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The aims of the study were to investigate whether an elevated CA 125 level signals malignancies other than ovarian cancer and to find the cause of death for 247 women with elevated values among the 5550 women screened in 1986-1988 in the Stockholm population.The Swedish Regional Cancer Registry delivered malignancy diagnoses among the 5550 women screened. The Cause of Death Registry gave the cause of death among the women with elevated CA 125 values.Patients with ovarian cancer were excluded. In 44 women with elevated CA 125 values other malignancies were reported to the Cancer Registry. They represent 18% of the entire group with elevated values. Among the 5297 women with normal CA 125 values 13% developed various malignancies. The difference between incidence of malignant disease in women with elevated values and women with normal values is significant, P = 0.02. Especially during the test-related period, from 1 year before to 1 year after the test, malignancies were detected in 6.9% of the population with elevated values and in only 1.6% with normal values (P =0.001). Breast cancer and lung cancer were overrepresented among women with elevated CA 125 values (P = 0.015 and0.001, respectively). Of the total 5500 women screened, 358 women died with different diagnoses. Elevated CA 125 values had been noted earlier in 25 women, and of these 20 died of malignant diseases, predominantly ovarian, breast, and lung cancer.Asymptomatic postmenopausal women with elevated CA 125 levels in ovarian carcinoma screening trials should, if ovarian cancer is excluded, be investigated for possible breast or lung cancer. The findings also suggest that elevated CA 125 level is a risk factor for death from malignant disease.

The usefulness of adjuvant therapy in early ovarian cancer is a matter of controversy and there is a need for predictive methods to distinguish between low and high risk patients. Specimens from 95 early-stage ovarian cancer patients have been analysed for conventional clinical variables as well as for the biological markers--DNA content, MIB-1, p53, WAF-1--and correlated to survival. Prognostic significance achieved in univariate analysis could be improved by using a score based on several biological markers. Using a score based on DNA content, MIB-1, p53 and WAF-1, a significant predictor could be achieved with the aim of determining the postsurgical therapy. By using this tool, it is hoped that adjuvant therapy can be avoided for one-third of the patients with early-stage ovarian cancer.

Stored samples from women in the Stockholm screening study were reassayed for CA125II (Centocor, Malvern, PA) and OVX1. The postmenopausal women older than age 50 without ovarian cancer were randomly split into a training set to develop a screening test based on longitudinal marker levels and a second set to validate the test. The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CA125II) on time since first sample. The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot. A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women ; it delineated a screening test. The specificity of this test was examined on the validation set with a specificity of 99.8%. Bayes' theorem was used to calculate the risk of ovarian cancer (ROC) based on the intercept, slope, and assay variability. It is important to account for assay variability because it can produce large slopes over short periods of time. The maximum risk, which identified 83% (5 of 6) of the ovarian cancers detected within a year of last assay, was applied as a test to the training set and confirmed a high specificity of 99.7%. With this specificity and sensitivity, the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16%, substantially greater than the positive predictive value based on a single assay. Further study is planned to confirm the sensitivity of this approach.

Serum levels of squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), CA 125 and tissue polypeptide antigen (TPA) were serially determined in 116 patients with cervical carcinoma. Serum levels of SCC or TPA levels were elevated in the 12 patients with residual tumour after primary therapy. In patients who were clinically in complete remission, SCC and TPA levels were elevated in 7/69 and 5/70 patients, respectively. Three of the 7 with positive SCC and 4 of the 5 patients with positive TPA levels had a recurrence during follow-up. Elevated levels of SCC or CA 125 or TPA preceded the clinical detection of recurrence in 13 of 18 patients (median time was 7 months for SCC and 6 months for CA 125 and TPA).

During recent decades it has become apparent that there are two types of vulvar disease: the classic type found in elderly women with unicentric and unifocal lesions, and the type found in younger women, in which precancerous and invasive changes develop in the anogenital lower tract in a multicentric and multifocal fashion, often over a long period of observation. The laminin-5 gamma 2 chain is an extracellular protein that is a component of the basement membrane. Recently its expression has been recognized as a marker in cervical cancer that permits identification of invasive capacity. The aim of our study was to determine if laminin-5 gamma 2 chain antibody can act as a sensitivity marker of invasive capacity in precancerous and invasive carcinoma in women with uni- and multifocal changes in the anogenital tract. The result showed that all patients in the older group of women with invasive carcinoma of the vulva had moderate to high positive expression of the laminin-5 gamma 2 chain. In the group of younger patients with multifocal precancerous changes observed over long periods, most of the patients with vulva intraepithelial neoplasia (VIN) 3 showed laminin-5 gamma 2 chain positivity already in the precancerous changes, and all of them developed invasivity during the period of observation. Normal epithelium without atypia was mostly negative or of low immunoreactivity of laminin-5. In conclusion, positive laminin-5 gamma 2 chain expression seems to indicate the invasiveness potential of precancerous lesions and is also expressed in all investigated invasive carcinomas of the anogenital tract.

