[Follow up of thyroglobulin levels in patients with surgically treated, highly differentiated thyroid cancer]. / Magasan differenciált pajzsmirigyrák miatt mütött betegek követése thyreoglobulin szint meghatározással.

The highly differentiated thyroid tumours account for 0.80 percent of all human malignancies. The papillary and follicular tumour tissues of this tumour type are relatively benign, hormone dependent and beside their treatment specificity they secrete the tumour specific thyreoglobulin. Thus it becomes possible to follow the development of metastases, the effectiveness of therapy applied as well as the history of the disease. The authors studied the change of thyreoglobulin level in 153 patients with highly differentiated thyroid cancer. In 29 of 32 metastatic patients pathologically elevated (70 to 100 ng/ml) thyreoglobulin level was observed. This proves the 91 percent specificity of the method in verified metastatic tumours. Compared to the total body scintigraphy 3 false negative cases were found. The authors establish that, irrespective of the site of metastasis, the thyreoglobulin level is higher in the follicular than in the papillary subtype. It is concluded that the measurement of the serum thyreoglobulin level is a suitable marker of the highly differentiated thyroid cancer since it represents the local recurrence of distant metastases with a significant increase while the therapy-resultant tumour diminution with a marked decrease, respectively.

[Coagulation inhibitors in patients with neoplasms]. / Inhibidores de la coagulación en pacientes neoplásicos.

Mean plasma concentrations of the main inhibitors of blood coagulation antithrombin III (AT III), protein C and protein S were determined in 149 patients with different local and disseminated malignancies. Results were compared with findings in 44 healthy subjects. No statistical significant differences for AT III, protein C and free protein S were found between patients and controls. However, total protein S showed a significant increase in the patient group (p less than 0.0003). None of the parameters analyzed showed differences according to the degree of tumoral activity nor to the tumour localization. We conclude that the main inhibitors of the blood coagulation seem not to play an important role in the pathogenesis of the hypercoagulable state in malignancy. The increased levels in total protein S would indicate endothelial synthesis in response to thrombogenic stimuli.

A new biomarker in monitoring breast cancer: CA 549.

Serum biomarkers are not very reliable in assessing outcome or predicting recurrence of breast cancer. Clinically, carcinoembryonic antigen (CEA) is widely used and is elevated in a majority of patients with metastatic breast cancer. However, it is falsely elevated in a wide range of nonmalignant conditions and correlates poorly with disease progression. We evaluated a newly described monoclonal antibody, CA 549, in an immunoradiometric assay which uses two monoclonal antibodies directed against tumor and milk fat globule membranes. CA 549 and CEA were studied in 682 patients, 331 of whom had breast diseases and 99 of whom were followed with multiple serum samples. Of 69 patients with benign breast diseases, 1.5% had elevated CA 549, 0% of 30 pregnant women had elevated CA 549, and 26% of patients with nonmalignant liver disease had CA 549 elevation. In metastatic cancer of prostate, ovary, endometrium, colon, and lung CA 549 was elevated in 12% to 50% of cases with levels less than 120 U/mL. In breast cancer, CA 549 was elevated in 11% of 88 patients who received adjuvant chemotherapy and had no evidence of metastasis; in 23% of 16 patients in complete remission after chemotherapy; in 63% of 52 patients in partial remission after therapy; and in 83% of 106 patients with progression of breast cancer compared with 63% with elevated CEA (P = .001). In diseases of the breast, CA 549 has a sensitivity In diseases of the breast, CA 549 has a sensitivity and specificity of 77% and 92% v 61% and 92% for CEA. Of 99 patients serially monitored with clinically documented breast cancer progression, regression, or stability of disease, CA 549 was statistically significantly superior to CEA in monitoring a greater than 25% change in those patients with metastatic progression (P = .03). CA 549 is a new serum marker that should be control tested in prospective clinical trials alone or in conjunction with other markers.

Double antibody radioimmunoassay for monitoring metastatic breast cancer.

We previously reported the production of a panel of murine monoclonal antibodies which recognize glycoproteins abnormally expressed in human breast tumours. Using two of these antibodies, a double antibody radioimmunoassay was designed to quantify levels of these breast tumour marker glycoproteins in serum. Marker levels greater than 28 units were considered abnormal. Using this criterion, 63% and 75% of patients with breast cancer stages I and II, respectively, and 88% of those with metastatic disease were found to have elevated marker levels. Thirteen percent of patients with non-malignant breast disease also had elevated marker levels. Elevated marker levels were also detected in patients with non breast neoplasms. One hundred and eleven women with metastatic disease were followed. Eighty-two percent of those with progressive disease and 73% of those where disease regressed had 20% changes in marker levels. These changes in marker levels preceded by up to 6 months changes in disease state. From these results we conclude that this assay may be useful for monitoring the course of disease in breast cancer patients.

Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients.

We studied 302 consecutive autopsied patients who presented with carcinoma of unknown primary origin. The most frequent metastatic sites were the nodes, lung, and bone. The primary site was identified while patients were alive in 27% and at autopsy in 57%; the site remained unidentified in 16%. The pancreas (26.5%), lung (17.2%), kidney (4.6%), and colorectum (3.6%) were the most frequent primary sites, but the reliability of diagnostic tests used in the search for this site was disappointing. Survival was identical in patients whose primary site was discovered while alive, at autopsy, or remained unknown. The number of metastases at presentation was the major prognostic factor. Analysis of autopsy data demonstrated that patients with carcinoma of unknown primary origin pursue a different course than expected when the primary site is the first manifestation of the disease. On the basis of these results and the results of other modern series, we suggest an approach consisting of a limited initial workup but with greater emphasis on modern histochemistry studies and immunohistopathologic and other kinetic and morphologic parameters to understand the patient tumor characteristics better and base the clinical management on an individual basis.

Platelet contribution to the formation of metastatic foci: the role of cancer cell-induced platelet activation.

Platelets are thought to be involved in the development of blood borne metastasis. Ultrastructural and experimental studies demonstrate that association between tumor cells and platelets with subsequent activation of the coagulation cascade takes place in malignancy. Several hypotheses have been proposed to explain the mechanisms by which tumor cells activate platelets including generation of thrombin, ADP release and involvement of arachidonate metabolism. Perfusion studies with human homologous systems showed that intact tumor cells and tumor cell microvesicles were able to induce platelet thrombogenicity under defined flow conditions. The presence of divalent cations and plasma factors was necessary for the cancer cells to exert their activating capacity. These results suggest a role for platelets in the development of secondary metastasis as well as in the thrombotic events of malignancy.

Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels.

Serum thyroglobulin (Tg) measurements in patients with treated differentiated thyroid cancer are usually well correlated with the presence or absence of residual or metastatic thyroid tissue. However, it is not rare to find a patient with detectable serum Tg levels but negative 131I whole-body scan (WBS) and no evidence of disease activity. To clarify the reason for this discrepancy, we decided to perform the WBS after the administration of a therapeutic dose of 131I in 17 consecutive patients in whom serum Tg was detectable while the WBS performed with a 5 mCi tracer dose was negative (12.6% of 135 patients studied with both WBS and serum Tg). The result of this study demonstrated that after this procedure the WBS became positive for significant residual or metastatic areas of radioiodine uptake in all patients but one. Such data indicate that in our patients the presence of circulating Tg is not a false-positive Tg result, but is due to the presence of residual or metastatic tissue that is not detected in the conventional WBS, that can be visualized using therapeutic doses. Preliminary follow-up data indicate that this procedure may also have therapeutic effect, although the relevance of this aspect remains to be established.

Plasma selenium levels in patients with advanced upper gastrointestinal cancer.

Plasma selenium levels were determined at various intervals during hospitalization of 71 patients with upper gastrointestinal and other malignancies. These patients often require frequent nutritional as well as surgical or medical intervention. Attempts were made to identify, evaluate, and compensate for numerous confounding variables at each of the 374 plasma selenium determinations. Selenium levels in stable patients who were neither receiving aggressive antineoplastic therapy, nor septic, nor taking corticosteroids and who had no clinically significant metabolic imbalance were then separately analyzed. In 55 stable patients selenium levels were 28% lower than those found in 20 normal controls (mean 61.8 micrograms/L, P less than 0.0005). An analysis of all the readings showed that selenium levels were substantially decreased by recent radiotherapy or sepsis, by regional tumor spread and increased tumor burden, and by intravenous and/or enteral hyperalimentation and intravenous lipids. In contrast to these findings, levels were relatively higher in patients with an adequate oral diet or with a lesser tumor burden. The comparison between selenium levels in stable and in aggressively treated or septic patients supports the importance of the relationship of nutrition to selenium levels in cancer patients.

Prognostic parameters in metastatic spread of laryngeal cancer: clinico-histopathological correlations.

The authors present a series of 130 patients with laryngeal tumours submitted to total or horizontal laryngectomy and to neck dissection. The possible correlations between the staging and histology of the primary lesion, tumour marker (LASA) and the incidence of lymph node metastases are examined. The information provided by clinical and histopathological parameters is no doubt useful, but the margin of clinical error is high. On the contrary, the tumour marker concentration (LASA) was significantly higher in the patients whose lymph nodes were found to be histologically invaded, than in those without metastatic spread. Consequently, the LASA test may assume clinical importance before surgical therapy and in the follow-up of treated patients.

