Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study

Michael Manz, Emanuel Burri, Claude Rothen, Nuschin Tchanguizi, Christian Niederberger, Livio Rossi, Christoph Beglinger, Frank Serge Lehmann, Michael Manz, Emanuel Burri, Claude Rothen, Nuschin Tchanguizi, Christian Niederberger, Livio Rossi, Christoph Beglinger, Frank Serge Lehmann

Abstract

Background: The evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort.

Methods: In an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values.

Results: Median calprotectin levels were higher in patients with significant findings (N = 212, median 97 μg/g, IQR 43-185) than in patients without (N = 326, 10 μg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 μg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165).

Conclusion: In patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.

© 2012 Manz et al; licensee BioMed Central Ltd.

Figures

Figure 1
Figure 1
Study flow. Study flow of patients referred for colonoscopy and esophagogastroduodenoscopy (EGD). A total of 37 patients were excluded from the final analysis, in 29 patients because follow-up endoscopy was not performed as required by the protocol (no clinically significant lesion on endoscopy but fecal calprotectin > 50 μg/g)
Figure 2
Figure 2
Receiver Operating Characteristics Curve. To identify clinically significant findings in the gastrointestinal tract, fecal calprotectin had an area under the receiver operating characteristics (ROC) curve of 0.877 (95% CI 0.85-0.90) (Figure 2A). The AUC of fecal calprotectin to identify clinically significant findings was better in the lower intestinal tract (AUC 0.912, 95%CI 0.88-0.94) (Figure 2C) than in the upper intestinal tract (AUC 0.730, 95%CI 0.66-0-79, P < 0.001) (Figure 2B).
Figure 3
Figure 3
Diagnostic accuracy of fecal calprotectin. The overall test accuracy of fecal calprotectin was 85% when 50 μg/g was used as cut off value (upper panel) and was 68% when 10 μg/g was used (lower panel).
Figure 4
Figure 4
Fecal calprotectin and severity of mucosal damage. Boxplots (median, 25th and 75th percentile) of fecal calprotectin values in patients with normal endoscopic findings (normal), gastric erosions (erosion), gastric ulcer (ulcer), and gastric cancer (carcinoma). * P < 0.001 against normal, # P = 0.002 against normal, § P = 0.157 against ulcer, † P = 0.027 against carcinoma, $ P = 0.088 against carcinoma.

