The serum hyaluronan levels of 37 patients with malignant mesothelioma were followed during the course of treatment (high doses of methotrexate were given to 32 of these patients). The patients could be divided into the following two groups: (1) those with progressive disease (n = 17) or (2) those showing improvement during therapy (complete remission [n = 2], partial remission, or no change [n = 18]). On admission to the hospital, the patients with progressive disease showed significantly higher initial serum hyaluronan levels (median value, 250 micrograms/l) than those in the second group (median value, 97 micrograms/l) (P less than 0.005, Wilcoxon). Serum hyaluronan as a predictor of progressive disease has a sensitivity of 65% and a specificity of 85%. There was a significant increase in serum hyaluronan levels during treatment in patients with progression (P less than 0.01). In three patients with initially high levels there was a clear decrease in parallel with the reduction in tumor burden. In the remaining patients of the responder group, the values were constantly low. There was no significant correlation between the hyaluronan level and any other laboratory test performed on blood samples. Pleural fluid was removed for medical reasons from 13 patients. Neither the presence of pleural fluid nor its hyaluronan level were correlated to the progression of the disease. However, there was an interesting negative correlation between serum and pleural hyaluronan levels, indicating that an elevated serum hyaluronan level does not reflect high production in the pleural cavity.
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