Sampling endoscopically normal large bowel mucosa from patients presenting with elevated faecal calprotectin levels is not clinically justified

2021 ◽  
pp. jclinpath-2020-207343
Author(s):  
Newton A C S Wong ◽  
Michael John Wallage ◽  
Paul Virgo ◽  
Hannah Lowes
Keyword(s):  
Primary Care ◽  
Large Bowel ◽  
Detection Rate ◽  
Acute Inflammation ◽  
Intestinal Inflammation ◽  
Faecal Calprotectin ◽  
Inflammatory Bowel ◽  
Repeat Colonoscopy ◽  
Small Intestinal ◽  
Bowel Mucosa

Aims and methodsFaecal calprotectin (FCP) measurement is used especially to investigate for inflammatory bowel disease (IBD). To assess the utility of sampling endoscopically normal large bowel among patients first presenting with elevated FCP, this study identified 115 such patients out of 652 patients with elevated FCP from approximately 6000 primary care tests processed over 15 months.Results23 cohort patients showed histologically abnormal large bowel biopsies. Only four cases demonstrated acute inflammation and two such patients only showed scattered cryptitis and did not develop IBD. A third patient demonstrated similar histology but, following repeat colonoscopy, her elevated FCP was attributed to small intestinal inflammation. Only the fourth patient’s large bowel biopsies showed features suggesting Crohn’s disease, but this represented an IBD detection rate out of 115 sets of large bowel biopsies of 0.9%.ConclusionsSampling of endoscopically normal large bowel among patients first presenting with elevated FCP is not clinically justified.

Use of faecal immunochemical testing as an alternative to faecal calprotectin in children

2021 ◽  
pp. 000456322198935
Author(s):  
Kirn Sandhu ◽  
Sandhia Naik ◽  
Ruth M Ayling
Keyword(s):  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Paediatric Population ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
Non Invasive ◽  
Three Samples ◽  
Immunochemical Test ◽  
Inflammatory Bowel ◽  
Rule Out

Background Faecal calprotectin has been widely used as a non-invasive marker of intestinal inflammation in children. Measurement of faecal haemoglobin using faecal immunochemical test is well established in adults for detection of colorectal cancer. In adults, faecal haemoglobin has been recommended as a reliable tool to aid identification of those at low risk of significant bowel disease and has also been used in inflammatory bowel disease to assess mucosal healing. Aims We aimed to evaluate the performance of faecal haemoglobin in the paediatric population and compare it with faecal calprotectin. Methods Children being assessed in the paediatric gastroenterology clinic for bowel symptoms had a sample sent for both faecal calprotectin and faecal haemoglobin. Samples were collected over a 10-month period from November 2018 to September 2019. Faecal haemoglobin was measured using an OC-Sensor. Faecal calprotectin was measured using Liason®Calprotectin. Results One hundred forty three samples were returned for faecal haemoglobin and in 107 a paired faecal calprotectin was also available. Faecal haemoglobin correlated with faecal calprotectin, Spearman’s rank coefficient 0.656 ( P < 0.0001). There were 35 patients with faecal haemoglobin >20 μg/g and in 32 of these patients faecal calprotectin was >200 μg/g; 74 patients with faecal haemoglobin and 38 patients with faecal calprotectin underwent colonoscopy. Patients with normal histology had faecal haemoglobin <4 μg/g; faecal haemoglobin >20 µg/g was associated with signification inflammation Conclusion Our study is the first to compare faecal haemoglobin and faecal calprotectin in a paediatric population. Results suggest that faecal haemoglobin correlates with faecal calprotectin and, as in adults, may be useful to rule out significant bowel disease. A faecal haemoglobin >20 μg/g was consistent with significant histological inflammation.

