DNA- versus RNA-based methods for human papillomavirus detection in cervical neoplasia.

OBJECTIVE: To compare DNA-based and mRNA-based methods for detection of high-grade cervical neoplasia in Norway. METHODS: HPV prevalence was analyzed in 383 women with positive index cytology, selected from gynecology clinics. All patients were investigated by a new PAP smear, histology, and two commercially available HPV tests: Hybrid Capture II (Digene, Gaithersburg, MD) and the Pre Tect HPV-Proofer (NorChip AS). Cases with positive DNA test and negative mRNA test and cases with high-grade histology and negative HPV tests were retested with PCR and sequencing. We regarded the infection as latent or transient if sequencing revealed an HPV type included in both assays. RESULTS: High-risk HPV was detected in 99.7% of the histological confirmed high-grade lesions (CIN2+) (290/291). The DNA test was positive in 95% (275/291), and the mRNA test was positive in 77% (225/291) of the histological confirmed high-grade lesions. All invasive carcinomas were mRNA positive. The DNA test was significantly more often positive in benign and low-grade lesions, some of which were found to be false positive due to cross-contamination with unrelated types. High-grade histology was detected in 83% of women with normal cytology and positive mRNA test. Latent or transient infections were detected in 11 low-grade and 12 high-grade preinvasive lesions. Sequencing revealed high-risk HPV types included only in the DNA test in 35 high-grade preinvasive lesions, HPV 52 and 58 were the most prevalent HPV types. CONCLUSIONS: These HPV tests have the potential to improve the detection rate of high-grade cervical neoplasia, with some limitations. The mRNA test seems to be more appropriate for risk-evaluation. Larger scale, population based studies are necessary to evaluate the predictive values of HPV testing in Norway.

[Examination, treatment and follow-up of ovarian cancer in Norway]. / Utredning, behandling og etterkontroll av eggstokkreft i Norge.

BACKGROUND: In order to improve our knowledge about the medical examination, treatment and follow of cancer patients, suggestions have been put forward for a system for quality assurance of clinical data on cancer in Norway (Government White Paper 20: 1997). MATERIAL AND METHODS: In spring 2000, a questionnaire was sent to 41 gynaecological departments with focus on ovarian cancer patients. Four of the departments were regional cancer centres. RESULTS: All gynaecological departments answered the questionnaire. Standard gynaecological examination, vaginal ultrasonography and CA-125 determination were included in the diagnostic procedures in all departments. Some differences were detected: Cytological examination of pleural effusions as part of the staging procedure was not performed by all hospitals. In one health region, hospitals used a Risk of Malignancy Index for referring women with suspected malignant pelvic masses to a centralised gynaecologic oncology unit for primary surgery. Sixteen hospitals out of 37 operated on patients with FIGO stage I disease without performing lympadenectomy. When operating on suspected FIGO stage II-IV disease, three out of 22 local hospitals never performed surgery of the intestines in order to achieve optimal tumour reduction. All regional hospitals gave adjuvant chemotherapy to high-risk FIGO stage I patients. Standard treatment in advanced stages was paclitaxel/carboplatinum. Some hospitals participated in randomized trials on chemotherapy. Third-line treatment depended on the patient's condition, earlier toxicity and response. One regional centre preferred not to give any third-line chemotherapy. Only a few hospitals recorded the patient's performance status (WHO or Karnofsky's grading table) during the treatment and follow-up. Most of the gynaecological departments referred the patients to the regional hospital at the time of recurrence. About half of the outpatient departments gave a written report to the regional hospital. INTERPRETATION: There are differences between the hospitals in how they handle ovarian cancer patients. One cannot, however, determine from this inquiry what kind of medical examination, treatment and follow-up is best. An extended registration of ovarian cancer organised by the Cancer Registry of Norway will be started with the aim of providing reliable population-based data (the OVANOR project).

[Palliative treatment in gynecologic cancer]. / Palliativ behandling ved gynekologisk kreft.

