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Biomedical subjects

D H Oram

Publications and source records attributed to D H Oram.

29 records · Page 2Linked to original sources

Differential diagnosis of ovarian cancer with tumour markers CA 125, CA 15-3 and TAG 72.3.

OBJECTIVE: To determine the accuracy of tumour associated antigens CA 125, CA 15-3 and TAG 72.3 in the differential diagnosis of benign and malignant pelvic masses and to compare the results with a previously defined risk of malignancy index (RMI). DESIGN: Retrospective analysis of samples collected during a prospective observational study. SETTING: Department of Obstetrics and Gynaecology, the Royal London Hospital and Duke University Medical Center. SUBJECTS: One hundred and forty-three consecutive patients undergoing surgery for an adnexal mass. METHOD: Tumour marker levels were determined by radio-immunoassay in stored serum samples obtained from 143 study subjects. RESULTS: The highest diagnostic accuracy of the tumour marker panel was achieved by defining a positive result as elevation of any two of CA 125 (> 30 u/ml), CA 15-3 (> 30 u/ml) and TAG 72.3 (> 10 u/ml), (sensitivity 66.7%, specificity 93.1%). Similar diagnostic accuracy could be achieved by CA 125 alone using an upper limit of 50 u/ml (sensitivity 66.7%, specificity 94.1%). Inclusion of CA 15-3 or TAG 72.3 in stepwise logistic regression analysis did not improve the discriminative performance of the RMI. CONCLUSION: The risk of malignancy index incorporating CA 125, menopausal status and ultrasound is superior to the panel of three tumour markers for pre-operative differential diagnosis of the pelvic mass.

Antigens, Neoplasm↗

Strategies for improving the specificity of screening for ovarian cancer with tumor-associated antigens CA 125, CA 15-3, and TAG 72.3.

OBJECTIVE: To assess different strategies for improving the specificity of screening for ovarian cancer with tumor-associated antigens, including concomitant measurement of multiple tumor markers and serial measurement of CA 125. METHODS: A combination of CA 125, CA 15-3, and TAG 72.3 was evaluated in serum samples from 217 of 1010 apparently healthy postmenopausal women who had participated in a study of screening for ovarian cancer and who had a serum CA 125 level of 20 U/mL or greater. In addition, serial serum CA 125 levels were determined in 30 women with an initially elevated CA 125 level (30 U/mL or more) and 30 women with a CA 125 level less than 30 U/mL. RESULTS: The specificity of CA 125 at upper limits of 30 and 50 U/mL was increased from 97.0 and 99.5%, respectively, to 98.9 and 99.9% when a positive test was defined as an elevated serum CA 125 level in combination with either a CA 15-3 greater than 30 U/mL or a TAG 72.3 greater than 10 U/mL. Definition of a positive result as a serum CA 125 level greater than 50 U/mL at the initial test and greater than 30 U/mL at 3-month follow-up achieved a specificity of 99.6%. CONCLUSION: Levels of specificity suitable for screening asymptomatic postmenopausal women can be achieved using tumor-associated antigens measured serially or in combination. Further studies are required to determine the sensitivity of these strategies for preclinical ovarian cancer.

Antigens, Neoplasm↗

A new treatment for endometrial cancer with gonadotrophin releasing-hormone analogue.

OBJECTIVE: To test the antitumour effect of gonadotrophin releasing-hormone (GnRH) analogues in women with recurrent endometrial cancer. DESIGN: An open phase II observational trial of GnRH analogues. Serial measurements of gonadotrophins, sex hormones and tumour dimensions were made together with repeat biopsy when possible to assess the response to treatment. SETTING: The outpatient clinics of the Department of Medical Oncology at The Royal London, Royal Marsden and St Bartholomew's hospitals. SUBJECTS: 17 patients with endometrial cancer which had recurred after surgery, radiotherapy and progesterone treatment and was symptomatic, progressive and assessable for response. INTERVENTION: Monthly subcutaneous injection of GnRH analogue. MAIN OUTCOME MEASURES: Reduction in serum gonadotrophins and reduction in tumour dimensions. RESULTS: Six out of 17 patients (35%, 95% CI 12.6-58%) achieved a complete or partial remission which continues for a median of 20 months with no adverse effects. CONCLUSION: GnRH analogues have a significant antitumour effect in recurrent endometrial cancer which warrants further examination in comparison with progestogens.

Adenocarcinoma↗

Serum levels of CA 125 during the first trimester of normal outcome, ectopic and anembryonic pregnancies.

Single serum samples were obtained during the first trimester of pregnancies with a retrospectively normal outcome (n = 150), ectopic pregnancies (n = 38) and anembryonic pregnancies (n = 78). Serial samples during the first trimester were also obtained from 43 women achieving pregnancy following successful treatment for infertility and with a retrospectively defined normal outcome. Significant variation in serum CA 125 levels in relation to gestational age was observed in pregnancies with a normal outcome (P less than 0.0001). Peak serum CA 125 levels were observed at 6-7 weeks, the mean level at this gestation being 40.1 U/ml (range 31.7-50.7 U/ml) in the normal conception/normal outcome group and 36.5 U/ml (range 25.6-52.0 U/ml) in the assisted conception/normal outcome group. A rise and fall in serum CA 125 levels during the first trimester was observed in 42 of 43 assisted conceptions monitored serially, with peak levels ranging from 7 to 1398 U/ml (median 48.8 U/ml) occurring at 28-61 days (median 45 days) gestation. Mean serum CA 125 levels were higher in the anembryonic pregnancy group at 4-5 and 6-7 weeks gestation than in both normal pregnancy outcome groups (P less than 0.01).

