Five-year survival versus initial concentrations and longitudinal serum CEA patterns in patients with colorectal carcinoma.

Patients (n = 464) with colorectal carcinoma in stages A to D2 were studied; 230 had CEA determined preoperatively and 433 serially. Actuarial life table analysis and the Mantel-Cox test showed that overall 5-yr survival was 59.2% and that the differences among the stages were highly significant. Survival rates for patients with CEA over the cutpoints at 3.2, 5, 10, and 20 ng/ml decreased from 53.8% to 21.9%. When analyzed in Cox multivariate regression, stage, initial CEA, age, and location of cancer affected survival. Postoperatively, three CEA patterns were found: 1) CEA was always normal; 2) initially elevated CEA was decreasing to the normal range to remain so thereafter; or 3) CEA started to increase from any nadir some time after surgery. The 5-yr survival rate was 73.3% for patients with the normal, 44.5% with the decreasing, and 30.1% with the increasing CEA pattern. When the postoperative CEA, pattern was added to the preoperative covariates in 196 patients for whom both the initial CEA, and postoperative patterns were available, only the stage, postoperative CEA pattern, and location of cancer affected survival. After elimination of initial CEA 433 patients with postoperative serum were analyzed, and again, only stage, postoperative CEA pattern, and location of cancer appeared to affect survival. Stage of disease, initially elevated serum CEA, age over 60 yr, location of cancer in the rectum, and CEA increasing after surgery appear to be independent ominous prognostic indicators.

Interleukin-1 alpha (IL-1 alpha) production by alveolar macrophages in patients with acute lung diseases: the influence of zinc supplementation.

The relationship between zinc treatment and interleukin-1 alpha (IL-1 alpha) production by cultured alveolar macrophages (AM) in patients with pulmonary tuberculosis and bacterial pneumonia was investigated. AM (1 x 10(6) cells/ml) from 6 patients with pulmonary tuberculosis, 7 patients with bacterial pneumonia and 4 healthy volunteers were cultured with either two different concentrations of zinc chloride (Znl = 1 microgram/ml and Zn2 = 5 micrograms/ml) or cell culture media alone (control) for an initial period of 6 hours and then stimulated with 3 different immunomodulator agents and reincubated for a further 24 h. IL-1 alpha in culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA). In the absence of Znl or Zn2 Polyinosinic:Polycytidylic acid (Poly I:C 1 microgram/ml), Lipopolysaccharide (LPS 100 ng/ml) and Tumour necrosis factor-alpha (TNF-alpha 10 ng/ml) significantly increased the production of IL-1 alpha from AM in both patients and healthy subjects (p < 0.001) compared to control (media only). Zn1 and Zn2 significantly increased the production of IL-1 alpha (p < 0.001) in culture supernatants in the absence of either Poly I:C, LPS or TNF-alpha in patients but not in healthy group. In contrast, the presence of LPS or TNF-alpha significantly reduced Zn1 or Zn2-stimulated release of IL-1 alpha from AM in patients and healthy subjects (p < 0.01). However, Poly I:C decreased only Zn1-stimulated release of IL-1 alpha. These results suggest that zinc can regulate the production of IL-1 alpha from AM in patients with pulmonary tuberculosis or bacterial pneumonia.

Serum CA-15.3 and CEA patterns in postsurgical follow-up, and in monitoring clinical course of metastatic cancer in patients with breast carcinoma.

Serum CA-15.3 and CEA levels were longitudinally determined in 307 patients with breast carcinoma during postsurgical follow-up and/or therapy. Of 120 patients with no apparent disease, the specificity of marker levels fluctuating within the normal range (true-negative) was 98% for CA-15.3 alone (P = 0.004) and about 88% for CEA alone or for the tests combined. However, the false-negative levels in patients with progressive cancer reduced the predictive value of the tandem to around 76%, i.e. normal levels of both markers correctly predicted uneventful postsurgical course in only three fourths of the patients. Of 187 patients with active disease, the sensitivity of raised or increasing marker levels was around 70% for CA-15.3 alone or CEA alone, and 82% for the tests combined (P = 0.006). The 11% false-positive rate of CEA in patients with no apparent disease decreased the predictive value of a positive test from 98% for CA-15.3 alone (P = 0.006) to 91% for CEA alone or the tandem. Serum CA-15.3 or CEA paralleled the site of relapse: at least one marker was found elevated in 60% of patients with locoregional disease or with metastases to the lungs or bones exclusively, and in 90% of those with metastases to the lungs and bones or to the liver. A concurrent decrease of both marker levels reflected response to therapy while an increase of at least one marker level reflected treatment failure. It may be concluded that the marker tandem was better than either marker alone for follow-up aimed at detection of relapse, and that the tests were approximately 80% accurate for follow-up and/or monitoring therapy.

Serum AFP, hCG and CEA in the management of patients with testicular, ovarian and extragonadal germ cell tumors.

Serum levels of AFP, hCG and CEA were initially and serially measured in 59 patients with testicular germ cell tumors, and serially in 37 with ovarian and 3 with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature teratoma had normal serum AFP and sporadically slightly elevated hCG. Some patients with embryonal carcinoma, pure or with admixture of seminoma, had serum AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited. Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those with choriocarcinoma had elevated hCG, and those with compound tumors had one or more of the markers highly elevated. High AFP and/or hCG levels indicated the presence of the relevant tumor cells both in the primary and in residual tumor and/or metastases, also those missed in histological material, and thus were useful in restaging. Unfortunately, their absence in serum did not exclude the presence of marker-negative subpopulations of tumor cells. Changes in marker values paralleled the effects of treatment: the level increasing from any nadir heralded recurrence in patients in remission; elevated or increasing levels during therapy implied resistance to the therapy; decreasing levels indicated regression even though a return to the normal range did not mean eradication of all tumor cells.

Preoperative and longitudinal serum levels of CA 125 and CA 15.3 in patients with breast cancer.

Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative in patients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent: CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.

Carcinoembryonic antigen and breast carcinoma antigen (CA 15.3) in preoperative staging and postoperative monitoring of patients with carcinoma of the breast.

Serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen (CA 15.3) were determined in patients with breast carcinoma: in 129 before initial surgical or nonsurgical treatment and in 134 afterwards. Before any initial treatment, CEA was elevated in 15% of patients with Stage IV disease and CA 15.3 was high in 11% with Stage III and 48% with Stage IV. While monitoring management active disease was associated with elevated serum CEA in 66% of the patients, with elevated CA 15.3 in 73% and with at least one of the markers elevated in 86%. Both tests had high specificity (93% and 98%). The rise in serum CEA and, even more so, of serum CA 15.3 roughly paralleled the increase in bulk of the tumor: from locoregional disease through metastases to the lungs, bones, lungs with bones, and liver. Decreases in the levels of serum CEA and CA 15.3 reflected response to therapy, increases in the level of at least one marker-treatment failure, and levels fluctuating above the normal range indicated stationary disease. During follow-up, the predictive value of a negative test (levels within the normal range), suggesting that the patient might be free of disease, was 61% for CEA alone, 67% for CA 15.3 alone, and 80% for the two tests combined. We conclude that an elevated serum level of only one of the markers was useful for staging, implying advanced disease. Determination of both markers jointly was useful for monitoring the effectiveness of the therapy and for follow-up aimed at detection of relapse.