Search

Detection of ovarian cancer at an early stage should reduce the mortality associated with this disease. Through the Stockholm Population Registry, 5550 apparently healthy women were enrolled in a study designed in part to define the use of the CA 125 radioimmunoassay (RIA) as an initial test for early detection of ovarian cancer. Women whose CA 125 levels were elevated and an equal number of age-matched controls with normal levels were followed by means of pelvic examinations, transabdominal sonography, and serial CA 125 determinations. Of the 175 women with high CA 125 levels, six were found to have ovarian cancer: two each in stages IA, IIB, and IIIC. Of those with normal-range CA 125 levels, three had ovarian cancer as identified through the Swedish Cancer Registry; all three were under 50 years of age. Ovarian cancer was diagnosed on laparotomy in six of the women age 50 or over. Using thresholds of 30 and 35 U/mL, the rates of specificity for the CA 125 RIA were 97 and 98.5%, respectively, for women age 50 or older, and 91 and 94.5%, respectively, for those younger than 50 years of age. Thus, the specificity of the CA 125 RIA is adequate in postmenopausal women to undertake a larger study to determine whether screening using CA 125 influences survival of patients with ovarian cancer.

Changes in serum alkaline DNase activities might predict the therapeutic response in various malignant diseases. A decrease in serum alkaline DNase activity within days from the onset of therapy has been related to tumour necrosis and may be a possible sign of clinical response to effective treatment. To study if changes in serum alkaline DNase activity could be induced by non-tumour related tissue destruction, sera were collected on several occasions perioperatively in 18 patients undergoing surgery for benign gynaecological disease. Thirty apparently healthy women served as the control group. A significant decrease (P less than 0.001) in serum alkaline DNase activity was observed after an overnight fast in both groups of women. In contrast to the control women, the operated patients showed a significant decrease (P less than 0.001) in serum alkaline DNase activity throughout the operative period and 1 week postoperatively. We conclude that serum alkaline DNase activity is influenced by dietary factors as well as surgical trauma. These factors may limit the clinical usefulness of SADA in patients with cancer.

Serum levels of squamous cell carcinoma antigen SCC, carcinoembryonic antigen CA 125, and tissue polypeptide antigen were determined in 142 patients with primary cervical carcinoma, 60 patients with precancerous lesions and in 129 healthy women. With regard to elevated tumour marker levels, specificity ranged from 94.6% to 97.7%. Sensitivity was highest (44.4%) for SCC. A stage relation was found for all tumour markers except for carcinoembryonic antigen. In stage Ib, SCC levels increased according to tumour volume. SCC, CA 125 or both markers were elevated in 7 of 8 patients with pelvic lymph node metastases compared with only 17 of 58 patients with negative nodes (P = 0.005). In a multivariate analysis, pretreatment serum levels of SCC and CA 125 were found to be significantly related to patient survival, in addition to stage. In cervical SCC, the risk of a fatal outcome increased 16 times with SCC levels > or = 4.5 ng/ml, compared with SCC levels < or = 1.3 ng/ml. We conclude that pretreatment serum levels of SCC may be of value as an adjunct to clinical staging. In addition, serum determinations of SCC and CA 125 seem to be useful in predicting the risk of pelvic lymph node metastases and as prognostic risk factors for disease outcome.

In order to evaluate the potentially additive information of some acute phase reactants to that provided by a general tumour marker, pretreatment concentrations of C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and tissue polypeptide antigen were determined in serum from healthy women, patients with dysplasia/or carcinoma in situ and patients with primary cervical carcinoma. Specificity varied from 95-100% and sensitivity from 16-29%. A correlation with clinical stage was found for all analytes except for alpha 1-antitrypsin. The latter was the most frequently elevated analyte in early Stages (11/43 in Stage Ib/IIa) and uniquely elevated in 7 cancer patients. Although tissue polypeptide antigen predominantly signaled in advanced stages, 3 women in early stages had elevated tissue polypeptide antigen levels. One of these women died and she was also the only woman with raised alpha 1-antitrypsin who died. It is discussed whether elevated tissue polypeptide levels might represent an unfavourable sign for the individual and if alpha 1-antitrypsin is a favourable sign in early stages of cervical carcinoma. C-reactive protein results were obscured in early stages of disease by the presence of intercurrent illness and the results were regarded as inconclusive. Haptoglobin and alpha 1-acid glycoprotein concentrations provided no additional information to serum alpha 1-antitrypsin levels. However, haptoglobin was elevated in 64% (36/56) of the women with dysplasia/carcinoma in situ of the cervix uteri.

The objective was to evaluate if variations in serum alkaline DNase activity (SADA) can predict the effects of therapy in women with early stages of primary cervical carcinoma. 29 out of 33 patients had no evidence of disease after therapy. Only 5 out of the 29 women showed increased SADA levels after therapy compared with the pretreatment SADA value. Of the 4 women with evidence of disease after therapy, 3 had unchanged or decreased SADA levels. We conclude that serum alkaline DNase activity seems to have little to offer in predicting the effects of treatment in stage I and stage II cervical carcinoma.

