A randomized trial comparing whole abdominal radiotherapy with chemotherapy following cisplatinum cytoreduction in epithelial ovarian cancer. West Midlands Ovarian Cancer Group Trial II.

The potential role of consolidation therapy has been tested in a randomized trial in ovarian cancer. Patients were randomized to receive either whole abdominal radiotherapy using the moving strip technique (n = 56) or one year of chlorambucil (n = 53) following primary surgery, five courses of cisplatinum 100 mg/m2, and second look laparotomy. Overall survival at two years was 35%. There was no significant difference in survival between the two groups, and in spite of the observation that approximately 50% of the patients were optimally debulked prior to consolidation, no subgroups in either arm could be identified who might benefit from consolidation therapy. Toxicity was considerable in both arms, and almost 50% of patients were unable to complete the planned treatment in both arms. These results suggest that after primary surgery and cisplatinum chemotherapy, there is no indication for consolidation therapy with either radiotherapy or alkylating agents.

Failure of second-look laparotomy to influence survival in epithelial ovarian cancer.

The survival benefit of second-look laparotomy after completion of primary chemotherapy in patients with epithelial ovarian cancer has been assessed in a prospective randomised trial of 166 patients. Patients were randomised into three groups. All were initially treated with cisplatin (100 mg/m2 x 5) after primary laparotomy. Group A (n = 53) was scheduled to have a second-look laparotomy, followed by cyclical oral chlorambucil. Group B (n = 56) was scheduled to have a second-look laparotomy, followed by total abdominal and pelvic irradiation, and group C (n = 57) received oral chlorambucil as for group A but had no second-look operation. With a median follow up of 46 months (range 21-64), no differences in survival were noted between the three groups. The median survival for group A was 21 months (95% CI 11-31 months), for group B 15 months (11-19), and for group C 17 months (8-26). Thus second-look laparotomy after completion of first-line single-agent cisplatin chemotherapy did not confer any survival benefit on patients with epithelial ovarian cancer.

Residual disease after cone biopsy: completeness of excision and follow-up cytology as predictive factors.

Residual disease was identified in the hysterectomy specimen in 19 of 65 patients (29%) previously found to have cervical intraepithelial neoplasia and in four of 19 (21%) found to have early stromal invasion on histologic examination of a cone biopsy. Residual disease was found in six of 34 cases (18%) of cervical intraepithelial neoplasia and zero of 12 cases of early stromal invasion after complete excision, and in 13 of 31 cases (42%) of cervical intraepithelial neoplasia and four of seven cases (57%) of early stromal invasion after incomplete excision by cone biopsy. Sixteen of 28 women (57%) with abnormal cytology after cone biopsy were found to have residual disease at the time of hysterectomy. In contrast, no residual disease was found in 35 patients who had no evidence of cytologic abnormality after the initial treatment. The finding of abnormal cytology after cone biopsy is shown to be a more useful prognostic indicator than histologic examination of excision margins. Therefore, we believe that a policy of expectant management, based on regular cytologic examination, is justified when histologic assessment has shown the lesion to extend to the line of excision.

Negative cone biopsies after colposcopy and their prediction.

A retrospective study of 899 cone biopsies revealed significantly more cones containing no dysplastic epithelium in patients who had a prior colposcopic assessment compared with those who had not been so assessed. A case-control study of 48 'negative' cones, 47 cones containing intraepithelial neoplasia (CIN), 44 microcarcinoma containing cones and 27 occult Ib containing cones has allowed five variables to be identified which can predict the presence of dysplastic or neoplastic tissue in the cone specimen. These variables include a colposcopic suspicion of invasion; a positive or worse pre-cone smear; two severely dyskaryotic smears within a 12-month observation period, previous abnormal histology and previous treatment for CIN. Using these criteria, 44% of 'negative' cones could be avoided without overlooking any cases of microcarcinoma or occult carcinoma.

The management of cervical intraepithelial neoplasia by coagulation electrodiathermy.

Of 140 women with cervical intraepithelial neoplasia treated with a single application of coagulation electrodiathermy, 123 (88%) remain cytologically free of disease after a median follow-up of 3 years. The new squamocolumnar junction was colposcopically visible in 70% of the 130 patients assessed after treatment. In 15 of 17 women requiring further treatment, residual disease was suspected at the time of the first postoperative assessment. The incidence of significant morbidity following this procedure was 4%. In selected patients coagulation electrodiathermy is an effective method of treating pre-invasive disease of the cervix.

The treatment of cervical intraepithelial neoplasia by laser vaporization.

Of 711 women with cervical intraepithelial neoplasia (CIN) treated by laser vaporization 675 (95%) remain colposcopically and cytologically free from disease after a median follow-up of 20 months. Thirty-six patients needed other forms of treatment to eradicate suspected residual disease. One patient presented with invasive carcinoma of the cervix 34 months after treatment with the carbon dioxide laser. It is concluded that in selected cases laser vaporization is an effective method of treating pre-invasive disease of the cervix.

Complications of cone biopsy related to the dimensions of the cone and the influence of prior colposcopic assessment.

