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Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations.

BACKGROUND: The presence of deleterious mutations in breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2) significantly increases the risk of developing some cancers, such as breast and high-grade serous cancer (HGSC) of ovarian, tubal and peritoneal origin. Risk-reducing salpingo-oophorectomy (RRSO) is usually recommended to BRCA1 or BRCA2 carriers after completion of childbearing. Despite prior systematic reviews and meta-analyses on the role of RRSO in reducing the mortality and incidence of breast, HGSC and other cancers, RRSO is still an area of debate and it is unclear whether RRSO differs in effectiveness by type of mutation carried. OBJECTIVES: To assess the benefits and harms of RRSO in women with BRCA1 or BRCA2 mutations. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 7) in The Cochrane Library, MEDLINE Ovid, Embase Ovid and trial registries, with no language restrictions up to July 2017. We handsearched abstracts of scientific meetings and other relevant publications. SELECTION CRITERIA: We included non-randomised trials (NRS), prospective and retrospective cohort studies, and case series that used statistical adjustment for baseline case mix using multivariable analyses comparing RRSO versus no RRSO in women without a previous or coexisting breast, ovarian or fallopian tube malignancy, in women with or without hysterectomy, and in women with a risk-reducing mastectomy (RRM) before, with or after RRSO. DATA COLLECTION AND ANALYSIS: We extracted data and performed meta-analyses of hazard ratios (HR) for time-to-event variables and risk ratios (RR) for dichotomous outcomes, with 95% confidence intervals (CI). To assess bias in the studies, we used the ROBINS-I 'Risk of bias' assessment tool. We quantified inconsistency between studies by estimating the I2 statistic. We used random-effects models to calculate pooled effect estimates. MAIN RESULTS: We included 10 cohort studies, comprising 8087 participants (2936 (36%) surgical participants and 5151 (64%) control participants who were BRCA1 or BRCA2 mutation carriers. All the studies compared RRSO with or without RRM versus no RRSO (surveillance). The certainty of evidence by GRADE assessment was very low due to serious risk of bias. Nine studies, including 7927 women, were included in the meta-analyses. The median follow-up period ranged from 0.5 to 27.4 years. MAIN OUTCOMES: overall survival was longer with RRSO compared with no RRSO (HR 0.32, 95% CI 0.19 to 0.54; P < 0.001; 3 studies, 2548 women; very low-certainty evidence). HGSC cancer mortality (HR 0.06, 95% CI 0.02 to 0.17; I&#xb2; = 69%; P < 0.0001; 3 studies, 2534 women; very low-certainty evidence) and breast cancer mortality (HR 0.58, 95% CI 0.39 to 0.88; I&#xb2; = 65%; P = 0.009; 7 studies, 7198 women; very low-certainty evidence) were lower with RRSO compared with no RRSO. None of the studies reported bone fracture incidence. There was a difference in favour of RRSO compared with no RRSO in terms of ovarian cancer risk perception quality of life (MD 15.40, 95% CI 8.76 to 22.04; P < 0.00001; 1 study; very low-certainty evidence). None of the studies reported adverse events.Subgroup analyses for main outcomes: meta-analysis showed an increase in overall survival among women who had RRSO versus women without RRSO who were BRCA1 mutation carriers (HR 0.30, 95% CI 0.17 to 0.52; P < 0001; I&#xb2; = 23%; 3 studies; very low-certainty evidence) and BRCA2 mutation carriers (HR 0.44, 95% CI 0.23 to 0.85; P = 0.01; I&#xb2; = 0%; 2 studies; very low-certainty evidence). The meta-analysis showed a decrease in HGSC cancer mortality among women with RRSO versus no RRSO who were BRCA1 mutation carriers (HR 0.10, 95% CI 0.02 to 0.41; I&#xb2; = 54%; P = 0.001; 2 studies; very low-certainty evidence), but uncertain for BRCA2 mutation carriers due to low frequency of HGSC cancer deaths in BRCA2 mutation carriers. There was a decrease in breast cancer mortality among women with RRSO versus no RRSO who were BRCA1 mutation carriers (HR 0.45, 95% CI 0.30 to 0.67; I&#xb2; = 0%; P < 0.0001; 4 studies; very low-certainty evidence), but not for BRCA2 mutation carriers (HR 0.88, 95% CI 0.42 to 1.87; I&#xb2; = 63%; P = 0.75; 3 studies; very low-certainty evidence). One study showed a difference in favour of RRSO versus no RRSO in improving quality of life for ovarian cancer risk perception in women who were BRCA1 mutation carriers (MD 10.70, 95% CI 2.45 to 18.95; P = 0.01; 98 women; very low-certainty evidence) and BRCA2 mutation carriers (MD 13.00, 95% CI 3.59 to 22.41; P = 0.007; very low-certainty evidence). Data from one study showed a difference in favour of RRSO and RRM versus no RRSO in increasing overall survival (HR 0.14, 95% CI 0.02 to 0.98; P = 0.0001; I&#xb2; = 0%; low-certainty evidence), but no difference for breast cancer mortality (HR 0.78, 95% CI 0.51 to 1.19; P = 0.25; very low-certainty evidence). The risk estimates for breast cancer mortality according to age at RRSO (50 years of age or less versus more than 50 years) was not protective and did not differ for BRCA1 (HR 0.85, 95% CI 0.64 to 1.11; I&#xb2; = 16%; P = 0.23; very low-certainty evidence) and BRCA2 carriers (HR 0.88, 95% CI 0.42 to 1.87; I&#xb2; = 63%; P = 0.75; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very low-certainty evidence that RRSO may increase overall survival and lower HGSC and breast cancer mortality for BRCA1 and BRCA2 carriers. Very low-certainty evidence suggests that RRSO reduces the risk of death from HGSC and breast cancer in women with BRCA1 mutations. Evidence for the effect of RRSO on HGSC and breast cancer in BRCA2 carriers was very uncertain due to low numbers. These results should be interpreted with caution due to questionable study designs, risk of bias profiles, and very low-certainty evidence. We cannot draw any conclusions regarding bone fracture incidence, quality of life, or severe adverse events for RRSO, or for effects of RRSO based on type and age at risk-reducing surgery. Further research on these outcomes is warranted to explore differential effects for BRCA1 or BRCA2 mutations.

