Saul B. Gusberg

Proliferative endometrial response to theca-granulosa cell tumors

Abstract It is possible at times to observe derangements of homeostasis in the human being that may afford answers to unresolved metabolic or proliferative problems. Such is the case with certain functioning ovarian tumors. We have studied the endometrium from 115 patients with so-called feminizing ovarian tumors recorded in the Ovarian Tumor Registry and in our Institution to ascertain the endometrial response to more or less continuous endogenous estrogen stimulation. We noted cancer precursors in 43 per cent of this series and carcinoma in 21 per cent. Problems of selection and the possibility of other endocrinopathies prevent firm conclusions about the carcinogenic activity of estrogen in human beings.

Estradiol binding and metabolism in human endometrial hyperplasia and adenocarcinoma.

Abstract The levels of estradiol receptors (E 2 R), estimated from the amounts of E 2 tightly bound to nuclei after incubation of tissue with excess [ 3 H]-E 2 , were high in normal proliferative endometrium and postmenopausal hyperplasia. Postmenopausal adenocarcinoma, well- or poorly-differentiated, showed lower levels in untreated patients and higher in patients who had taken Premarin. Significantly lower values were found in normal secretory endometrium and premenopausal adenocarcinoma, likely due to progestational effects. A decline in E 2 R levels was seen after administration of Provera to postmenopausal patients with endometrial cancer. The E 2 17β dehydrogenase (E 2 DH) activities, estimated from the rate of conversion of [ 3 H]-E 2 to [ 3 H]-estrone under substrate and NAD saturating conditions, were low in all specimens of hyperplastic and neoplastic endometrium from postmenopausal patients. These levels correspond to those of normal proliferative or postmenopausal tissue. Higher levels, typical of normal secretory endometrium, were found in the premenopausal, well-differentiated adenocarcinoma analyzed. Provera treatment of patients with endometrial carcinoma increased the levels of E 2 DH. The E 2 R and E 2 DH levels observed in patients with endometrial cancer can be explained on the basis of the hormonal environment of the tissue at the time of sampling (e.g., relative proportion of E 2 and progesterone) without postulating drastically altered binding and metabolism of E 2 in abnormal endometrium.

Ovarian dysplasia. A Study of identical twins

The normal, identical twin sisters of patients who had been the subjects of ovarian cancer were subjected to prophylactic oophorectomy after the menopause. The finding of epithelial abnormality suggests a precancerous change similar to other genital epithelial dysplasia.

Estrogen metabolism in normal and neoplastic endometrium

Studies on normal endometrium at different phases of the menstrual cycle have shown that progesterone and synthetic progestins reduce the levels of estradiol receptors in the tissue and increase the activity of estradiol-17beta-dehydrogenase, an enzyme that converts estradiol to estrone. These effects may account for the antiestrogenic characteristics of the progestins. Similar effects were obtained in some postmenopausal patients with endometrial adenocarcinoma treated for two to 10 days with oral medroxyprogesterone acetate. These results point to the potential usefulness of a short-term, in vivo biochemical test which, combined with histologic observations, may identify patients who are likely to respond to treatment with progestins.

Estrogen metabolism in patients at high risk for endometrial carcinoma

Numerous clinical studies have demonstrated an ill-defined relationship between the development of endometrial neoplasia and estrogen production. We have previously demonstrated that postmenopausal women with endometrial carcinoma excrete less estriol glucosiduronate in proportion to estrone glucosiduronate than do normal women. This study investigated the per cent of conversion of androstenedione in the production of such women. Twenty-one postmenopausal women with endometrial carcinoma received tagged estrone and androstenedione. Twelve healthy postmenopausal women served as controls. It was demonstrated that significant amounts of androstenedione are metabolized to estrone. There was a significantly greater percentage of conversion of androstenedione to estrone as compared to that found in healthy postmenopausal women in the control study.

Endolymphatic stromal myosis — A Grade I endometrial sarcoma

Abstract A review of 182 cases of endolymphatic stromal myosis is presented. Although the histological appearance is that of a benign lesion, data regarding extent of this neoplastic process at primary operation, frequency of recurrence and metastasis, and death show that this disease must be regarded as having a great potential for malignant behavior. Though regarded by many as benign, there appears to be a role for a more radical surgical approach to the management of this unique lesion. Since it is of connective tissue origin, the best description of this disease is Grade I or low grade endometrial stromal sarcoma.