A retrospective study of the complications of cone biopsy showed that among 915 women examined between the years 1976 and 1982, 121 (13%) had primary or secondary haemorrhage, 153 (17%) cervical stenosis and 39 (4%) subsequent infertility or an abnormal pregnancy. Cervical stenosis was commonest among women who had had long cones removed. Stenosis occurred more often in the group of women who had been assessed by colposcopy before operation but this was due to the fact that prior colposcopy selected a favourable group of patients with lesions of limited extent that were susceptible to treatment by local destructive therapy, so that prior colposcopic assessment resulted in the removal of longer cones.

The management of vaginal intraepithelial neoplasia after hysterectomy.

Twenty-three patients with vaginal intraepithelial neoplasia (VaIN) presented between 6 months and 13 years after hysterectomy for cervical intraepithelial neoplasia. All were discovered by cytological follow-up, were colposcopically assessed and diagnosis confirmed by histological examination before treatment. The CO2 laser was used as the initial treatment in 14, but only six remain free of disease after mean follow-up of 30 months. The reasons for the disappointing results with this form of therapy are discussed and it is suggested that its use may be inappropriate in the management of VaIN following hysterectomy as atypical epithelium may frequently be inaccessible as a result of being sequestered above the vault suture line or hidden in the recesses of the angles of the vaginal vault.

Mullerian mixed tumour of the uterine corpus: a clinical histopathological review of 28 patients.

Clinical and histopathological features of 28 patients with Mullerian mixed tumours of the uterine corpus presenting to the Birmingham and Midland Hospital for Women between 1972 and 1977 are reviewed. The 5-year survival value for this group of patients was 25% with 53.5% of patients dying within 12 months of diagnosis. The most important finding of prognostic value was the extent of the tumour at the time of diagnosis and where this was localized to the uterus, there was a 50% 5-year survival. The presence of specific types of heterotopic elements or numbers of mitotic elements were not correlated with outcome. Five patients had previously received radium for induction of a radiation menopause and the relevance of this treatment and other factors in the aetiology of the tumour are discussed.

[Endometrial disease after treatment with oestrogens and progestogens in the climateric (author's transl)]. / Pathologie endometriale apres traitement par estrogenes et progestatifs a la menopause.

PIP: This study was undertaken to examine the frequency of histologic endometrial anomalies with different types of estrogen therapy, whether or not associated to progesterone treatment. 1002 endometrial biopsies were done on 745 women who had received: 1) cyclic treatment with low-dose estrogen; 2) cyclic treatment with high-dose estrogen; 3) sequential estrogen-progestogen treatment; and 4) subcutaneous implant of estradiol. Frequency of abnormalities was 7.0% in the first group, 14.8% in the second group, 1.2% in the third group, and 14.8% in the fourth group. Without drawing definitive conclusions from these results, it seems possible to affirm that the use of progestogen diminishes the risk of endometrial cancer during menopause.^ieng

Endometrial disease after treatment with oestrogens and progestogens in the climacteric.

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.

Prevention and treatment of endometrial disease in climacteric women receiving oestrogen therapy.

The treatment regimens are described in 74 patients with endometrial disease among 850 climacteric women receiving oestrogen therapy. Cystic hyperplasia was associated with unopposed oestrogen therapy without progestagen. Two courses of 21 days of 5 mg norethisterone daily caused reversion to normal in all 57 cases of cystic hyperplasia and 6 of the 8 cases of atypical hyperplasia. 4 cases of endometrial carcinoma referred from elsewhere demonstrated the problems of inappropriate and unsupervised unopposed oestrogen therapy and the difficulty in distinguishing severe hyperplasia from malignancy. Cyclical low-dose oestrogen therapy with 7--13 days of progestagen does not seem to increase the risk of endometrial hyperplasia or carcinoma.

Relations between bleeding pattern, endometrial histology, and oestrogen treatment in menopausal women.

Vacuum curettage was performed on 348 women who had received various regimens of oestrogen treatment for an average of 9.7 months for climacteric symptoms. In 62 cases (18%) the specimens were unsatisfactory for histological assessment; among the remainder, however, they showed a normal endometrium in 257 cases (90%), cystic hyperplasia in 21 (7%), adenomatous hyperplasia in 7 (2%), and endometrial adenocarcinoma in one. Cyclical unopposed oral oestrogen treatment (98 cases) was associated with a 12% incidence of endometrial hyperplasia, but among those given an additional five-day course of progestogen in each cycle (37 cases) the incidence was only 8%. No case of hyperplasia occurred among 102 women taking regimens including 10 or 13 days of progestogen. Among women treated with subcutaneous oestradiol implants and monthly five-day courses of oral progestogen (50 cases) there was a 28% incidence of hyperplasia including the one case of carcinoma, though some of those with hyperplasia may not have taken the full course of progestogen. Regular withdrawal bleeding during treatment was associated with a lower incidence of endometrial hyperplasia (6%) than unscheduled breakthrough bleeding (28%), but the one patient with carcinoma had experienced regular bleeding only.The risk of developing endometrial carcinoma from oestrogen treatment may be reduced by avoiding the use of unopposed oestrogen regimens, the addition of more than five days' treatment with a progestogen, and recognising that a regular bleeding response to oestrogen is no guarantee of a healthy endometrium.