UK study of intrapartum care for low risk primigravidas: a survey of interventions.

STUDY OBJECTIVE: To determine the extent of intrapartum intervention received by primigravidas. DESIGN: Cross sectional survey of NHS hospitals in the UK. SETTING: One hundred and one randomly selected hospital maternity units. PARTICIPANTS: Forty consecutive primigravid women, judged to be at low risk at the start of labour, in each hospital. MAIN OUTCOME MEASURES: Seven groups of interventions or monitoring procedures were identified from the first, second, and third stages of labour: fetal monitoring, vaginal examinations, artificial rupture of membranes, augmentation of labour, pain relief, type of delivery, and episiotomy. Data were collected during 1993. MAIN RESULTS: Ninety eight hospitals took part in the study and data were collected on 3160 low risk primigravidas. Seventy four per cent of these women had continuous cardiotocography. The proportion of women having restrictive or invasive fetal monitoring showed appreciable geographical variation for both the first and second stages of labour. Using the criterion of a vaginal examination every four hours and allowing for the length of each woman's labour, 72% had more vaginal examinations than expected; there was a significant geographical variation in the number of women receiving more than five examinations. Fifty three per cent had artificial rupture of membranes; the procedure was performed over a wide range of cervical dilatations (0 cm-10 cm). Thirty eight per cent of labours were augmented, most commonly by intravenous syntocinon; the procedure showed significant geographical variation. Twenty eight per cent had a spinal block or epidural analgesia for the relief of pain; this intervention varied by geographical region only for the second stage of labour. Over one quarter of the women required instrumental delivery. Forty six per cent had an episiotomy; the frequency of this intervention varied substantially by region. There were no infant deaths. Twelve babies were recorded at birth as having a congenital anomaly. CONCLUSIONS: The rates of several interventions seem high for this low risk group and there was substantial geographical variation in the use of six interventions. Clinical trials are needed to evaluate the optimum criteria for using these interventions from which guidelines should be drawn up by local groups and the Royal College.

A randomised dose intensity study in ovarian carcinoma comparing chemotherapy given at four week intervals for six cycles with half dose chemotherapy given for twelve cycles.

BACKGROUND: The importance of dose intensity has not been clearly defined in ovarian cancer and we present a prospectively randomised trial of dose intensity in patients with ovarian cancer. PATIENTS AND METHODS: Ninety-nine patients with FIGO stage Ic, II, III and IV epithelial ovarian cancer were randomised to receive cycles of standard dose cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with adriamycin (50 mg/m2) and ifosfamide (5 G/m2) for 6 cycles at monthly intervals (49 patients) or cycles of half dose cyclophosphamide (300 mg/m2) and carboplatin (150 mg/m2) alternating with adriamycin (25 mg/m2) and ifosfamide (2.5 G/m2) for 12 cycles at monthly intervals (50 patients). Patients in each arm were well balanced for major prognostic factors. RESULTS: The combined clinical response rate (complete response and partial response) on the 6 month arm was 76% compared with 48% on the low dose intensity arm (p = 0.009). With a median follow up of 25.7 months the median survival on the low dose intensity arm is 20.9 months. The median survival point on the 6 month arm has not yet been reached. The median progression free interval on the 12 month arm was 19.8 months, the median value has not yet been reached on the standard arm. The amount of residual tumour following initial laparotomy was the only significant independent variable affecting survival (p = 0.0001). The mean received dose intensity of each drug was greater than 80% of the planned dose intensity. More patients had clinical disease progression during treatment on the low dose intensity arm (42%) when compared to the standard dose intensity arm (8%) (p = 0.0003). Fifteen patients on the standard dose arm experienced a total of 18 delays and 5 patients on the low dose arm experienced 17 delays. Nausea, vomiting and diarrhoea were similar for both standard and low dose cycles of chemotherapy with a consequent benefit for patients receiving fewer cycles even though these were of higher dose. CONCLUSIONS: The combination studied was more effective when given at the higher dose intensity and the improved response and survival was not accompanied by a significant increase in toxicity.

Carcinoma of the cervix: an analysis of prognostic factors, treatment and patterns of failure following Wertheims hysterectomy.

