Carbohydrate antigen 19-9 elevation without evidence of malignant or pancreatobiliary diseases

Abstract

Although carbohydrate antigen 19-9 (CA 19-9) may be elevated in benign diseases, elevated CA 19-9 may cause a fear of cancer and unnecessary follow-up studies. Research on how to approach systematically in this case is very limited. The purpose of this study was to analyze the clinical features and the causes of CA 19-9 elevation without evidence of malignant or pancreatobiliary diseases. We retrospectively reviewed the medical records of patients who had CA 19-9 elevation (≥80 U/mL) and were found to be unrelated to cancer after follow-up. After exclusion, 192 patients were included in this study. The median level of CA 19-9 was 136.5 U/mL. The causes of CA 19-9 elevation were determined in 147 (76.6%) patients, and that was unknown in 45 (23.4%). The estimated causative diseases were hepatic diseases in 63 patients, pulmonary diseases in 32, gynecologic diseases in 38, endocrine diseases in 13, and spleen disease in 1. Of 45 patients with unknown cause, 35 had normalization of CA 19-9 and 10 had persistently elevated CA 19-9. In conclusion, CA 19-9 elevation without malignancies or pancreatobiliary diseases should be systematically evaluated and followed up. We suggest an algorithm to investigate the causes and follow up these patients. Tumor markers are useful for screening and diagnosis of cancer in high-risk patients, evaluating the response to cancer treatment and detecting the recurrence of cancer. As health checkups are becoming widely available, tumor markers are being checked in asymptomatic healthy people for screening purposes. Among the many tumor markers, carbohydrate antigen 19-9 (CA 19-9) has a relatively high sensitivity and specificity for pancreatic and biliary tract tumors 1,2. According to previous studies, the sensitivity of CA 19-9 in diagnosing pancreatic cancer ranges between 79% and 95%, and the specificity ranges between 82% and 91% 3,4. CA 19-9 has its diagnostic value when the patient has symptoms such as weight loss, abdominal pain, and jaundice or when imaging studies indicate a tumor. However, in asymptomatic patients, there is little evidence of its clinical value in screening for cancer 5-8. In a study conducted with 70,940 asymptomatic individuals, the positive predictive value of CA 19-9 was only 0.9% including ineffectiveness in screening for pancreatic cancer 8. CA 19-9 is synthesized in the normal pancreatic parenchyma and biliary tract. It is also produced from the epithelial cells of the gastric, colonic, and uterine mucosa, as well as the salivary glands 9. From a malignant tumor perspective, CA 19-9 has been reported to be increased in stomach, colorectal, lung, thyroid, as well as biliary and pancreatic cancer 10. CA 19-9 is often elevated in benign pancreatobiliary diseases such as cholangitis, obstructive jaundice and pancreatitis 11,12. Additionally, it has been reported that elevated CA 19-9 levels can be found in other non-malignant conditions such as pulmonary and thyroidal diseases, diabetes mellitus, and gynecologic diseases 5,13,14. In patients with an elevated...

Carbohydrate antigen 19-9 — tumor marker: Past, present, and future

“…This may increase the accuracy of CA 19-9 in screening DM patients for PDAC[ 11 ]. Recently, Kim et al [ 2 ] postulated that CA 19-9 values should only be considered as a screening marker for PDAC in a radiologically-normal patient whose CA 19-9 remains persistently elevated after intensive blood sugar control and normalization of HbA1c[ 2 ]. These algorithms need prospective validation.…”

“…Incidents of elevated CA 19-9 are reported in a range of benign hepatic diseases, such as liver cysts and hepatitis secondary to alcohol abuse, drugs, autoimmune diseases, and acute and chronic viral infections[ 2 ].…”

“…While its key implication is in pancreatic ductal adenocarcinoma (PDAC), CA 19-9 is also overexpressed in a wide gamut of benign and malignant, gastrointestinal, and extra-gastrointestinal diseases. Benign conditions include pancreatitis, pancreatic cysts, diabetes mellitus (DM), liver fibrosis, benign cholestatic diseases, and other urological, pulmonary, and gynecological diseases (Figure 1 )[ 2 - 4 ]. Inflammation or obstruction of biliary and respiratory tracts lead to elevated CA 19-9[ 2 ].…”

“…Benign conditions include pancreatitis, pancreatic cysts, diabetes mellitus (DM), liver fibrosis, benign cholestatic diseases, and other urological, pulmonary, and gynecological diseases (Figure 1 )[ 2 - 4 ]. Inflammation or obstruction of biliary and respiratory tracts lead to elevated CA 19-9[ 2 ]. Malignancies include pancreatic, biliary, hepatocellular, gastrointestinal, urological, pulmonary, gynecological, thyroid, and salivary gland cancers[ 2 , 5 , 6 ].…”

“…Inflammation or obstruction of biliary and respiratory tracts lead to elevated CA 19-9[ 2 ]. Malignancies include pancreatic, biliary, hepatocellular, gastrointestinal, urological, pulmonary, gynecological, thyroid, and salivary gland cancers[ 2 , 5 , 6 ]. During carcinogenesis, epigenetic silencing of the gene for 2->6 sialyltransferase, responsible for the attachment of an extra sialic acid residue in Disialyl Lewis-a, occurs.…”