Cell culture of biopsied endometriomas after danazol/hormonal therapy: a study of growth features and fertility effects.

The growth features of cells from endometriomas biopsied from patients who had been treated with Danazol or with hormones have not been studied in vitro. Danazol is a versatile drug and despite its recognised efficacy in controlling endometriosis, little is known about is cytotoxicity and mechanism of action. Culture of the biopsied endometriomas permitted qualitative cytotoxic assessments by way of comparison with cultured normal uterine endometrial cells treated in vitro with Danazol. The growth characteristics were studied in monolayer and collagen gel cultures. Cytopathology was characterised by light and electron microscopy. Since endometriosis is associated with infertility in women, data from in vitro fertilisation (IVF) were analysed with respect to treatment modalities as compared with cases suffering fallopian occlusion. Danazol reduced pregnancy chances. Two factors may be responsible: (a) altered follicle development resulting in poor oocyte quality (b) reduced nidation because of long-lasting endometrial cytotoxicity. The experimental findings reported here support the latter explanation. Consequently, Danazol therapy should be conditional; patients wishing to achieve pregnancy should preferably receive hormonal therapy.

[Lung metastasis after pelviscopic salpingectomy in therapy of tubal pregnancy]. / Lungenmetastasierung nach pelviskopischer Salpingektomie zur Therapie einer Tubargravidität.

UNLABELLED: A 34-year old VI gravida, II para underwent a pelviscopic salpingectomy of the left fallopian tube for treatment of a repeated ectopic pregnancy. Histology revealed an invasive hydatidiform mole. The declining beta-hCG titers after surgery were not further controlled. Seven months later a secondary amenorrhoea occurred again; beta-hCG levels increased steadily. We could not obtain trophoblastic tissue by operative pelvis-copy (excision of the tubal stump on the left side and tubal sterilisation on the right side) nor by curettage of the uterine cave. A lesion of the lung was interpreted as a metastatic lesion following malignant transformation of the invasive hydatidiform mole and disappeared under cytotoxic therapy containing methotrexate with an uneventful follow-up period of now 4 years. RECOMMENDATION: In order not to overlook the presence of persistent trophoblastic tissue and the possible development of a choriocarcinoma, beta-hCG serum titers should be measured until they disappear, following the surgical therapy of an ectopic pregnancy.

Management of patients with persistent beta-hCG values following laparoscopic surgical and local drug treatment for ectopic pregnancy.

OBJECTIVES: To show that the beta-human chorionic gonadotropin (hCG) decline following tubal-preserving techniques for ectopic pregnancy (EP) can take a longer course than currently believed, indicating expectant management; and to define the indications for a second-look laparoscopy if beta-hCG persists. METHODS: Three hundred thirty-seven patients treated for EP were retrospectively reviewed. In order to define the 'normal' beta-hCG decline following tubal-preserving techniques we acquired a Kaplan-Meier curve for 98 patients treated by laparoscopic linear salpingotomy, the main method performed for EP (253 patients). The Mann-Whitney U-test served as a statistical test. The patient population requiring a second-look laparoscopy for proliferating trophoblastic remnants is described. RESULTS: Twenty-eight patients (8.3%) required a second-look laparoscopy (acute abdominal pain and sonographically suspect findings combined with increasing beta-hCG values). The majority (15 patients) underwent a preceding laparoscopic linear salpingotomy (6.5% unresolved cases). The relative beta-hCG values differed significantly from the unresolved group compared to the group with resolved EP starting at postoperative day 2 (P < 0.01). A maximal beta-hCG decline period of 77 days postoperatively was observed. CONCLUSIONS: Patients with slowly declining beta-hCG levels following tubal-preserving techniques for EP can be managed expectantly. Increasing beta-hCG values combined with abdominal pain and sonographically suspect observations indicate a second-look laparoscopy.

[Effect of danazol on growth of endometrial and endometriotic cells in vitro].

The cells from entopic and ectopic endometrial tissues were primarily cultured in collagen gel and passaged for secondary culture. The grown cells were treated respectively with danazol (2.5 micrograms/ml and 5 micrograms/ml) and without danazol in medium. In control culture without danazol, the cells presented normal growth, had stellate appearance and were connected with each other by cytoplasmic projections. Cell growth was suppressed after being treated with both concentrations of danazol. Attachment potential of passaged cells in 24 hours appeared to be damaged, some cells revealed lethal pathological features. Ultrastructural changes induced by danazol included numerous vacuoles and lipid droplets, increased lysosomes including autolysosome, oncotic mitochondria in cytoplasm, irregular nucleus, etc. The results suggest that collagen gel culture is suitable for culturing endometrial cells, and danazol has a direct effect on human endometrial and endometriotic tissues.

Treatment of precursors of endometrial cancer.

From 1985 to 1991, 73 hysterectomies were performed on patients suffering from histologically demonstrated adenomatous hyperplasia, grades 1-3, at the Kiel University Hospital of Gynecology. The operations were done within a month from the diagnosis. Three of the patients were under 40 years of age. An exact correspondence between the grade of adenomatous hyperplasia in the abraded material and the uterus specimen was found in only 44% of the cases. In the patients over 40 with adenomatous hyperplasia of any grade demonstrated in the abraded material, an already well-differentiated endometrial carcinoma was found in 16% of the cases, while such a carcinoma was found in 57% of the cases with grade 3 adenomatous hyperplasia! Even though drug therapy with gestagen may have a beneficial effect, a hysterectomy is nevertheless the treatment of choice for adenomatous hyperplasia of grade 2 and grade 3 in patients over 40 because it is not absolutely certain from a diagnostic point of view that the material is representative of the entire mucosa. In women under 40 years of age it is necessary to plan therapy on an individual basis.

[Adenomatous hyperplasia--hysterectomy or drug therapy?]. / Adenomatöse Hyperplasie--Hysterektomie oder medikamentöse Therapie?

Adenomatous hyperplasia of the endometrium requires either gestagen treatment or hysterectomy, depending on the patient's age and grade of hyperplasia. 51 patients, in whom adenomatous hyperplasia of grade I-III had been ascertained by curettage, were hysterectomized not more than 4 weeks following diagnosis at the Kiel University Clinic of Obstetrics and Gynecology during the years 1985-1989. Only few of the patients received hormone treatment. For all grades of hyperplasia, histological findings from curettage and hysterectomy were identical in only 40% of the cases. In patients older than 40 years, 54% of 13 patients with adenomatous hyperplasia grade III in the curettage specimen had already developed a well differentiated adenocarcinoma, which was detected in the extirpated uterus. In our opinion, when adenomatous hyperplasia of grade II or III is present in a curettage specimen in the age group over 40 years women, hysterectomy should be recommended. For younger women and for adenomatous hyperplasia grade I, we recommend individual therapy.

[A non-specific vulvo-vagino-gingival syndrome]. / Syndrome vulvo-vagino-gingival non spécifique.

The case of a 29 year-old patient is reported who initially complained about gingivitis and one year later developed a colpitis. After two years the patient was admitted to our hospital where inflammatory erosive changes of the gingiva, the vagina and the vulva were seen. Neither laboratory parameters nor histological results allowed an exact diagnosis of these findings. Also a Lichen ruber erosive had been excluded by the microscopic findings of a gingival and vaginal biopsy. Thus, the diagnosis of a non-specific vulvo-vagino-gingival syndrome was established, whereby antiphlogistic treatment with corticosteroids led to an improvement of the patient's symptoms.