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Surgery for ovarian cancer carries a risk of bowel resection to either achieve optimal debulking or relieve obstruction. This prospective study assessed the likelihood of bowel resection in 842 women undergoing surgery for ovarian cancer and identified factors associated with increased risk. Bowel resection was performed in 8.6% of women. The likelihood of bowel resection increased significantly (p < 0.0001, chi2 test) with: Secondary surgery (22% vs 5.8% at primary surgery). Symptoms of bowel disturbance (21.9% vs 6.3% if no symptoms). FIGO stage III/IV disease (12.8% vs 2% in stage I/II). CA125 levels >or=2500 (12.9% vs 4.8% if CA125<2500). These women should be selectively offered pre-operative computerised tomography, stoma marking and counselling by stoma nurses. The 5-year survival was 14% in patients following bowel resection compared with 44% in patients not having bowel resection. Bowel resection should be performed only if it will result in optimal debulking or it relieves imminent bowel obstruction.

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This article aims to cover current concepts and controversies in the surgical management of ovarian cancer. While there have been significant advances in the surgical management of vulval, cervical and even endometrial cancer there have been few developments in the surgical management of ovarian cancer. This situation is likely to continue until we get a clearer understanding of the natural history of this disease and better therapeutic options become available.

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Residual disease following primary debulking surgery is a recognized prognostic factor in ovarian cancer. Few studies have looked at the effect of initial ovarian tumor diameter on survival. As larger tumors are more likely to be detected by ultrasound, this information may be important in determining a survival benefit in screen-detected cancers. We reviewed the case notes and pathology of 168 consecutive cases of primary debulking surgery in epithelial ovarian cancer. We examined the influence of ovarian tumor diameter on survival and its relationship to CA125 levels and stage. For the purposes of analyses, we divided subjects into two groups: those with tumors < 6 cm and those with tumors > 6 cm. There were significant differences between the groups, with smaller tumors having more advanced stage disease compared to larger tumors (chi23 = 15.7, P = 0.0013) The median survival for tumors less than or equal to 6 cm was 17months (95% confidence interval [95% CI], 12 to 22), while for tumors greater than 6cm, the median survival was 36 months (95% CI, 13 to 59; logrank test = 8.61, P = 0.003). However, stage is also an important predictor of survival, and in a multivariate analysis, tumor size was not found to be an independent prognostic factor. There was no significant difference between the groups for CA125 levels. As larger diameter ovaries are more likely to be detected by ultrasound, it may be that screen-detected ovarian cancers will show a survival benefit simply because they detect a subset of ovarian cancers that are associated with a better prognosis.

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This study examined the relationships among age (2-20 years) and the impacts of 12 common triggers in episodes of childhood asthma. The triggers were: air pollution, allergy problems, cigarette smoke, stress or worry, anger, excitement, laughter, high/low environmental temperature, high humidity, respiratory infection, nighttime hours, and physical activity. Data were analyzed from families with asthmatic children (n = 119) as part of a larger study of biological and psychosocial factors in asthma and other illnesses. Positive correlations were found for age and the trigger impacts of allergy problems (p = 0.025) and physical activity (p = 0.004); negative correlations were found for age and the trigger impacts of nighttime hours (p = 0.002) and respiratory infection (p = 0.002). Age was also negatively correlated with the frequency of recent respiratory infections (p = 0.000) and positively correlated with the intensity of hay fever episodes (p = 0.047). These findings indicate that as children with asthma get older, their asthma episodes are more likely to be influenced by allergy problems and physical activity, and less likely to be associated with nighttime hours and respiratory infections.

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We present a prospective observational study of ovarian function following Wertheim's hysterectomy and its relationship to age at hysterectomy. Serum gonadotrophin measurements were made annually on 55 women following Wertheim's hysterectomy with ovarian preservation. Within 1 year of surgery four women (4/54) had biochemical evidence of ovarian failure, three of whom were over the age of 40 at operation. At 2 years eight women (8/51) had ovarian failure, seven of these women were over the age of 40 at the time of surgery. After 4 years 11 women had ovarian failure (11/34), eight of these were over the age of 40 at operation. Ovarian function following Wertheim's hysterectomy is well maintained in women under the age of 40 at the time of their surgery, 87% of these women had normal gonadotrophin levels 4 years after their surgery. For women over the age of 40 ovarian function is poorly maintained, with only 27% with normal gonadotrophins 4 years following surgery. These data suggest that we should carefully consider recommending bilateral oophorectomy at Wertheim's hysterectomy in women over the age of 40.

