Original article
Vol. 153 No. 3 (2023)
Faecal calprotectin increases the diagnostic yield in patients with suspected small bowel disease – a multicenter retrospective cohort study
- Aisha Abo El Ela
- Nina Meuli
- Petr Hruz
- Emanuel Burri
Summary
AIM OF THE STUDY: Diagnosing small bowel pathology is challenging, and the diagnostic yield of small bowel capsule endoscopy is highly variable. Faecal calprotectin is a non-invasive intestinal inflammation marker that could be used as a selection tool to identify patients who might benefit from small bowel capsule endoscopy and increase its diagnostic yield. This study aimed to investigate the value of faecal calprotectin in detecting small bowel lesions in an unselected patient population.
METHODS: We performed a retrospective analysis of consecutive patients who underwent small bowel capsule endoscopy at the University Hospital Basel and the University Medical Clinic Cantonal Hospital Baselland, Switzerland, between 2010 and 2018. Patients without faecal calprotectin testing were excluded from the analysis. The primary endpoint was the presence of a clinically significant small bowel finding.
RESULTS: Patients with positive faecal calprotectin results were more likely to have small bowel findings (66.7% vs 39.4%; P = 0.007). The optimal faecal calprotectin cut-off to identify clinically significant small bowel lesions was 63 μg/g with 78.3% (95% confidence interval: 66.7–87.9) sensitivity, 47.9% (33.3–62.8) specificity, 1.50 (1.1–2.0) positive and 0.45 (0.3–0.8) negative likelihood ratios, 68.4% (61.6–74.4) positive and 60.5% (47.3–72.4) negative predictive values, and 65.0% overall accuracy. Faecal calprotectin performed best in patients with suspected inflammatory bowel disease, with 66.7% (48.2–82.0) sensitivity, 70.6% (44.0–89.7) specificity, 2.27 (1.0–4.9) positive and 0.47 (0.3–0.8) negative likelihood ratios, 81.5% (67.0–90.5) positive and 54.5% (39.7–68.6) negative predictive values, and 71.4% overall accuracy.
CONCLUSION: Faecal calprotectin testing increases the diagnostic yield of small bowel capsule endoscopy and may help identify patients at risk of small bowel disease.
References
- Gerson LB , Fidler JL , Cave DR , Leighton JA . ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding. Am J Gastroenterol. 2015 Sep;110(9):1265–87. https://doi.org/10.1038/ajg.2015.246
DOI: https://doi.org/10.1038/ajg.2015.246
- Pennazio M , Spada C , Eliakim R , Keuchel M , May A , Mulder CJ , et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2015 Apr;47(4):352–76. https://doi.org/10.1055/s-0034-1391855
DOI: https://doi.org/10.1055/s-0034-1391855
- Samuel S , Bruining DH , Loftus EV Jr , Becker B , Fletcher JG , Mandrekar JN , et al. Endoscopic skipping of the distal terminal ileum in Crohn’s disease can lead to negative results from ileocolonoscopy. Clin Gastroenterol Hepatol. 2012 Nov;10(11):1253–9. https://doi.org/10.1016/j.cgh.2012.03.026
DOI: https://doi.org/10.1016/j.cgh.2012.03.026
- Van Assche G , Dignass A , Panes J , Beaugerie L , Karagiannis J , Allez M , et al.; European Crohn’s and Colitis Organisation (ECCO) . The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohn’s Colitis. 2010 Feb;4(1):7–27. https://doi.org/10.1016/j.crohns.2009.12.003
DOI: https://doi.org/10.1016/j.crohns.2009.12.003
- Gomollón F , Dignass A , Annese V , Tilg H , Van Assche G , Lindsay JO , et al.; ECCO . 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1: Diagnosis and Medical Management. J Crohn’s Colitis. 2017 Jan;11(1):3–25. https://doi.org/10.1093/ecco-jcc/jjw168
