I. Stabile

Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.

OBJECTIVE--To assess the performance of the sequential combination of serum CA 125 measurement and ultrasonography in screening for ovarian cancer. DESIGN--The serum CA 125 concentration of each subject was determined and those with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. If ultrasonography gave abnormal results surgical investigation was arranged. Volunteers were followed up by annual postal questionnaire. SETTING--General practice, occupational health departments, ovarian cancer screening clinic. SUBJECTS--22,000 women volunteers who were postmenopausal and aged over 45 years. MAIN OUTCOME MEASURES--Apparent sensitivity, specificity, positive predictive value, years of cancer detected. RESULTS--41 women had a positive screening result and were investigated surgically. 11 had ovarian cancer (true positive result) and 30 had other disorders or no abnormality (false positive result). Of the 21,959 volunteers with a negative screening result, eight subsequently presented clinically with ovarian cancer (false negative result) and 21,951 had not developed ovarian cancer during follow up (apparent true negative result). The screening protocol achieved a specificity of 99.9%, a positive predictive value of 26.8%, and an apparent sensitivity of 78.6% and 57.9% at one year and two year follow up respectively. The estimated number of years of cancer detected by the prevalence screen was 1.4 years. CONCLUSIONS--This screening protocol is highly specific for ovarian cancer and can detect a substantial proportion of cases at a preclinical stage. Further investigation is required to determine the effect of the screening protocol on the ratio of early to late stage disease detected and on mortality from ovarian cancer.

MULTIMODAL APPROACH TO SCREENING FOR OVARIAN CANCER

1010 postmenopausal women were recruited for an ovarian cancer screening programme incorporating serum CA-125 measurement and vaginal examination as initial tests and real-time ultrasonography as a secondary procedure in selected cases. The normal range for serum CA-125 in postmenopausal women was established. The specificity for ovarian cancer of serum CA-125 measurement and vaginal examination were 97.0% and 97.3%, respectively. The combinations of serum CA-125 measurement with ultrasound and vaginal examination with ultrasound achieved specificities of 99.8% and 99.0%, respectively. 100% specificity was achieved by serum CA-125 measurement with vaginal examination and by the combination of all three tests. The findings indicate that no individual screening test has acceptable specificity for ovarian cancer in postmenopausal women. However, the combination of CA-125 measurement with ultrasound did achieve acceptable specificity and offers the most hope of a specific and sensitive method for early detection.

Clinical obstetrics and gynaecology

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ULTRASONIC ASSESSMENT OF COMPLICATIONS DURING FIRST TRIMESTER OF PREGNANCY

624 women were referred to an emergency gynaecological ultrasound clinic with a provisional diagnosis of threatened miscarriage based on a history of amenorrhoea and vaginal bleeding with or without abdominal pain. High-resolution abdominal sector scanning was used to assess fetal size and viability, as well as uterine and placental size, to identify features which might indicate imminent fetal death. In 158 women there was no evidence of pregnancy; 60 women had an ectopic pregnancy. In the remaining 406 women ultrasound examination correctly identified the underlying cause of vaginal bleeding at first presentation in all but the 6 who subsequently aborted. 3.9% of the patients had a second empty sac and 5.4% had an intrauterine haematoma; none of these women subsequently aborted. 2 patients had early-onset oligohydramnios and spontaneous abortion occurred in both.

The distribution of CA 125 in the reproductive tract of pregnant and non-pregnant women

Summary. Investigation of serum and tissue homogenates obtained from first, second and third trimester pregnancies, and from nonpregnant women, has provided further insight into the possible origin of the CA 125 antigen. Serum CA 125 levels were higher in the first trimester (median 53.6 U/ml, range 15.6.268.3 U/ml) than in nonpregnant women (median 19.3 U/ml, range 7.2.27.0 U/ml) and later in pregnancy (second trimester: median 18.5 U/ml, range 12.0.25.1 U/ml, third trimester: median 19.2 U/ml, range 16.8.43.8 U/ml) (P<0.05) but were two orders of magnitude less than in second trimester amniotic fluid (median 4825 U/ml, range 3200.9300 U/ml). Fetal serum CA 125 activity was consistently <20 U/ml. The highest tissue levels of CA 125 were detected in first trimester decidual homogenate (median 4547 U/ 100 mg, range 340.4–20 851 U/100 mg) and were greater than in nonpregnant endometrium (median 388 U/100 mg, range 100.9–3341 U/100 mg) (P<0.01) and term decidua (median 116 U/100 mg, range 32.7–449.9 U/100 mg) (P<0.01). These observations suggest that CA 125 is synthesized by normal endometrium and decidua and that increased CA 125 activity during pregnancy is of decidual origin.