Adult

International trends in concurrent hysterectomy at risk-reducing surgery in BRCA1/2 pathogenic variant carriers: a mixed-methods study.

BACKGROUND: BRCA1/2 pathogenic variant carriers are advised to undergo a risk-reducing salpingo-oophorectomy between the ages of 35 and 45 due to their increased risk of tubo-ovarian cancer. A concurrent hysterectomy may be performed at the time of risk-reducing salpingo-oophorectomy. Currently, the international execution of hysterectomy during risk-reducing surgery and the factors guiding related decision-making are unknown. OBJECTIVE: We aimed to evaluate the international execution of concurrent hysterectomy during risk-reducing surgery for tubo-ovarian cancer and factors guiding providers' decision-making about this. STUDY DESIGN: We conducted a mixed-methods study. First, we executed a quantitative analysis with data from the Women choosIng Surgical Prevention (WISP) and TUBectomy with delayed oophorectomy as Alternative for risk-reducing salpingo-oophorectomy in high-risk Women to assess the Safety of Prevention (TUBA-WISP II) study, both prospective preferential trials assessing surgical strategies for tubo-ovarian cancer prevention. Data were collected via electronic case report forms. Concurrent hysterectomy during risk-reducing salpingo-oophorectomy was compared between Europe, North- and South America, and Australia using Kruskal-Wallis tests. We used univariable logistic regression models to estimate the association of personal and prevention-related characteristics with the execution of hysterectomy at risk-reducing salpingo-oophorectomy in women from North- and South America. Subsequently, we conducted focus group interviews with gynecologic providers from 12 countries who provide preventive care for individuals at increased risk of tubo-ovarian cancer to identify indications, barriers, and facilitators for the execution of hysterectomy with risk-reducing salpingo-oophorectomy. RESULTS: In the quantitative analysis, we included 2181 participants, of whom 1647 (75.5%) were from Europe, 498 (22.8%) from North- and South America, and 36 (1.7%) from Australia. Execution of hysterectomy at risk-reducing salpingo-oophorectomy differed substantially between continents, with an execution of 48.8% in North- and South America, 14.2% in Australia, and 2.8% in Europe (P<.001). Execution of concurrent hysterectomy at risk-reducing salpingectomy in women from North- and South America occurred more often in women with a BRCA1 pathogenic variant compared to a BRCA2 pathogenic variant (adjusted odds ratio 0.4 [95% confidence interval, 0.2-0.7]). In the qualitative analysis, we interviewed 23 healthcare providers and identified 31 barriers and 32 facilitators regarding hysterectomy execution during risk-reducing salpingo-oophorectomy. A total of 8 different indications were mentioned, but opinions varied on the validity and weight given to each indication. Providers indicated that important barriers or facilitators for concurrent hysterectomy included a lack of clear guidelines, cultural variation between countries, (lack of) consensus within departments, and different interpretation of the endometrial cancer risk. CONCLUSION: Internationally, there is a large variation in execution of hysterectomy during risk-reducing surgery with frequent utilization in North- and South America, and rare utilization in Europe. This could be explained by the interpretation of indications for hysterectomy by providers, which might be explained by cultural variation, the absence of clear guidelines, and limited scientific evidence.

