Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013, 157(2):91-97 | DOI: 10.5507/bp.2013.027

Laboratory screening markers in gastroenterology - state of the art

Petr Kocnaa, Zdislava Vanickovaa, Tomas Zimaa
a Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

Introduction: Screening tests for gastrointestinal diseases acceptable for population with a high sensitivity and high specificity can now be offered by clinical laboratories. This paper summarizes major recent advances in this area of laboratory medicine.

Methods: Relevant articles published within the last 5 years in the NLM (National Library of Medicine) PubMed - Medline database covering the three gastrointestinal diseases - colorectal cancer, coeliac disease, and atrophic gastritis were included for this overview.

Results: In Europe, colorectal cancer (CRCA) is the second most frequent malignant disease. Quantitative immunochemical analysis of the stool for haemoglobin provides the best screening test to date, with both sensitivity and specificity approaching 95%. Even though coeliac disease (CD) affects approximately 1% of the general population, it remains largely unrecognised. Recommended methods for screening currently involve the detection of IgA and IgG antibodies against tissue transglutaminase and deamidated gliadin peptide. Evaluations of screening are now discussed for other diseases of the gastrointestinal tract - such as chronic atrophic gastritis (CAG), and inflammatory bowel disease (IBD). Detection of infection by Helicobacter pylori and stomach-specific plasmatic biomarkers, especially pepsinogen I/II ratio, could help with the prevention of gastric carcinomas. The use of faecal calprotectin as a screening test could substantially reduce the number of invasive methods necessary for the diagnostic work-up of patients with IBD.

Conclusions: Screening tests for CRCA and CD have been used worldwide for many years. Screening strategies for gastrointestinal diseases are suggested in the text, based on recent basic science, clinical papers as well as our own experience.

Keywords: gastroenterology, screening, colorectal cancer, coeliac disease, chronic atrophic gastritis, inflammatory bowel disease

Received: October 1, 2012; Accepted: April 10, 2013; Prepublished online: May 3, 2013; Published: June 21, 2013  Show citation

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Kocna, P., Vanickova, Z., & Zima, T. (2013). Laboratory screening markers in gastroenterology - state of the art. Biomedical papers157(2), 91-97. doi: 10.5507/bp.2013.027
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References