Faecal calprotectin is not necessarily required as a screen for significant bowel disease in primary care

2021 ◽  
pp. 000456322110634
Author(s):  
Matthew Malcolm Andrew Waite ◽  
Louise Langmead ◽  
Ruth M Ayling
Keyword(s):  
Primary Care ◽  
Bowel Disease ◽  
Test Performance ◽  
Faecal Calprotectin ◽  
Immunochemical Test ◽  
Inflammatory Bowel ◽  
Clinical Records ◽  
Sensitivity Specificity ◽  
Disease Specific ◽  
Rule Out

Objective NICE recommends measurement of faecal haemoglobin (f-Hb) using faecal immunochemical test (FIT) when colorectal cancer is suspected and calprotectin (f-Cal) in the context of inflammatory bowel disease, though neither is disease specific. During the COVID-19 pandemic, f-Hb has been a requirement prior to referral for endoscopy in England; f-Cal is often performed simultaneously. The aim of this study was to investigate test performance of both tests for significant bowel disease in those patients referred. Design All adult patients with simultaneous measurements of f-Hb and f-Cal between April 2019 and September 2020 were included. For those referred, outcomes were determined from clinical records. Results 650 patients with simultaneous samples for f-Hb an f-Cal were managed in Primary Care; 319 patients were referred to hospital; SBD was found in 32 (10.0%) (CRC 5, high risk adenomas 5, IBD 22). At a cut-off of 10 μg/g for f-Hb and 200 μg/g for f-Cal, the sensitivity, specificity and negative predictive value for diagnosis of SBD were 84.4%, 58.2% and 96.7% and 68.8%, 89.6% and 95.7%, respectively. Performance of both tests would have enabled diagnosis of two more cases of significant, but non-malignant, bowel disease but required over 4% more referrals for investigation. Conclusion Use of FIT has become established to assist prioritisation of patients for referral from Primary Care. Whilst introduced specifically for CRC, FIT performs well as a rule out for IBD in Primary Care and the use of f-Cal is not required.

scholarly journals Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism

2018 ◽  
Vol 115 (43) ◽  
pp. 11036-11041 ◽  
Author(s):  
Yasuharu Nagahama ◽  
Mayuko Shimoda ◽  
Guoliang Mao ◽  
Shailendra Kumar Singh ◽  
Yuuki Kozakai ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Purine Metabolism ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Epithelial Regeneration ◽  
Mtorc1 Signaling ◽  
Inflammatory Bowel

Damage to intestinal epithelial cell (IEC) layers during intestinal inflammation is associated with inflammatory bowel disease. Here we show that the endoribonuclease Regnase-1 controls colon epithelial regeneration by regulating protein kinase mTOR (the mechanistic target of rapamycin kinase) and purine metabolism. During dextran sulfate sodium-induced intestinal epithelial injury and acute colitis, Regnase-1∆IEC mice, which lack Regnase-1 specifically in the intestinal epithelium, were resistant to body weight loss, maintained an intact intestinal barrier, and showed increased cell proliferation and decreased epithelial apoptosis. Chronic colitis and tumor progression were also attenuated in Regnase-1∆IEC mice. Regnase-1 predominantly regulates mTORC1 signaling. Metabolic analysis revealed that Regnase-1 participates in purine metabolism and energy metabolism during inflammation. Furthermore, increased expression of ectonucleotidases contributed to the resolution of acute inflammation in Regnase-1∆IEC mice. These findings provide evidence that Regnase-1 deficiency has beneficial effects on the prevention and/or blocking of intestinal inflammatory disorders.

scholarly journals Faecal calprotectin to detect inflammatory bowel disease: a systematic review and exploratory meta-analysis of test accuracy

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e027428 ◽  
Author(s):  
Karoline Freeman ◽  
Brian H Willis ◽  
Hannah Fraser ◽  
Sian Taylor-Phillips ◽  
Aileen Clarke
Keyword(s):  
Systematic Review ◽  
Primary Care ◽  
Inflammatory Bowel Disease ◽  
Sensitivity And Specificity ◽  
Bowel Disease ◽  
Secondary Care ◽  
Meta Analysis ◽  
Test Accuracy ◽  
Faecal Calprotectin ◽  
Inflammatory Bowel