Humans

Estimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer.

IMPORTANCE: Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking. OBJECTIVE: To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements. DESIGN, SETTING, AND PARTICIPANTS: In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohort study (N&#x2009;=&#x2009;1250 recruited from January 1, 2019, to December 31, 2024) evaluating RRES and DO for OC surgical prevention. Participants were premenopausal women 30 years or older at increased OC risk due to BRCA1/BRCA2 pathogenic variants. Participants could choose RRES, RRSO, or no surgery at entry. Sample size requirements used initial data (eg, age and BRCA1/2 distribution) from PROTECTOR (analysis undertaken from January 1, 2024, to December 31, 2025). MAIN OUTCOMES AND MEASURES: Incidence of OC after (not at) RRES and before or at DO in women with normal histologic analysis findings at surgery. The proportion of cancers prevented was estimated as the completement of the observed (O) to expected (E; assuming no preventive effect of surgery) number of cancers detected (1&#x2009;-&#x2009;O/E). RESULTS: Initial data were obtained from 889 women in PROTECTOR (overall mean [SD] age, 39 [5] years), with 255 (28.7%) choosing RRSO (mean [SD] age, 42 [4] years), 405 (45.5%) choosing RRES (mean [SD] age, 38 [4] years), and 229 (25.7%) choosing no surgery (mean [SD], 38 [5] years). The preferred estimand outcome was OC incidence after surgery (RRES or RRSO) with a "while on intervention" strategy to account for intercurrent events. The primary target measure was the proportion of cancers prevented for RRES vs no surgery with superiority testing. The secondary target measure was noninferiority of RRES vs RRSO. An estimated 1150 RRES participants with 8 to 10 years of follow-up would provide approximately 92% power to show that 20% or more of cancers are prevented using a 1-sample binomial test of the O:E risk (external reference) at the 5% level under a range of assumptions and at least the same power for a noninferiority margin for the proportion of cancers prevented by RRES of those prevented by RRSO. Estimands based on incidence ratios had an infeasible sample size. CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of UK BRCA carriers, the estimand differed from other ongoing clinical effectiveness studies of RRES and DO. Advantages include direct use of expected risk at baseline (unknown at design stage), easier interpretation across cohorts than absolute risk differences, and providing a feasible recruitment target for PROTECTOR to evaluate clinical effectiveness.

Humans

Health-related quality of life after risk-reducing hysterectomy: a randomised vignette study.