The magnitude and distribution of infectious intestinal disease in Malta: a population-based study

Routine sources of information on infectious intestinal disease (IID) capture a fraction of the actual disease burden. Population studies are required to measure the burden of illness. A retrospective age-stratified cross-sectional telephone study was carried out in Malta in order to estimate the magnitude and distribution of IID at population level. A random sample of 3504 persons was interviewed by a structured questionnaire between April 2004 and December 2005. The response rate was 99.7%. From the study, the observed standardized monthly prevalence was 3.18% (95% CI 0.7-5.74) with 0.421 (95% CI 0.092-0.771) episodes of IID per person per year. The monthly prevalence was higher in the <5 years age group and in females aged 31-44 years. The mean duration of illness was 6.8 days and a median duration of 3 days. A bimodal seasonal distribution was observed with peaks in June-July and October-November.

Complement factors in fetal and maternal blood and amniotic fluid during the second trimester of normal pregnancy

Summary. Complement factors (C3, C4, C5; Factors B, H and I) were measured in maternal and fetal serum and amniotic fluid obtained from 55 women with singleton pregnancy undergoing diagnostic fetoscopy at 15 to 28 weeks gestation. Maternal serum levels were consistently 10 times higher than fetal levels which in turn were 10 times higher than levels in amniotic fluid. Spearman rank correlation analysis at weeks 20 to 22 (n= 20) revealed a statistically significant correlation between maternal and fetal levels of C3 and Factors B and I, and between maternal and amniotic fluid levels of Factors B and I. A significant increase in fetal levels of C3, C4 and Factor H, and in amniotic fluid levels of C3 and Factor B was seen in relation to advancing gestational age. These differences were not seen in maternal scrum during the short interval of pregnancy studied. These data confirm earlier assumptions of fetal synthesis of complement factors, and provide normal reference ranges of complement factors in fetal blood and amniotic fluid.

Ultrasound and circulating placental protein measurements in complications of early pregnancy

Maternal serum levels of human chorionic gonadotrophin (hCG), Schwangerschaftsprotein 1 (SP1) and pregnancy‐associated plasma protein A (PAPP‐A) were measured in an unselected group of 624 women presenting with amenorrhoea and vaginal bleeding with or without abdominal pain to an emergency gynaecological ultrasound clinic. Abdominal sector scanning was used to assess uterine contents. Pregnancy was confirmed by ultrasound in 406 pregnancies. Histological confirmation was obtained in each case of pregnancy failure. A live fetus was demonstrated in 259 women of whom six subsequently miscarried; one of these had markedly depressed serum hCG and PAPP‐A, but normal SP1 levels, and two had oligohydramnios. Of the 147 women without ultrasound evidence of fetal heart action 67 had a correct ultrasound diagnosis of anembryonic pregnancy. The predictive value of a depressed serum hCG level was 70% in this group, and 31% in samples taken at ≤7 weeks. The predictive value of a normal hCG level was 96%. In 34 women missed miscarriage was diagnosed readily by ultrasound; all but five had depressed hCG and PAPP‐A levels. A clinical diagnosis of a complete or incomplete miscarriage was made in 45 women and easily confirmed by ultrasound. All of them had depressed hCG, SP1 and PAPP‐A levels. These results indicate that the diagnostic value of ultrasound in threatened miscarriage is often better than that of biochemical tests.

Can ultrasound reliably diagnose ectopic pregnancy

Summary. A total of 252 women with amenorrhoea and with abdominal pain or vaginal bleeding, or both, had an emergency high‐resolution ultrasound sector scan. In 100 women the symptoms were unrelated to any identifiable abnormal ultrasound rinding, none of them was pregnant and their symptoms settled spontaneously; 33 other women had follicular or luteal cysts and 30 had pelvic inflammatory disease, Histological examination confirmed an ectopic pregnancy in 60 women (24%); in seven a live fetus was observed outside the uterus allowing a confident diagnosis of ectopic pregnancy; in 27 the thickness of the endometrium was >10mm (sensitivity 50%, specificity 84%, positive predictive value 28%, negative predictive value 87%); in 15 the uterine area measurement was <20 cm2 (sensitivity 72%, specificity 41 %, positive predictive value 20%, negative predictive value 79%); and 43 had an adnexal mass volume >10ml separate from the ovary (sensitivity 85%, specificity 37%, positive predictive value 23%, negative predictive value 90%). Only three had negative ultrasound findings. The negative predictive value of an ultrasound examination could be increased to 96% by using a combination of these ultrasound features. The addition of hCG (>25 i.u./l) improved the specificity to 98% and the negative predictive value to 100%. These criteria may improve the ultrasound diagnosis of ectopic pregnancy.

Circulating levels of placental protein 14 in ectopic pregnancy

Objective To determine circulating levels of placental protein 14 (PP14) in complications of early pregnancy.