Total laparoscopic radical hysterectomy: a change in practice for the management of early stage cervical cancer in a U.K. cancer center.

In order to evaluate the safety, surgical, and oncological outcomes of the introduction of a total laparoscopic radical hysterectomy (TLRH) service, the authors conducted a retrospective review of all TLRHs performed in the present centre from the beginning of the service in August 2010. TLRH appears in this series to be safe. Complication rates were comparable to National Institute for Health and Clinical Excellence (NICE) and literature standards. Oncological outcomes, despite the short follow up period, appear acceptable. TLRH is a valuable alternative to open surgery for the treatment of early cervical cancer.

Routine follow-up after treatment for a gynecological cancer: a survey of practice.

The objective of this study was to determine current practice with regards to follow-up after gynecological malignancy. A questionnaire survey of all lead clinicians in gynecological cancer centers in England was done. The most common duration of routine follow-up was 5 years for all of the main gynecological cancers (ovarian, endometrial, vulval, and cervical). The most common follow-up patterns were three monthly for 2 years then six monthly for 3 years after ovarian cancer; three monthly for the first year, four monthly for the second year, six monthly for the third year then annually for 1 year after endometrial cancer; three monthly for the first year, four monthly for the second year, six monthly for the third and fourth years, then annually for 1 year after vulval cancer; three monthly for the first year, four monthly for the second year, six monthly for the third and fourth years, then annually for 1 year after cervical cancer. The test for CA125 was routinely performed by 67% of cancer networks to detect recurrence after ovarian cancer. Routine follow-up after gynecological cancer continues to be standard practice, despite limited evidence to support its use. Prospective research is needed to determine best practice.

The outcome of referral with postcoital bleeding (PCB).

We reviewed 284 women with postcoital bleeding (PCB) seen in colposcopy and gynaecology clinics over eight years. 166 women were referred with PCB alone (group 1) and 118 with PCB and abnormal cervical cytology (group 2). The aim was to assess the validity of the Department of Health (DoH) referral guidelines for suspected cancer in women with PCB, to measure the frequency of abnormal findings in these women, and to review the management of PCB with the aim of identifying and addressing deficiencies. No pathology was identified in half of women in group one and in 17% of group two. The rate of cervical cancer was 3.6% in group one and 5% in group two. The equivalent figures for CIN were 9% and 66.1% respectively. There was no significant difference in the prevalence of cervical cancer or CIN between women >?35 years and the rest of women in group one. The management of PCB was inconsistent. Neither age nor duration of PCB was a reliable indicator for cervical cancer. A normal smear record must not be regarded as reassuring in a woman with PCB.

The role of routine follow-up after gynecological malignancy.

The objective of this article was to determine the evidence base for routine follow-up after gynecological malignancy. Only articles with a survival analysis were included. Relevant articles were identified by a comprehensive literature search of the main biomedical databases, hand searching of references of selected articles, and expert spotting of relevant journals and proceedings of international meetings. A two-stage extraction of data was undertaken. No prospective trials were identified. Twenty-nine retrospective case series analyses and one poster presentation met the inclusion criteria. Eight articles and one letter on endometrial cancer, six articles and one poster presentation on cervical cancer, and two articles in vulval cancer were reviewed. Only one article in endometrial cancer showed any survival benefit from routine follow-up, but it was of very poor methodologic quality. Two articles found a survival benefit from routine follow-up after cervical cancer. The two articles on vulval cancer did not find any survival benefit from routine review. There is no prospective research on the benefits of routine follow-up after gynecological cancer. Retrospective evidence calls in to question the benefit of universal follow-up. Prospective research is urgently needed.

Preconceptions versus experience of transvaginal ultrasonography in older women.

OBJECTIVE: To determine whether women find that having a transvaginal ultrasound scan is better or worse than they had expected. METHODS: Fifty-four consecutive women in an ovarian cancer screening trial filled in linked questionnaires before and after having a transvaginal ultrasound scan. RESULTS: The women found that having a transvaginal scan was less painful (P = 0.003) and less embarrassing (P = 0.001) than they had expected. They found it less uncomfortable than expected in comparison to having mammography (P = 0.013) or a cervical smear (P = 0.004). CONCLUSIONS: Women attending for a transvaginal scan can be reassured that it will not be as painful or embarrassing as they fear, and that it is not as uncomfortable as having mammography or a cervical smear.