The metabolism and production rates of 3 alpha-hydroxy-5 alpha-pregnan-20-one sulfate and the 3-sulfate and 3,20-disulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol in pregnant women were studied. The steroid sulfates were labeled with deuterium in the 3 beta,11,11- or 3 beta,11,11,20 beta-positions and were injected intravenously. The deuterium content of steroids in the monosulfate and disulfate fraction of plasma collected at different times after the injection was determined by capillary column gas chromatography/mass spectrometry. The injected steroid sulfates underwent oxidoreduction at C-20 and 16 alpha-hydroxylation. In addition, the 3-sulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol became hydroxylated at C-21. The pregnanediol and pregnanetriol monosulfates were also converted to disulfates. No evidence was obtained for a metabolic sequence involving hydrolysis, oxidoreduction, and resulfation at the C-3 position. Production rates and rates of metabolic transformations were determined using different one- and two-pool models. The production rate of the pregnanolone/pregnanediol monosulfate couple was 0.08 to 0.5 mmol/24 h, the variability probably depending both on individual factors and stage of pregnancy. The half-life time for oxidation and reduction at C-20 was 0.1 to 0.4 hours, reduction being the faster process. The half-life time for the turnover of the steroid skeleton was 1.3 to 3.3 hours. The injected steroid monosulfates were 16 alpha-hydroxylated at a rate of 1 to 8 mumol/24 h. A significant fraction of these 16 alpha-hydroxylated steroid sulfates, 0.5 to 25 mumol/24 h, was formed from other, probably unconjugated, precursors. The 16 alpha-hydroxylated steroid monosulfates underwent rapid oxidoreduction at C-20. The 3-sulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol was hydroxylated at C-21. The production rate of 5 alpha-pregnane-3 alpha,20 alpha,21-triol 3-sulfate was 8 to 36 mumol/24 h in four women and 180 mumol/24 h in one woman, and this steroid was not formed from other precursors to a significant extent. 5 alpha-Pregnane-3 alpha,20 alpha-diol disulfate was a metabolic end product accounting for a major part of the elimination of the steroids injected. Its half-life time was 1.4 to 2.8 hours. The results show that the formation of sulfated steroids with a 3 alpha-hydroxy-5 alpha configuration may account for 50% of the metabolism of progesterone in late pregnancy.

Preoperative radiotherapy in advanced ovarian carcinoma was evaluated. The overall 5-year survival rate in the irradiated group was 27%. When tumour mass remaining after operation was less than 2 cm in diameter, this figure rose to 52%. Comparison was made between those in whom operation became feasible only after preoperative irradiation and patients in advanced stages who were primarily successfully operated to less than 2 cm and with a 5-year survival rate of 44%. Selection of the cases for preoperative radiotherapy is obviously necessary. Fixed, bulky tumours in the pelvis, with or without metastases, may be suitable for preoperative radiotherapy.

Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

A simple method for screening of the endometrium is a desirable complement to the gynecological examination. Between February and June, 1984, 94 patients underwent cytological sampling by the Gynoscann method immediately before dilatation and curettage at the Department of Gynecological Oncology, Radiumhemmet, and at the Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm. Ninety-six per cent of the cytological samples were adequate for cytological diagnosis and the same proportion of the curettage specimens for histology. The correlation between cytology and histology was correct in 84% of the cases. Among the 26 cases of endometrial carcinoma, 21 (80%) were correctly diagnosed by cytology. There were no false-positive diagnoses for carcinoma. Atypical hyperplastic endometrium was found in 2 cases by curettage and was correctly correlated with cytology in one case. The sensitivity for endometrial carcinoma was 81% and the specificity 100%. Our conclusion is that the Gynoscann method is safe, easy to use and has proved reliable for the diagnosis of endometrial carcinoma. Further evaluation with larger series giving the cytopathologists increased experience is needed before optimal sensitivity can be achieved.

A new sampling method for uterine cervical cancer detection is described. In this method, sampling of cytologic material is done by using a pulse wash instrument. Liquid jets with a diameter of 0.2 mm at a speed of 20 m/s create a successful rinsing effect of cervical epithelial cells due to the high kinetic energy produced. Because cells are suspended in the flushing liquid it is possible to collect material for additional cytochemical, immunocytochemical, and microbiologic diagnostic techniques in addition to a conventional smear technique. Compared to a conventional Papanicolaou smear technique performed in 75 women at two cervical atypia clinics at the Karolinska Hospital, the pulse wash technique is suggested to result in a more representative cellular sample, thus offering a method to decrease false negative diagnoses in uterine cervical cancer detection.

The symptomatology of ovarian cancer was retrospectively reviewed in 362 patients. According to the stage at diagnosis, the disease was classified as early (stages IA-IIA) or advanced (stages IIB-IV). The most common initial symptoms were abdominal swelling and/or palpable tumour, pain and gastro-intestinal symptoms. The initial symptoms, however, were not necessarily those that prompted the patients to seek medical advice. Most were first seen by a gynecologist, which possibly explains the shortness of doctor's delay in the urbanized catchment region.

To achieve better understanding of the factors influencing local control of ovarian cancer, an analysis of failure in early stages of ovarian carcinoma has been carried out. The material consisted of 185 patients diagnosed in early stages; 40 of them failed in their disease, 17 with local recurrence, 23 with distant metastases. The material was analyzed with respect to age, histology, grade, size and surface of the tumor, the surgical procedure and treatment modalities, and the time between treatment and recurrence, and recurrence and death. In the analysis, both the behavior of the ovarian cancer tumor and the pattern of failure was shown to be different for each histological group.