19 healthy volunteers are included in study group. Diagnoses were exposed on the basis of clinical, laboratory, endoscopic and morphological data. Healthy volunteers had no symptoms of bowel disease and were not subjected to abdominal surgical interventions. Active ulcerative colitis was assessed by an index Schroeder (Mayo Clinic UC DAI). Lactoferrin was determined in stool samples taken from a stool, enzyme immunoassay (ELISA) using kits ELISA TEST KIT Hycult Biotechnology (Netherlands). Calprotectin were determined in stool samples of patients taken from a stool, immunnofermentnym analysis using a standard set of firm «Nova Tec Immundiagnostica GmbH», Germany. Established that the diagnostic value of faecal calprotectin in the diagnosis of colorectal cancer (AUC: 0,945 ± 0,0262) and ulcerative colitis (AUC: 0,893 ± 0,032) did not differ from lactoferrin (p = 0,9547 and p = 0,9645 respectively). In the differential diagnosis of organic and functional bowel disease markers also had no reliable statistical differences on this parameter (AUC: 0,938 ± 0,0207; p = 0,8124).

46. Increased eosinophils and mast cells in the irritable bowel syndrome

Background Irritable bowel syndrome is a functional bowel disorder, the aetiopathogenesis of which has been poorly understood. It appears to be multifactorial and to involve altered gastrointestinal motor function, enhanced perception of visceral stimuli and psychosocial factors. Only a few studies have analysed the involvement of inflammatory cells in this condition. The aim of this study was to determine whether eosinophils and mast cells were increased in the colonic mucosa in irritable bowel syndrome compared to controls. Method Slides of 20 colonic biopsy materials of patients with irritable bowel syndrome who had endoscopically and histologically normal colonic mucosa were analysed. Twenty normal controls that had random colonic biopsies with macroscopic and histologic normal colonic mucosa and no organic or functional bowel disease were enrolled. Quantification of eosinophils and mast cells was performed on three non-overlapping fields of lamina propria at ×40 magnification. Eosinophil degranulation was semi-quantitatively estimated assessing the extent of free granules within the lamina propria. Results Among the total of 20 tests and 20 controls, the majority were females (75% and 65%, respectively). Diarrhoea predominant irritable bowel syndrome was the most common mode of presentation. Eosinophil number, degranulation and mast cell count were significantly high in colonic biopsies obtained from irritable bowel syndrome compared to control. Comment Elevated mast cells have already been reported in the colonic and ileal biopsies and there were a few proposals predicting the involvement of eosinophils in the pathogenesis of the irritable bowel syndrome. This study supports this finding and explains the possible neural – mast cell – eosinophil interaction in generating the symptoms of functional gastrointestinal disorders including irritable bowel syndrome.

Intestinal fermentation in patients with self-reported food hypersensitivity: painful, but protective?

Enterometabolic disturbances may cause meal-related symptoms. We performed a functional evaluation of the intestinal microflora in patients with unexplained, self-reported food hypersensitivity by measuring fecal short-chain fatty acids (SCFAs). Thirty-five consecutive patients with self-reported food hypersensitivity and 15 healthy volunteers of similar age, gender, and body mass index collected all feces for 72 hours. Fecal concentrations of acetic, propionic, n-butyric, i-butyric, n-valeric, i-valeric, n-caproic, and i-caproic acids were analyzed by gas-liquid chromatography. Concentrations and excretions (output) of SCFAs in patients and controls were compared and related to gastrointestinal symptoms. Despite nonsignificant differences between patients and controls for both total and individual SCFA concentrations and excretions, n-butyric acid comprised a higher (P = 0.035) and acetic acid a lower (P = 0.012) proportion of total SCFA in patients compared to controls. There were no significant correlations between symptom scores and concentrations or excretions of individual or total SCFAs, but the proportion of n-butyric acid was significantly higher in patients with severe symptoms compared to patients with moderate symptoms (P = 0.016). The results indicate an enterometabolic disturbance in patients with self-reported food hypersensitivity. Higher proportions of n-butyric acid may be related to abdominal symptom generation, but may also protect against organic bowel disease. Further studies are needed to clarify these aspects.