The clinical value and the cost-effectiveness of follow-up in endometrial cancer patients.

The aim of the present article was to evaluate the cost-effectiveness of follow-up in endometrial cancer patients. A literature review was performed regarding the studies that addressed routine follow-up of endometrial cancer. For each published study, the costs of the follow-up program were calculated according to Belgium standards. A mean total of 13% relapsed. Symptomatology and clinical examination detected over 83% of the recurrences. The follow-up cost in euro after 5 and 10 years ranged between 127.68 and 2,028.78 and between 207.48 and 2,353.48, respectively. Based on the available data, there is little evidence of routine follow-up improving survival rates. Multiple protocols are used in practice without an evidence base. There is an urgent need for prospective randomized studies to evaluate the value of the current so-called 'standard medical practice of follow-up.' It is to be expected that the cost of follow-up could be reduced considerably, for instance, by tailoring to low- and high-risk groups, or by abandoning routine follow-up. Symptomatic patients, however, should be evaluated immediately. A reduction in the number of visits and examinations would mean an enormous reduction in costs. This economic benefit would be warmly welcomed in the times of increased health costs and decreased budgets.

Tolerability of transvaginal ultrasonography as an ovarian cancer screening test.

OBJECTIVE: To evaluate the acceptability of transvaginal ultrasonography as a screening tool. DESIGN: Prospective survey of women attending for screening within a randomised controlled trial. SETTING: University Hospital in Teesside. PARTICIPANTS AND METHODS: 54 women completed a questionnaire immediately after their first transvaginal ultrasound scan. RESULTS: 52 of 54 (96%) questionnaires were suitable for full analysis. The women were unlikely to find the scan was painful, 47 vs three (p<0.001), or embarrassing 45 vs five (p<0.001). Women were more likely to find both a smear, 42 vs eight (p<0.001) and a mammogram, 47 vs two (p<0.001) was more uncomfortable than transvaginal ultrasonography. CONCLUSIONS: Transvaginal ultrasonography is an acceptable tool for screening for ovarian cancer. It is better tolerated than other screening tools such as cervical smear and mammography.

Medical termination of pregnancy at 63 to 83 days gestation.

OBJECTIVE: To assess the efficacy of a medical regimen for the termination of pregnancy within the gestational age range of 63 to 83 days. DESIGN: Prospective observational study. SETTING: Gynaecology department within a district general hospital. POPULATION: Women attending the pregnancy advisory clinic between June 1996 and December 1997. METHODS: The medical regimen used was mifepristone 200 mg orally followed after 36 to 48 h by misoprostol 800 microg administered vaginally. MAIN OUTCOME MEASURES: The success rate of the medical termination of pregnancy regimen, where success was defined as achieving complete abortion without the need for secondary intervention by either surgical or repeat medical means. RESULTS: Primary medical termination of pregnancy was chosen by 253 (80.8%) of the 313 women and was successful in 239 (94.5%). Repeat medical treatment achieved completion of the abortion in a further three women (1.2%) and surgical evacuation of the uterus was required in 10 (4.0%). One woman declined further intervention after failed medical treatment but subsequently miscarried. CONCLUSIONS: The combination of mifepristone and misoprostol is effective for the termination of pregnancy for gestations of 63 to 83 days.

Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group.

PURPOSE: In 1992, we reported the first results of a randomized study in ovarian cancer, comprising two doses of cisplatin and indicated a significant difference (P = .0008) in median survival. Four years later, we now describe the results of this trial. PATIENTS AND METHODS: After a median follow-up of 4 years and 9 months, 115 of 159 cases of advanced ovarian cancer, originally randomized to receive six cycles of cyclophosphamide 750 mg/m2 and either a high dose (HD) of 100 mg/m2 cisplatin or a low dose (LD) of 50 mg/m2 (LD) cisplatin, have now died. RESULTS: The overall survival for HD and LD patients is 32.4% and 26.6%, respectively, and the overall relative death rate is 0.68 (P = .043). This represents a reduction in overall benefit with longer follow-up compared with the first 2 years (relative death rate of 0.52). Toxicity, particularly neurotoxicity, is still evident in the fourth year (10/31 on HD compared with 1/24 on LD). CONCLUSION: Our recommended dose of cisplatin in combination schedule is therefore 75 mg/m2, representing the optimal balance between efficacy and toxicity.

Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, pre-eclampsia and hydatidiform mole.

OBJECTIVE: To examine the behaviour of the major inhibitors of fibrinolysis (PAI-1 and PAI-2) in normal pregnancy and pregnancy complicated by either pre-eclampsia or hydatidiform mole. DESIGN: Prospective study. SETTING: Antenatal Clinic and Maternity Hospital. SUBJECTS: Eleven women with established pre-eclampsia and eleven women, matched by age, parity, and duration of pregnancy who were undergoing uncomplicated pregnancy. Two women having surgery for hydatidiform mole. MAIN OUTCOME MEASURE: Plasma levels of PAI-1 and PAI-2 antigens determined by sensitive specific ELISA. Functional identification of PAI-2 by nondenaturing gel electrophoresis with overlay zymography. RESULTS: In pre-eclampsia PAI-2 antigen was significantly lower than in normal pregnancy (105.3 +/- 34.9 versus 187.1 +/- 67.9 ng/ml; P < 0.001). In contrast PAI-1 antigen was significantly higher in pre-eclampsia than in normal pregnancy (170.7 +/- 71.2 versus 113.8 +/- 35.6 ng/ml; P < 0.05). In consequence the ratio of PAI-1/PAI-2 increased markedly in pre-eclampsia (2.5 versus 0.6). No PAI-2 was detected in plasma of women with hydatidiform moles. CONCLUSIONS: PAI-2 levels fell significantly in pre-eclampsia probably as a result of decreased placental mass or function. The raised PAI-1 level in pre-eclampsia may reflect a response to hypertension or renal damage that is not specific to pregnancy or may reflect altered placental function. The use of the ratio of PAI-1/PAI-2 assists in separating normal from abnormal pregnancies.

Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer.

Cisplatin is generally accepted to be the most active cytotoxic agent for the treatment of ovarian cancer but the optimum dose remains unclear. We have performed a randomised trial to assess the importance of cisplatin dose in the treatment of advanced epithelial ovarian cancer. Patients were randomly assigned treatment with 50 mg/m2 (low dose) or 100 mg/m2 (high dose) cisplatin plus 750 mg/m2 cyclophosphamide, for a maximum of six cycles with intervals of 3 weeks. We planned to recruit 300 patients, but an interim analysis on the first 165 indicated a highly significant survival difference (p = 0.0008). Recruitment was therefore stopped and the trial patients were followed-up for 12 months longer. The relative progression rate (high-dose/low-dose) after 12 months' extra follow-up was 0.55 (95% confidence interval 0.37-0.81, p = 0.003) and the relative death rate 0.53 (0.34-0.81, p = 0.003). Overall median survival was 69 weeks in the low-dose group and 114 weeks in the high-dose group. Residual disease extent before chemotherapy had an important influence--patients with lesions of less than 2 cm did best; if given high-dose cisplatin their median survival was 3 years. 56 low-dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9 patients, respectively, were withdrawn early because of progressive disease and treatment was stopped in 6 and 25, respectively, because of unacceptable side-effects or patient refusal. Toxic effects were significantly greater in the high-dose group, especially those on the nervous system and ears, alopecia, vomiting, and anaemia. Although the higher dose of cisplatin clearly leads to better results in terms of survival, its overall clinical benefit in the management of ovarian cancer will depend on further improvements in measures to alleviate toxic effects.

Does labetalol influence the development of proteinuria in pregnancy hypertension? A randomised controlled study.