BACKGROUND: Risk-reducing hysterectomy (RRH) is the most effective endometrial cancer preventive strategy. Understanding health-related quality-of-life using health-related utility-scores (HRUS) is essential for counselling, shared decision-making, and informing health-economic evaluations of endometrial cancer prevention. This study aimed to determine HRUS for premenopausal RRH, with and without bilateral salpingo-oophorectomy (BSO). METHODS: Preventing Endometrial-Cancers: Comparing Risk-Reducing Strategies (PRESCORES) (ISRCTN17432105) part-2 is a UK-based randomised vignette study. Following a robust development process, vignettes described four postoperative health-states for a 40-year-old otherwise-healthy woman: "RRH at 1-month", "RRH at 1-year", "RRH-BSO at 1-month", "RRH-BSO at 1-year". These were valued using EQ-5D by participants recruited from the UK general-population and HRUS calculated. Utilities were subsequently adjusted by age-and sex-matched general-population reference values. Association of variables was explored with ordinary-least-squares regression with non-parametric bootstrapping. FINDINGS: Overall, 1001 women were included and randomised to 1-of-4 groups. The mean-age(&#xb1;SD) was 53.6 (&#xb1;11.4) years. Mean(&#xb1;SD) HRUS were 0.942 (&#xb1;0.072) for "RRH at 1-year", 0.841 (&#xb1;0.137) for "RRH-BSO at 1-year", 0.670 (&#xb1;0.149) for "RRH at 1-month", and 0.733 (&#xb1;0.190) for "RRH-BSO at 1-month", with significant difference between each group (p&#xa0;<&#xa0;0.001). Adjusting for age-sex-matched population reference utilities, HRUS were 1.000(95% CI:1.00-1.00), 0.994(95% CI:0.97-1.00), 0.866(95% CI:0.84-0.90) and 0.791(95% CI:0.77-0.81), respectively. Participant factors associated with vignette valuations included age, obesity, heavy menstrual-bleeding, higher income and mixed/other ethnicity. CONCLUSION: This randomised study provides HRUS following premenopausal RRH with and without BSO at two postoperative time-points, with adjustment against the age-and sex-matched general reference-population. These values are of relevance for informing counselling of women at increased endometrial cancer-risk regarding RRH and for health-economic evaluations.

Humans

Endodermal sinus tumor of the ovary: a clinical and pathologic analysis of 71 cases.

The clinical and pathologic features of 71 endodermal sinus tumors of the ovary were studied in an effort to delineate the histogenesis and biologic behavior of this neoplasm and to evaluate the efficacy of different forms of treatment. Alpha-fetoprotein (AFP) was identified in hyaline droplets, cell cytoplasm, and intercellular spaces of all 15 tumors examined by an immunoperoxidase technique; this supports the view that the neoplasm simulates yolk sac endoderm. There were only nine survivors among 65 patients on whom follow-up information was available; the actuarial survival was 13% at 3 years. Of the neoplasms that recurred, 93% did so within 1 year, and of those patients who died, 93% did so within 2 years. The size and stage of the tumor had prognostic significance, but the patient's age, the mitotic activity, and histologic pattern did not. Although 71% of the patients had Stage I tumors at the time of diagnosis, subclinical metastasis was present in 84% of Stage I patients. Triple chemotherapy (vincristine, actinomycin D, and cyclophosphamide (VAC)) employed after unilateral salpingo-oophorectomy in four patients with Stage I tumors resultivors among 12 Stage I patients treated with combined surgery and radiation. The finding of AFP in all tumors in which this was evaluated suggests that serum radioimmunoassay might be useful to monitor response to therapy.

Adolescent

Spontaneous regression of pulmonary leiomyomas during pregnancy.

Multiple pulmonary nodular densities simulating metastastic cancer were discovered in a routine chest roentgenogram of a 30-year-old pregnant woman. Lung biopsy revealed nodules composed of smooth muscle and collagenous tissue containing entrapped glandular elements. The lesions were initially interpreted as multiple pulmonary fibroleiomyomatous hamartomas (MPFLH). During pregnancy and the post-partum period, the pulmonary nodules regressed spontaneously. Critical analysis of the published cases as well as our own case indicates that multiple pulmonary fibroleiomyomatous hamartomas (MPFLH) cannot be distinguished from benign metastasizing leiomyoma (BML) by either clinical, roentgenographic, or pathologic criteria and that all represent pulmonary metastases from a primary uterine neoplasm. The spontaneous regression of the pulmonary nodules in the present case as well as the increased risk for development of progressive pulmonary insufficiency in the pre-menopausal patients indicates an apparent hormonal dependence. Total abdominal hysterectomy and bilateral salpingo-oophorectomy appears to be the treatment of choice.

Adult

Malignancy arising in extragonadal endometriosis: a case report and summary of the world literature.