BACKGROUND: Data on the need for palliative care related to disease groups are very limited. MATERIAL AND METHODS: A retrospective analysis was performed on the hospital records of 228 patients who died from gynaecologic cancer during the 1988-1997 period. RESULTS: 76% of deaths took place in hospital; 12% at home. Median terminal hospital stay was 13 days. Symptoms from intestinal obstruction were dominating in 30% of cases and most frequently seen in patients with ovarian cancer. Palliative intestinal surgery was performed in 38% of patients with ovarian cancer, median survival being 5 months (range 10 days-7 years), perioperative mortality (within 30 days) 13%. Cachexia dominated in 27% and was more often present when death occurred at home. Assistance from a gastroenterologic surgeon, urologist, haematologist or anaesthesiologist was needed in 32% of cases. One in two patients received parenteral pain relief in the terminal phase, for a median period of five days. Palliative radiotherapy was given 21% of the patients, most often in cervical and endometrial cancer, and chemotherapy or hormonal therapy was used in 36%. Minor interventions like laparocentesis, pleurocentesis, tumour resections, and various forms of urinary deviations were frequent. INTERPRETATION: Hospital deaths are more common among patients suffering from gynaecologic cancer than among cancer patients in general (55% in Norway), and the need for multimodal hospital service is large. We see substantial benefits in the Norwegian model in which a gynaecologist experienced in oncology has comprehensive responsibility for the treatment, supported by other specialists and the primary health service.

10-Gy single-fraction pelvic irradiation for palliation and life prolongation in patients with cancer of the cervix and corpus uteri.

OBJECTIVE: The goal of this study was to evaluate the effects of single fractions of 10 Gy pelvic irradiation for palliation and life prolongation in patients with cancer of the uterine cervix or corpus. METHODS: A retrospective analysis was performed on 37 cervical cancer and 27 corpus cancer patients treated in the period 1988-1998. All patients had a life expectancy of less than 1 year. Due to stage of disease, age (median 82 years), or comorbidity they were considered unapt for surgery or conventional radiotherapy. Eleven patients with recurrence within irradiated field or early progression received one, 51 patients received two, and 2 patients received three fractions with a 4-week interval. RESULTS: Vaginal bleeding stopped in 90% and malodorous discharge in 39% of the patients. Among 46 patients with advanced disease treated for palliation, 10 (22%) showed complete tumor responses. Median time to progression was 6 months, and median survival, 9 months. Eighteen patients with early-stage disease and serious comorbidity were treated with life prolongation and symptom prevention as intention, and showed seven complete responses. Median survival was 13 months, and half the deaths were caused by intercurrent disease. Median hospital stay was 5 days and rehabilitation was easy. Fifty-six percent of the patients experienced no acute side effects and 33% had minor gastrointestinal problems. Three patients (6%) had serious late bowel complications, one with a fatal outcome, the symptoms appearing 9-10 months posttreatment. CONCLUSION: The 10-Gy single-fraction pelvic radiation regimen is an effective means of symptom palliation and is well tolerated. Tumor responses are obtained. The risk of late bowel complications is a concern for patients with a life expectancy greater than 9 months.

Late reactions after postoperative high-dose-rate intravaginal brachytherapy for endometrial cancer: a comparison of standardized and individualized target volumes.

