1H NMR spectroscopy of ascitic fluid:: discrimination between malignant and benign ascites and comparison of the results with conventional methods

It is often difficult to distinguish benign ascites from malignant ascites by conventional examination of ascitic fluid. Therefore, H-1 NMR spectroscopy of ascitic fluid specimens was explored as a one-shot experiment to identify potentially interesting metabolic indices that might help to differentiate between the two. Seventy ascitic fluid specimens (15 cytologically positive for malignant cells, eight cytologically negative for malignant cells but remaining suspicious for malignant ascites, and 47 due to liver cirrhosis) were subjected to H-1 NMR spectroscopy for quantitative estimation of 14 metabolites. Mean concentrations of the metabolites were compared with the Mann-Whitney U test. Multivariate discriminant function analysis was performed to determine important descriptors in the discrimination process. The sensitivity and specificity of the proposed model were compared with conventional methods using ascitic fluid protein and serum ascitic albumin gradient. Then, probable predictions for the doubtful cases were made using the proposed model. Patients with malignant ascites had significantly higher mean concentrations (mu M) of beta-hydroxybutyrate (594 vs 61), lactate (5384 vs 2104), acetone (136 vs 69), and acetoacetate (122 vs 48) than patients with cirrhotic ascites, and significantly lower concentrations of glutamine (359 vs 615), citrate (62 vs 118), glucose (4933 vs 8411), tyrosine (44 vs 124), and phenylalanine (51 vs 93) (P < 0.05 for all). In the discriminant function analysis model, the best discrimination (P < 0.001) was achieved when beta-hydroxybutyrate, lactate, citrate and tyrosine were considered together as markers. Sensitivity and specificity of the proposed model, ascitic fluid protein and serum ascitic albumin gradient were found to be 100% and 97.9%, 53.3% and 76.6%, and 60% and 87.2%, respectively. The proposed model put five of the eight doubtful cases in the malignant group. This is encouraging and may provide useful information for clinical purposes. Copyright (C) 2008 John Wiley & Sons, Ltd.