A case of clear cell carcinoma arising in endometriosis of the retroperitoneum is presented. It occurred 5 years after supracervical hysterectomy and bilateral salpingo-oophorectomy and following 4 years of estrogen therapy. The literature concerning malignancy developing in extragonadal endometriosis has been reviewed and is summarized as follows: 1) 45 cases have been compiled, of which 32 were carcinomas and 13 sarcomas; 2) adenocarcinoma was the most common histologic type, although virtually every tumor of müllerian derivation has been described; 3) the typical patient was nulliparous and perimenopausal; 4) the rectovaginal septum was the most common site, and in general the frequency of malignancy in a given site parallels the frequency of endometriosis in that location; 5) simultaneous tumors of the uterus or ovary were present in seven cases (15%); 6) prognosis appeared affected by site and histologic type; 7) a history of prior pelvic irradiation to effect castration was present in three (9%) of the patients with adenocarcinoma; and 8) four (12%) of the patients with adenocarcinoma were subjected to exogenous estrogens or estrogen-secreting ovarian tumors.

Adenocarcinoma, Papillary

Effects of irradiation on mixed müllerian tumors of the uterus.

A retrospective study of 54 patients with histologically proven malignant mixed müllerian tumors of the uterus was undertaken with main emphasis on the evaluation of the effects of irradiation on pelvic tumor control. The tumors were staged according to the FIGO classification for endometrial carcinoma and 24 were classified as Stage I, 10 as Stage II, 13 as Stage III and seven as Stage IV. Patients with Stage I and II were treated with surgery alone (9 patients, three surviving) or preoperative intracavitary irradiation (13 patients, eight surviving) or preoperative combination of intracavitary and external irradiation (12 patients, six surviving). Five patients with Stage III and IV were treated with surgery alone, two were treated with a combination of irradiation and surgery and 11 with radiation alone. None of these patients survived. In seven patients showing no residual tumor in the uterine specimen after irradiation, no pelvic failures were noted, whereas seven of 17 (41.2%) with residual tumor developed pelvic recurrences. In patients with Stage I treated with surgery alone, three out of six recurred in the pelvis whereas only three of 17 (17%) receiving preoperative irradiation developed pelvic recurrences. However, in Stage II six of eight patients treated with preoperative irradiation failed in the pelvis. Correlation with the doses of irradiation given to the uterus or the pelvic lymph nodes indicate that with doses below 5000 rads a significantly higher number of pelvic recurrences take place, whereas these are uncommon with doses over 6000 rads. The difference in pelvic recurrences between dosage levels is not, however, statistically significant. It is suggested that patients with Stage I and II malignant mixed müllerian tumors of the uterus should be treated with preoperative radiation and total hysterectomy with bilateral salpingo-oophorectomy. Patients with more advanced disease have extremely poor prognosis and should be treated with radiation therapy alone. This tumor has a high propensity to spread through lymphatics and hematogenous metastases are seen in approximately 75% of the patients. Because of this dissemination, significant improvements in survival rate will not be seen until effective cytotoxic agents are available.

Female

Ovarian tumours in childhood: a 27-year review.

Twenty-five children treated for ovarian neoplasms at the Royal Hospital for Sick Children, Yorkhill,Glasgow, between 1947 and 1974 are reported. Eight of the patients had malignant tumours and 17 benign. The patients with benign tumours were treated by either salpingo-oophorectomy or oophorectomy. The malignant cases were treated with either surgery alone or in combination with deep X-ray therapy and/or chemotherapy. Two patients died of malignant teratoma, but the remaining 6 with malignant teratoma, dysgerminoma or endodermal sinus are well. The management of these patients is discussed.

Adolescent

[Aminoacid-p-nitroanilides splitting activities in the mature human placenta (author's transl)].

