Adjusting CA19-9 values to predict malignancy in obstructive jaundice: influence of bilirubin and C-reactive protein

World J Gastroenterol. 2012 Aug 21;18(31):4150-5. doi: 10.3748/wjg.v18.i31.4150.

Abstract

Aim: To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ).

Methods: All patients admitted for obstructive jaundice, in the period 2005-2009, were prospectively enrolled in the study, obtaining a total of 102 patients. On admission, all patients underwent complete standard blood test examinations including C-reactive protein (CRP), bilirubin, CA19-9. Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL). The standard cut-off level for CA19-9 was 32 U/mL, whereas for CRP this was 1.5 mg/L. The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value. The patients were divided into 2 groups, MJ and BJ, and after the adjustment a comparison between the 2 groups of patients was performed. Sensitivity, specificity and positive predictive values were calculated before and after the adjustment.

Results: Of the 102 patients, 51 were affected by BJ and 51 by MJ. Pathologic CA19-9 levels were found in 71.7% of the patients. In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years), whereas in the MJ group there were 24 (47%) males and 27 (53%) females, with a mean age of 70 years (range 30-92 years). Pathologic CA19-9 serum level was found in 82.3% of MJ. CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ. Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P = 0.000 and P = 0.02), while the CRP level was significantly higher in BJ (P = 0.000). Considering a CA19-9 cut-off level of 32 U/mL, 82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P = 0.002). A CA19-9 cut-off of 100 U/mL increases the difference between the two groups: 35.3% in BJ and 68.6% in MJ (P = 0.0007). Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value (P = 0.003), while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value (P = 0.000004). Sensitivity, specificity, positive predictive values of CA19-9 > 32 U/mL were 82.3%, 45% and 59.1%; when the cut-off was CA19-9 > 100 U/mL they were, respectively, 68.6%, 64.7% and 66%. When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values, these became 49%, 78.4%, 69.4% and 76.5%, 68.6%, 70.9%, respectively.

Conclusion: The present study proposes CRP as a new and useful correction factor to improve the diagnostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.

Keywords: Biliary stones; Bilirubin; C-reactive protein; CA19-9; Pancreato-biliary malignancy; Tumor marker.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / complications*
  • Bile Duct Neoplasms / diagnosis*
  • Bile Ducts, Intrahepatic
  • Bilirubin / blood*
  • Biomarkers, Tumor / blood
  • C-Reactive Protein / metabolism*
  • CA-19-9 Antigen / blood*
  • Cholangiocarcinoma / complications
  • Cholangiocarcinoma / diagnosis
  • Diagnosis, Differential
  • Female
  • Gallbladder Neoplasms / complications
  • Gallbladder Neoplasms / diagnosis
  • Humans
  • Jaundice, Obstructive / diagnosis*
  • Jaundice, Obstructive / etiology*
  • Liver Neoplasms / complications
  • Liver Neoplasms / diagnosis
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / diagnosis
  • Predictive Value of Tests
  • Prospective Studies
  • Retrospective Studies
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • C-Reactive Protein
  • Bilirubin