The lack of correlation between experimental metastatic potential and platelet aggregating activity of B16 melanoma clones viewed in relation to tumor cell heterogeneity.

Two widely used B16 melanoma cell lines of low and high lung colonizing potential (B16-F1 and B16-F10) were compared in their ability to induce platelet aggregation. The results of these experiments showed a reproducible difference in platelet aggregating activity of these two cell lines which directly correlated with their lung colonizing potentials. However, when clones were derived from these heterogeneous cell lines and tested for experimental metastatic potential, platelet aggregating ability and Met-72 expression, no correlation could be attached to the platelet aggregating activity of the clones. Results of these experiments provide direct evidence that platelet aggregation is not an accurate index of experimental metastatic potential of tumor cell clones, nor is it an essential trait of all metastatic cells. The ability of tumor cells to induce platelet aggregation is examined and discussed in the context of cellular heterogeneity.

Comparison of serum CEA, PHI, and TPA as tumor markers in breast cancer patients.

The purpose of this study was to evaluate the clinical significance of different serum tumor markers in patients with breast cancer who developed recurrent disease. Determined were tissue polypeptide antigen (TPA), carcinoembryonic antigens (CEA), and phosphohexose isomerase (PHI). Serum samples of 411 breast cancer patients with either locoregional or metastatic recurrence were analyzed. Positive rates of all three markers depended on the clinical stage of the disease, with highest rates of elevated titers in advanced disease. In comparison, CEA and TPA are more sensitive markers than PHI. According to the site of recurrence, CEA exhibited the highest rate of elevated titers in patients with bone metastases and PHI in patients with visceral metastases. Using PHI in combination with CEA, sensitivity (ie, at least one marker is elevated) was increased by 6-20% compared to the results obtained with single marker analysis. However, for easier interpretation of the tumor marker results in clinical practice, it may be helpful to employ a product value of CEA and PHI.

The erythrocyte sedimentation rate. Guidelines for rational use.

The erythrocyte sedimentation rate (ESR) is seldom the sole clue to disease in asymptomatic persons and is not a useful screening test. When the rate is increased, a careful history and physical examination will generally disclose the cause. An unexplained increase in the ESR is generally transitory and seldom due to serious disease. The test is most useful in diagnosing temporal arteritis and monitoring the patient's response to treatment. The test has little diagnostic value in rheumatoid arthritis but may be useful in monitoring disease activity when clinical findings are equivocal. The ESR is often normal in patients with cancer, infection, and connective tissue disease and is therefore of little use in excluding these diseases in patients with vague complaints.

Correlation of thyroglobulin measurements and radioiodine scans in the follow-up of patients with differentiated thyroid cancer.

Correlation of radioiodine (131I) scans and serum thyroglobulin (Tg) concentrations were performed in the follow-up of 85 differentiated thyroid cancer patients who had undergone total thyroidectomy. Tg results were also compared with the control group of 33 thyroidectomized patients with no evidence of thyroid carcinoma and normal values for Tg established. Excellent correlation between Tg and scans was noted in patients with scan evidence of metastasis distant from the neck. Poor correlation was present in patients with scan evidence of local neck metastasis only, thyroid bed activity, and those with mediastinal activity. In addition, in 8% of the patients, the Tg assay could not be performed because of interfering antibodies. The conclusion is that elevated Tg concentration is a good indicator of metastasis outside of the neck as detected by 131I scans. Caution should be used when Tg alone is used in evaluating local neck metastasis demonstrated on scans. The significance of mediastinal activity warrants further investigation.

Platelet-aggregating activities of metastasizing tumor cells. III. Platelet aggregation as resulting from thrombin generation by tumor cells.

Thrombin generated in the process of platelet aggregation induced by three metastasizing murine tumors was measured using a chromogenic substrate specific for thrombin. Addition of B16 cells or 3LL cells to the platelet-rich plasma induced the generation of a significant amount of thrombin during the lag period preceding aggregation, while that of MH134 cells did not. Thrombin generation was observed in both the presence and the absence of platelets, indicating that platelets are not necessarily required for thrombin generation by these tumor cells. This suggests that the adherence of platelets to tumor cells is not an essential step for the initiation of thrombin-mediated aggregation induced by B16 and 3LL cells. Furthermore, the results of a one-stage clotting assay using plasma deficient in coagulation factors indicated that B16 and 3LL cells generated thrombin through direct activation of factor X.