A long experience in the treatment of endometrial cancer shows that the therapeutic measures vary considerably with regard to the extention of the tumor, the age of the patient and her general condition. This circumstances and particularly the critical study of the therapeutical results give the limits, within a certain kind of operation can reasonably be recommended. The intercurrent deaths are an important factor in the statistical evaluation of therapeutical success. As long as the tumor is limited to the body of the uterus, the corrected 5-year recoveries are about 90%. Considering all the circumstances, it becomes obvious, that in this stage, the simple abdominal hysterectomy with removal of the adnexa is still the operation of choice. Beside the histological degree of differentiation, the depth of the muscular invasion is the most important prognostic factor which might lead to additional measures. Postoperative radiation therapy of the vagina reduces considerably the incidence possibility of vaginal apex recurrence. In stage II radical hysterectomy must be considered, although we are aware of the fact, that a simple hysterectomy and bilateral salpingo-oophorectomy combined with radiation treatment may yield just as good results. In the clinical stage III laparotomy ought to be used more frequently. Also in case of operative intervention additional radiotherapy is mostly useful.

Amino Acids

Effect of premenopausal castration and incremental dosages of conjugated equine estrogens on plasma follicle-stimulating hormone, luteinizing hormone, and estradiol.

Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured serially in 11 premenopausal patients before and after hysterectomy with bilateral salpingo-oophorectomy. One week after operation an incremental dosage regimen of conjugated estrogens (CEE) in tablet form was commenced on a basis of two weeks with therapy (0.3, 0.625, 1.25, and finally 2.5 mg.), with each dose interspersed by two weeks without therapy. FSH, LH and E2 levels were measured at the end of each period with and without therapy. E2 levels fell within 24 hours of operation while FSH and LH levels rose gradually. CEE therapy produced an elevation of E2, but circulating concentrations comparable to the premenopausal values were only maintained during the dosage periods of 0.625 and 1.25 mg. of CEE. In only one instance did CEE succeed in reducing FSH to premenopausal levels, and that was at a dosage of 2.5 mg., in which instance the E2 level was higher than the premenopausal value. LH was never reduced to a premenopausal level. Thus, the data indicate that CEE alone in dosages up to 2.5 mg. per day was unable to reproduce in postmenopausal women the gonadotropin and E2 blood serum levels shown to exist prior to oophorectomy. Usual CEE treatment after menopause, therefore, in itself does not represent physiologic "hormone replacement therapy," if defined as the dosage required to maintain premenopausal circulating concentrations of reproductive hormones.

Castration

Malignant germ cell tumors of the ovary.

This article reviews 281 malignant germ cell tumors of the ovary from the Armed Forces Institute of Pathology and highlights their distinctive clinical and pathologic features. Emphasis is placed on the importance of a combined therapeutic approach utilizing surgery, chemotherapy, and radiation. The rationale for unilateral salpingo-oophorectomy in conjunction with chemotherapy for certain types of neoplasm confined to one ovary (stage 1a) is emphasized, and the role of human chorionic gonadotropin and alpha-fetoprotein as tumor markers in the management of patients with these tumors is discussed.

Adolescent

Primary carcinoma of stomach with uterine metastasis.

Curettings from a 42-year-old woman who suffered from heartburn, weight loss and irregular vaginal bleeding showed apparently metastatic mucoid adenocarcinoma in the endocervix. The primary site of tumour was not evident. At laparotomy a gastric adenocarcinoma was found and total hysterectomy with bilateral salpingo-oophorectomy and partial gastrectomy were performed. Histological examination showed a diffuse mucoid adenocarcinoma of stomach with metastases to lymph nodes, uterine body, cervix and one ovary. The literature about metastasis of extragenital cancer to the uterus is reviewed and possible mechanisms are discussed.

Adenocarcinoma, Mucinous

Giant cell arteritis of the female genital tract.

In a patient who had a hysterectomy and bilateral salpingo-oophorectomy for endometrial adenocarcinoma, a giant cell arteritis was found in many of the myometrial and tubal vessels and in a few of the small arteries of the cervix and ovaries. On subsequent questioning, a history of treatment for polymyalgia rheumatica during the preceding 12 months was elicited. Of the three previously reported patients with giant cell arteritis of the uterus, two were suffering from polymyalgia rheumatica whilst one possibly had disseminated visceral giant cell arteritis.

Female

Proliferating ovarian "epithelial" tumours: a clinico-pathological analysis of 144 cases.