  1. Holland WW, Stewart S, Masseria C. Screening in Europe-Policy Brief. European Observatory on Health Systems and Policies, WHO European Centre for Health Policy 2006; pp.1-72.
  2. Thorner RM, Remein QR. Principles and Procedures in the Evaluation of Screening for Disease. Public Health Monograph no. 67, Washington, Public Health Service. 1961.
  3. Wilson JMG, Jungner G. Principles and Practice of Screening for Disease. Geneva, World Health Organization 1968.
  4. Stockbrugger R. Isolated colorectal cancer screening or integrated cancer prevention? A provocative suggestion! Dig Dis 2012;30(3):316-9. Go to original source... Go to PubMed...
  5. Zavoral M, Suchanek S, Zavada F, Dusek L, Muzik J, Seifert B, Fric P. Colorectal cancer screening in Europe. World J Gastroenterol 2009;15(47):5907-15. Go to original source... Go to PubMed...
  6. Miller S, Steele S. Novel Molecular Screening Approaches in Colorectal Cancer. Journal of Surgical Oncology 2012;105:459-67. Go to original source... Go to PubMed...
  7. Wong JL, Hawkins NJ, Ward RL. Colorectal cancer: A model for epigenetic tumorigenesis. Gut 2007;56:140-1. Go to original source... Go to PubMed...
  8. Fric P, Zavoral M, Dvorakova H, Zoubek V, Roth Z. An adapted program of colorectal cancer screening-7 years experience and cost-benefit analysis. Hepatogastroenterology 1994;41:413-6. Go to PubMed...
  9. Damery S, Smith S, Clements A, Holder R, Nichols L, Draper H, Clifford S, Parker L, Hobbs R, Wilson S. Evaluating the effectiveness of GP endorsement on increasing participation in the NHS Bowel Cancer Screening Programme in England: study protocol for a randomized controlled trial. Trials 2012;13:18. Go to original source... Go to PubMed...
  10. Qaseem A, Denberg TD, Hopkins RH, Humphrey LL, Levine J, Sweet DE, Shekelle P. Screening for colorectal cancer: a guidance statement from the American College of Physicians. Ann Intern Med 2012;56(5):378-86. Go to original source...
  11. Scholefield JH, Moss SM, Mangham CM, Whynes DK, Hardcastle JD. Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up. Gut 2012;61(7):1036-40. Go to original source... Go to PubMed...
  12. Rabeneck L, Rumble RB, Thompson F, Mills M, Oleschuk C, Whibley A, Messersmith H, Lewis N. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Can J Gastroenterol 2012;26(3):131-47. Go to original source... Go to PubMed...
  13. Brenner H, Haug U, Hundt S: Inter-test agreement and quantitative cross-validation of immunochromatographical fecal occult blood tests. Int J Cancer 2010;127(7):1643-9. Go to original source... Go to PubMed...
  14. Sheng JQ, Li SR, Wu ZT, Xia CH, Wu X, Chen J, Rao J. Transferrin dipstick as a potential novel test for colon cancer screening: a comparative study with immuno fecal occult blood test. Cancer Epidemiol Biomarkers Prev 2009;18(8):2182-5. Go to original source... Go to PubMed...
  15. Chalkias A, Nikotian G, Koutsovasilis A, Bramis J, Manouras A, Mystrioti D, Katergiannakis V. Patients with colorectal cancer are characterized by increased concentration of fecal hb-hp complex, myeloperoxidase, and secretory IgA. Am J Clin Oncol 2011;34(6):561-6. Go to original source... Go to PubMed...
  16. Duffy MJ, van Rossum LG, van Turenhout ST, Malminiemi O, Sturgeon C, Lamerz R, Nicolini A, Haglund C, Holubec L, Fraser CG, Halloran SP. Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper. Int J Cancer 2011;128(1):3-11. Go to original source... Go to PubMed...
  17. Levin TR, Jamieson L, Burley DA, Reyes J, Oehrli M, Caldwell C. Organized colorectal cancer screening in integrated health care systems. Epidemiol Rev 2011;33(1):101-10. Go to original source... Go to PubMed...
  18. Park DI, Ryu S, Kim YH, Lee SH, Lee CK, Eun CS, Han DS. Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening. Am J Gastroenterol 2010;105(9):2017-25. Go to original source... Go to PubMed...
  19. Guittet L, Guillaume E, Levillain R, Beley P, Tichet J, Lantieri O, Launoy G. Analytical comparison of three quantitative immunochemical fecal occult blood tests for colorectal cancer screening. Cancer Epidemiol Biomarkers Prev 2011;20(7):1492-501. Go to original source... Go to PubMed...
