Keywords
pancreatic carcinoma, chronic pancreatitis, carbohydrate antigen, diagnosis, meta-analysis
How to Cite
Su, S.-B., Qin, S.-Y., Chen, W., Luo, W., & Jiang, H.-X. (2016). Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis. Herald of Pancreatic Club, 30(1), 20-31. https://doi.org/10.33149/vkp.2016.01.03
Abstract views: 387 PDF Downloads: 243 PDF Downloads: 124
Abstract
Aim. To evaluate the utility of carbohydrate antigen 19-9 (CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis.
Methods. We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis. Pooled analysis was performed using random-effects models, and receiver operating characteristic (ROC) curves were generated. Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools.
Results. A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included. Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81 (95% CI: 0.80–0.83); specificity, 0.81 (95% CI: 0.79–0.82); positive likelihood ratio, 4.08 (95% CI: 3.39–4.91); negative likelihood ratio, 0.24 (95% CI: 0.21–0.28); and diagnostic odds ratio, 19.31 (95% CI: 14.40–25.90). The area under the ROC curve was 0.88. No significant publication bias was detected.
Conclusion. Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy.
References
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6. CA 242, a new tumour marker for pancreatic cancer: a comparison with CA 19-9, CA 50 and CEA / C. Haglund, J. Lundin, P. Kuusela, P. J. Roberts // Br. J. Cancer. – 1994. – Vol. 70. – P. 487–492.
7. CA 494 – a new tumor marker for the diagnosis of pancreatic cancer / H. Friess, M. Büchler, B. Auerbach [et al.] // Int. J. Cancer. – 1993. – Vol. 53. – P. 759–763.
8. CA19-9 antigen levels can distinguish between benign and malignant pancreaticobiliary disease / G. Morris-Stiff, M. Teli, N. Jardine, M. C. Puntis // Hepatobiliary Pancreat. Dis. Int. – 2009. – Vol. 8. – P. 620–626.
9. Cancer statistics, 2008 / A. Jemal, R. Siegel, E. Ward [et al.] // CA Cancer J. Clin. – 2008. – Vol. 58. – P. 71–96.
10. Chung H. W. Clinical significance of serum levels of immune-associated molecules, uric acid and soluble MHC class I chain-related molecules A and B, as diagnostic tumor markers for pancreatic ductal adenocarcinoma / H. W. Chung, J. B. Lim // Cancer Sci. – 2011. – Vol. 102. – P. 1673–1679.
11. Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma / S. Zhang, Y. M. Wang, C. D. Sun [et al.] // World J. Gastroenterol. – 2008. – Vol. 14. – P. 3750–3753.
12. Clinical value of serum neopterin, tissue polypeptide-specific antigen and CA19-9 levels in differential diagnosis between pancreatic cancer and chronic pancreatitis / R. Talar-Wojnarowska, A. Gasiorowska, M. Olakowski [et al.] // Pancreatology. – 2010. – Vol. 10. – P. 689–694.
13. Clinical value of serum TAG-72 as a tumor marker for pancreatic carcinoma. Comparison with CA 19-9 / C. Pasquali, C. Sperti, A. A. D’Andrea [et al.] // Int. J. Pancreatol. – 1994. – Vol. 15. – P. 171–177.
14. Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head / Q. Liao, Y. P. Zhao, Y. C. Yang [et al.] // Hepatobiliary Pancreat. Dis. Int. – 2007. – Vol. 6. – P. 641–645.
15. Comparative effectiveness of the tumour diagnostics, CA 19-9, CA 125 and carcinoembryonic antigen in patients with diseases of the digestive system / K. Sakamoto, Y. Haga, R. Yoshimura [et al.] // Gut. – 1987. – Vol. 28. – P. 323–329.
16. Conducting systematic reviews of diagnostic studies: didactic guidelines / W. L. Devillé, F. Buntinx, L. M. Bouter [et al.] // BMC Med. Res. Methodol. – 2002. – Vol. 2. – P. 9.
17. Deeks J. J. Systematic reviews in health care: Systematic reviews of evaluations of diagnostic and screening tests / J. J. Deeks // BMJ. – 2001. – Vol. 323. – P. 157–162.
18. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews / P. Whiting, A. W. Rutjes, J. B. Reitsma [et al.] // BMC Med. Res. Methodol. – 2003. – Vol. 3. – P. 25.