A clinicopathologic analysis of 70 patients treated by radiotherapy and/or chemotherapy following primary radical surgery has been undertaken. Clinical stage at presentation was IB (58 patients) and IIA (12 patients). Thirty-five patients (50%) had squamous carcinoma, 23 (33%) had adenosquamous carcinoma, 9 (13%) had adenocarcinoma and 3 (4%) had an undifferentiated neoplasm. The reasons for further treatment were: (i) pelvic lymph node metastases (PLNM), 35 (50%); (ii) inadequate central clearance (ICC), 13 (18%); (iii) recurrent disease (RD), 17 (24%); (iv) others, 5 (8%) cases. Sixty-seven patients had radiotherapy, one of whom also received adjuvant chemotherapy, three patients had chemotherapy alone, and 12 patients received chemotherapy for recurrence following radiotherapy. The 5-year survival in the above referral groups were: (i) 66%; (ii) 62%; (iii) 12%. The site of relapse following treatment was primarily pelvic in groups 2 (ICC) and 3 (RD) and extrapelvic in group 1 (PLNM). Of the histologic parameters studied the only factor of statistical significance in predicting outcome in this group who are recognized to have a generally poor prognosis was the presence of parametrial extension (P = 0.0066). Six cases (9%) developed complications following therapy, lymphoedema being the most common (66%).

Cervical carcinoma: a hazard model in early stage disease.

The 235 patients with stage IB/IIA cervical carcinoma treated by Wertheim's hysterectomy, as a primary procedure, at St Mary's Hospital, Manchester between 1975 and 1989 inclusive, form the basis of this study. Using Cox's regression model, four variables were shown to have independent prognostic significance. These were: (1) lymphatic permeation (adjacent to the tumor); (2) tumor volume; (3) being pregnant at diagnosis and (4) lymph node metastases. A heuristic model was formulated which was based upon these four factors and by using this information it was possible to separate the patients into four distinct prognostic groups. It is suggested that this model may prove useful in identifying those patients at a higher risk of dying of disease and who would benefit from early adjuvant systemic therapy.

Five year follow-up and dose delivery analysis of cisplatin, iproplatin or carboplatin in combination with cyclophosphamide in advanced ovarian carcinoma.

Eighty eight patients with FIGO stage IIb/c (postoperative residual) or III/IV epithelial ovarian cancer were randomised to receive cycles of cyclophosphamide (600 mg/m2) with either iproplatin (240 mg/m2), cisplatin (100 mg/m2) or carboplatin (300 mg/m2). A total of six cycles were given at monthly intervals. Patients were well-balanced for major prognostic factors. There was no significant difference in overall response rate (iproplatin arm, 64.3%, cisplatin arm 72.7% and carboplatin arm 66.7%). There were more complete remissions on the carboplatin arm, 45.8% compared with 21.4% on iproplatin and 22.7% on cisplatin but the difference was not statistically significant (p = 0.11). With a median follow up of 50 months the median survival for the iproplatin arm is 18 months, for the cisplatin arm 19 months and for the carboplatin arm 24 months (p = 0.15). Toxicity was greatest with cisplatin and least with carboplatin. Myelotoxicity limited the dose delivery of iproplatin as measured by total dose, dose intensity and dose intensity product. Carboplatin is at least as effective and less toxic than cisplatin when used in conjunction with cyclophosphamide for the treatment of ovarian carcinoma, and this analogue has been selected for dose intensification studies in this tumour at the Christie Hospital.

Post-surgical pyoderma gangrenosum of the vaginal vault associated with ulcerative colitis and Behçet's disease; a case report.

A case is described in which a patient with ulcerative colitis developed chronic vaginal ulceration around the incision lines after cone biopsy. The ulcers persisted at the vaginal vault after abdominal hysterectomy and removal of a cuff of vagina. Non-specific histological features compatible with pyoderma gangrenosum were found on biopsy. The auto-immune nature of this chronic ulcer is further supported by its rapid response to steroid therapy and the subsequent development of Behçet's syndrome.

The role of postoperative alkylating agent therapy in early-stage epithelial ovarian cancer.

Forty-six patients with early (Stage I and II) ovarian cancer referred as free of residual disease after primary surgery, selected for high-risk features, were treated with adjuvant single-agent alkylating therapy comprising either intravenous cyclophosphamide (1 g/m2) in 36 patients, or oral melphalan (0.2 mg/kg daily for 5 days) in eight. Cyclophosphamide was repeated every 3 weeks for 10 cycles and melphalan every 6 weeks for 12 cycles. With a median follow-up of 36+ months, 18 patients have relapsed. The actuarial 5-year relapse-free survival was 48% and the overall 5-year survival was 54%; median survival was 84 months. Pretreatment FIGO stage was the single most important predictor of relapse-free and overall survival duration. For patients with Stage IA and IB tumours the 5-year actuarial relapse-free survival was 89%; for patients with stage IC and II (all substages), the 5-year relapse-free survival was 24% (P = 0.001). For this latter group adjuvant single alkylating agent therapy was not adequate and alternative therapeutic regimens are required. The problem of suboptimal primary surgical staging is also addressed.

A novel approach for monitoring the endometrial cycle and detecting ovulation.