PURPOSE: To compare retrospectively two treatment protocols for postoperative intravaginal brachytherapy as to frequency of late radiation reactions and vaginal recurrence of disease. METHODS AND MATERIALS: Two hundred seventeen patients with Stage I-II endometrial carcinoma underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by high-dose-rate (HDR) intracavitary irradiation, 5.5 Gy x 4 (22 Gy), to the upper 5 cm of the vagina. From 1988 to August 1991, the reference isodose was at 5 mm from the mucosal surface (standard treatment, 96 pts). From September 1991 to June 1996, the reference isodoses were chosen at 3 mm, 4 mm, or 5 mm depth depending on a clinical estimation of the mucosal thickness (individualized treatment, 121 pts). Maximum bladder and rectum doses were calculated from orthogonal X-ray films. RESULTS: The patients were followed for 3 to 10 years. The rate of late vaginal reactions Grade 1 and 2 were 26% and 8%, respectively, after standard treatment, vs. 17% and 1% after individualized treatment (p = 0.005). Bladder reaction rates were 9% Grade 1 and 1% Grade 2 after standard treatment vs. 1% Grade 1 after individualized treatment (p = 0.005). Rectum reactions Grade 1 were seen in 5% and 1%, respectively. No Grade 3 reactions were observed. The reactions appeared after a median time interval of 9 months and 11 months, respectively. The rate of vaginal reactions was strongly correlated to the dose on the surface of the vaginal applicator, and the bladder reaction rate correlated with the calculated maximum bladder dose. Local vaginal recurrences were seen in 1 patient (1.0%) in the standard treatment group and in 3 patients (2.5%) in the individualized treatment group (p = 0.78). CONCLUSIONS: By individualizing the depth of the reference dose in the vaginal mucosa according to its thickness and avoiding applicators with small diameters, the rate of reactions can be reduced without any significant increase in vaginal recurrences.

Primary treatment of cervical carcinoma. Ten years experience from one Norwegian health region.

OBJECTIVE: To study the primary care of cervical carcinoma with regard to clinical and pathological factors, treatment decisions, complications and survival. DESIGN: A historical cohort comprising all women hospitalized with invasive cervical carcinoma (n=293) during the period 1987-1996. RESULTS: Median age was 52 years (range 23-90). FIGO stage distribution was 62%, 15%, 18% and 5% in stages I, II, III and IV, respectively. Early stage disease correlated with young age. Histologic types were: squamous cell carcinoma 84%, adenocarcinoma 11%, adenosquamous carcinoma 4% and small cell/anaplastic carcinoma 1%. Primary therapies were: surgery 188 women (64%), radiotherapy 99 women (34%), chemotherapy two women (0.7%); four women not treated (1.3%). Complications after surgery in 25 women (13%), none were fatal. Acute or late complications after primary or postoperative radiotherapy in 39 women (25%), seven (4.6%) were late serious complications. Three women died from complications related to radiotherapy. Mean follow-up of surviving patients was 58 months. Overall disease specific five-year survival was 70%. Five-year survival in stages IA, IB, II and III was 100%, 88%, 58% and 20%, respectively. One-year survival in stage IV was 31%. Median survival in stages III and IV according to curative or palliative aim of treatment was 20 and 6 months, respectively (p<0.005). CONCLUSION: Satisfactory quality of diagnosis and therapy have been maintained through regional care for cervical cancer patients.

Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument.

PURPOSE: Adjuvant chemotherapy versus observation and chemotherapy at progression was evaluated in 162 patients in a prospective randomized multicenter study. We also evaluated DNA-measurements as an additional prognostic factor. PATIENTS AND METHODS: Patients received adjuvant carboplatin AUC 7 every 28 days for six courses (n = 81) or no adjuvant treatment (n = 81). Eligibility included surgically staged and treated patients with FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cell carcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific (DSS) survival were end-points. RESULTS: Median follow-up time was 46 months and progression was observed in 20 patients in the treatment group and 19 in the control group. Estimated five-year DFS and DSS were 70% and 86% in the treatment group and 71% and 85% in the control group. The hazard ratio was 0.98 (95% confidence interval (95% CI): 0.52-1.83) regarding DFS and 0.94 (95% CI: 0.37-2.36) regarding DSS. No significant differences in DFS or DSS could be seen when the log-rank test was stratified for prognostic variables. Therefore, data from both groups were pooled for the analysis of prognostic factors. DNA-ploidy (P = 0.003), extracapsular growth (P = 0.005), tumor rupture (P = 0.04), and WHO histologic grade (P = 0.04) were significant independent prognostic factors for DFS with P < 0.0001 for the model in the multivariate Cox analysis. FIGO substage (P = 0.01), DNA ploidy (P < 0.05), and histologic grade (P = 0.05) were prognostic for DSS with a P-value for the model < 0.0001. CONCLUSIONS: Due to the small number of patients the study was inconclusive as regards the question of adjuvant chemotherapy. The survival curves were superimposable, but with wide confidence intervals. DNA-ploidy adds objective independent prognostic information regarding both DFS and DSS in early ovarian cancer.