It is the development of proteinuria in pregnancy-induced hypertension which is associated with an increased perinatal mortality. There is some evidence to suggest that labetalol may diminish the amount of proteinuria in patients who have already developed proteinuric pre-eclampsia. A randomised controlled study design was used to investigate whether labetalol treatment, started when a persistent diastolic blood pressure greater than 90 mmHg was observed, influenced the subsequent development of proteinuria. One hundred and fourteen women with singleton pregnancies and hypertension in the absence of proteinuria were randomised to receive either labetalol or no antihypertensive therapy. At recruitment maternal age, blood pressure and gestation were similar in both the labetalol and control groups. There was no difference in the frequency, quantity or timing of subsequent proteinuria between treatment and control groups. Overall 34% of primigravidae and 10% of parous women developed proteinuria. Labetalol did, however, control the blood pressure in 45 of the 51 treated women (88%) within 24 h. This effect was often shortlived requiring dose escalation after 3 to 5 days in the majority of cases. Labetalol was well tolerated and no significant maternal toxicity was noted.

An independent evaluation of the potential clinical usefulness of proposed CA-125 indices previously shown to be of prognostic significance in epithelial ovarian cancer.

CA-125 levels were assessed prior to each of the first three cycles of chemotherapy, in 81 patients with epithelial ovarian cancer receiving first-line chemotherapy. All patients have at least 1 year's follow-up. Thirty-nine patients (48%) have progressed clinically or have died within 1 year of treatment (treatment 'failures'). Three CA-125 indices previously shown to be of prognostic value are assessed for their ability to pick-out these 'failures'. When the indices examined are modified to obtain a specificity for picking out failures just exceeding 90%, the maximum sensitivity obtained was 46%. The use of CA-125 for clinical decision making in ovarian cancer requires further investigation to determine and validate a prognostic index with acceptable sensitivity and specificity, and to determine the clinical impact of treatment decisions made using such an index.

CA125-response assessment in epithelial ovarian cancer.

To assess the clinical potential of serial serum CA125 measurements in the follow-up of patients with epithelial ovarian cancer, 74 consecutive unselected patients with histologically confirmed ovarian carcinoma were studied prospectively. There was an 83% concordance between clinical assessment and CA125 assessment of response. The positive predictive values of a rising CA125 for disease progression and a falling CA125 for disease regression were 0.93 and 0.94, respectively. The absolute CA125 values during observations of complete response (mean 96 U/ml; 95% confidence interval; 33 to 128 U/ml), partial response (mean 134 U/ml; 95% confidence interval; 98 to 159 U/ml) and stable or progressive disease (mean 391 U/ml; 95% confidence interval; 282 to 545 U/ml) were significantly different. A randomized study is required to determine whether CA125 monitoring has any benefit in terms of outcome, and particularly survival, in epithelial ovarian cancer.

The multidisciplinary management of a family with epithelial ovarian cancer.

OBJECTIVE: To describe the management of a family with an inherited predisposition to ovarian and breast cancer. Particular attention is paid to the problems of contraception, screening, prophylactic surgery and hormone replacement therapy. SETTING: The multidisciplinary Grampian Familial Epithelial Ovarian Cancer Study Group. SUBJECTS: 162 members of a family extending over five generations. In the third generation, five of the 10 women died with epithelial ovarian cancer. Three women in generation IV have developed pre-menopausal breast cancer. There are now 78 family members in the fifth generation aged between 2 and 22 years. INTERVENTIONS: Counselling of female family members is started at the age of 18 years. The combined oral contraceptive pill is advocated to suppress ovulation. Gynaecological follow-up after the age of 28 includes yearly pelvic examination, transvaginal ultrasonography and serum CA125 estimation. Laparoscopy with peritoneal cytology is indicated if any part of this yearly assessment is abnormal. Prophylactic oophorectomy is advised between the ages of 35 and 40 years after the family is complete. In generation IV, 20 of the 29 women have undergone prophylactic oophorectomy. Oestrogen hormone replacement therapy with a cyclical progestogen is recommended after prophylactic oophorectomy. Breast cancer screening starts at the age of 25 and involves annual clinical breast examination augmented by mammography and breast ultrasound. CONCLUSIONS: Only by the careful questioning and recording of family history, including at least third degree relatives (cousins), will similar groups with familial ovarian/breast cancer be identified. When predisposing genes are characterized it will be possible to identify carriers within the family and concentrate clinical effort on them while offering appropriate reassurance to those with decreased risk.