19. Diagnosing acute cardiac ischemia in the emergency department: a systematic review of the accuracy and clinical effect of current technologies / J. Lau, J. P. Ioannidis, E. M. Balk [et al.] // Ann. Emerg. Med. – 2001. – Vol. 37. – P. 453–460.
20. The diagnostic odds ratio: a single indicator of test performance / A. S. Glas, J. G. Lijmer, M. H. Prins [et al.] // J. Clin. Epidemiol. – 2003. – Vol. 56. – P. 1129–1135.
21. Diagnostic value of CA 19-9 in patients with pancreatic cancer and nonspecific gastrointestinal symptoms / F. Safi, W. Schlosser, G. Kolb, H. G. Beger / J. Gastrointest. Surg. – 1997. – Vol. 1. – P. 106–112.
22. Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA / F. Maire, S. Micard, P. Hammel [et al.] // Br. J. Cancer. – 2002. – Vol. 87. – P. 551–554.
23. Effectiveness of multivariate analysis of tumor markers in diagnosis of pancreatic carcinoma: a prospective study in multiinstitutions / N. Kuno, K. Kurimoto, M. Fukushima [et al.] // Pancreas. – 1994. – Vol. 9. – P. 725–730.
24. Elevated tumor marker CA 19-9 in the differential diagnosis of pancreatic mass lesions / G. Cwik, G. Wallner, T. Skoczylas [et al.] // Ann. Univ. Mariae Curie Sklodowska Med. – 2004. – Vol. 59. – P. 213–218.
25. Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer / K. F. Kuhlmann, J. W. van Till, M. A. Boermeester [et al.] // Cancer Epidemiol. Biomarkers Prev. – 2007. – Vol. 16. – P. 886–891.
26. Expression and diagnostic evaluation of the human tumor-associated antigen RCAS1 in pancreatic cancer / T. Akashi, H. Oimomi, K. Nishiyama [et al.] // Pancreas. – 2003. – Vol. 26. – P. 49–55.
27. Goonetilleke K. S. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer / K. S. Goonetilleke, A. K. Siriwardena // Eur. J. Surg. Oncol. – 2007. – Vol. 33. – P. 266–270.
28. Guidelines for meta-analyses evaluating diagnostic tests / L. Irwig, A. N. Tosteson, C. Gatsonis [et al.] // Ann. Intern. Med. – 1994. – Vol. 120. – P. 667–676.
29. High sensitivity and specificity of CA 19-9 for pancreatic carcinoma in comparison to chronic pancreatitis. Serological and immunohistochemical findings / F. Safi, R. Roscher, R. Bittner [et al.] // Pancreas. – 1987. – Vol. 2. – P. 398–403.
30. Improved diagnosis of pancreatic adenocarcinoma using haptoglobin and serum amyloid A in a panel screen / M. A. Firpo, D. Z. Gay, S. R. Granger [et al.] // World J. Surg. – 2009. – Vol. 33. – P. 716–722.
31. Moses L. E. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations / L. E. Moses, D. Shapiro, B. Littenberg // Stat. Med. – 1993. – Vol. 12. – P. 1293–1316.
32. Mu D. Q. p53 protein expression and CA19.9 values in differential cytological diagnosis of pancreatic cancer complicated with chronic pancreatitis and chronic pancreatitis / D. Q. Mu, G. F. Wang, S. Y. Peng // World J. Gastroenterol. – 2003. – Vol. 9. – P. 1815–1818.
33. Neopterin serum levels in pancreatic adenocarcinoma / G. Manes, O. A. Spada, P. G. Rabitti [et al.] // Int. J. Pancreatol. – 1999. – Vol. 25. – P. 31–37.
34. A new strategy for the application of CA19-9 in the differentiation of pancreaticobiliary cancer: analysis using a receiver operating characteristic curve / H. J. Kim, M. H. Kim, S. J. Myung [et al.] // Am. J. Gastroenterol. – 1999. – Vol. 94. – P. 1941–1946.
35. Noninvasive diagnosis of advanced pancreatic cancer by real-time ultrasonography, carcinoembryonic antigen, and carbohydrate antigen 19-9 / T. H. Wang, J. T. Lin, D. S. Chen [et al.] // Pancreas. – 1986. – Vol. 1. – P. 219–223.