Malignant rhabdoid tumor of the vulva. Case report.

The poor prognosis of malignant rhabdoid tumor is emphasized and histopathological criteria for distinction from epithelial sarcoma of the vulva are discussed. Immunohistochemical analyses were performed by using nine different antigens including vimentin, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, desmin, muscle-specific actin, S-100 protein, AP-15, neuron specific enolase. This is the sixth reported case of a malignant rhabdoid tumor of the vulva. The patient died eight months after the initial diagnosis in spite of a combination of surgery, adjuvant chemotherapy and external radiotherapy.

The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals.

OBJECTIVE: To assess the risk-of-malignancy index (a scoring system based on menopausal status, ultrasound features, and serum CA 125) at district hospitals for referral of women with suspected malignant pelvic masses for primary surgery at a central gynecologic oncology unit. METHODS: All seven hospitals in Health Region IV, Norway, agreed to refer women with pelvic masses and risk-of-malignancy indices of 200 or more for centralized primary surgery. In total, 365 women 30 years of age or older, admitted consecutively at the local hospitals, were enrolled in the study from February 1, 1995, to January 31, 1997. RESULTS: Compliance with the study was satisfactory; 84% (65 of 77) of women with risk-of-malignancy indices of at least 200 were referred for centralized primary surgery. Sensitivity and specificity to malignancy were 71% and 92%, respectively, which is in agreement with previous validation of the risk-of-malignancy index in teaching hospital settings. False negatives were due mainly to stage Ia (18 of 24) ovarian cancer, whereas 27 of 28 stage II-IV ovarian cancer cases were identified correctly. CONCLUSION: The risk-of-malignancy index identified women with malignant pelvic masses efficiently. Our study showed the risk-of-malignancy index strategy in a practical setting to be able to centralize primary surgery for advanced ovarian cancer from local hospitals to a subspecialty unit. We recommend the risk-of-malignancy index for detection of patients with advanced ovarian cancer for centralized primary surgery.

A pharmacokinetic and clinical evaluation of thio-TEPA in combination with cisplatin as first-line chemotherapy for advanced epithelial ovarian carcinoma.

The purpose of the study was to explore the combination of thio-TEPA with cisplatin in first-line chemotherapy of epithelial ovarian cancer with special reference to pharmacokinetic and pharmacodynamic relationships. Ten women with advanced disease were included. Pharmacokinetics of thio-TEPA were similar to those in previous studies of single drug therapy with rapid first order elimination of the parent drug and substantial intra- and interindividual variation of the area under the concentration-time curve (AUC). No effects of the drug sequence or repeated treatments were seen on the pharmacokinetics of thio-TEPA, indicating no significant influence from the coadministration of cisplatin on the distribution, metabolism or excretion of thio-TEPA. Pharmacokinetic--pharmacodynamic relationships were less pronounced compared to previous studies, probably due to the influence from cisplatin. Prolongation of treatment intervals, dosage reduction, and withholding of thio-TEPA were required due to myelosuppression, which was the dominating toxicity. Non-hematological toxicity was moderate and easily manageable, cisplatin-related toxicity did not seem to be aggravated. Response rate based on CA 125 fluctuations was 80%, overall median survival was 18 months. In conclusion, the pharmacokinetics of thio-TEPA does not seem to be significantly influenced by concomitant administration of cisplatin in female patients. Manageable toxicity, largely restricted to myelosuppression, and high response rate justify further evaluation of the current regimen.

A phase II study of biweekly administration of paclitaxel in patients with recurrent epithelial ovarian cancer.

