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An adjunct to cytology to differentiate between malignancy-related ascites and benign causes of ascites formation
Malignancy accounts for approximately 7% of cases of ascites formation. Malignant disease can cause ascites by various mechanisms including: peritoneal carcinomatosis (53%), massive liver metastasis causing portal hypertension (13%), peritoneal carcinomatosis plus massive liver metastasis (13%), hepatocellular carcinoma plus cirrhosis (7%), and chylous ascites due to lymphoma (7%). The evaluation and diagnosis of malignancy-related ascites is based on the patient clinical history, ascites fluid analysis, and imaging tests.
The overall sensitivity of cytology for the detection of malignancy-related ascites ranges from 58% to 75%. Cytology examination is most successful in patients with ascites related to peritoneal carcinomatosis as viable malignant cells are exfoliated into the ascitic fluid. However, only approximately 53% of patients with malignancy-related ascites have peritoneal carcinomatosis. Patients with other causes of malignancy-related ascites almost always have a negative cytology.
Carbohydrate antigen 19-9 (CA 19-9) is a modified Lewis(a) blood group antigen. CA 19-9 may be elevated in the serum patients with gastrointestinal malignancies such as cholangiocarcinoma, pancreatic cancer, or colon cancer. Measurement of CA 19-9 in ascitic fluid is sometimes used in combination with cytology for detecting malignancy-related ascites.
An interpretive report will be provided.
A peritoneal fluid carbohydrate antigen 19-9 (CA 19-9) concentration >32 U/mL is suspicious, but not diagnostic, of a malignancy-related ascites. This clinical decision limit cutoff yielded 44% sensitivity and 93% specificity in a study of 137 patients presenting with ascites. However, ascites caused by malignancies not associated with increase serum CA 19-9 concentrations, including lymphoma, mesothelioma, leukemia, and melanoma, routinely had CA 19-9 concentrations <32 U/mL. Therefore, negative results should be interpreted with caution, especially in patients who have or are suspected of having a malignancy not associated with elevated CA 19-9 levels in serum.
Twelve hours before this blood test, do not take multivitamins or dietary supplements containing biotin or vitamin B7 that are commonly found in hair, skin and nail supplements and multivitamins.
Do not use peritoneal fluid carbohydrate antigen 19-9 (CA 19-9) levels concentration as absolute evidence of the presence or the absence of malignant disease. The CA 19-9 result should be interpreted in conjunction with information from the clinical evaluation of the patient and other diagnostic procedures.
Approximately 10% of the Caucasian population does not express CA 19-9 due to the deficiency of a fucosyltransferase enzyme. Consequently, low values in these individuals are not informative regarding malignancy-related ascites.
Immunometric assays can, in rare occasions, be subject to interferences such as "hooking" at very high analyte concentrations (false-low results) and heterophilic antibody interference (false-high results). If the clinical picture does not fit the laboratory result, these possibilities should be considered.
CA 19-9 values are method-dependent; therefore, the same method should be used to serially monitor patients.
An in-house study was performed to select a clinical decision limit to differentiate between malignancy-related benign causes of ascites with high specificity. The study included 83 cases of benign ascites and 54 cases of malignancy-related ascites. Within the malignancy-related ascites, there were 9 specimens with malignancies known not to secrete carbohydrate antigen 19-9 (CA 19-9) in serum (lymphoma, leukemia, melanoma, sarcoma, and neuroendocrine tumors). Amongst the group that are known to secrete CA 19-9 in serum (n=45), there were the following malignancies: pancreatic, breast, gastric, colon, bladder, cholangiocarcinoma, gynecological cancers, peritoneal carcinomatosis, and hepatocellular carcinoma. Using a clinical decision limit cutoff of >32 U/mL, the specificity was 93% for the benign ascites group. The sensitivity was 49% for those malignancies associated with elevated CA 19-9 in serum.
1. Trape J, Molina R, Sant F: Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions. Tumour Biol 2004 Sep-Dec;25(5-6):276-281
2. Sari R, Yildirim B, Sevinc A, et al: The importance of serum and ascites fluid alpha-fetoprotein, carcinoembryonic antigen, CA 19-9, and CA 15-3 levels in differential diagnosis of ascites etiology. Hepatogastroenterology 2001 Nov-Dec;48(42):1616-1621