  20. Omata F, Shintani A, Isozaki M, Masuda K, Fujita Y, Fukui T. Diagnostic performance of quantitative fecal immunochemical test and multivariate prediction model for colorectal neoplasms in asymptomatic individuals. Eur J Gastroenterol Hepatol 2011;23(11):1036-41. Go to original source... Go to PubMed...
  21. Park MJ, Choi KS, Lee YK, Jun JK, Lee HY. A comparison of qualitative and quantitative fecal immunochemical tests in the Korean national colorectal cancer screening program. Scand J Gastroenterol 2012;120474:461-6. Go to original source... Go to PubMed...
  22. Hol L, van Leerdam ME, van Ballegooijen M, van Vuuren AJ, van Dekken H, Reijerink JC, van der Togt AC, Habbema JD, Kuipers EJ. Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy. Gut 2010;59(1):62-8. Go to original source... Go to PubMed...
  23. van Roon AH, Wilschut JA, Hol L, van Ballegooijen M, Reijerink JC, 't Mannetje H, Kranenburg LJ, Biermann K, van Vuuren AJ, Francke J, van der Togt AC, Habbema DJ, van Leerdam ME, Kuipers EJ. Diagnostic yield improves with collection of 2 samples in fecal immunochemical test screening without affecting attendance. Clin Gastroenterol Hepatol 2011;9(4):333-9. Go to original source... Go to PubMed...
  24. Goede SL, van Roon AH, Reijerink JC, van Vuuren AJ, Lansdorp-Vogelaar I, Habbema JD, Kuipers EJ, van Leerdam ME, van Ballegooijen M. Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening. Gut 2013;62:727-34. doi:10.1136/gutjnl-2011-301917 Go to original source... Go to PubMed...
  25. Wilschut JA, Hol L, Dekker E, Jansen JB, Van Leerdam ME, Lansdorp-Vogelaar I, Kuipers EJ, Habbema JD, Van Ballegooijen M. Cost-effectiveness analysis of a quantitative immunochemical test for colorectal cancer screening. Gastroenterology 2011;41(5):1648-55. Go to original source...
  26. van Rossum LG, van Rijn AF, Verbeek AL, van Oijen MG, Laheij RJ, Fockens P, Jansen JB, Adang EM, Dekker E. Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis. Int J Cancer 2011;128(8):1908-17. Go to original source... Go to PubMed...
  27. Kovarova JT, Zavoral M, Zima T, Zak A, Kocna P, Kohout P, Granatova J, Vanickova Z, Vranova J, Suchanek S, Benes Z, Celko MA, Povysil C. Improvements in colorectal cancer screening programmes - quantitative immunochemical faecal occult blood testing - how to set the cut-off for a particular population. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012,156(2):143-50. doi: 10.5507/bp.2012.030 Go to original source... Go to PubMed...
  28. Fraser CG, Allison JE, Halloran SP, Young GP. A Proposal to Standardize Reporting Units for Fecal Immunochemical Tests for Hemoglobin. J Natl Cancer Inst 2012;6;104(11):810-4. Go to original source... Go to PubMed...
  29. Allison JE, Fraser CG, Halloran SP, Young GP. Comparing fecal immunochemical tests: improved standardization is needed. Gastroenterology 2012;142(3):422-4. Go to original source... Go to PubMed...
  30. Zauber AG, Levin TR, Jaffe CC, Galen BA, Ransohoff DF, Brown ML. Implications of new colorectal cancer screening technologies for primary care practice. Med Care 2008;46:138-46. Go to original source...
  31. Li BS, Wang XY, Xu AG, Ma FL, Ma QY, Li Z, Liu JH, Gan AH, Yu ZJ, Zhang XH, Jiang B. High-Resolution Melting Assay (HRMA) is a Simple and Sensitive Stool-Based DNA Test for the Detection of Mutations in Colorectal Neoplasms. Clin Colorectal Cancer 2012;11(4):280-90. Go to original source... Go to PubMed...
  32. Ahlquist DA, Zou H, Domanico M, Mahoney DW, Yab TC, Taylor WR, Butz ML, Thibodeau SN, Rabeneck L, Paszat LF, Kinzler KW, Vogelstein B, Bjerregaard NC, Laurberg S, Sørensen HT, Berger BM, Lidgard GP. Next-generation stool DNA test accurately detects colorectal cancer and large adenomas. Gastroenterology 2012;142(2):248-56. Go to original source... Go to PubMed...
  33. Miller S, Steele S. Novel molecular screening approaches in colorectal cancer. J Surg Oncol 2012;105(5):459-67. Go to original source... Go to PubMed...