The purpose of this study was to assess the efficacy and toxicity of single agent paclitaxel administered biweekly to patients with relapse of epithelial ovarian cancer previously treated with platinum-based regimen. Forty patients received an initial paclitaxel dose of 134 mg/m2 administered intravenously over three hours every two weeks. 283 cycles were given. All 40 patients were evaluable for toxicity, which mainly consisted of granulocytopenia, myalgia/arthralgia, and peripheral neuropathy. Two patients developed severe hypersensitivity reactions. Dose escalation was possible by one level in 11 patients and by two levels in 12 patients, dose reductions were not necessary. Thirty-five patients were evaluated for response. Five obtained complete response (14%), eight obtained partial response (23%), and nine had stable disease (26%), while 11 patients showed progression (31%). The overall response rate was 37% (95% confidence interval 22-57%). The median duration of responses (complete and partial) was six months. Overall median time to progression and overall median survival for eligible patients (n = 35) was 4.3 months and 11 months, respectively. We conclude that biweekly administration of paclitaxel in recurrent epithelial ovarian carcinoma was active with manageable toxicity.

Long-term results from a phase II study of single agent paclitaxel (Taxol) in previously platinum treated patients with advanced ovarian cancer: the Nordic experience.

BACKGROUND: Owing to the wide spread perception of a possible benefit from paclitaxel in the second-line situation the Nordic Gynecologic Oncology Group (NGOG) conducted two prospective phase II studies of paclitaxel single agent treatment (175 mg/m2, three-hour i.v. infusion with standard pre-medication every third week) in patients with relapsing or progressing epithelial ovarian cancer following platinum. PATIENTS AND METHODS: Between 1992-1994 138 patients in total were enrolled of whom 136 received paclitaxel and were included in the toxicity and survival analysis, while 112 were evaluable for response. RESULTS: The overall response rate (CR + PR) was 28% with 16 patients achieving a CR (14%). The estimated median (range) time to progression was 4.1 (0.7-60.7) months. The projected four-year overall survival was 7%, with a median (range) of 9.6 (0.3-60.7) months. A multivariate logistic regression analysis showed that platinum resistance, and WHO performance status at baseline, independently correlated with survival at all three time points (median survival time 9.6, 18, and 24 months). Patients with platinum sensitive tumors and WHO performance status 0 had a median survival of 25.6 months compared to 7.0 months for the rest of the patients (P < or = 0.0001). No serious toxicity was registered. CONCLUSION: Paclitaxel could safely be administered in an outpatient setting using this schedule. Patients with platinum sensitive tumors and a good performance status were most likely to survive. However, these patients are also most likely to respond to re-treatment with a platinum compound. With reference to the reasonably good tumor control and limited toxicity observed in this study, we conclude that paclitaxel single agent therapy is a viable option in the salvage situation, which in some patients can give long-lasting responses. However, although responses can be induced in a significant number of patients, the survival figures remain poor.

CA 125--epitopes and molecular size.

CA 125 has two main immunogenic areas reactive with mouse and rat monoclonal antibodies. These areas are defined by the antibodies OC 125 and M11, respectively. Antibodies related to the main groups are named OC 125-like and M 11-like antibodies. The OC 125-like antibodies can be subgrouped into four sets, whereas the M 11-like antibodies segregate into many closely related binding specificities. One M 11-like antibody, ZR38, is not fully inhibited by any other M 11-like antibody and therefore represents a distinct subgroup. A single antibody, OV 197, is related to some OC 125-like antibodies, but not to OC 125. However, OC 125 enhances binding of OV 197 to its epitope. A new antibody, 7C 12, induces conformation changes, affecting binding of some M 11-like and some OC 125-like antibodies. CA 125 exists as very large molecules that can be partly disrupted by SDS and heat. The form found in serum might be a degradation product from a larger molecule found in the abdominal and other serous cavities.

Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses.