Radiosensitivity and virulence factors in cervical cancer: Individualization of treatment

Several biologic characteristics may be utilized in making the choice of treatment by radiotherapeutic or surgical modalities. A test dose of radiation (RST) enables us to discriminate between good responders in Stages I and II with an expected relative cure rate of 72.1 per cent under those with poor response whose relative cure rate declines to 32.5 per cent under the same radiotherapeutic treatment. Another group with poor response subjected to radical surgery achieved a relative cure rate of 56 per cent. Tumor virulence has also been assayed by recording lymphatic invasion in the control biopsies. The validity of age and geographic tumor configuration as measures of tumor virulence were not established. A protocol of individualized treatment for cervix cancer, based on these considerations, is presented.

Estrogen metabolism in patients at high risk for endometrial carcinoma: I. Urinary metabolites of H3-estradiol in normal postmenopausal women and those with endometrial carcinoma

Of 51 patients more than 2 years beyond the menopause, 34 had a diagnosis of endometrial carcinoma. Any with liver involvement were not included. 14 were found to have abnormal glucose metabolism. Each patient received an intravenous infusion of 8 mcc of bata-6, 7H-3 dissolved in 10 cc of 10% propylene glycol. 96 hour urine collections were obtained by an indwelling catheter. Values for the recovery of radioactivity associated with estrone, estradio, estriol, and estriol/estrone + estradiol expressed in percent of injected radioactivity are given. A wide range of values was obtained and great variations in ratios. Generally the results were similar to those obtained from studies on menstruating females. There was no significant difference between patients with or without endometrial carcinoma in terms of recovered radioactivity or of the estriol quotient. However, methoxgestrone, epiestriol, and the alpha-ketols which make up a significant portion of theurinary metabolites of estradiol 17 beta were not studied. Restudy of 6 patients with carcinoma produced constant patterns of metabolism. A significantly lower specific activity of estriol as compared to that of estrone was demonstrated in both groups of patients when estradiol 17 beta had been administered. However, this difference was less precursons of urinary estriol. Androstenedione may be one of these. Reasonable radiochemical purity of each final metabolite was verified by recrystallization to constant specific activity following the addition of nouradioactive estrone or estriol.

Estrogen Use and Postmenopausal Women: A National Institutes of Health Consensus Development Conference

The concensus conclusions reached at a concensus development conference on Estrogen Use and Postmenopausal Women in September 1979 are based on 3 position papers prepared for the conference, the response of the panel, and the general discussion by the audience, followed by the panel and other conference participants. The evidence for the efficacy of estrogens in treating specific conditions associated with menopause was reviewed 1st. It was accepted that estrogens are more effective than placebo in decreasing the frequency and severity of vasomotor symptoms. Estrogens are effective in overcoming the atrophy of the vaginal epithelium and the associated symptoms. Present evidence does not justify the use of estrogens to treat primary psychological problems. The validity of 3 randomized trials indicating that exogenous estrogens can retard bone loss if given around the time of menopause was acknowledged. There is no convincing evidence that estrogens in customary doses increase the risk of thromboembolic phenomena, stroke, or heart disease in women who have undergone natural menopause. Evidence was also reviewed concerning adverse effects associated with post-menopausal estrogen use. In the absence of exogenous estrogens, the incidence of endometrial cancer is about 1/1000 postmenopausal women per year. This rate increases severalfold beginning after about 2-4 years of use of 0.625 or 1.25 mg of conjugated estrogens daily. Cystic hyperplasia of the endometrium, regarded as a premalignant condition, has been associated with unopposed estrogen, whether endogenous or exogenous.

Chemosensitivity testing with cis-platinum(II) diamminedichloride: II. Preliminary experience in the treatment of carcinoma of the cervix

Abstract Nineteen previously untreated patients with invasive squamous cell carcinoma of the cervix were given a test dose of cis -platinum(II) diamminedichloride (DDP) prior to treatment with radiotherapy or initial surgery. Two patients who had failed radiation therapy were also tested. Histologic and cytologic characteristics in sequential cervical biopsies and clinical response were employed to determine sensitivity of tumor to platinum and to identify the patient who would most benefit from systemic platinum chemotherapy. No serious side effects were encountered. Standard treatment could be administered without unexpected toxicities or delay.