DOI: https://doi.org/10.1093/ecco-jcc/jjw168
- Vavricka SR , Spigaglia SM , Rogler G , Pittet V , Michetti P , Felley C , et al.; Swiss IBD Cohort Study Group . Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease. Inflamm Bowel Dis. 2012 Mar;18(3):496–505. https://doi.org/10.1002/ibd.21719
DOI: https://doi.org/10.1002/ibd.21719
- Enns RA , Hookey L , Armstrong D , Bernstein CN , Heitman SJ , Teshima C , et al.; Clinical Practice Guidelines for the Use of Video Capsule Endoscopy . Clinical Practice Guidelines for the Use of Video Capsule Endoscopy. Gastroenterology. 2017 Feb;152(3):497–514. https://doi.org/10.1053/j.gastro.2016.12.032
DOI: https://doi.org/10.1053/j.gastro.2016.12.032
- Luján-Sanchis M , Sanchis-Artero L , Larrey-Ruiz L , Peño-Muñoz L , Núñez-Martínez P , Castillo-López G , et al. Current role of capsule endoscopy in Crohn’s disease. World J Gastrointest Endosc. 2016 Sep;8(17):572–83. https://doi.org/10.4253/wjge.v8.i17.572
DOI: https://doi.org/10.4253/wjge.v8.i17.572
- Xue M , Chen X , Shi L , Si J , Wang L , Chen S . Small-bowel capsule endoscopy in patients with unexplained chronic abdominal pain: a systematic review. Gastrointest Endosc. 2015 Jan;81(1):186–93. https://doi.org/10.1016/j.gie.2014.04.062
DOI: https://doi.org/10.1016/j.gie.2014.04.062
- Teshima CW , Kuipers EJ , van Zanten SV , Mensink PB . Double balloon enteroscopy and capsule endoscopy for obscure gastrointestinal bleeding: an updated meta-analysis. J Gastroenterol Hepatol. 2011 May;26(5):796–801. https://doi.org/10.1111/j.1440-1746.2010.06530.x
DOI: https://doi.org/10.1111/j.1440-1746.2010.06530.x
- Lim YJ , Lee OY , Jeen YT , Lim CY , Cheung DY , Cheon JH , et al.; Korean Gut Image Study Group . Indications for Detection, Completion, and Retention Rates of Small Bowel Capsule Endoscopy Based on the 10-Year Data from the Korean Capsule Endoscopy Registry. Clin Endosc. 2015 Sep;48(5):399–404. https://doi.org/10.5946/ce.2015.48.5.399
DOI: https://doi.org/10.5946/ce.2015.48.5.399
- Koulaouzidis A , Rondonotti E , Giannakou A , Plevris JN . Diagnostic yield of small-bowel capsule endoscopy in patients with iron-deficiency anemia: a systematic review. Gastrointest Endosc. 2012 Nov;76(5):983–92. https://doi.org/10.1016/j.gie.2012.07.035
DOI: https://doi.org/10.1016/j.gie.2012.07.035
- Yung DE , Rondonotti E , Giannakou A , Avni T , Rosa B , Toth E , et al.; And the Capsule Endoscopy in Young Patients with IDA research group . Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy. United European Gastroenterol J. 2017 Nov;5(7):974–81. https://doi.org/10.1177/2050640617692501
DOI: https://doi.org/10.1177/2050640617692501
- Olano C , Pazos X , Avendaño K , Calleri A , Ketzoian C . Diagnostic yield and predictive factors of findings in small-bowel capsule endoscopy in the setting of iron-deficiency anemia. Endosc Int Open. 2018 Jun;6(6):E688–93. https://doi.org/10.1055/a-0593-5915
DOI: https://doi.org/10.1055/a-0593-5915
- Choi M , Lim S , Choi MG , Shim KN , Lee SH . Effectiveness of Capsule Endoscopy Compared with Other Diagnostic Modalities in Patients with Small Bowel Crohn’s Disease: A Meta-Analysis. Gut Liver. 2017 Jan;11(1):62–72. https://doi.org/10.5009/gnl16015
DOI: https://doi.org/10.5009/gnl16015