Antigens, Tumor-Associated, Carbohydrate↗

Early diagnosis of ovarian cancer.

In spite of recent therapeutic advances, earlier diagnosis seems to be the best hope of significantly improving the prognosis in ovarian cancer. This paper discusses the various screening modalities available, and presents the interim results of one large screening project.

Biomarkers, Tumor↗

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

Investigation of serum and tissue homogenates obtained from first, second and third trimester pregnancies, and from non-pregnant 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 non-pregnant 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 less than 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 less than 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 non-pregnant endometrium (median 388 U/100 mg, range 100.9-3341 U/100 mg) (P less than 0.01) and term decidua (median 116 U/100 mg, range 32.7-449.9 U/100 mg) (P less than 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.

Antigens, Tumor-Associated, Carbohydrate↗

Stage III epithelial ovarian cancer: the role of maximal surgical reduction.

One hundred forty-two cases of ovarian cancer of epithelial origin treated at Georgetown University Hospital between 1974 and 1980 were analyzed. Seventy-five patients (52.8%) were found to have Stage III disease at the time of the initial laparotomy, and the purpose of this study was to assess the outcome of the management in this group of patients. In spite of an aggressive approach, complete tumor excision could only be affected in 13 of the 75 Stage III cases (17.3%). Residual disease of less than 2 cm was achieved in a further 8 cases (10.7%). The ability to perform complete tumor clearance bore no relationship to the grade of the tumor. The survival rate in the complete clearance group was 100% with a mean survival time of 45 months (range 10-90 months) and 10 of these patients have been shown to be free of disease by second-look laparotomy. The outcome in terms of survival and disease-free status in these two groups of patients was unaffected by various chemotherapy regimens and the only factor of importance appeared to be the success of the initial surgery in clearing the disease.

Female↗

Endocrine changes and symptomatology after oophorectomy in premenopausal women.

The symptomatic and endocrine changes following hysterectomy and bilateral oophorectomy have been studied in 100 patients, 1 to 31 years after surgery. The most frequent symptoms at the time of interview were depression (62 patients), insomnia (48 patients), loss of libido (46 patients) and dyspareunia (38 patients). Vasomotor symptoms were recorded in 28 patients. Although 94 patients claimed that hot flushes were the first symptomatic changes noticed, 60 had complete relief from these symptoms within 6 months of surgery; 34 patients had no symptoms and only 4 patients were taking oestrogen therapy at the time of interview. Plasma oestradiol and testosterone levels were 78 per cent and 27 per cent respectively below the mean values of day 1 to 10 of the menstrual cycle, similar to those found at comparable years after a normal menopause. The plasma FSH level was about 14 times and the plasma LH level about twice the respective preoperative value. Unlike after the normal menopause, these gonadotrophin levels did not show any decline with increasing age. There was no correlation between plasma hormone levels and the presence of vasomotor symptoms or depression.

Castration↗

Effect of hormone replacement therapy on glucose tolerance in postmenopausal women.

Oral glucose tolerance tests were performed on 50 symptomatic postmenopausal women before and after three months of hormone replacement therapy. All patients were randomly allocated to one of five groups treated with various synthetic or so-called naturally occurring oestrogens. Therapy produced a significant deterioration of carbohydrate tolerance with sequential preparations containing 100 microgram of ethinyl oestradiol or graduated doses of mestranol up to 50 microgram. The conjugated equine oestrogen (1.25 mg daily) and oestrogen valerate (2 mg daily) treated groups did not show abnormal glucose tolerance. The decreased glucose tolerance may be due as much to dosage levels as to any metabolic characteristics of the various oestrogens prescribed.

Adult↗

Hormonal profiles after the menopause.

The endocrinological changes of the climacteric have been defined by studying the concentrations of follicle-stimulating hormone (FSH), luteinising hormone (LH), androstenedione, testosterone, oestrone, and oestradiol in 60 normal postmenopausal women of different menopausal ages. The women were studied in six groups, according to the number of years since their menopause. One year after the menopause androstenedione, oestrone, and oestradiol concentrations were reduced to about 20% of the values recorded during the early proliferative phase of the menstrual cycle. At the same time the mean concentration of FSH had risen by a factor of 13-4 and that of LH by a factor of 3-0. Concentrations of both gonadotrophins reached a peak of 18-4 and 3-4 times the proliferative phase value respectively after two to three years, and then gradually declined in the next three decades to values that were 40-50% of these maximal levels. Testosterone concentrations remained mostly in the normal range for premenopausal women but were depressed to 60% of these levels two to five years after the menopause, and the mean androstenedione levels showed a significant increase in the same group of women. The concentrations of both oestrone and oestradiol remained consistently low for 10 years after the menopause, but oestradiol concentrations inexplicably increased in the last two decades, with levels at the lower end of normal range for reproductive women in six patients.

Age Factors↗