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The aetiology of postoperative back pain is contentious. Although the role of the surgical position has not been fully established, the lithotomy position is often implicated. In order to investigate this common surgical complication further, a prospective study has been performed on 101 hysterectomy patients. The supine (52 patients) and the lithotomy (49 patients) positions have been compared and contrasted within this series. Ten patients in the supine group (20%) and seven patients in the lithotomy group (14%) developed postoperative low back pain (p > 0.1). The mean duration of symptoms postoperatively for the whole series was 7 months. We conclude that postoperative backache is an under-estimated complication of surgery and that this problem occurs equally whether the supine or the lithotomy positions are used.

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Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy. Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy, but many patients are treated with radical radiotherapy. At present there is no method of accurately identifying patients at high risk of recurrence in the latter group. A retrospective analysis of 141 surgically managed cases with stage I/II a cervical cancer is presented. The study aims were to characterize patients at high risk of relapse, identify independent prognostic variables predicting for relapse and, using these variables, develop a model, that would accurately predict high-risk patients. Univariate analysis identified depth of invasion, substage, lymph node involvement, lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables. After stratification for depth of invasion, which did not conform to the proportional hazards assumption implicit in the Cox model, Cox regression analysis showed substage, lymphatic and vascular invasion and histological tumour type to be independent prognostic variables. Using these variables, classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy. Applying the models to 110 cases with greater than 18 months follow-up, 11/18 (61%) and 11/19 cases (58%) predicted as being at high risk of relapse have developed recurrence. Highly active chemotherapy is now available for this disease. We have demonstrated that combined bleomycin, ifosfamide and cisplatin (BIP) is one of the most active regimens in this disease. BIP produces cytoreduction in around 70% of patients with recurrent and primary advanced disease. Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy. A multicentre, prospective randomized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress. A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy is in preparation.

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The smear histories of 312 women with cancer of the cervix have been determined. Eighty nine women had had at least one negative smear reported in the 10 years before a diagnosis of cancer and 14 had had more than one negative smear. Fifty six of the 89 women had had a negative smear in the three years preceding the diagnosis of cancer. The highest number of negative smears (61) reported was among the 115 women aged under 45. Fifty eight slides reported as negative were submitted to independent review; 13 were subsequently reported as negative, 11 as unsatisfactory, and 34 as abnormal. These findings may in part explain why in this region there has been a disappointing reduction in the incidence of clinically invasive cervix cancer, and our findings may also apply elsewhere. Nevertheless, the confirmed negative smears chiefly occurred within three years of clinical cancer, particularly in the younger women, and this finding suggests that these women may have a short preinvasive phase.

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The effects of the climacteric and sequential mestranol and norethisterone on the epithelium of the cervix and genital tract were determined in 12 postmenopausal women. Before treatment the squamocolumnar junction was visible in only six of the 12 women, but after treatment with sequential mestranol and norethisterone the squamocolumnar junction became visible due to a minor degree of eversion. Mucus, which was always absent before therapy, was always seen afterwards and any atrophic effects were reversed by therapy within 3 months. The effects of oestrogen and progestogen deficiency were more easily seen by scanning electron microscopy (SEM) than with conventional histology. Before treatment six of the nine women studied by SEM had a cervix covered by mature squamous epithelium, but after therapy all the women had mature squamous epithelium. The pretreatment lateral vaginal wall and urinary sediment smears showed mainly immature squamous cells; this correlated poorly with the histology and SEM of the cervix. There was a good correlation between urinary sediment and lateral vaginal wall smears both before and after treatment.

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A randomised, double-blind, cross-over study into the effect of graded sequential mestranol and norethisterone on climacteric symptoms was performed. The study group consisted of 23 post-menopausal women who had previously undergone hysterectomy. Active therapy resulted in a significant reduction in hot flushes and night sweats. There was a slight improvement in insomnia, lack of energy and confidence but the other symptoms were not significantly altered. A small placebo effect was noted but this was only significant 1 mth after active treatment had been discontinued in the group of women receiving placebo second. Active treatment also resulted in a significant reduction in serum sodium, calcium, albumin, alkaline phosphatase and cholesterol, and increase in serum triglycerides, but no alteration in the other biochemical parameters, weight or blood pressure.

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A randomized double-blind cross-over study into the effect of northisterone on climacteric symptoms was performed on 23 postmenopausal women. Active therapy resulted in a significant reduction in the number and severity of hot flushes and night sweats. There was also a slight improvement in memory, insomnia and lack of energy but the other climacteric symptoms were not consistently altered. Side effects were minimal. There was a significant reduction in serum calcium, alkaline phosphatase, cholesterol, triglycerides, follicle-stimulating hormone and luteinizing hormone levels. There was a variable effect on serum creatinine and urea but there was no significant alteration in the other biochemical profiles, liver-function tests, weight or blood pressure.