- Carter D , Katz LH , Bardan E , Salomon E , Goldstein S , Ben Horin S , et al. The accuracy of intestinal ultrasound compared with small bowel capsule endoscopy in assessment of suspected Crohn’s disease in patients with negative ileocolonoscopy. Therap Adv Gastroenterol. 2018 Apr;11:1756284818765908. https://doi.org/10.1177/1756284818765908
DOI: https://doi.org/10.1177/1756284818765908
- Goldstein JL , Eisen GM , Lewis B , Gralnek IM , Aisenberg J , Bhadra P , et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther. 2007 May;25(10):1211–22. https://doi.org/10.1111/j.1365-2036.2007.03312.x
DOI: https://doi.org/10.1111/j.1365-2036.2007.03312.x
- Maiden L , Thjodleifsson B , Theodors A , Gonzalez J , Bjarnason I . A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005 May;128(5):1172–8. https://doi.org/10.1053/j.gastro.2005.03.020
DOI: https://doi.org/10.1053/j.gastro.2005.03.020
- Shimoyama T , Yamamoto T , Umegae S , Matsumoto K . Faecal biomarkers for screening small bowel inflammation in patients with Crohn’s disease: a prospective study. Therap Adv Gastroenterol. 2017 Aug;10(8):577–87. https://doi.org/10.1177/1756283X17717683
DOI: https://doi.org/10.1177/1756283X17717683
- Monteiro S , Barbosa M , Cúrdia Gonçalves T , Boal Carvalho P , Moreira MJ , Rosa B , et al. Fecal Calprotectin as a Selection Tool for Small Bowel Capsule Endoscopy in Suspected Crohn’s Disease. Inflamm Bowel Dis. 2018 Aug;24(9):2033–8. https://doi.org/10.1093/ibd/izy098
- Egea Valenzuela J , Pereñíguez López A , Pérez Fernández V , Alberca de Las Parras F , Carballo Álvarez F . Fecal calprotectin and C-reactive protein are associated with positive findings in capsule endoscopy in suspected small bowel Crohn’s disease. Rev Esp Enferm Dig. 2016 Jul;108(7):394–400.
DOI: https://doi.org/10.17235/reed.2016.4318/2016
- Jensen MD , Kjeldsen J , Nathan T . Fecal calprotectin is equally sensitive in Crohn’s disease affecting the small bowel and colon. Scand J Gastroenterol. 2011 Jun;46(6):694–700. https://doi.org/10.3109/00365521.2011.560680
DOI: https://doi.org/10.3109/00365521.2011.560680
- Kopylov U , Yung DE , Engel T , Avni T , Battat R , Ben-Horin S , et al. Fecal calprotectin for the prediction of small-bowel Crohn’s disease by capsule endoscopy: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2016 Oct;28(10):1137–44. https://doi.org/10.1097/MEG.0000000000000692
DOI: https://doi.org/10.1097/MEG.0000000000000692
- Koulaouzidis A , Douglas S , Rogers MA , Arnott ID , Plevris JN . Fecal calprotectin: a selection tool for small bowel capsule endoscopy in suspected IBD with prior negative bi-directional endoscopy. Scand J Gastroenterol. 2011 May;46(5):561–6. https://doi.org/10.3109/00365521.2011.551835
DOI: https://doi.org/10.3109/00365521.2011.551835
- Yablecovitch D , et al. The Lewis score or the capsule endoscopy Crohn’s disease activity index: which one is better for the assessment of small bowel inflammation in established Crohn’s disease? Therap Adv Gastroenterol, 2018. 11: p. 1756283X17747780.
DOI: https://doi.org/10.1177/1756283X17747780
- Koulaouzidis A , Sipponen T , Nemeth A , Makins R , Kopylov U , Nadler M , et al. Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy: A Multicenter Retrospective Study. Dig Dis Sci. 2016 Jul;61(7):2033–40. https://doi.org/10.1007/s10620-016-4104-7
DOI: https://doi.org/10.1007/s10620-016-4104-7
- Koulaouzidis A , Nemeth A , Johansson GW , Toth E . Dissecting Lewis score under the light of fecal calprotectin; an analysis of correlation of score components with calprotectin levels in capsule endoscopy. Ann Gastroenterol. 2015;28(2):259–64.