  34. Jin X, Lin M, Zhang H, Han Y, He Y, Zhang Q, Yu S, Chen L, Dong W, Wang W, Sun W, Yin L. Serum biomarkers of colorectal cancer with AU and NP20 chips including a diagnosis model. Hepatogastroenterology 2012;59(113):124-9. Go to original source... Go to PubMed...
  35. Warren JD, Xiong W, Bunker AM, Vaughn CP, Furtado LV, Roberts WL, Fang JC, Samowitz WS, Heichman KA. Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer. BMC Med 2011;9:133. Go to original source... Go to PubMed...
  36. Ahlquist DA, Taylor WR, Mahoney DW, Zou H, Domanico M, Thibodeau SN, Boardman LA, Berger BM, Lidgard GP. The stool DNA test is more accurate than the plasma septin 9 test in detecting colorectal neoplasia. Clin Gastroenterol Hepatol 2012;10(3):272-7. Go to original source... Go to PubMed...
  37. Tao S, Haug U, Kuhn K, Brenner H. Comparison and combination of blood-based inflammatory markers with faecal occult blood tests for non-invasive colorectal cancer screening. Br J Cancer 2012;106(8):1424-30. Go to original source... Go to PubMed...
  38. Newton KF, Newman W, Hill J. Review of biomarkers in colorectal cancer. Colorectal Dis 2012;14(1):3-17. Go to original source... Go to PubMed...
  39. Lumachi F, Marino F, Orlando R, Chiara GB, Basso SM. Simultaneous multianalyte immunoassay measurement of five serum tumor markers in the detection of colorectal cancer. Anticancer Res 2012;32(3):985-8.
  40. Pox C. Colon cancer screening: which non-invasive filter tests? Dig Dis 2011;29,Suppl 1:56-9. Go to original source... Go to PubMed...
  41. Fatela-Cantillo D, Fernandez-Suarez A, Moreno MA, Gutierrez JJ, Iglesias JM. Prognostic value of plasmatic tumor M2 pyruvate kinase and carcinoembryonic antigen in the survival of colorectal cancer patients. Tumour Biol 2012;33(3):825-32. Go to original source... Go to PubMed...
  42. Li R, Liu J, Xue H, Huang G. Diagnostic value of fecal tumor M2-pyruvate kinase for CRC screening: A systematic review and meta-analysis. Int J Cancer 2012;131(8):837-45. Go to original source...
  43. Jiskra J, Limanova Z, Vanickova Z, Kocna P. IgA and IgG Antigliadin, IgA Anti-tissue Transglutaminase and Antiendomysial Antibodies in Patients with Autoimmune Thyroid Diseases and Their Relationship to Thyroidal Replacement Therapy Physiol Res 2003;52:79-88.
  44. Vancikova Z, Chlumecky V, Sokol D, Horakova D, Hamsikova E, Fucikova T, Janatkova I, Ulcova-Gallova Z, Stepan J, Limanova Z, Dvorak M, Kocna P, Sanchez D, Tuckova L, Tlaskalova-Hogenova H. The Serologic Screening for Celiac Disease in the General Population (Blood Donors) and in Some High-Risk Groups of Adults (Patients with Autoimmune Diseases, Osteoporosis and Infertility) in the Czech Republic. Folia Microbiol 2002;47(6):753-58. Go to original source... Go to PubMed...
  45. Marchese A, Lovati E, Biagi F, Corazza GR. Coeliac disease and type 1 diabetes mellitus: epidemiology, clinical implications and effects of gluten-free diet. Endocrine. 2013;43(1):1-2. Go to original source... Go to PubMed...
  46. Hansen D, Brock-Jacobsen B, Lund E, Bjørn C, Hansen LP, Nielsen C, Fenger C, Lillevang ST, Husby S. Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years' follow-up. Diabetes Care. 2006;29(11):2452-6. Go to original source... Go to PubMed...
  47. Tio M, Cox MR, Eslick GD. Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy. Aliment Pharmacol Ther. 2012;35(5):540-51. Go to original source... Go to PubMed...
  48. Gujral N, Freeman HJ, Thomson AB. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment. World J Gastroenterol. 2012;18(42):6036-59. Go to original source... Go to PubMed...
  49. Mubarak A, Houwen RH, Wolters VM. Celiac disease: an overview from pathophysiology to treatment. Minerva Pediatr 2012;64(3):271-87. Go to PubMed...
  50. Kocna P, Vanickova Z, Perusicova J, Dvorak M. Tissue Transglutaminase-Serology Markers for Coeliac Disease. Clin Chem Lab Med 2002;40(5):485-92. Go to original source... Go to PubMed...
  51. Giersiepen K, Lelgemann M, Stuhldreher N, Ronfani L, Husby S, Koletzko S, Korponay-Szabo IR; ESPGHAN Working Group on Coeliac Disease Diagnosis. Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report. J Pediatr Gastroenterol Nutr 2012;54(2):229-41. Go to original source... Go to PubMed...