References

    1. Kay L, Jorgensen T. Abdominal symptom associations in a longitudinal study. Int J Epidemiol. 1993;22(6):1093–1100. doi: 10.1093/ije/22.6.1093.
    1. Kay L, Jorgensen T, Schultz-Larsen K. Abdominal pain in a 70-year-old Danish population. An epidemiological study of the prevalence and importance of abdominal pain. J Clin Epidemiol. 1992;45(12):1377–1382. doi: 10.1016/0895-4356(92)90199-W.
    1. Group TDDS. Value of the unaided clinical diagnosis in dyspeptic patients in primary care. Am J Gastroenterol. 2001;96(5):1417–1421.
    1. Jellema P, van der Windt DAWM, Schellevis FG, van der Horst HE. Systematic review: accuracy of symptom-based criteria for diagnosis of irritable bowel syndrome in primary care. Alimentary Pharmacology & Therapeutics. 2009;30(7):695–706. doi: 10.1111/j.1365-2036.2009.04087.x.
    1. Hillila MT, Farkkila MA. Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther. 2004;20(3):339–345. doi: 10.1111/j.1365-2036.2004.02034.x.
    1. Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada J-R, Stanghellini V. Functional gastroduodenal disorders. Gastroenterology. 2006;130(5):1466–1479. doi: 10.1053/j.gastro.2005.11.059.
    1. Dalrymple J, Bullock I. Diagnosis and management of irritable bowel syndrome in adults in primary care: summary of NICE guidance. BMJ. 2008;336(7643):556–558. doi: 10.1136/.
    1. Drossman DA, Corazziari E, Delvaux M, Spiller R, Talley NJ, Thompson WG. [Appendix B: Rome III diagnostic criteria for functional gastrointestinal disorders.] Rev Gastroenterol Mex. 2010;75(4):511–516.
    1. Roseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol. 1999;34(1):50–54. doi: 10.1080/00365529950172835.
    1. 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;41(1):56–66. doi: 10.1016/j.dld.2008.05.008.
    1. 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;341:c3369. doi: 10.1136/bmj.c3369.
    1. Tibble JA, Sigthorsson G, Foster R, Forgacs I, Bjarnason I. Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology. 2002;123(2):450–460. doi: 10.1053/gast.2002.34755.
    1. D'Inca R, Dal Pont E, Di Leo V, Ferronato A, Fries W, Vettorato MG, Martines D, Sturniolo GC. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis. 2007;22(4):429–437. doi: 10.1007/s00384-006-0159-9.
    1. D'Inca R, Dal Pont E, Di Leo V, Benazzato L, Martinato M, Lamboglia F, Oliva L, Sturniolo GC. Can calprotectin predict relapse risk in inflammatory bowel disease? Am J Gastroenterol. 2008;103(8):2007–2014. doi: 10.1111/j.1572-0241.2008.01870.x.
    1. Tibble J, Sigthorsson G, Foster R, Sherwood R, Fagerhol M, Bjarnason I. Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Gut. 2001;49(3):402–408. doi: 10.1136/gut.49.3.402.
    1. Wildt S, Nordgaard-Lassen I, Bendtsen F, Rumessen JJ. Metabolic and inflammatory faecal markers in collagenous colitis. Eur J Gastroenterol Hepatol. 2007;19(7):567–574. doi: 10.1097/MEG.0b013e328058ed76.
    1. Shastri YM, Bergis D, Povse N, Schäfer V, Shastri S, Weindel M, Ackermann H, Stein J. Prospective multicenter study evaluating fecal calprotectin in adult acute bacterial diarrhea. Am J Med. 2008;121(12):1099–1106. doi: 10.1016/j.amjmed.2008.06.034.
    1. Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005;128(5):1172–1178. doi: 10.1053/j.gastro.2005.03.020.
    1. Summerton CB, Longlands MG, Wiener K, Shreeve DR. Faecal calprotectin: a marker of inflammation throughout the intestinal tract. Eur J Gastroenterol Hepatol. 2002;14(8):841–845. doi: 10.1097/00042737-200208000-00005.
    1. Roseth AG, Kristinsson J, Fagerhol MK, Schjonsby H, Aadland E, Nygaard K, Roald B. Faecal calprotectin: a novel test for the diagnosis of colorectal cancer? Scand J Gastroenterol. 1993;28(12):1073–1076. doi: 10.3109/00365529309098312.
    1. Meucci G, D'Inca R, Maieron R, Orzes N, Vecchi M, Visentini D, Minoli G, Dal Pont E, Zilli M, Benedetti E. et al.Diagnostic value of faecal calprotectin in unselected outpatients referred for colonoscopy: A multicenter prospective study. Dig Liver Dis. 2010;42(3):191–195. doi: 10.1016/j.dld.2009.07.002.
    1. Van Assche G, Dignass A, Panes J, Beaugerie L, Karagiannis J, Allez M, Ochsenkuhn T, Orchard T, Rogler G, Louis E. et al.The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Definitions and diagnosis. J Crohns Colitis. 2010;4(1):7–27.
    1. Stange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A, Feakins R, Flejou JF, Herfarth H, Hommes DW. et al.European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis. J Crohns Colitis. 2008;2(1):1–23.
    1. Allum WH, Griffin SM, Watson A, Colin-Jones D. Guidelines for the management of oesophageal and gastric cancer. Gut. 2002;50(Suppl 5):v1–23.
    1. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(9):627–637.
    1. Roseth AG, Fagerhol MK, Aadland E, Schjonsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol. 1992;27(9):793–798. doi: 10.3109/00365529209011186.
    1. Carley S, Dosman S, Jones SR, Harrison M. Simple nomograms to calculate sample size in diagnostic studies. Emerg Med J. 2005;22(3):180–181. doi: 10.1136/emj.2003.011148.
