From the Guidelines
Elevated Carbohydrate Antigen 19-9 (CA 19-9) levels can be caused by various conditions, including malignant diseases such as pancreatic cancer, cholangiocarcinoma, colorectal cancer, gastric cancer, and hepatocellular carcinoma, as well as benign conditions like pancreatitis, cholangitis, cirrhosis, gallstones, and inflammatory bowel disease. The causes of elevated CA 19-9 levels are diverse and not limited to digestive conditions, as non-digestive conditions like lung diseases, ovarian cysts, and endometriosis may also increase CA 19-9 levels 1. It is essential to note that CA 19-9 is not specific enough for cancer screening in the general population due to these varied causes and because approximately 5-10% of people cannot produce this marker due to genetic factors, such as the absence of the Lewis blood group antigen 1.
Key Considerations
- CA 19-9 levels can be influenced by genetic factors, including fucosyl-transferases 2 and 3 genotype, which may affect the sensitivity and specificity of the marker 1.
- The level of elevation may provide some clues, with very high levels (>1000 U/mL) more commonly associated with malignancies, though this is not definitive 1.
- A cut-off value of 129 U/mL showed a sensitivity of 78% and a specificity of 98%, whereas a cut-off value of 20 U/mL showed a sensitivity of 78% and a specificity of 67% 1.
Diagnostic Approach
When CA 19-9 is elevated, further diagnostic testing is typically needed to determine the underlying cause. This may include:
- Imaging studies (CT scans, MRIs, ultrasounds) to evaluate the biliary tree and detect potential malignancies 1.
- Endoscopic procedures, such as ERCP, to visualize the biliary tree and obtain tissue samples for histological examination 1.
- Biopsies to confirm the presence of malignancy or other conditions 1.
Clinical Implications
The diagnosis and management of elevated CA 19-9 levels require a comprehensive approach, taking into account the patient's clinical presentation, medical history, and genetic factors. A multidisciplinary approach, involving gastroenterologists, radiologists, and surgeons, is essential for the accurate diagnosis and effective management of patients with elevated CA 19-9 levels.
From the Research
Causes of Elevated Carbohydrate Antigen 19-9 (CA 19-9)
Elevated CA 19-9 levels can be caused by various factors, including:
- Malignant diseases, such as pancreatic cancer, cholangiocarcinoma, gallbladder cancer, ampullary carcinoma, and periampullary carcinoma 2
- Benign diseases, including xanthogranulomatous cholecystitis (XGC) 3, benign stricture of the common bile duct 4, cholestatic jaundice, and cholangitis 4
- Non-malignant diseases of the hepatobiliary system, such as pneumonia, pleural effusion, renal failure, and systemic lupus erythematosus (SLE) 5
- False elevation of CA 19-9 levels due to extrahepatic cholestasis and certain inflammatory diseases of the pancreas and hepatobiliary system 4
- Benign gastrointestinal disorders, such as gastritis, colon polyps, and other conditions that can cause overexpression of CA 19-9 6
Clinical Significance of Elevated CA 19-9 Levels
Elevated CA 19-9 levels can indicate:
- Unresectable lesions and poor prognosis in patients with pancreatic cancer 5
- Malignant diseases, but can also be elevated in benign conditions, making it essential to interpret CA 19-9 levels in the context of clinical presentation 5
- Tumor stage, treatment, and tumor location, with higher levels often associated with more advanced disease and poorer outcomes 2