We report the presence of a cycle-dependent sialoglycoprotein in the endometrium. A monoclonal antibody (D9B1) to this glycoprotein has been derived and used to study tissue from 24 women with normal menstrual cycles. Results obtained with peroxidase immunohistochemistry suggest a highly significant variation in concentration of the glycoprotein, which is absent in the proliferative phase and present at maximal levels in the early secretory phase. The amount of antigen then diminishes slowly through the latter part of the secretory phase. The glycoprotein is produced in epithelial cells of glands and uterine lumen before being secreted across the apical cell surface. The secretory response is uniform in different areas of the tissue and within individual glands. However, considerable differences in secretory activity can be observed between adjacent glands in any part of the endometrium. Binding of the antibody is shown to be a new and novel parameter in characterization and standardization of the normal function of endometrium in response to ovarian hormones.

Pelvic lymphocysts occurring after Wertheim's operation: a review of 11 years' experience

In an analysis of 100 cases of radical hysterectomy with extraperitoneal lymphadenectomy performed for carcinoma of the cervix, postoperative pelvic lymphocysts were detected in 11 patients (11 per cent). Eight of these (73 per cent) were asymptomatic. Although potentially serious complications are known to occur with lymphocysts. Only minor ones were encountered. This paper outlines the clinical features and management in this group of patients. A system of management dependent on the size and symptoms of the cyst is proposed

Surgery and radiotherapy in the treatment of primary carcinoma of the Fallopian tube--report of 18 cases.

Eighteen cases of primary Fallopian tube carcinoma referred to Christie Hospital, Manchester over the years 1966 to 1980 are reviewed. The overall 5-year survival rate was 14.4%. Treatment by total hysterectomy and bilateral salpingo-oophorectomy resulted in a longer survival compared to bilateral salpingo-oophorectomy or removal of the tumour alone. Postoperative radiotherapy did not seem to improve survival.

Primary carcinoma of the fallopian tube: favourable response to new chemotherapeutic agent, CHIP.

Two cases are reported of recurrent fallopian tube carcinoma treated with CHIP (cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV), a new cis-platinum analogue, resulting in one complete (though transient) and one good partial remission.

Maternal diabetes and neonatal respiratory distress. II. Prediction of fetal lung maturity.

Fifty babies were born at less than or equal to 37 weeks to mothers with diabetes. Delivery was undertaken in all patients with the reassurance that the L/S ratio was greater than or equal to 2.0 within the preceding 72 h. Five babies (10%) developed respiratory distress syndrome (RDS). Prediction of fetal lung maturity was improved dramatically by measuring amniotic fluid concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylglycerol (PG). Fourteen babies were predicted as having 'no surfactant' (PC less than 20 mg/l, PI less than 2 mg/l and PG less than 2 mg/l), five developed RDS. None of the remaining 36 babies developed the illness: they were predicted as having either 'early surfactant' (PC greater than or equal to 20 mg/l, PI greater than or equal to 2 mg/l but PG less than 2 mg/l) or 'late surfactant' (PC greater than or equal to 20 mg/l, PI greater than or equal to 2 mg/l and PG greater than or equal to 2 mg/l). Measurement of PC levels alone was the most was the most accurate method of predicting RDS. There was a significant association between low surfactant phospholipid concentrations and the development of transient tachypnoea of the newborn.

Maternal diabetes and neonatal respiratory distress. I. Maturation of fetal surfactant.

The phospholipid composition of amniotic fluid samples from 30 normal patients and 44 diabetic patients over the last 10 weeks of pregnancy was studied. Higher levels of phosphatidylcholine (PC) and phosphatidylinositol (PI) were found in diabetic pregnancies where there was excellent glucose control. These differences were statistically significant at 34-36 weeks. Phosphatidylglycerol (PG) appeared significantly earlier in the well controlled diabetic pregnancies, but even in the poorly controlled diabetics the levels of PC, PI and PG were comparable to those in normal pregnancies. There was no evidence of delayed appearance of fetal surfactant phospholipids in either the well or poorly controlled diabetic pregnancies. The absolute lecithin (PC)/sphingomyelin (SM) ratio in diabetic pregnancies was generally greater for any given gestational age than those in normal pregnancies. Whilst in most cases this was due to a higher PC concentration, in a few poorly controlled diabetics it was the result of a lower concentration of SM.

Is the lecithin/sphingomyelin ratio outdated?

The lecithin/sphingomyelin (L/S) ratio in amniotic fluid is an excellent predictor of fetal lung maturity in most pregnancies but today its value is limited. A review of the use of the L/S ratio service in Manchester from 1975 to 1981 (inclusive) shows a dramatic and consistent fall in the number of requests made over the last 18 months of this period resulting in inconvenience and inefficiency in the laboratory service. Possible explanations for the declining use of the L/S ratio service are discussed with particular reference to St Mary's Hospital, Manchester and a regional re-organization of laboratory assessment of fetal lung maturity is proposed.