    1. Sonnenberg A, Amorosi SL, Lacey MJ, Lieberman DA. Patterns of endoscopy in the United States: analysis of data from the Centers for Medicare and Medicaid Services and the National Endoscopic Database. Gastrointest Endosc. 2008;67(3):489–496. doi: 10.1016/j.gie.2007.08.041.
    1. Heuss LT, Froehlich F, Beglinger C. Changing patterns of sedation and monitoring practice during endoscopy: results of a nationwide survey in Switzerland. Endoscopy. 2005;37(2):161–166. doi: 10.1055/s-2004-826143.
    1. Vader JP, Wietlisbach V, Harris JK, Burnand B, Froehlich F, Gonvers JJ. Gastroenterologists overestimate the appropriateness of colonoscopies they perform: an international observational study. Endoscopy. 2005;37(9):840–846. doi: 10.1055/s-2005-870193.
    1. Wallace MB, Durkalski VL, Vaughan J, Palesch YY, Libby ED, Jowell PS, Nickl NJ, Schutz SM, Leung JW, Cotton PB. Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study. Gut. 2001;49(1):29–34. doi: 10.1136/gut.49.1.29.
    1. Lasson A, Kilander A, Stotzer PO. Diagnostic yield of colonoscopy based on symptoms. Scand J Gastroenterol. 2008;43(3):356–362. doi: 10.1080/00365520701679116.
    1. Ang YS, Macaleenan N, Mahmud N, Keeling PW, Kelleher DP, Weir DG. The yield of colonoscopy in average-risk patients with non-specific colonic symptoms. Eur J Gastroenterol Hepatol. 2002;14(10):1073–1077. doi: 10.1097/00042737-200210000-00007.
    1. Lieberman DA, de Garmo PL, Fleischer DE, Eisen GM, Chan BK, Helfand M. Colonic neoplasia in patients with nonspecific GI symptoms. Gastrointest Endosc. 2000;51(6):647–651. doi: 10.1067/mge.2000.105082.
    1. Vader JP, Burnand B, Froehlich F, Dubois RW, Bochud M, Gonvers JJ. The European Panel on Appropriateness of Gastrointestinal Endoscopy (EPAGE): project and methods. Endoscopy. 1999;31(8):572–578. doi: 10.1055/s-1999-71.
    1. Juillerat P, Peytremann-Bridevaux I, Vader JP, Arditi C, Schussele Filliettaz S, Dubois RW, Gonvers JJ, Froehlich F, Burnand B, Pittet V. Appropriateness of colonoscopy in Europe (EPAGE II). Presentation of methodology, general results, and analysis of complications. Endoscopy. 2009;41(3):240–246. doi: 10.1055/s-0028-1119643.
    1. Appropriate use of gastrointestinal endoscopy. American Society for Gastrointestinal Endoscopy. Gastrointest Endosc. 2000;52(6):831–837.
    1. Chan YM, Goh KL. Appropriateness and diagnostic yield of EGD: a prospective study in a large Asian hospital. Gastrointest Endosc. 2004;59(4):517–524. doi: 10.1016/S0016-5107(04)00002-1.
    1. Grassini M, Verna C, Niola P, Navino M, Battaglia E, Bassotti G. Appropriateness of colonoscopy: diagnostic yield and safety in guidelines. World J Gastroenterol. 2007;13(12):1816–1819. discussion 1819.
    1. van der Sluijs Veer G, van den Hoven B, Russel MG, van den Bergh FA. Time-resolved fluorimetric immunoassay of calprotectin: technical and clinical aspects in diagnosis of inflammatory bowel diseases. Clin Chem Lab Med. 2006;44(3):292–298. doi: 10.1515/CCLM.2006.051.
    1. Ikenberry SO, Harrison ME, Lichtenstein D, Dominitz JA, Anderson MA, Jagannath SB, Banerjee S, Cash BD, Fanelli RD, Gan S-I. et al.The role of endoscopy in dyspepsia. Gastrointest Endosc. 2007;66(6):1071–1075. doi: 10.1016/j.gie.2007.07.007.
    1. Buri L, Hassan C, Bersani G, Anti M, Bianco MA, Cipolletta L, Di Giulio E, Di Matteo G, Familiari L, Ficano L, Appropriateness Guidelines and Predictive Rules to Select Patients for Upper Endoscopy: A Nationwide Multicenter Study. Am J Gastroenterol. 2009.
    1. Miwa H, Yokoyama T, Hori K, Sakagami T, Oshima T, Tomita T, Fujiwara Y, Saita H, Itou T, Ogawa H. et al.Interobserver agreement in endoscopic evaluation of reflux esophagitis using a modified Los Angeles classification incorporating grades N and M: a validation study in a cohort of Japanese endoscopists. Dis Esophagus. 2008;21(4):355–363. doi: 10.1111/j.1442-2050.2007.00788.x.
    1. Joshi S, Lewis SJ, Creanor S, Ayling RM. Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers. Ann Clin Biochem. 2010;47(Pt 3):259–263.
    1. Montalto M, Santoro L, Dalvai S, Curigliano V, D'onofrio F, Scarpellini E, Cammarota G, Panunzi S, Gallo A, Gasbarrini A. et al.Fecal calprotectin concentrations in patients with small intestinal bacterial overgrowth. Digestive diseases (Basel, Switzerland) 2008;26(2):183–186. doi: 10.1159/000116777.
    1. Montalto M, Santoro L, Curigliano V, D'onofrio F, Cammarota G, Panunzi S, Ricci R, Gallo A, Grieco A, Gasbarrini A. et al.Faecal calprotectin concentrations in untreated coeliac patients. Scand J Gastroenterol. 2007;42(8):957–961. doi: 10.1080/00365520601173632.
    1. Carroccio A, Iacono G, Cottone M, Di Prima L, Cartabellotta F, Cavataio F, Scalici C, Montalto G, Di Fede G, Rini G. et al.Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clin Chem. 2003;49(6 Pt 1):861–867.
    1. Lorenz E, Muhlebach MS, Tessier PA, Alexis NE, Duncan Hite R, Seeds MC, Peden DB, Meredith W. Different expression ratio of S100A8/A9 and S100A12 in acute and chronic lung diseases. Respir Med. 2008;102(4):567–573. doi: 10.1016/j.rmed.2007.11.011.

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