Faecal calprotectin in differentiating between functional and organic bowel diseases

Background and study aims There is a frequent overlap between the clinical presentation of functional and organic bowel disorders. The aim of this study was to assess the role of faecal calprotectin in differentiating between both groups of patients in order avoid the use of invasive diagnostic procedures in patients with low probability of having functional disorders. Patients and methods We prospectively studied 39 patients presenting with lower gastrointestinal symptoms. On the basis of clinical and colonoscopic criteria 20 had functional and 19 had organic bowel disorder (10 had inflammatory bowel disease and 9 had organic non-inflammatory bowel diseases). Ten healthy subjects were included as controls. Faecal calprotectin was measured in patients and controls by enzyme linked immunosorbent assay. Results Patients with inflammatory bowel disease had faecal calprotectin levels of 379.2 ± 177.9 μg/g (mean ± SD); this was higher than in patients with functional bowel disease [(27.97 ± 15.2 μg/g); p: 0.004] and healthy controls [(21.64 ± 11.3 μg/g); p: 0.0002]. Patients with organic non-inflammatory bowel disease had faecal calprotectin levels of 273.4 ± 157.8 μg/g, which is higher than in patients with functional bowel disorders [(27.97 ± 15.2 μg/g); p: 0.002] and healthy controls [(21.64 ± 11.3 μg/g); p: 0.0001]. There was no statistically significant difference between faecal calprotectin in patients with functional bowel disease and healthy controls ( p: 0.264), and between both groups with organic bowel disease ( p: 0.312). Conclusion Faecal calprotectin is a sensitive non-invasive method which can be used to identify patients with organic bowel disorders. It is not, however, able to differentiate between different types of organic bowel diseases.

Anger and childhood sexual abuse are independently associated with irritable bowel syndrome

Irritable bowel syndrome (IBS) presents in the absence of identifiable organic pathology. Clinical and research literature has suggested that both childhood abuse and anger are linked to functional gastrointestinal conditions including IBS. The present study tested the predictions that IBS patients, when compared to patients with an organic bowel disease (Crohn's disease), have higher levels of trait and suppressed anger, and that these mediate the link between abuse and IBS. The study was a cross-sectional multivariate comparison between groups of patients with IBS and Crohn's disease. Levels of self-reported trait and suppressed anger and recalled childhood abuse in patients with IBS (N=75) or Crohn's disease (N=76) were compared, using self-report questionnaires and controlling for other psychological characteristics (anxiety, depression, and dissociation). Trait and suppressed anger were greater in IBS patients, and differences in trait anger remained significant after controlling for other psychological variables. Childhood sexual abuse was more prevalent in IBS than Crohn's disease patients but was unrelated to trait anger. Higher levels of anger characterize IBS patients when compared to an organic bowel disease group, but do not explain the link between childhood abuse and IBS.

Fecal dimeric M2-pyruvate kinase (tumor M2-PK) in the differential diagnosis of functional and organic bowel disorders

Fecal inflammatory markers have been shown to be useful as noninvasive screening tools to differentiate patients with functional from organic bowel pathology. Of these markers calprotectin has been the most intensively studied. More recently, the dimeric isoform of M2-pyruvate kinase (tumor M2-PK) has been suggested as a marker of gastrointestinal inflammation. The aim of this study was to investigate fecal tumor M2-PK in the differentiation of functional from organic bowel disease. Fecal calprotectin and tumor M2-PK were measured in 94 controls and 105 gastroenterology outpatients with a possible diagnosis of organic bowel disease. The diagnosis was made by clinical, endoscopic, and radiological criteria. Organic bowel disease was diagnosed in 14 patients (13%). Median calprotectin and tumor M2-PK concentrations were 24.5 microg/g and 1 U/mL in controls, 23 microg/g and 1 U/mL in functional, and 227.5 microg/g and 12.6 U/mL in organic bowel disease. Sensitivity, specificity, and positive and negative likelihood ratios for diagnosis of organic bowel disease were 93%, 92%, 11.6, and 0.07 for calprotectin and 67%, 88% 5.6, and 0.18 for tumor M2-PK, respectively. Calprotectin in combination with tumor M2-PK gave a sensitivity of 64%, specificity of 98%, and likelihood ratios of 32 and 0.03. Elevated calprotectin or tumor M2-PK decreased specificity to 87%, but increased sensitivity to 100%. Tumor M2-PK is able to differentiate organic from functional bowel disease but has a lower sensitivity, specificity, and predictive value than calprotectin. Further studies are required, alone or in combination with other markers, before its usefulness in this setting can be recommended.

