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


CONCLUSIONS
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.
Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, 95125 Catania, Italy.
Gaetano
G
La Greca
Maria
M
Sofia
Rosario
R
Lombardo
Saverio
S
Latteri
Agostino
A
Ricotta
Stefano
S
Puleo
Domenico
D
Russello
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000150:complications* / Q000175:diagnosis*; D001653:Bile Ducts, Intrahepatic; D001663:Bilirubin / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D018395:CA-19-9 Antigen / Q000097:blood*; D018281:Cholangiocarcinoma / Q000150:complications / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D005706:Gallbladder Neoplasms / Q000150:complications / Q000175:diagnosis; D006801:Humans; D041781:Jaundice, Obstructive / Q000175:diagnosis* / Q000209:etiology*; D008113:Liver Neoplasms / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000175:diagnosis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002097:C-Reactive Protein; D001663:Bilirubin