Benign ovarian cysts and ovarian cancer: a cohort study with implications for screening.

BACKGROUND: Whether some benign ovarian cysts can develop into cancerous cysts is not known. If a large proportion of ovarian cancers arose in this way, it might be possible to remove the benign cysts in a screening programme before they became malignant. We used follow-up data from a cohort of 5479 self-referred women without symptoms, who participated in a ultrasonographic-screening trial for early ovarian cancer between June, 1981, and August, 1987. We assessed whether the removal of persistent ovarian cysts from these women was associated with a reduction in the expected number of deaths from ovarian cancer in the cohort as a whole. METHODS: The expected number of deaths from all causes, all cancers, and ovarian, breast, and colorectal cancers were calculated for the study cohort by the standard life-table method. The actual number of deaths and each cause were obtained and the proportional mortality ratio was calculated for each cause of death. FINDINGS: 5135 (95%) of the participants in the original trial were traced. During the screening, five of these women were found to have stage I epithelial ovarian cancer and 88 had benign epithelial ovarian tumours. The number of reported deaths from all causes (387 [50% of expected]), all cancers (221 [71%]), and ovarian cancer (22 [90%]) was lower than expected because of the "healthy-volunteer effect". Proportional mortality ratios were 100% (by definition) for all cancers, 141% for breast cancer, 128% for ovarian cancer (95% CI 87.7-187.6, p=0.19), 84% for colorectal cancer, and 48% for lung cancer. INTERPRETATION: The removal of persistent ovarian cysts was not associated with a decrease in the proportion of expected deaths from ovarian cancer relative to other cancers during follow-up. For population-based screening of healthy women without a family history of ovarian cancer, a screening test is required that is specific and sensitive to early malignant disease, and inexpensive.

Gender differences in the treatment of patients with acute myocardial ischemia and infarction in England.

We conducted a retrospective cohort study based on a case note review to determine whether there are differences in the treatment pathways followed for men and women admitted with acute myocardial ischemia and infarction after adjusting for differences in case mix. Women were as likely as men to receive thrombolysis, but were less likely subsequently to undergo exercise testing (adjusted odds ratio, 0.58; 95% CI, 0.40-0.84) or angiography (adjusted odds ratio, 0.62; 95% CI, 0.39-0.99). Coronary anatomy was the strongest predictor of revascularization regardless of sex. Women with diagnosed cardiac pain are less likely than men to be placed on the investigative pathways that lead to revascularization. Those women who are investigated are as likely as men to undergo revascularization. These findings are independent of the effects of age, angina grade, comorbidity, or cardiac risk factors. Clinicians' and patients' beliefs and preferences about treatment require investigation.

Effects of indomethacin on follicular structure, vascularity, and function over the periovulatory period in women.

OBJECTIVE: To assess the effect of indomethacin (taken at defined times) on follicular rupture, indexes of intrafollicular blood flow, and steroidogenesis. PARTICIPANTS: Six healthy volunteers awaiting treatment for infertility by IVF-ET during subsequent natural cycles. INTERVENTIONS: All women were examined (at least every 8 hours) by transvaginal ultrasonography with color Doppler imaging and had samples of blood taken for hormone analysis. A self-test for urinary LH was performed before each scan. Indomethacin was first taken (50 mg three times per day) according to the maximum follicular diameter (first four women) or when the LH dipstick gave a positive result; the drug was taken for > or = 3 days. RESULTS: Follicular rupture was delayed in five of six cases (by 2 to 12 days). There was a reduction in intrafollicular peak systolic velocity before and after the positive urinary LH test compared with historical controls. Three follicles (50% of women) with the highest peak systolic velocity had an hemorrhagic appearance and persisted longer. There was no significant effect on menstrual cycle length or the levels of circulating FSH, E2, LH, or P. CONCLUSION: Indomethacin administered at the time of a positive self-test for urinary LH can delay follicular rupture with an associated reduction in intrafollicular blood flow but with no apparent effects on hormonal or menstrual status.

Use of transvaginal ultrasonography with color Doppler imaging to determine an appropriate treatment regimen for uterine fibroids with a GnRH agonist before surgery: a preliminary study.

The aim was to obtain data that could be used to determine the most appropriate treatment regimen for uterine fibroids with a gonadotropin releasing hormone analog (goserelin) before surgery. Fifteen premenopausal women (aged 27-53 years; mean 40 years) were referred from a gynecological outpatients' clinic. They all had uterine fibroids and were awaiting hysterectomy or myomectomy. All women were scheduled to receive an implant of goserelin (3.6 mg), undergo transvaginal ultrasonography and have a sample of peripheral blood taken at monthly intervals for 6 months. The main outcome measures were fibroid size and indices of blood flow (the pulsatility index and peak systolic velocity) in both uterine arteries and the principal artery supplying the largest fibroid. The concentrations of follicle stimulating hormone, estradiol, luteinizing hormone and progesterone were measured in peripheral plasma. Twelve women (80%) completed 2 months of treatment, but only three (20%) completed the study (due to side-effects of the drug). After 2 months of treatment, the plasma hormone levels were all in the low-normal range; the mean fibroid volume had decreased by 53% and the mean peak systolic blood velocity in the fibroid artery had decreased by 45%. Mean changes in all indices were < 10% over the next 4 months of treatment. Six women (40%) had fibroids with an initial volume of > 100 ml; these tumors showed the largest reduction in size. We conclude that women with a uterine fibroid of > 100 ml are the best candidates for treatment with goserelin (3.6 mg/month) before surgery. Two months' treatment effects a marked reduction in fibroid volume and blood flow and is associated with good compliance.