The Perspective of Patient with Organic and Functional Bowel Disease on Complementary and Alternative Medicine (CAM)

The Perspective of Patient with Organic and Functional Bowel Disease on Complementary and Alternative Medicine (CAM)

Immune Activation in Patients With Irritable Bowel Syndrome

We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines. We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs). PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (1 ng/mL) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6) was measured by enzyme-linked immunosorbent assay. Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale. IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients, whereas constipation-predominant IBS patients showed increased LPS-induced IL-1beta levels compared with HCs. Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than 3 bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .001) with anxiety in patients with IBS. Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.

A Prospective Comparison of Capsule Endoscopy and Double Balloon Enteroscopy in Small Bowel Disease

Backgrounds: Capsule endoscopy and double balloon enteroscopy opened the new era of small bowel disease and have demonstrated a useful tool for the diagnosis of small bowel lesions. But there were only a few studies in comparison capsule endoscopy with double balloon enteroscopy until recently. The aim of this study was to evaluate a usefulness of capsule endoscopy and double balloon enteroscopy in small bowel disease and compare capsule endoscoy with double balloon enteroscopy in diagnostic yield. Patients and Methods: From Nov. 2004 to Nov. 2005, eleven patients (5 male, 6 female; median age 44 years range 21-66 years) with obscure gastrointestinal bleeding and chronic abdominal pain were examined with capsule endoscopy and double balloon enteroscopy by separate examiners. The definite diagnosis for each study was defined as the correlation of clinical situation. Results: Indications of study were 8 obscure gastrointestinal bleeding and 3 chronic abdominal pain. Capsule endoscopy identified positive finding in seven patients (63.6%). Double balloon enteroscopy identified positive finding in nine patients (81.8%). One patient with chronic abdominal pain was excluded organic small bowel disease by capsule and double balloon enteroscopy. There were two discrepant results between capsule endoscopy and double balloon enteroscopy. One patient was nonspecific finding in capsule endoscopy and angiodysplasia in double balloon enteroscopy. The other patient was ileal erosion in capsule endoscopy and gastrointestinal stromal tumor in double balloon enteroscopy. Both examination were well tolerated and had not any complication of procedure. One patient with angiodysplasia underwent therapeutic enteroscopy by argon plasma coagulation. Conclusions: Both capsule endosocpy and double balloon enteroscopy showed high diagnostic yield without any complication. There was not statistical significance in diagnostic yield between capsule endoscopy and double balloon enteroscopy. Key words: Small bowel disease, capsule endoscopy, double balloon enteroscopy.

Clinical Analysis of Organic Bowel Disease as the Leading Indicator in 10 Pediatric Patients With Intussusception

Clinical Analysis of Organic Bowel Disease as the Leading Indicator in 10 Pediatric Patients With Intussusception

Irritable bowel syndrome: a little understood organic bowel disease?

Irritable bowel syndrome affects 10% of adults with an unexplained female predominance. Although only a few people see their family doctor, the disease causes reduced quality of life and represents a multi-billion pound health-care problem. The disorder clusters in families, which is possibly because of intra-familial learning and a genetic predisposition. Visceral hypersensitivity is a key feature in most patients. Results of imaging studies of regional cerebral blood flow during rectal distension suggest underlying disturbances of central processing of afferent signals, though this is not unique to the disorder, since it is seen in other chronic pain syndromes. Environmental factors that are strongly implicated in at least some patients include gastrointestinal infection and inflammation and chronic stress. Diagnosis is based on positive symptoms and absence of any alarm indicators. Treatment remains unsatisfactory and hinges on an excellent doctor-patient relationship, with drugs for symptom exacerbations. Cognitive behavioural treatment, psychotherapy, and hypnosis could provide long-lasting benefit in some patients. Tricyclic antidepressants in low doses seem to be the most effective class of drugs for the disorder on the basis of limited data.

Calprotectin, a faecal marker of organic gastrointestinal abnormality

Calprotectin may therefore exert its effects by reducing local concentrations of zinc, which indicates that it may be involved in the regulation of inflammatory reactions by its inhibition of several zinc-dependent metalloproteinases. The protein is remarkably resistant to degradation in vivo and in vitro in the presence of calcium, 5,6 so faecal samples can be sent to the laboratory by post. The upper reference limit in faeces is 10 mg/L, but with a recent refinement of the assay, which does away with the messy step of homogenisation and which increases yields, the limit is 50 mg/L. 7 Several groups have confirmed the observation 5 that calprotectin can be assayed in simple buffer extracts of small (5 g) faecal samples, and that increased concentrations (>10 mg/L) are found in most patients with inflammatory bowel disease (IBD) or gastric or colorectal cancer (panel). It was therefore quite clear at an early stage that the faecal calprotectin test was nonspecific for type of organic bowel disease. In different studies the median values in patients with colorectal cancer ranged from 33 to 214 mg/L. In one study 23 patients were also tested after resection, and the median dropped from 75 to 9 mg/L. 8