  52. Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease. Aliment Pharmacol Ther 2010;31(1):73-81. Go to original source... Go to PubMed...
  53. Aggarwal S, Lebwohl B, Green PH. Screening for celiac disease in average-risk and high-risk populations. Therap Adv Gastroenterol 2012;5(1):37-47. Go to original source... Go to PubMed...
  54. Volta U, Fabbri A, Parisi C, Piscaglia M, Caio G, Tovoli F, Fiorini E. Old and new serological tests for celiac disease screening. Expert Rev Gastroenterol Hepatol 2010;4(1):31-5. Go to original source... Go to PubMed...
  55. Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, Lelgeman M, Maki M, Ribes-Koninckx C, Ventura A, Zimmer KP. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54(1):136-60. Go to original source... Go to PubMed...
  56. Kneepkens CM, von Blomberg BM. Clinical practice : Coeliac disease. Eur J Pediatr 2012;171(7):1011-21. Go to original source... Go to PubMed...
  57. Rosen A, Emmelin M, Carlsson A, Hammarroth S, Karlsson E, Ivarsson A. Mass screening for celiac disease from the perspective of newly diagnosed adolescents and their parents: a mixed-method study. BMC Public Health 2011;11:822. Go to original source... Go to PubMed...
  58. Bonamico M, Nenna R, Montuori M, Luparia RP, Turchetti A, Mennini M, Lucantoni F, Masotti D, Magliocca FM, Culasso F, Tiberti C. First salivary screening of celiac disease by detection of anti-transglutaminase autoantibody radioimmunoassay in 5000 Italian primary schoolchildren. J Pediatr Gastroenterol Nutr 2011;52(1):17-20. Go to original source... Go to PubMed...
  59. Correa P, Piazuelo MB. The gastric precancerous cascade. J Dig Dis 2012;13(1):2-9. Go to original source... Go to PubMed...
  60. Vannella L, Lahner E, Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: A critical reappraisal. World J Gastroenterol 2012;18(12):1279-85. Go to original source... Go to PubMed...
  61. Ricci C, Holton J, Vaira D. Diagnosis of Helicobacter pylori: invasive and non-invasive tests. Best Pract Res Clin Gastroenterol 2007;21(2):299-313. Go to original source... Go to PubMed...
  62. Megraud F. The most important diagnostic modalities for Helicobacter pylori, now and in the future. Eur J Gastroenterol Hepatol 2012;9 Suppl 1:S13-5. Go to original source... Go to PubMed...
  63. Agreus L, Kuipers EJ, Kupcinskas L, Malfertheiner P, Di Mario F, Leja M, Mahachai V, Yaron N, van Oijen M, Perez Perez G, Rugge M, Ronkainen J, Salaspuro M, Sipponen P, Sugano K, Sung J. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol 2012;47(2):136-47. Go to original source... Go to PubMed...
  64. Leja M, Kupcinskas L, Funka K, Sudraba A, Jonaitis L, Ivanauskas A, Janciauskas D, Kiudelis G, Chiu HM, Lin JT. The validity of a biomarker method for indirect detection of gastric mucosal atrophy versus standard histopathology. Dig Dis Sci 2009;54(11):2377-84. Go to original source... Go to PubMed...
  65. Vaananen H, Vauhkonen M, Helske T, Kaariainen I, Rasmussen M, Tunturi-Hihnala H, Koskenpato J, Sotka M, Turunen M, Sandstrom R, Ristikankare M, Jussila A, Sipponen P. Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol 2003;15:885-91. Go to original source... Go to PubMed...
  66. Telaranta-Keerie A, Kara R, Paloheimo L, Harkonen M, Sipponen P. Prevalence of undiagnosed advanced atrophic corpus gastritis in Finland: an observational study among 4,256 volunteers without specific complaints. Scand J Gastroenterol 2010;45(9):1036-41. Go to original source... Go to PubMed...
  67. Mindemark M, Larsson A. Ruling out IBD: Estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin. Clin Biochem 2012;45(7-8):552-5. Go to original source... Go to PubMed...
  68. Burri E, Beglinger C. Faecal calprotectin-a useful tool in the management of inflammatory bowel disease. Swiss Med Wkly 2012;142:w13557. Go to original source... Go to PubMed...
  69. 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. Go to original source... Go to PubMed...
  70. Burri E, Beglinger C. Faecal calprotectin in the diagnosis of inflammatory bowel disease. Biochemia Medica 2011;21(3):245-53. Go to original source... Go to PubMed...