The potential role of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer.

We have assessed the potential role of a test based upon the measurement of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer. A sample of peripheral blood was taken from 1502 self-referred, asymptomatic women whose pedigree showed that at least one close relative had developed the disease. All women in the study underwent one screening by transvaginal ultrasonography (consisting of one or more scans) to detect any persistent lesion and a change in ovarian volume. Women with a positive result were referred for surgery. The concentration of serum CA 125 was measured in all samples at the end of the study. Seven ovarian cancers (4 invasive and 3 of borderline malignancy; 5 FIGO stage Ia, 1 stage IIa, 1 stage III) and 55 benign lesions were detected. We calculated the effect that a prescreening test (based on different threshold values for serum CA 125) would have had on the number of women entering the ultrasound-based screening program, and on the detection rate and false-positive rate of the overall procedure. There was a direct relationship between the number of women referred for ultrasound screening and the detection rate. The use of a threshold value for serum CA 125 > or = 20 U/ml would have meant that 380 women (25.3%) were referred for ultrasonography and 5 out of 7 cancers (71%) would have been detected with a false-positive rate of 1.1%. The odds of a woman with a positive screening result having cancer at surgery would have been about 1:3 (which would improve to about 1:1 if observational indices of color Doppler imaging and a morphological score had been used throughout). We concluded that a prescreening immunochemical test based on the measurement of serum CA 125 (with a threshold value of > or = 20 U/ml) would increase the prior odds for familial ovarian cancer by 2.8, but would lower the overall detection rate by 29% at the prevalence screening.

Transvaginal color blood flow imaging of the periovulatory follicle.

OBJECTIVE: To assess intrafollicular blood flow in relation to ovarian morphology and function during the periovulatory period. DESIGN: A prospective, longitudinal study of random, natural ovarian cycles. SETTING: The Ovarian Screening Clinic and Endocrine Laboratory of the Department of Obstetrics and Gynaecology, King's College Hospital, London, United Kingdom. PATIENTS: Women with apparently normal ovarian function awaiting treatment for infertility by IVF-ET during subsequent natural cycles. INTERVENTIONS: All women were examined by transvaginal ultrasonography with color flow imaging and had a sample of peripheral venous blood taken at each scan for hormone analysis. MAIN OUTCOME MEASURES: The minimum pulsatility index (PI) and maximum peak systolic velocity from vessels within the dominant follicle; the maximum follicular diameters (and hence volume); serum FSH, E2, LH, and P. RESULTS: The dominant follicle ruptured in 10 of 11 women. The median interval between the two scans that delineated the time of follicular rupture was 9.5 hours (range, 0.0 to 24.5 hours). These cycles appeared to be morphologically and endocrinologically normal. There was an apparent increase in intrafollicular blood flow over the periovulatory period with an insignificant trend toward lower values for the mean PI and a significant increase in the peak systolic velocity. These changes appeared to follow the rise in circulating LH. CONCLUSION: Indexes of blood flow at a given site within the leading follicle can be monitored by transvaginal ultrasonography with color Doppler imaging over the periovulatory period. The increase in the peak systolic velocity and the relatively constant PI suggest a marked increase in blood flow at this time during the ovarian cycle.

Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging.

OBJECTIVE: To assess the value of transvaginal ultrasonography with colour blood flow imaging in detecting early ovarian cancer in women with a family history of the disease. DESIGN: Study of self referred symptomless women with a close relative who had developed the disease. Each woman was screened to detect persistent lesions and defined changes in ovarian volume. Morphological score and pulsatility index were recorded. SETTING: Ovarian screening clinic. SUBJECTS: 1601 self referred women. INTERVENTIONS: Women with a positive screening result were recommended to have further investigations. MAIN OUTCOME MEASURES: Findings at surgery and histology of abnormal ovaries. Morphological score > or = 5 and pulsatility index < 1.0 at last scan. RESULTS: Women were aged 17 to 79 (mean 47) years; 959 (60%) were premenopausal, 469 (29%) were naturally postmenopausal, and 173 (11%) had had a hysterectomy. 157 women had a pedigree suggestive of the site specific ovarian cancer syndrome and 288 of multiple site cancers. 61 women had a positive screening result (3.8%, 95% confidence interval 2.9 to 4.9%), six of whom had primary ovarian cancer detected at surgery (five stage Ia, one stage III). Use of a high morphological score or a low pulsatility index increased the odds of finding ovarian cancer from 1:9 to about 2:5 (1:1 in the highest risk groups). Five interval cancers were reported (three ovarian and two peritoneal). Eight of the 11 cancers developed in women with pedigrees suggestive of inherited cancer. CONCLUSIONS: Transvaginal ultrasonography with colour flow imaging can effectively detect early ovarian cancer in women with a family history of the disease. The screening interval should be less than two years.