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Serum biochemical profiles were compared in matched groups of premenopausal and postmenopausal women. Significantly higher concentrations of sodium, urea, calcium, albumin and alkaline phosphatase were found in the postmenopausal group. In the postmenopausal group, following treatment with sequential mestranol and norethisterone, significant reductions were recorded in the concentrations of sodium, urea, calcium, albumin, alkaline phosphatase and glucose and significant increases were recorded in the concentration of globulin and in body weight. The findings suggest that haemoconcentration may take place after the menopause and that this effect may be modified by hormone treatment. No adverse effect on liver function was noted following the hormone treatment.

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The serum cholesterol and triglyceride concentrations of 84 postmenopausal women both before and after 2, 6 and 12 months therapy with various regimens of hormone therapy were measured. There was little alteration in mean serum cholesterol concentration with cyclical oestrogens but both sequential mestranol and norethisterone and sequential oestradiol valerate and norgestrel significantly reduced the mean serum cholesterol concentration to a level similar to that found in age-matched premenopausal women. There was a small and sometimes significant rise in serum triglyceride concentration with cyclical oestrogens. Sequential mestranol and norethisterone significantly elevated serum triglyceride levels, but sequential oestradiol valerate and norgestrel significantly depressed them. The results suggest that the progestogenic agent norgestrel has an important role to play in reducing both serum cholesterol and triglyceride levels, and that the sequential preparations, by virtue of their greater cholesterol lowering effect, should perhaps be preferred to cyclical oestrogens.

PIP: The serum cholesterol and triglyceride concentrations of 84 postmenopausal women both before and after 2, 6 and 12 months therapy with various regimens of hormone therapy were measured. There was little alteration in mean serum cholesterol concentration with cyclical estrogens but both sequential mestranol and norethisterone and sequential estradiol valerate and norgestrel significantly reduced the mean serum cholesterol concentration to a level similar to that found in age-matched premenopausal women. There was a small and sometimes significant rise in serum triglyceride concentration with cyclical estrogens. Sequential mestranol and norethisterone significantly elevated serum triglyceride levels, but sequential estradiol valerate and norgestrel significantly depressed them. The results suggest that the progestogenic agent norgestrel has an important role to play in reducing both serum cholesterol and triglyceride levels, and that the sequential preparations, by virtue of their greater cholesterol lowering effect, should perhaps be preferred to cyclical estrogens.

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A prospective study of 745 women receiving different regimens of hormone treatment for the climacteric for a total of 21 736 months was performed. There was a lower incidence of endometrial hyperplasia in biopsy specimens in the women receiving cyclical low-dose oestrogen by mouth than in those receiving cyclical high-dose oestrogen by mouth. The incidence of abnormalities in the women receiving sequential oestrogen and progestogen was lower than in either of these two groups. Among the women receiving subcutaneous oestrogen implants the incidence was higher still, but over half of the abnormal specimens were from women who had not taken their progestogen. The incidence of hyperplasia fell with longer courses of progestogen, and no hyperplasia was found in patients taking progestogen for over 10 days each month. The incidence of adenomatous and atypical hyperplasia is significantly reduced by a progestogen when taken for 10 or more days monthly. The absence of vaginal bleeding or of a regular bleeding response does not guarantee histologically normal endometrium in patients taking oestrogens without progestogen.

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The serum cholesterol, triglycerides and electrophoretic lipoprotein patterns of 35 postmenopausal women, who subsequently received sequential mestranol and norethisterone, were compared with those of 35 premenopasual women of the same age and weight. The postmenopausal women had a significantly higher level of serum cholesterol (p less than 0.01) than the premenopausal women, and a significant reduction (p less than 0.001) occurred in this group after two months of therapy. There was no significant difference in level of serum cholesterol between the premenopausal group and the postmenopausal group receiving sequential mestranol and norethisterone for two months. The serum triglycerides were not significantly higher in the postmenopausal group but there was a significant increase (p less than 0.001) after two months of therapy. The marked alteration in lipid levels at the menopause may in part account for the great increase in coronary artery disease in postmenopausal women but whether these changes are reversible by giving hormone therapy remains speculative.

PIP: Incidence of cardiovascular disease increases in postmenopausal women and may be related to elevated serum lipid concentrations. The serum cholestrol, triglycerides, and electrophoretic lipoprotein patterns of 35 postmenopausal women receiving sequential mestranol and norethisterone showed a reduction of serum cholesterol with concurrent increase in serum triglycerides after 2 months therapy. Postmenopausal women who were not treated had greater serum cholesterol concentration than either the treated postmenopausal women or 35 premenopausal women matched for age and weight. However, there were no significant concentration differences between the treated postmenopausal women and premenopausal women. It is uncertain whether reduced serum cholesterol levels will reduce the incidence of coronary artery disease nor whether administering estrogens and progestogens will reduce coronary artery disease since there is a marked alteration in lipid metabolism at menopause.

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