Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions

Abstract

Background/Aims: Despite the presence of many diagnostic methods, the differential diagnosis between benign and malignant biliary obstructions is still not easy. We aimed to evaluate the role of serum/biliary carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor receptor-3(VEGFR-3), and total antioxidant capacity (TAC) tests in this differential diagnosis. Materials and Methods: Patients (n:225; 110♂, 115♀) with diagnosis of malignant (n:96) or benign (n:129) biliary obstruction were included in this cross-sectional study. Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests were analyzed, statistics were obtained, and significance was defined as p<0.05. Results: Mean age was 54.9±16.4 for the benign and 54.2±19.6 for the malignant group (p=0.89). Head of pancreas cancer (18.2%), cholangiocarcinoma (11.4%) and choledochal stone (48%) were the most common etiologies. The area under the curve (AUC)s by ROC analysis of serum/biliary CA 19-9, VEGFR-3, and TAC and serum CEA were 0.701/0.616, 0.622/0.663, 0.602/0.581, and 0713, respectively. Serum TAC had higher sensitivity (61.1%) and CEA had lower sensitivity (42.7%), whereas CEA had higher specificity (89.9%) and TAC had lower specificity (60.5%). In biliary tumor markers, CA 19-9 had higher sensitivity (74%) and VEGFR-3 had lower sensitivity (56.2%); however, VEGFR-3 had higher specificity (79.1%) and CA 19-9 had lower specificity (34.1%). Additionally, combination of serum CEA (p<0.001), CA 19-9 (p<0.001), VEGFR-3 (p<0.001), and biliary CA 19-9 (p=0.028) markers achieved 95% estimation probability, and the sensitivity, specificity, and accuracy were 88.5%, 45.7%, and 64%, respectively. Conclusion: Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests would not be useful in the differentiation between malignant and benign biliary obstructions.

CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma

“…Despite the existence of more or less standardized preoperative assessment algorithms (including imaging, liver function tests and the clinical performance status) it has remained challenging to predict which patients will actually benefit from extended liver surgery in terms of postoperative survival. At present, CA19-9 represents the clinically most established biomarker for CCA 24 , but its potential for the detection of CCA and its capabilities to predict patients’ outcome is still controversial 16 , 21 , 29 . Here, we showed in large cohort of CCA patients undergoing tumor resection at a tertiary referral centre that preoperative levels of circulating CEA but not CA19-9 are an independent prognostic factor and its diagnostic value for early detection of CCA might even be superior to CA19-9 in the setting of a pre-existing benign cholangiopathy like PSC.…”

“…Besides, CA19-9 has also been suggested as a prognostic marker for CCA patients undergoing tumor resection 17 , 18 and patients receiving chemotherapy 19 . Nevertheless, serum levels of CA19-9 are also elevated in patients with non-malignant biliary diseases such as primary sclerosing cholangitis or biliary obstruction due to choledocholithiasis 20 , 21 , implying that CA19-9 might not be the ideal tool for surveillance of patients with benign biliary disease. Carcinoembryonic antigen (CEA), a well-established tumor marker particularly in the field of colorectal and other adenocarcinomas 22 , 23 , has gained increasing attention as a potential biomarker for hepatobiliary malignancies 24 .…”

Circulating Biomarkers for Cholangiocarcinoma

“…False positive test results are also common, as CA19–9 can be elevated in other benign or malignant medical conditions such as PSC [18-20]. A similar restricted diagnostic potential was described for CEA, which only shows a sensitivity of 42.7–53.3% and a specificity of 86.7–89.9% for the detection of CCA [21, 22]. …”

Looks can be Deceiving: A Case Report on the Clinical Value of CA 19-9 in Obstructive Jaundice

“…CA 19-9 levels are known to be elevated in malignant conditions such as cholangiocarcinoma and pancreatic, hepatocellular, and ovarian cancer [2]. Normal CA19-9 levels range between 0-37 U/L.…”

“…Whenever present, clinicians must be aware that its elevation may not only be related to malignancies but can also be present in benign conditions associated with jaundice, such as acute cholangitis, choledocholithiasis, benign bile duct strictures, and primary biliary cirrhosis, among others [2].…”