- Sipponen T , Haapamäki J , Savilahti E , Alfthan H , Hämäläinen E , Rautiainen H , et al. Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn’s disease detected by wireless capsule endoscopy. Scand J Gastroenterol. 2012 Jul;47(7):778–84. https://doi.org/10.3109/00365521.2012.677953
DOI: https://doi.org/10.3109/00365521.2012.677953
- Hale MF , Drew K , McAlindon ME , Sidhu R . The diagnostic accuracy of faecal calprotectin and small bowel capsule endoscopy and their correlation in suspected isolated small bowel Crohn’s disease. Eur J Gastroenterol Hepatol. 2016 Oct;28(10):1145–50. https://doi.org/10.1097/MEG.0000000000000696
DOI: https://doi.org/10.1097/MEG.0000000000000696
- Olsen PA , Fossmark R , Qvigstad G . Fecal calprotectin in patients with suspected small bowel disease—a selection tool for small bowel capsule endoscopy? Scand J Gastroenterol. 2015 Mar;50(3):272–7. https://doi.org/10.3109/00365521.2014.1003395
DOI: https://doi.org/10.3109/00365521.2014.1003395
- Yousuf H , Aleem U , Egan R , Maheshwari P , Mohamad J , McNamara D . Elevated Faecal Calprotectin Levels are a Reliable Non-Invasive Screening Tool for Small Bowel Crohn’s Disease in Patients Undergoing Capsule Endoscopy. Dig Dis. 2018;36(3):202–8. https://doi.org/10.1159/000485375
DOI: https://doi.org/10.1159/000485375
- Zittan E , Kelly OB , Gralnek IM , Silverberg MS , Hillary Steinhart A . Fecal calprotectin correlates with active colonic inflammatory bowel disease but not with small intestinal Crohn’s disease activity. JGH Open. 2018 Jul;2(5):201–6. https://doi.org/10.1002/jgh3.12068
DOI: https://doi.org/10.1002/jgh3.12068
- Lasson A , Stotzer PO , Öhman L , Isaksson S , Sapnara M , Strid H . The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis. J Crohn’s Colitis. 2015 Jan;9(1):26–32.
DOI: https://doi.org/10.1016/j.crohns.2014.06.002
- Schoepfer AM , Dehlavi MA , Fournier N , Safroneeva E , Straumann A , Pittet V , et al.; IBD Cohort Study Group . Diagnostic delay in Crohn’s disease is associated with a complicated disease course and increased operation rate. Am J Gastroenterol. 2013 Nov;108(11):1744–53. https://doi.org/10.1038/ajg.2013.248
DOI: https://doi.org/10.1038/ajg.2013.248
- Gisbert JP , McNicholl AG . Questions and answers on the role of faecal calprotectin as a biological marker in inflammatory bowel disease. Dig Liver Dis. 2009 Jan;41(1):56–66. https://doi.org/10.1016/j.dld.2008.05.008
DOI: https://doi.org/10.1016/j.dld.2008.05.008
- von Roon AC , Karamountzos L , Purkayastha S , Reese GE , Darzi AW , Teare JP , et al. Diagnostic precision of fecal calprotectin for inflammatory bowel disease and colorectal malignancy. Am J Gastroenterol. 2007 Apr;102(4):803–13. https://doi.org/10.1111/j.1572-0241.2007.01126.x
DOI: https://doi.org/10.1111/j.1572-0241.2007.01126.x
- van Rheenen PF , Van de Vijver E , Fidler V . Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010 Jul;341 jul15 1:c3369. https://doi.org/10.1136/bmj.c3369
DOI: https://doi.org/10.1136/bmj.c3369
- D’Angelo F , Felley C , Frossard JL . Calprotectin in Daily Practice: Where Do We Stand in 2017? Digestion. 2017;95(4):293–301. https://doi.org/10.1159/000476062
DOI: https://doi.org/10.1159/000476062
- Freeman K , Ryan R , Parsons N , Taylor-Phillips S , Willis BH , Clarke A . Faecal calprotectin testing in UK general practice: a retrospective cohort study using The Health Improvement Network database. Br J Gen Pract. 2021 Oct;71(712):e854–61. https://doi.org/10.3399/BJGP.2021.0125
DOI: https://doi.org/10.3399/BJGP.2021.0125
- Monteiro S , Barbosa M , Cúrdia Gonçalves T , Boal Carvalho P , Moreira MJ , Rosa B , et al. Fecal Calprotectin as a Selection Tool for Small Bowel Capsule Endoscopy in Suspected Crohn’s Disease. Inflamm Bowel Dis. 2018 Aug;24(9):2033–8. https://doi.org/10.1093/ibd/izy098
DOI: https://doi.org/10.1093/ibd/izy098
- Conroy S , Hale MF , Cross SS , Swallow K , Sidhu RH , Sargur R , et al. Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care. J Clin Pathol. 2018 Apr;71(4):316–22. https://doi.org/10.1136/jclinpath-2017-204506
DOI: https://doi.org/10.1136/jclinpath-2017-204506