Baseline serum/cerebrospinal fluid ratio of carcinoembryonic antigen and carbohydrate antigen series biomarkers in non-neoplastic diseases: a cross-sectional study on 224 patients.

BACKGROUND: The measurement of carcinoembryonic antigen, carbohydrate antigen series biomarkers in cerebrospinal fluid (CSF), is useful for the diagnosis of brain metastasis and leptomeningeal metastases to a certain extent. Their serum/CSF ratios may be of benefit to earlier diagnosis and treatment. However, the normal reference values of the ratios were not available. Accordingly, in this study we analyzed the serum/CSF ratios of tumor markers levels in non-neoplastic diseases patients for possible normal values. MATERIAL AND METHODS: We screened our database for paired CSF and serum samples which have been collected by lumbar puncture. 224 pairs of CSF and serum samples were obtained and compared. The 97.5th percentile, maximum value, and their serum/CSF ratios were obtained. RESULTS: The 97.5th percentile and maximum value of CSF CEA, CA125, CA19-9, CA15-3, CA724, and CYFRA21-1 concentration for overall participants were 0.572 µ/mL, 4.343 µ/mL, 2.872 µ/mL, 2.108 µ/mL, 1.62 µ/mL, and 1.997 µ/mL, respectively. Gender had no significant difference in these CSF biomarkers except CA15-3. The 97.5th percentile serum/CSF ratio of CEA, CA125, CA19-9, CA15-3, CA724, and CYFRA21-1 level were 34.554, 44.772, 51.232, 20.941, 20.737, and 5.389 respectively. The serum/CSF ratios in different age groups were also described. CONCLUSIONS: Here, serum/CSF ratios of six tumor markers were determined in non-neoplastic diseases. The usefulness of this index for diagnosis, management, and prognostic utility of leptomeningeal metastases must be validated in larger cohort studies over the long term.

First human treatment of resistant neoplastic meningitis by intrathecal administration of MTX plus (125)IUdR.

PURPOSE: Neoplastic meningitis is often the final outcome of disseminated cancer and is rapidly lethal. Its limited treatment relies on systemic or intrathecal chemotherapy with methotrexate (MTX) or thiotepa. When 5-iodo-2'-deoxyuridine labeled with (125)I ((125)IUdR) is incorporated into the DNA of mitotic tumor cells, the Auger electrons emitted during iodine decay are highly cytotoxic. The radiotherapeutic efficacy of (125)IUdR administered intrathecally has also been established in animals bearing spinal cord tumors, and MTX is known to potentiate the response. This approach has not been tested in the clinic. METHODS: A 44-year-old woman, with locally advanced pancreatic cancer, was treated for three years with complete systemic remission, but then relapsed with cytologically proven neoplastic meningitis. The patient was given four successive intrathecal injections of MTX (10 mg) every 12 h and, with the fourth dose, 1850 MBq (125)IUdR, followed by four additional MTX doses. The response was monitored by cytology and CA19.9 (carbohydrate antigen 19.9) levels in the cerebrospinal fluid (CSF) as well as by clinical status of the patient. RESULTS: The follow-up of cytology and CA19.9 levels in the CSF showed dramatic improvement within 26 days followed by a biological relapse on Day +36. There was no evidence of local central nervous system toxicity. Three months later, neoplastic meningitis recurred and meningeal tumor infiltration was observed on magnetic resonance imaging. Six months after MTX-(125)IUdR treatment, the patient died. CONCLUSION: (125)IUdR treatment proved to be feasible without acute neurological toxicity and seemed to have produced a biological response. This attempt provides the basis for designing prospective clinical trials.

[A case of leptomeningeal carcinomatosis: demonstration of CA19-9 and CEA positive malignant cells in the CSF and particular elevation of CA19-9 level in the CSF].

A 44-year-old male was admitted for diplopia, headache and gait disturbance. Neurological examination revealed the meningeal irritation sign, the Vth, VII, VIth, IXth and the Xth nerve palsies and cerebellar ataxia of all four limbs. Laboratory studies carried out on the day of admission demonstrated the elevation of serum levels of both tumor markers, carbohydrate 19-9 (CA19-9) and carcinoembryonic antigen (CEA). The estimated serum concentrations of CA19-9 and CEA were 39.4 U/ml and 81.1 ng/ml, respectively. The cerebrospinal fluid (CSF) contained 9 cells/mm3 which consisted of the mixture of malignant cells with appearance strongly suggestive of poorly differentiated adenocarcinoma and of hemosiderinphagocytizing macrophages. Detection of both CA19-9 and CEA in the tumor cells in the CSF was undertaken by the avidin biotinylated peroxidase complex method by use of monoclonal antibodies against each marker. As the results the following findings were obtained. Namely, although all the tumor cells isolated from the CSF were found to contain both tumor markers, CA19-9 and CEA, there was found a difference in the concentration ratio in CSF vs serum between the markers. The estimated concentration of CA19-9 (61.4 U/ml) in CSF was approximately 1.6 times higher than that in serum. On the other hand, the CSF concentration of CEA remained constantly very low (1.1 ng/ml) as compared with that in the serum throughout the whole course of the disease. In response to intrathecal administration of cytarabine and brain irradiation, the CSF cytological findings became normal and concomitant decrease in the concentration of CA19-9 was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)