36. PAM4 enzyme immunoassay alone and in combination with CA 19-9 for the detection of pancreatic adenocarcinoma / D. V. Gold, J. Gaedcke, B. M. Ghadimi [et al.] // Cancer. – 2013. – Vol. 119. – P. 522–528.
37. Pancreatic cancer / D. Li, K. Xie, R. Wolff, J. L. Abbruzzese // Lancet. – 2004. – Vol. 363. – P. 1049–1057.
38. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database / S. F. Sener, A. Fremgen, H. R. Menck, D. P. Winchester // J. Am. Coll. Surg. – 1999. – Vol. 189. – P. 1–7.
39. Potentials of plasma NGAL and MIC-1 as biomarker(s) in the diagnosis of lethal pancreatic cancer / S. Kaur, S. Chakraborty, M. J. Baine [et al.] // PLoS One. – 2013. – Vol. 8. – P. e55171.
40. The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour / N. Teich, J. Kleeff, H. Lochs [et al.] // BMC Gastroenterol. – 2005. – Vol. 5. – P. 20.
41. Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer / S. Boeck, P. Stieber, S. Holdenrieder [et al.] // Oncology. – 2006. – Vol. 70. – P. 255–264.
42. A prospective multicenter trial evaluating diagnostic validity of multivariate analysis and individual serum marker in differential diagnosis of pancreatic cancer from benign pancreatic diseases / T. Hayakawa, S. Naruse, M. Kitagawa [et al.] // Int. J. Pancreatol. – 1999. – Vol. 25. – P. 23–29.
43. Ramesh H. Surgery in tropical pancreatitis: analysis of risk factors / H. Ramesh, P. Augustine // Br. J. Surg. – 1992. – Vol. 79. – P. 544–549.
44. Resected adenocarcinoma of the pancreas 616 patients: results, outcomes, and prognostic indicators / T. A. Sohn, C. J. Yeo, J. L. Cameron [et al.] // J. Gastrointest. Surg. – 2000. – Vol. 4. – P. 567–579.
45. The role of different tumor markers in the early diagnosis and prognosis of pancreatic carcinoma and chronic pancreatitis / J. Hamori, P. Arkosy, A. Lenkey, P. Sapy // Acta Chir. Hung. – 1997. – Vol. 36. – P. 125–127.
46. Rosty C. Early detection of pancreatic carcinoma / C. Rosty, M. Goggins // Hematol. Oncol. Clin. North Am. – 2002. – Vol. 16. – P. 37–52.
47. Rothlin M. A. CA 242 is a new tumor marker for pancreatic cancer / M. A. Rothlin, H. Joller, F. Largiader // Cancer. – 1993. – Vol. 71. – P. 701–707.
48. Satake K. Comparison of CA19-9 with other tumor markers in the diagnosis of cancer of the pancreas / K. Satake, T. Takeuchi // Pancreas. – 1994. – Vol. 9. – P. 720–724.
49. Sawabu N. Serum tumor markers and molecular biological diagnosis in pancreatic cancer / N. Sawabu, H. Watanabe, Y. Yamaguchi // Pancreas. – 2004. – Vol. 28. – P. 263–267.
50. Serum heat shock protein 27 is increased in chronic pancreatitis and pancreatic carcinoma / W. C. Liao, M. S. Wu, H. P. Wang [et al.] // Pancreas. – 2009. – Vol. 38. – P. 422–426.
51. Serum level of TSGF, CA242 and CA19-9 in pancreatic cancer / J. T. Jiang, C. P. Wu, H. F. Deng [et al.] // World J. Gastroenterol. – 2004. – Vol. 10. – P. 1675–1677.
52. Specific antigen in serum of patients with colon carcinoma / H. Koprowski, M. Herlyn, Z. Steplewski, H. F. Sears // Science. – 1981. – Vol. 212. – P. 53–55.
53. Standardized peptidome profiling of human serum for the detection of pancreatic cancer / E. Zapico-Muniz, A. Farre-Viladrich, N. Rico-Santana [et al.] // Pancreas. – 2010. – Vol. 39. – P. 1293–1298.
54. Suzuki S. The conditional relative odds ratio provided less biased results for comparing diagnostic test accuracy in meta-analyses / S. Suzuki, T. Moro-oka, N. K. Choudhry // J. Clin. Epidemiol. – 2004. – Vol. 57. – P. 461–469.
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