OBJECTIVE: To evaluate the ability of a risk of malignancy index (RMI), based on a serum CA125 level, ultrasound findings and menopausal status, to discriminate a benign from a malignant pelvic mass and to discriminate early stage (Figo Stage I) from Stages II, III and IV of ovarian cancer. DESIGN: A prospective study. SETTING: Department of Gynaecology, Trondheim University Hospital, Trondheim, Norway. PARTICIPANTS: One hundred and seventy-three women, 30 years or older, consecutively admitted between February 1992 and February 1994 for primary laparotomy of a pelvic mass. MAIN OUTCOME MEASURES: The sensitivity, specificity and positive predictive value of serum CA125 level, ultrasound findings and menopausal status, separately and combined into the RMI, to diagnose ovarian cancer. RESULTS: The RMI was more accurate than any individual criterion in diagnosing cancer. Using a RMI cut-off level of 200 to indicate malignancy, the RMI derived from this dataset gave a sensitivity of 80%, specificity of 92% and positive predictive value of 83%. Applying RMI criteria developed by others, the following test performance was found: sensitivity 71%, specificity 96% and positive predictive value 89%. For the Stages II, III and IV of ovarian cancer the sensitivity increased to approximately 90% without any substantial loss in specificity. CONCLUSIONS: The risk of malignancy index is able to correctly discriminate between malignant and benign pelvic masses. It is a scoring system which can be introduced easily into clinical practice to facilitate the selection of patients for primary surgery at an oncological unit.

Radiotherapy and neoadjuvant chemotherapy for cervical carcinoma. A randomized multicenter study of sequential cisplatin and 5-fluorouracil and radiotherapy in advanced cervical carcinoma stage 3B and 4A.

BACKGROUND: The locoregional failure rate remains high in advanced cervical carcinoma. Chemotherapy (CT) was added to radiotherapy (RT) in order to increase disease control and to improve 5-year survival. METHODS: CT + RT included cisplatin administered 100mg/m2, d.1 plus 5-fluorouracil 1000 mg/m2 D.1 to 5, ci (120 hrs), q every 3rd week for 3 cycles, followed by RT. RT included external beam irradiation 64.8 Gy in 1.8 Gy fractions, five days a week, by 4-field box technique. The median follow-up was 46 months. Ninety-four patients were evaluable for survival, 47 in the CT + RT group and 47 in the RT group. Ninety-two patients were evaluable for response. Known prognostic factors were equally distributed between the two groups. RESULTS: Of the 43 patients evaluable before RT, 31 (72%) achieved a partial or complete response after CT alone. After RT, 52 patients attained a complete response, 25 in the CT + RT group and 27 in the RT-group. Sixty-three patients developed distant metastases or local relapse, 30 in the CT + RT group and 33 in the RT group. In the CT + RT group 6 of the 9 patients with metastases also had local progression at relapse, in the RT group, 7 of 17 patients. The survival rates for the two groups are not statistically different. Thirty-seven patients are alive, 29 have no evidence of disease. Fifty-seven have died, 29 in the CT + RT group and 28 in the RT group. Fifty-four deaths were related to cancer, and 3 to therapy. CONCLUSIONS: Sequential CT and RT did not improve the survival, local control, or metastasis rate compared with RT alone.

[Increasing use of cesarean section, even in developing countries]. / Okende bruk av keisersnitt også i utviklingsland.

At Kaziba hospital in rural Zaire, the frequency of deliveries by Caesarean section rose from 6.2% in 1971 to 12% in 1992, and the fraction of repeated sections rose from 17% to 49%. During the same period, the overall maternal mortality decreased from 0.3% to 0.12%, and deaths connected with Caesarean section from 3.2% to 0.7%, but still the risk of dying remained 13 times higher for births by Caesarean section compared with vaginal deliveries. The frequency of vacuum deliveries was halved during the period, and mean birth weight decreased by about 100 g. Perinatal mortality remained at about 2%. Among 760 Caesarean sections performed in the years 1991 and 1992, 93% were emergency cases. Spinal anesthesia was used in 97%, and blood transfusion was given to 4% of the women. The main indications were mechanical (30%), previous Caesarean section (20%), foetal asphyxia (19%), and suspected uterine rupture (10%). Uterine rupture was verified in 37 cases (4.9%), of which 27 were Caesarean scar ruptures. 259 of the operations were performed by a nurse or a dentist. Operations carried out by persons other than physicians were complicated by wound infections at a higher rate (20.8%) than those carried out by experienced doctors (11.2%). In areas with a poorly developed health system, a high rate of Caesarean section represents a hazard to maternal health. The need for knowledge about alternative methods like vaginal extraction, symphyseotomy and active management of labour is underlined.

