Elevation of serum CA125 in carcinomas of the fallopian tube, endometrium, and endocervix

An immunoradiometric assay with the use of a monoclonal antibody can detect an antigenic determinant (CA125) in peripheral blood from more than 80% of patients with epithelial ovarian cancer. In this report elevated levels of CA125 were detected in serum from patients with adenocarcinomas of the fallopian tube, endometrium, and endocervix. Among patients with endometrial cancer, CA125 levels were elevated in recurrent or disseminated disease but not with tumors confined to the uterus.     

The design of clinical trials in the therapy of ovarian carcinoma

Ovarian carcinoma continues to be a major cause of death in women in spite of the effective use of operation, radiotherapy, and chemotherapy in some patients. Improved survival will depend upon proper definition of prognostic factors, adequate and standardized staging, and upon prospective randomized clinical trials to define optimal existing therapy. With optimal existing therapy as a base line, newer therapeutic and combined modality approaches may be compared to optimal existing therapy in a systematic way. Results of such trials should improve survival of patients with ovarian carcinoma.     

Comparison between tissue and serum content of CA 125, CA 19-9, and carcinoembryonic antigen in ovarian tumors

Tumor markers CA 125, CA 19-9, and carcinoembryonic antigen (CEA) were detected by immunohistochemistry in paraffin embedded tissue samples obtained from two different locations in 35 ovarian tumors. In addition, serum concentrations of these tumor markers were measured before cytoreductive surgery. The staining reaction was heterogeneous in different parts of the tumor as well as within the parenchyma. Of the marker positive tumors, a staining reaction was observed in both tissue samples in only 10 of 22 cases for CA 125, in eight of 13 cases for CEA, and in three of eight cases for CA 19-9. Eighty-one percent of the patients whose tumor was positive for CA 125 also showed elevated serum levels of this marker. A poor correlation was found between tissue and circulating CA 19-9 levels. CEA was detected in 28% of the tumors and seemed to be valuable only for monitoring in rare cases of ovarian cancer. For purposes of selecting a marker for monitoring of patients with ovarian carcinoma, immunohistochemistry has a predictive value for CA 125 only. In order to better define the marker expressed in a tumor, it is necessary to examine at least two samples of different parts of the malignant tissue.     

Tamoxifen and endometrial carcinoma: alterations in estrogen and progesterone receptors in untreated patients and combination hormonal therapy in advanced neoplasia

Estrogen receptors and progesterone receptors were measured in tumors from patients with previously untreated endometrial carcinoma before and after a 5-day course of tamoxifen citrate. On initial biopsy, 13 of 25 tumors (52%) were progesterone receptor-positive, whereas 21 of 25 tumors (84%) were progesterone receptor-positive after tamoxifen. Grades 1 and 2 tumors were more likely to demonstrate this increased incidence of measurable progesterone receptors. Considering these results, and the work of others who have shown that progesterone receptor-positive metastatic endometrial cancer is more responsive to progestin therapy than are progesterone receptor-negative tumors, we instituted a phase II clinical trial of tamoxifen plus progestin for patients with recurrent endometrial carcinoma. Thus far, however, the 33% total response rate achieved with the combination therapy has not been superior to standard progestin therapy.     

Human chorionic gonadotropin and thyroid function in patients with hydatidiform mole

In view of the controversy regarding the role of human chorionic gonadotropin as the stimulator of thyroid function in patients with trophoblastic tumors, especially hydatidiform mole, we conducted studies to explore whether a correlation between serum human chorionic gonadotropin levels and thyroid function was demonstrable in such patients. Among 47 patients studied, only one was clinically hyperthyroid, although 10 had serum total thyroxine values exceeding those found in normal pregnancy (8 to 17 micrograms/dl). Among 34 patients in whom free thyroxine indices could be calculated, 18 had elevated values for the free thyroxine index (greater than 10.6), and nine had elevated values for both total thyroxine and free thyroxine index. Serum total 3,5,3'-triiodothyronine concentrations were also measured in 17 patients, and only one of them had a value (400 ng/dl) above the normal limit for pregnancy (greater than 350 ng/dl). Among the 13 patients for whom free 3,5,3'-triiodothyronine indices were calculated, three had values above the normal range (greater than 215). A weakly positive correlation (r = 0.35, p less than 0.05, n = 47) between the serum human chorionic gonadotropin levels and serum total thyroxine concentrations was observed in these patients. However, no correlation was found between serum human chorionic gonadotropin levels and free thyroxine index values (r = 0.32, p greater than 0.05, n = 34). Also there was no correlation between serum human chorionic gonadotropin levels and either serum total 3,5,3'-triiodothyronine concentrations (r = 0.32, p greater than 0.1, n = 17) or free 3,5,3'-triiodothyronine index values (r = 0.27, p greater than 0.1, n = 13). chi 2 Analysis revealed no significant relationship between elevations of serum human chorionic gonadotropin concentration and abnormally high values of the free thyroxine index. These studies do not support the premise that human chorionic gonadotropin per se is the thyroid stimulator of molar pregnancy and suggest that a substance or substances, distinct from human chorionic gonadotropin and elaborated by the gestational trophoblastic tissue, are responsible for thyrotoxicosis observed in patients with trophoblastic tumors.     

