CA19-9 antigen levels can distinguish between benign and malignant pancreaticobiliary disease

BACKGROUND:CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia.However,it may also be elevated in patients with jaundice in the absence of a tumor due to biliary obstruction,and in other non-hepato-pancreatico-biliary conditions.This study aimed to evaluate whether CA19-9 levels could accurately differentiate between benign and malignant pancreatobiliary disease.METHODS:All patients referred to a single surgeon for investigation of pancreaticobiliary disease in 2003 in whom a firm diagnosis had been established were included.For malignant disease,a histological diagnosis was required but for benign disease a firm radiological diagnosis was deemed adequate.The patients were divided into 4 categories:pancreatic adenocarcinoma(PCa);cholangiocarcinoma(CCa);chronic pancreatitis(CP)and biliary calculous disease(Calc).Bilirubin and alkaline phosphatase levels corresponding to the point of assessment of CA19-9 were also noted.RESULTS:Final diagnoses were made of pancreatic adenocarcinoma(PCa,n=73),cholangiocarcinoma(CCa,n=19),ampullary carcinoma(Amp,n=7),neuroendocrine carcinoma(Neu,n=4),duodenal carcinoma(Duo,n=3),chronic pancreatitis(CP,n=115),and biliary calculous disease(Calc,n=27).Median CA19-9 levels(U/ml)were:PCa,653;CCa,408;Duo,403;Calc,27;CP,19;Neu,10.5;Amp,8(reference range:0-37).The CA19-9 levels were significantly greater for malignant than for benign disease,could differentiate PCa from CCa/Duo,and were significantly higher in unresectable than in resectable PCa.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)for CA19-9 were 84.9%,69.7%,67.7%and 86.1%,respectively.A ROC analysis provided an area under the curve for CA19-9 of 0.871(0.820-0.922),giving an optimal CA19-9 of 70.5 U/ml for differentiating benign from malignant pathology.Using this cut-off,the sensitivity was 82.1%,while specificity,PPV and NPV improved to 85.9%,81.3%and 86.5%,respectively.When standard radiology was included(US/ CT/MRCP)in the decision process,the results improved to 97.2%,88.7%,86.6%,and 97.7%.For benign disease,the CA19-9 correlated directly with the serum bilirubin,but for malignant disease,CA19-9 levels were elevated independent of the bilirubin level.CONCLUSIONS:CA19-9 is useful in the differentiation of pancreatobiliary disease and when using an optimized cut-off and combining with routine radiology,the diagnostic yield is improved significantly,thus stressing the