Establishment and morphologic characterization of normal human endometrium in vitro.

Tissue culture offers a model system with which to study the endocrine-mediated growth, differentiation, and metabolic activities of the endometrium. We have established and continue to maintain monolayer cultures of normal human endometrial epithelial cells from each phase of the menstrual cycle. At present, eight proliferative, two secretory, and two menstrual phase cultures have been established. These have been passed at least three times. One proliferative phase culture has been growing for 18 mo, and passed 10 times. Colonies of epithelioid cells as well as single cells appear in the cultures within 2 to 8 h of initial culture and maintain this appearance throughout long-term growth. The cells are periodic acid Schiff positive for carbohydrates and positive for keratin, an immunochemical marker for epithelial tissues. Studies comparing the ultrastructure of the cultures with fresh endometrial tissue revealed morphologic features common to both, including prominent nucleoli, Golgi, mitochondria-rough endoplasmic reticulum complexes, and abundant glycogen. The cells are not tumorigenic in the nude mouse and do not form colonies on soft agarose, confirming the nonneoplastic identity of the cells.

Gonadal dysgenesis with mosaicism and a nonfluorescent Y chromosome: report of two cases with correlation of clinical, pathologic, and cytogenetic findings.

Two phenotypic girls with nonfluorescent Y chromosome mosaicism and histologic streak gonads were presented. H-Y antigen (a Y chromosome--determined antigen) was negative in both patients. Electron microscopic findings of "streak gonads" were presented for the first time. The authors recommend bilateral gonadectomy in patients with nonfluorescent Y chromosomes and correlation between the histologic findings and H-Y antigen status.

Abruptio placentae. An assessment of the time and method of delivery.

Abruptio placentae occurs once per 120 deliveries, but accounts for 15--25% of all perinatal mortality. Several series in the literature suggest that an abnormal fetal-maternal relationship exists in patients with abruptio placentae weeks prior to the actual placental separation and that the separation is only the terminal event. A review of the literature and an analysis of 388 cases of abruptio placentae from the US Navy Coding System were undertaken. It was found that approximately 75% of fetal deaths occurred more than 90 minutes after admission to the hospital and almost 70% of all perinatal mortality occurred in infants who were delivered more than 2 hours from the time of diagnosis. Delivery by cesarean section improved survival in those infants weighing 1500 g or greater and reduced perinatal mortality as much as fourfold in some reports. A prospective study is proposed which would compare two methods of management of this condition.

Estrogen and endometrial carcinoma.

1. It has become evident that the estrogen secreting tumors of the ovary are associated with endometrial carcinoma, but this association is most easily observed in the postmenopausal patient where the incidence of carcinoma has been reported at 10.3% (1. 02) to 24% (83). 2. The most consistent association of endometrial carcinoma is with polycystic ovarian disease, where 19 (34), 21 (152), and 25% (150) of young women with endometrial carcinoma had Stein-Leventhal syndrome (67). 3. A very significant discovery became known in 1967 when the peripheral aromatization of delta4 androstenedione to estrone was reported by Kase (94) and MacDonald (111,112). Since that time we have learned that endometrial carcinoma patients have an increased peripheral conversion (139) (0.1% compared to 0.027%), which is similar to that found in obese and aging patients, by Hemsell, et al (77). This can be 2 to 4 times greater than the young adult or the patient without cancer. Estrone produced peripherally in normal postmenopausal women can amount to 40-60 microng/day and rise as high as 120-180 microng/day in the endometrial neoplasia group (39). Similarly patients with polycystic ovary disease, hyperthecosis and lipoid cell tumors of the ovary demonstrate androgen excess with extraglandular conversion to estrone (2). 4. It has become apparent that the principal estrogen in the postmenopausal patient is estrone and that the estrone-estradiol ratio in the serum is higher in postmenopausal women with corpus cancer than similar patients without cancer (135). Clearly, we must find the effect of this estrone excess at the nuclear "acceptor" level; and does this imbalance create a hormonal environment conducive to the development of endometrial carcinoma when age (an extremely important factor) and an oncogenic agent are added? 5. With the lack of ovarian estrogen there is a relative excess of adrenal testosterone, dihydrotestosterone and delta4 androstenedione, the available precursors of extraglandular estrone (1). 6. With the passage of time it appears that endometrial carcinoma is associated with hypothalamic "hyperactivity" (31) which exhibits immunologic-biologic dissociation of LH as previously observed in persistent trophoblastic disease when measuring hCG. The significance of this is still unknown. In a like fashion a significant number of the at risk polycystic ovary disease patients have an increased LH secretion. 7. Patient susceptibility is required as seen in animal experiments where prolonged administration of stilbestrol is used and still only rabbits and mice developed a malignant change. 8. Long term exogenous estrogen appears to have caused malignant changes in the endometrium, but it was universally given over a prolonged period (4 or more years). The recent retrospective studies demonstrate an association of oral estrogen therapy with endometrial cancer, but prospective studies investigating dose and duration of all estrogen preparations need to be undertaken. 9...

Carcinoma of the cervix: A third treatment.

A selected group of 136 patients with Stage I squamous cell carcinoma of the cervix was treated in six naval hospitals during the period 1957-1965 using a three-stage combined radiation therapy and surgery protocol. Treatment consisted of two radium applications to the cervix, followed in 6 weeks by extraperitoneal lymphadenectomy. If the lymph nodes were tumor-negative, simple hysterectomy in 6 to 6 months completed the protocol. If the nodes were tumor-postive, a course of external pelvic irradiation was given with midline shielding. The incidence of positive nodes was 9.6 per cent. Actuarial survival for all patients was 89.4 per cent, comparabale to the rate obtained by radical surgery or radiation alone. Postoperative and postradiation complications were minimal, with nourinary or bowel fistulas. There was no operative mortality.

Suction curettage: therapeutic effectiveness in dysfunctional uterine bleeding.

A group of 60 patients between the ages of 30 and 45 were randomly selected to have either a suction curettage or dilatation and curettage. The criteria used for patient selection was that they had dysfunctional uterine bleeding, a normal gynecologic examination, and were receiving no hormonal therapy. These patients were followed up for at least 3 months. Although the number of patients is relatively small, the results showed that, therapeutically, suction curettage was equal to dilatation and curettage in alleviating dysfunctional uterine bleeding.