Response of amenorrheic patients with normal serum prolactin to chlorpromazine during administration of human menopausal gonadotropin

To study the effects of graded amounts of estrogens on prolactin (PRL) secretion, PRL response to chlorpromazine (CPZ) during administration of human menopausal gonadotropin (hMG) was determined. A control CPZ test was done prior to initiation of hMG therapy and the test was repeated when endogenous estrogen secretion reached the physiologic range (350 to 400 pg. per milliliter) which stimulates luteinizing hormone surge in the normal ovulatory menstrual cycle. Six euprolactinemic women with secondary amenorrhea were studied. Studies showed that there was no significant change in the mean serum prolactin concentrations during control and repeat CPZ testing procedure (5.8 +/- 2 and 10.8 +/- 2 ng. per milliliter, p less than 0.1). The maximal response of PRL to CPZ was significantly higher during hMG-induced high estrogenic state than during control testing (69.9 and 32.3 ng. per milliliter, p less than 0.01). This findings suggests that endogenous estrogen may play a role in the regulation of serum prolactin concentration during the menstrual cycle.     

The development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma

Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinations as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was vitually no correlation (r2 - 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay.     

Long-term effects of labor and delivery on offspring: a matched-pair analysis

An investigation was undertaken in an effort to learn whether the type of delivery or the pattern of labor progression has any lasting effect on the infant. Paired-data design was chosen to ensure that the comparisons between homogeneous groups would be valid. Our objective was to reduce potential bias based on unequal distribution of patient characteristics that might be more or less commonly associated with abnormal labors or with difficult deliveries. Seven-year intelligence quotient data for matched pairs of cases showed significant long-range adverse impact from midforceps operations but not from low-forceps procedures. Comparable paired-data analysis for the effect of labor disorder on the infant verified a similar deleterious influence from both arrest and protraction patterns.     

Implantation site in complete molar pregnancy: a study of immunologically competent cells with monoclonal antibodies

The nature and intensity of inflammatory cellular infiltrate in the implantation sites of 10 complete molar pregnancies were evaluated by immunohistochemical staining of frozen tissue sections with monoclonal antibodies. As compared to the implantation site in normal pregnancy, there was an increase in the number of infiltrating inflammatory cells in the molar implantation site. Most of the inflammatory cells were T cells with predominance of T4+ (Leu-3a+) cells over T8+ cells. Inflammatory cells were not detected in the molar vesicles. The possible implications of these findings in molar pregnancy are discussed.     

Radical hysterectomy: a critical review of twenty-two years' experience.

One hundred seventy-eight patients who had radical hysterectomy performed for management of invasive carcinoma of the cervix over 22 year period at the Medical University of South Carolina were critically analyzed. The degree of differentiation of the malignancy appeared to be of more significance than tumor size in Stage 1 lesions. With proper patient selection and excellent operative technique, survival rates well over 90% with minimal complications can be obtained. The radical hysterectomy should never be used in association with irradiation.     

Ontogeny of human fetal plasma progesterone, deoxycorticosterone, and deoxycorticosterone sulfate

The concentrations of progesterone, deoxycorticosterone (DOC), and deoxycorticosterone sulfate (DOC-SO4) were determined in mixed umbilical cord plasma of abortuses and newborn infants delivered between 18 and 42 weeks' gestation. A wide range of values among individual samples was found for progesterone (224 to 2,152 ng/ml), DOC (1.6 to 10.4 ng/ml), and DOC-SO4 (17 to 154 ng/ml). Levels of progesterone and DOC in mixed umbilical cord plasma were not correlated; those of DOC and DOC-SO4 were positively correlated significantly (r = 0.3945, P less than 0.001). Whereas the mean plasma levels of DOC were similar throughout gestation, significant variation, as a function of gestational age, was found for progesterone and DOC-SO4, with levels of these steroids generally being higher near term than earlier in gestation. The administration of glucocorticosteroids to the mother resulted in a significant decrease (p less than 0.001) in plasma concentrations of DOC and DOC-SO4 in the newborn infant; levels of progesterone in umbilical cord plasma were not affected by maternal glucocorticosteroid treatment. These results suggest that the fetal adrenal glands play a direct, or possibly an indirect, role in the production of the DOC and DOC-SO4 that is present in the fetal compartment. In addition, since fetal plasma levels of progesterone are quite high throughout gestation, the potential exists for circulating progesterone to serve as a precursor for adrenal and extra-adrenal production of DOC and DOC-SO4.     

Six years' experience with screening of a diethylstilbestrol-exposed population.

The physician population delivering obstetric care in Philadelphia between 1950 and 1970 was contacted to ascertain their use of diethylstilbesterol (DES) during pregnancy. Of the 31.8% of the physicians who responded to the questionnaire, 71.8% used DES during pregnancy and 12.7% desired assistance in review of their records. During the 6 years from the initial survey, 830 young women exposed to DES in utero were periodically screened for cervicovaginal abnormalities and clear cell adenocarcinoma. Of these 830 patients 61.7% were found to have cervicovaginal abnormalities, and 65.9% of the patients showed either adenosis or evidence of the prior existence of vaginal adenosis. Eight patients were treated for clear cell adenocarcinoma. Two cases were detected while asymptomatic. Seven of the patients are living with no evidence of cancer, and two of these have survived over 5 years.     

Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study.

During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy.     

Results of prior cytologic screening in patients with a diagnosis of Stage I carcinoma of the cervix

Cervical carcinoma is a disease which lends itself to prevention and diagnosis by cytologic screening. The results of previous Papanicolaou smears were obtained in 84 patients. Of 197 Papanicolaou smear results obtained prior to diagnosis of Stage I carcinoma, 63 (31%) were positive; and of 51 such smears obtained 1 year prior to diagnosis, 30 (59%) were positive. Possible explanations for negative screening prior to development of carcinoma are given. The need for centralized cytologic screening programs on a provincial basis is stressed.