In a 25-year period, 144 patients with proliferating epithelial ovarian tumours were treated at the King George V Memorial Hospital. These tumours were classified according to the World Health Organisation (WHO) Histological Classification of Ovarian Tumours and subsequently divided into 4 grades of proliferation, again on histological criteria. The tumours were staged at laparotomy in accord with the recommendations of the International Federation of Gynecology and Obstetrics (FIGO). Follow-up data, analysed by a life-table method, were correlated against histological type of tumour, histological grade of proliferation, clinical/laparotomy stage, and mode of surgical therapy. Stage 1 proliferating tumours may be treated by surgery alone, including unilateral salpingo-oophorectomy in selected cases. Stage 2 and Stage 3 tumours should be treated similarly to invasive ovarian carcinomas of the same stage, despite their overall favourable prognosis.

Castration

Serum testosterone, FSH/LH and urinary excretion of estrogens and corticoids during treatment with an injectable, longacting estrogen-DHEA preparation.

Ten weeks after total hysterectomy and bilateral salpingo-oophorectomy, nine women were treated with injections of Gynodian, composed of 4 mg estradiol valerate and 200 mg dehydroepiandrosterone enanthate, followed by injections of Primodian, composed of 4 mg estradiol valerate and 90.27 mg testosterone enanthate. Before commencement of treatment estimation of serum FSH, LH and testosterone, and analyses for total estrogen, 17-ketogenic steroids and fractionated 17-ketosteroids in 24-hour urine samples were carried out in all patients. The same serum and urine analyses were made 2 weeks after the first Gynodian injection and the first Primodian injection respectively. Serum testosterone concentrations did not change during treatment with Gynodian, whereas they rose markedly after administration of Primodian. Two weeks after the first injection of Gynodian and also of Primodian, the total estrogen excretion was only slightly increased in comparison with the value measured before start of treatment, and the serum FSH/LH ratio was only slightly depressed. The daily urinary excretion of 17-ketogenic steroids and of fractionated 17-ketosteroids were unchanged during treatment.

17-Ketosteroids

The steroid profile of a virilizing ovarian tumor.

A case report of a 25-year-old female with a sex cord stromal virilizing ovarian tumor is presented. The pathway of ovarian steroid secretion in this tumor is elucidated with the dominant elements being pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, androstenedione, and testosterone. The tumor primarily made testosterone (T) with lesser elevations of androstenedione (A), dehydroepiandrosterone (DHEA), and dihydrotestosterone (DHT). Expert pathologic opinions differed whether this neoplasm was a Sertoli-Leydig tumor or a virilizing granulosa tumor; therefore, it was probably a gynandroblastoma. A unilateral salpingo-oophorectomy was performed and the patient promptly resumed normal ovarian function with ovulation.

17-alpha-Hydroxypregnenolone

Serum 17 alpha-hydroxyprogesterone in patients with gestational trophoblastic neoplasms.

Serum 17alpha-hydroxprogesterone (17-OHP), progesterone (P), and human chorionic gonadotropin (hCG) levels were measured by specific radioimmunoassay in 19 patients undergoing laparoscopy or laparotomy with either unevacuated molar pregnancy or nonmetastatic gestational trophoblastic neoplasms (GTN), in 10 normal pregnant patients at equivalent gestational age (7-21 weeks), and in 4 patients with metastaic GTN following hysterectomy and bilateral salpingo-oophorectomy. All patients with theca lutein cysts had significantly elevated serum 17-OHP levels compared to those in 1) normal pregnancy, 2) patients with GTN and normal-size ovaries, 3) patients with metastatic GTN in the absence of ovaries (P less than 0.02). Levels of serum 17-OHP but not P correlated with the degree of ovarian enlargement (r = 0.87, P less than 0.05). Serum P concentrations in patients with theca lutein cysts, although higher than the levels in cases of GTN with normal-size ovaries, were not significantly different from the levels in normal pregnancy (P greater than 0.05). Serum hCG levels in patients with theca lutein cysts, though higher than the normal pregnancy levels (P less than 0.05), were not significantly different from those in cases of GTN with normal-size ovaries and GTN without ovaries (P greater than 0.05). Under the conditions studied, no correlation was observed between serum hCG and P levels in our cases of GTN. Increased serum 17-OHP level in a patient with GTN suggests the presence of theca lutein cysts.

Castration