OBJECTIVE: To compare folic acid (FA) levels in patients being treated with methotrexate (MTX) with those of untreated patients in order to investigate potential folate depletion by MTX and its possible relationship to the drug's efficacy. METHODS: In 33 patients on low-dose MTX therapy and in 24 controls, FA and cyanocobalamin (B12) levels were determined in serum and red blood cells (RBC). In addition, MTX levels in the RBC and serum were measured, and clinical and laboratory measures of disease activity were evaluated. RESULTS: MTX treated patients had lower FA levels than controls (median 4.36 vs 7.37 ng/ml, p < 0.001). A significant correlation between serum FA and MTX/RBC (p < 0.01) and between the weekly dose and MTX/RBC (p < 0.01) was seen. There was apparently no correlation between FA and the cumulative total MTX. MTX patients had lower B12/RBC levels than the controls (p < 0.001); the serum levels of B12 were not different. Clinical features, ESR and CRP did not correlate with FA, B12 or MTX levels. CONCLUSIONS: The degree of folate depletion during MTX therapy depends primarily upon the weekly administered dose. Folate depletion may be related to B12 deficiency in RBC. Since FA levels were not related to parameters of disease activity it is conceivable that MTX does not exert its action in RA primarily by inhibiting dihydrofolatereductase. Therefore, additional folate compounds, if necessary, should not lead to a reduction in the efficacy of MTX.

Adult↗

PubMedDate not supplied

Tumor-associated trypsin inhibitor (TATI) and cancer antigen 125 (CA125) in patients with epithelial ovarian cancer.

In 180 patients with epithelial ovarian cancer and 214 women with benign pelvic pathologies, serum levels of TATI (cut-off point 21 ng ml-1) and CA 125 (cut-off point 35 U ml-1) were determined. Data were correlated with tumour stage, histological type and tumour grade. Overall, when used as a single marker, TATI showed a sensitivity of 63% and a specificity of 72%, whereas the sensitivity and specificity of CA 125 > 35 U ml-1 were 80% and 82% respectively. A combination of the two markers increased the sensitivity to 91% (TATI > 21 ng ml-1 or CA 125 > 35 U ml-1), whereas the specificity decreased to 65%. TATI was clearly superior in diagnosing mucinous carinomata of the ovaries; the rate of true positive findings was 64% versus 50% for CA 125. Unlike CA 125, TATI levels correlated well with tumour grade. In conclusion, CA 125 remains the single tumour marker of choice in the diagnosis of malignant epithelial ovarian cancer, while TATI appears to be a valuable complementory marker with a higher sensitivity in cases of poorly differentiated and mucinous carcinomata.

Adenocarcinoma, Mucinous↗

PubMedDate not supplied

TATI (tumor associated trypsin inhibitor) and cancer antigen 125 (CA 125) in patients with early-stage endometrial cancer.

BACKGROUND: In patients with gynecologic malignancies, a 6 kD polypeptide known as the tumor-associated trypsin inhibitor (TATI) is present in high concentrations, both in the urine and the serum. This study attempts to evaluate the usefulness of pretreatment serum levels of TATI (cutoff level 21 ng ml-1) and CA 125 (cutoff levels 35 U ml-1 and 65 U ml-1) in the prediction of early endometrial cancer. PATIENTS AND METHODS: One hundred twenty-seven patients with stage I and II endometrial carcinomas, 110 healthy women and 258 women with benign pelvic pathologies were evaluated. The data obtained were correlated with the tumor stage and tumor grade. RESULTS: Overall, TATI showed a sensitivity of 31% and a specificity of 81%. The sensitivity and specificity of CA 125 > 35 U ml-1 was 25% and 86%, respectively. When both serum tumor markers were combined the sensitivity increased to 48% (CA 125 > 35 U ml-1), with a specificity of 71%. A correlation with the depth of myometrial infiltration was found for neither of the tumor markers under investigation. In addition, neither TATI nor CA 125 correlated well with tumor grade. The combination of TATI and CA 125 had a high positive predictive value (84%) when no other gynecologic pathologies were present. Furthermore, if TATI and CA 125 levels are within normal ranges and gynecological examination does not show other abnormalities besides vaginal bleeding, endometrial carcinoma appears to be very unlikely. CONCLUSION: We concluded that, while TATI and CA 125 may not be recommended as a screening method for the detection of endometrial cancer, the combination of TATI and CA 125 is a valuable additional tool for further evaluation of women with suspected uterine cancer.

Adult↗