title: CA19-9 antigen levels can distinguish between benign and malignant pancreaticobiliary disease.
abstract: 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 importance of a multi-disciplinary approach to pancreatobiliary disease.
authors.affiliation: Department of Surgery, University Hospital of Wales, Cardiff, Wales, UK. garethmorrisstiff@hotmail.com
authors.forename: Gareth
authors.initials: G
authors.lastname: Morris-Stiff
authors.forename: Mary
authors.initials: M
authors.lastname: Teli
authors.forename: Nicky
authors.initials: N
authors.lastname: Jardine
authors.forename: Malcolm Ca
authors.initials: MC
authors.lastname: Puntis
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D001650:Bile Duct Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000276:immunology; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood*; D002769:Cholelithiasis / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000276:immunology; D003937:Diagnosis, Differential; D006801:Humans; D041781:Jaundice, Obstructive / Q000000981:diagnostic imaging / Q000209:etiology* / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000276:immunology; D050500:Pancreatitis, Chronic / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000276:immunology; D011237:Predictive Value of Tests; D012372:ROC Curve; D011859:Radiography; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D018395:CA-19-9 Antigen; D000469:Alkaline Phosphatase; D001663:Bilirubin