ObjectiveTest accuracy of faecal calprotectin (FC) testing in primary care is inconclusive. We aimed to assess the test accuracy of FC testing in primary care and compare it to secondary care estimates for the detection of inflammatory bowel disease (IBD).MethodsSystematic review and meta-analysis of test accuracy using a bivariate random effects model. We searched MEDLINE, EMBASE, Cochrane Library and Web of Science until 31 May 2017 and included studies from auto alerts up until 31 January 2018. Eligible studies measured FC levels in stool samples to detect IBD in adult patients with chronic (at least 6–8 weeks) abdominal symptoms in primary or secondary care. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. We followed the protocol registered as PROSPERO CRD 42012003287.Results38 out of 2168 studies were eligible including five from primary care. Comparison of test accuracy by setting was precluded by extensive heterogeneity. Overall, summary estimates of sensitivity and specificity were not recorded. At a threshold of 50 µg/g, sensitivity from separate meta-analysis of four assay types ranged from 0.85 (95% CI 0.75 to 0.92) to 0.94 (95% CI 0.75 to 0.90) and specificity from 0.67 (95% CI 0.56 to 0.76) to 0.88 (95% CI 0.77 to 0.94). Across three different definitions of disease, sensitivity ranged from 0.80 (95% CI 0.76 to 0.84) to 0.97 (95% CI 0.91 to 0.99) and specificity from 0.67 (95% CI 0.58 to 0.75) to 0.76 (95% CI 0.66 to 0.84). Sensitivity appears to be lower in primary care and is further reduced at a revised threshold of 100 µg/g.ConclusionsConclusive estimates of sensitivity and specificity of FC testing in primary care for the detection of IBD are still missing. There is insufficient evidence in the published literature to support the decision to introduce FC testing in primary care. Studies evaluating FC testing in an appropriate primary care setting are needed.

scholarly journals Faecal calprotectin: A reliable diagnostic and prognostic biomarker in inflammatory bowel disease

2017 ◽  
Vol 8 (1) ◽  
pp. 12-15
Author(s):  
Ripon Barua ◽  
Najmun Nahar ◽  
Jogendra Nath Sarker ◽  
Sultana Razia ◽  
Abu Naser Ibne Sattar ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Medical Treatment ◽  
Disease Control ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Cross Sectional Study ◽  
Faecal Calprotectin ◽  
Cross Sectional ◽  
Healthy Control ◽  
Inflammatory Bowel

Faecal calprotectin (FC) is supposed to be a reliable biomarker that quantifies intestinal inflammation in inflammatory bowel disease (IBD). This cross sectional study was aimed to determine the role of FC level in screening of suspected IBD patients and monitoring treatment response. This study was conducted by measurement of FC using a commercially available ELISA kit among 50 patients with chronic diarrhea who underwent colonoscopic evaluation (25 IBD cases, 10 other organic bowel diseases and 15 disease control) and 12 healthy control. IBD patients were followed up after one month of medical treatment. FC level showed significantly higher value (p<0.001) among IBD patients (496.7±127.15?g/g) than those in disease control (82.17±75.64?g/g) and healthy control (27±18.2?g/g). Measurement of FC in diagnosing IBD revealed the sensitivity 100%, specificity 66%, PPV 83% and NPV 100%. The FC level decreased significantly (p<0.001) after one month of medical treatment of IBD patients (90±43?g/g) from pre treatment value (607.56±94?g/g). FC can be used as a reliable biomarker in screening of suspected IBD patients and to monitor treatment response.Bangladesh J Med Microbiol 2014; 08 (01): 12-15

scholarly journals Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care

2017 ◽  
Vol 71 (4) ◽  
pp. 316-322 ◽  
Author(s):  
Samantha Conroy ◽  
Melissa F Hale ◽  
Simon S Cross ◽  
Kirsty Swallow ◽  
Reena H Sidhu ◽  
...  
Keyword(s):  
Primary Care ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Predictive Value ◽  
Gastrointestinal Endoscopy ◽  
Faecal Calprotectin ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
Low Sensitivity ◽  
Single Laboratory

BackgroundFaecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited.AimsTo assess the yield of IBD from FC testing in primary care.MethodsRetrospective review of hospital records to assess the outcome following FC testing in primary care. Investigations for all patients undergoing FC testing in a single laboratory for 6 months from 1 October 2013 to 28 February 2014 were reviewed.Results410 patients (162 male; median age 42; range 16–91) were included. FC>50 µg/g was considered positive (FC+). 148/410 (36.1%; median age 44 (17–91)) were FC+ (median FC 116.5 µg/g (51–1770)). 122/148 FC-positive patients (82.4%) underwent further investigation. 97 (65.5%) underwent lower gastrointestinal endoscopy (LGIE), of which 7 (7.2%) had IBD. 49/262 (18.7%) FC-negative (FC−) patients (FC ≤50 µg/g) (median age 47 (19–76)) also underwent LGIE, of whom 3 (6.1%) had IBD.IBD was diagnosed in 11/410 (2.7%; 4 ulcerative colitis, 3 Crohn’s disease, 4 microscopic colitis). 8/11 were FC+ (range 67–1170) and 3 FC−. At a 50 µg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 64.9%, positive predictive value (PPV) 5.41% and negative predictive value 98.9%. Increasing the threshold to 100 µg/g reduced the sensitivity of the test for detecting IBD to 54.6%.ConclusionsFC testing in primary care has low sensitivity and specificity with poor PPV for diagnosing IBD. Its use needs to be directed to those with a higher pretest probability of disease. Local services and laboratories should advise general practitioners accordingly.

scholarly journals P151 Can two different faecal calprotectin assays be used interchangeably in inflammatory bowel disease treatment?

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S213-S213
Author(s):  
E Van Wassenaer ◽  
K Diederen ◽  
A Kindermann ◽  
E M M van Leeuwen ◽  
G R D’Haens ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Weighted Kappa ◽  
Systematic Difference ◽  
Mean Difference ◽  
Faecal Calprotectin ◽  
Thermo Fisher Scientific ◽  
Inflammatory Bowel ◽  
The Mean

Abstract Background Faecal calprotectin (FC) is a broadly used sensitive biomarker for intestinal inflammation in inflammatory bowel disease (IBD) patients. However, in practice, interpretation of results can be complicated due to the use of different assays to determine FC. There is a lack of data comparing different FC assays. This study aimed to assess the agreement between two different assays for determining FC in patients with IBD. Methods Between January and April 2017, faecal samples of known IBD patients were tested with two assays: (1) EliA 2 Calprotectin, (Thermo Fisher Scientific Phadia, Sweden) and (2) ELISA tests (EK-Cal, Bühlmann Laboratories, Switzerland). FC measurements &gt;1800 mg/kg were displayed as 1800, as the EK-Cal test could not measure higher values. Samples were not homogenised before testing, and they were tested on the same day. Inter-assay variability was first displayed in a Bland-Altman plot, and then difference in the categorisation of the FC result(1: 0–250 mg/kg, 2: 250–500 mg/kg, 3: &gt;500 mg/kg) was assessed with the linear weighted Kappa (κ). Values for agreement were judged as follows: κ &lt;.0: poor, .0-.20: slight, .21-.40: fair, .41-.60: moderate, .61-.80: substantial, &gt;.80: almost perfect. Results A total of 171 patients (mean age 33 years (range: 7–81), 92 (54%) female, 117 (68%) Crohn’s disease, 53 (31%) ulcerative colitis, 1 (1%) IBD-U) were included in this study. Median FC levels were 242 mg/kg (range: 4−1800), and the mean difference between the two assays was 89 mg/kg (range: -1341 – 1140). The mean difference was largest in the high FC category, (3: 200 mg/kg, n = 60), and smallest in the low FC category (1: 5 mg/kg, n = 82)). There was no systematic difference between the two assays (Figure 1). In five out of 171 (3%) patients there was a difference of two categories between the two assays and in 25 out of 171 (15%), there was a difference of one category. There was substantial agreement between the two assays (κ=.78). Conclusion There is no systematic difference in FC measurements between the Phadia and EK-Cal assay in this cohort of IBD patients, and agreement between the two is substantial. This suggests that these two assays can be used interchangeably for monitoring IBD patients in clinical practice.

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