Objectives. Seventy percent of ovarian cancer is diagnosed at advanced stages. Having a method for early diagnosis is a very attractive concept. Several attempts have been made, using monoclonal antibody-based immunoassays, ultrasound, or combinations of both, to identify methods that might prove to be sufficiently sensitive and specific as a screening test. Despite promising results, a mortality study of a large population has yet to be completed due in part to the high cost involved. Methods. One of the first studies aimed at devising a screening strategy for ovarian cancer used the CA 125 immunoassay followed by ultrasound. The study was performed in Stockholm from 1986 through 1988. Ten years now having passed, an analysis has been performed to further evaluate the results of that study. Results. Screening led to the diagnosis of ovarian cancer in six patients, five of whom have since died of the disease. By searching the Cancer Registry, we were able to identify 20 ovarian cancer patients who developed the disease after the screening period. Of these, 12 died of the disease, 2 are alive with disease, and 6 have no evidence of disease following treatment. The median survival for patients diagnosed by screening was 100 months. Median survival for ovarian cancer patients identified subsequent to screening was 20 months. Although there was no difference in survival between these two groups, median survival was better for women diagnosed by screening (borderline significance, P = 0.059). Conclusion. These results indicate that a study of a large number of women with a sufficiently long observation time will be required to establish whether or not screening can reduce ovarian cancer mortality. Such a study may also provide insight into the natural history of ovarian cancer.

Background and purpose : Irradiation of advanced ovarian cancer has been performed during the years 1976–1984 with six-field technique. Results of this treatment in a long follow-up have never before been evaluated. Material and methods : Seventy-five patients with stage IIb–IV of invasive ovarian cancer have been treated with a combination of surgery, radiotherapy and chemotherapy. The results of the treatment were compared with 98 patients treated during the year 1991–1992 with surgery and chemotherapy only. Results : After controlling for the differences in background factors between the groups considered, there was still a significantly better survival rate for the patients treated with radiotherapy. Conclusion : The results suggest that the role of radiotherapy in advanced ovarian cancer should be investigated in a prospective randomized trial.

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.

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, carcinoembryonic antigen, CA 125, tissue polypeptide antigen, CRP, alpha 1-antitrypsin and haptoglobin were determined peri- and postoperatively in patients undergoing surgery for benign gynecological disease (n = 18) and postoperatively in women operated for cervical carcinoma (n = 23). The only significant changes seen after premedication, during anesthesia and during surgery were a decrease in serum concentrations of alpha 1-antitrypsin and haptoglobin. We found no postoperative changes in the serum levels of squamous cell carcinoma antigen nor in carcinoembryonic antigen values. However, the latter analyte was influenced by smoking habits. Elevated levels of CA 125 and tissue polypeptide antigen were found in the cancer patients, predominantly within the first 1-3 weeks after surgery. These levels decreased to normal values within 4-6 weeks postoperatively. The median intraindividual coefficients of variation for the tumor markers ranged between 15% and 28% in 30 control women not having surgery. In general, it would seem advisable to wait 6 weeks after surgery before monitoring with CA 125 and TPA is started.

To determine the potential efficacy of the CA 125 assay as one component of a strategy for early detection of ovarian malignancy, serum CA 125 levels were determined in 1082 women 40 years of age or older in Stockholm. Initial serum CA 125 levels exceeded 35 U/ml in 36 women (3.3%) and 65 U/ml in 11 women (1.0%), placing the exact 95% upper confidence limits on false positive rates for a single screen at 4.3 and 1.7%, respectively. Followup CA 125 levels were obtained for those women with initially elevated levels and a group of age-matched controls. Mean CA 125 levels declined significantly for women with initially elevated levels ( P = 0.0014). Interindividual variation and variation within individual subjects over the entire follow-up period were 52 and 35%, respectively. Of the 36 subjects with initially elevated serum CA 125 levels, only 2 showed a doubling of these levels; in only 1 of these 2 was this increase sustained. Intensive clinical followup with pelvic examination and ultrasonography, with investigators blinded to CA 125 results, led to the diagnosis of Stage III ovarian cancer in the latter individual. Diagnosis was made 21 months after the initially elevated serum CA 125 measurement and 15 months after the first measured doubling of that level. Because no other malignancies were identified at entry or during the follow-up period (median 560 days) in the women with elevated CA 125 levels, the specificity of the assay over that time period would have been 99.9% using the doubling of an initially elevated value as the criterion for determining positivity and 100% using as the criterion a sustained increase in level for those with initially elevated levels that doubled. These results support the continued investigation of longitudinally collected CA 125 levels to identify individuals at high risk for ovarian malignancy.

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.

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.

Summary 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 2cm 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.

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.

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.