HIV infection is associated with significant mucosal inflammation

BACKGROUND: HIV preferentially infects activated, memory CD4+ lymphocytes expressing requisite co-receptors. The gut mucosa is the body s largest immune organ, which in the healthy, normal condition is characterised by low-level inflammation and constitutive expression of chemokines and cytokines. The gut contains the body s largest number of activated, memory T cells, which express high levels of CCR5 and CXCR4 A. Inflammation with chemotactic chemokines recruiting additional activated immune cells, would potentially further increase infectible targets for HIV spread. METHODS: Colon biopsies from 6 HIV-infected individuals, 8 Inflammatory Bowel Disease (IBD) patients and 5 seronegative, healthy controls without organic bowel disease were compared. All but one HIV infected was on HAART. Plasma viral load was undetectable in three patients and differed between 4.4 5.7 logs in three patients. IBD patients included 5 with active disease, 3 in remission. Samples were immunohistochemically stained with monoclonal antibodies against CCR5, CXCR4, RANTES, MlP-l a and MIP-l f3 with expression evaluated at the single cell level by computerized in situ imaging. RESULTS: The expression of chemokine receptors CCR5 and CXCR4 was significantly increased in HIV-infected mucosal sections compared to both IBD in remission (IBDr) and seronegative controls (p<0.05). Sections from patients with active IBD showed a similar pattern of increased chemokine receptor expression. f3-chemokines including RANTES and MIPlf3, were significantly upregulated in HIV compared to IBDr and healthy controls (p<0.05). In active IBD there was increased expression of RANTES, compared to IBDr (p<O.OI). The chemokine MIP-l a was expressed at low levels in all samples. CONCLUSIONS: HIV is characterized by a significant degree of mucosal inflammation. Our findings show that the levels of chemokines and chemokine receptors in HIV are similar to those levels seen in active IBD and are significantly higher than those from IBDr and healthy controls. This suggests that the inflammatory response in HIV is at least as potent as in IBD. Topical anti-inflammatories lead to remission and reduction in soluble and cellular markers of inflammation in IBD. Given the presence of marked inflammation, further investigation of the role of adjunctive treatment of HIV-patients with local anti-inflammatory drugs targeting the host immune response, deserves attention.

Airway responsiveness to inhaled methacholine in patients with irritable bowel syndrome

We examined whether patients with irritable bowel syndrome have increased airway responsiveness by measuring forced expiratory volumes in 1 second (FEV1) after inhalation of increasing concentrations of methacholine. Responses obtained in 11 IBS patients were compared with those obtained in 11 normal subjects and in 11 subjects with organic disease of the gut or its related organs. All subjects were selected so that other factors that might contribute to increased airway responsiveness were excluded. The methacholine concentration that caused a 20% fall in the FEV1 (PC20), as well as the reduction in FEV1 induced by each methacholine concentration, were used to assess airway responsiveness. The geometric mean PC20 was 197.6 mg/mL (%SEM, 1.15) for normal subjects, 83.9 mg/mL (%SEM, 1.51) for subjects with organic bowel disease (P = 0.012), and only 12.8 mg/mL (%SEM, 1.74) for IBS patients (P < 0.0001). The 22.5% ± 2.5% decrease in FEV1 induced by 64 mg/mL of methacholine in IBS patients was significantly greater than that of 12.3% ± 1.5% observed in healthy subjects (P = 0.003). In contrast, the 15.7% ± 2.0% decrease in FEV1 observed in patients with organic disease was not different from that seen in normal subjects (P = 0.189). We conclude that IBS is associated with increased airway responsiveness following challenge with methacholine.

Indiscretion enteritis. A rabelaisian syndrome

A 76-year-old man had small bowel obstruction and organic small bowel disease following a series of bizarre massive gustatory insults that involved food, medications, and mega-mineral-vitamin supplements. Intestinal obstruction required partial small bowel resection. The dietary indiscretions resulted in severe enteritis (indiscretion enteritis). The sequence has been termed a Rabelaisian syndrome after the great French writer and physician, François Rabelais, who vividly described bizarre gustatory habits. Gut injury may result from unwise oral intake of various foods and mineral supplements.