PIP: Available hospital statistics were used comparing the period of 1971-72 with 1991-92 with regard to births, Cesarean section, rupture of the uterus, vacuum delivery, birth weight, maternal mortality, and perinatal mortality at Kaziba Hospital in rural Zaire. In addition, a retrospective analysis was conducted of 760 Cesarean section cases performed in 1991 (386) and in 1992 (374) using data from operation protocols and patient journals. Furthermore, the partograms of 1423 women who gave birth vaginally in 1992 were analyzed as to height, weight, and parity of women as well as the birth weight of the child. The number of annual births trebled in the course of 20 years. During this time the incidence of Cesarean section increased from 6.2% to 12.0%; however, the incidence of vacuum delivery had been halved. The total maternal mortality decreased from .3% to .12%, while the mortality associated with Cesarean section dropped from 3.2% to .7%. In the first period the risk of death from Cesarean section was 31 times higher than from vaginal delivery, while in the second period the risk was 13 times higher. The perinatal mortality had stayed around 2% in these 20 years. The average birth weight was 2915 g in the first period vs. 2819 g in the last period. Repeated Cesarean sections escalated from 17.4% to 49%. Only 52 (6.9%) of 760 Cesarean sections done during the 1991-92 period were elective. 97.4% of these operations were performed under spinal anesthesia. Blood transfusions were given to 31 women (4.1%). The main indications were mechanical (30%), previous Cesarean section (20%), fetal asphyxia (19%), and suspected uterine rupture (10%). Uterine rupture was verified in 37 cases (4.9%), of which 27 were Cesarean scar ruptures. 249 operations were performed by a nurse or a dentist. In 20.8% of operations there were wound infections when the operation was carried out by a person other than a doctor vs. the 11.2% rate encountered with experienced doctors. The average operation time was 46 minutes for experienced surgeons vs. 53 minutes for less experienced surgeons, and 83 minutes for nondoctors (p .001).

Soluble tumor necrosis factor receptors and CA 125 in serum as markers for epithelial ovarian cancer.

Increased serum levels of soluble tumor necrosis factor receptors (TNFRs) have been observed in patients with various types of malignancies. For the monitoring of ovarian cancer during treatment serum TNFRs have given information equivalent or better than that obtained by CA 125. In this study, we compared the diagnostic value of TNFRs and CA 125 in discriminating ovarian cancer from benign pelvic masses. Preoperative serum levels of p55 and p75, two distinct types of TNFRs, and that of CA 125 were determined by immunoassays in 45 patients with malignant and 27 patients with benign tumors operated consecutively. A group of 26 healthy women served as controls. For each of the three markers the group with ovarian cancer showed significantly higher values than the group with benign masses (p < 0.01). The rate of marker elevation correlated with ovarian cancer staging. Using upper cutoff levels of 2.0 ng/ml (p55), 4.3 ng/ml (p75) and 20 U/ml (CA 125), the calculated sensitivities were 58% (p55), 16% (p75) and 82% (CA 125). The specificities were 89% (p55), 96% (p75) and 85% (CA 125), respectively. Adding p55 to CA 125 did not increase the diagnostic values compared to using the CA 125 test alone. Our data confirm the superiority of serum CA 125 as a marker for discriminating ovarian cancer from benign pelvic masses. The p75 marker was found to be of no value, and for the detection of early stage ovarian cancer the sensitivity of p55 was too low to be of clinical importance.