Obstetric management following fertility-sparing radical vaginal trachelectomy for cervical cancer.

Radical vaginal trachelectomy now affords a fertility-sparing procedure for the treatment of early-stage cervical cancer in young women. Subsequent obstetric management within this group of women remains a challenge to the obstetrician, with risks of premature labour a continuing probability throughout pregnancy. Here we describe four cases of successful pregnancy following radical vaginal trachelectomy within our unit. The merits of early antenatal intervention, regular lower uterine segment length monitoring and use of daily progesterone pessaries are discussed, alongside the current supportive evidence. We conclude with a discussion of proposed recommendations for obstetric management of pregnancy in women post-radical vaginal trachelectomy.

Phase I/II study of intraperitoneal iproplatin in patients with minimal residual disease following platinum-based systemic therapy for epithelial ovarian carcinoma.

13 patients with minimal residual disease following platinum-based systemic therapy for epithelial ovarian cancer were treated with intraperitoneal iproplatin. A total of three cycles were given at monthly intervals. All patients had minimal residual disease (defined as less than 2 cm in diameter) or positive cytology documented at second look laparotomy following systemic chemotherapy. Iproplatin was administered via a temporary dialysis catheter (n = 11) or a semi permanent Tenckhoff peritoneal dialysis catheter (n = 2). The dose of iproplatin ranged from 150 to 450 mg/m2. No responses to therapy were documented. In this trial the major toxic side effects of iproplatin were thrombocytopenia, diarrhoea, nausea and vomiting. The maximum tolerated dose was 300 mg/m2.

Carcinosarcoma of the ovary treated over a 10-year period at the Christie Hospital.

Carcinosarcomas (previously termed malignant mixed Müllerian tumors) are highly malignant but rare tumors of the ovary. Most patients have been treated according to a wide variety of protocols for soft tissue sarcoma or for epithelial ovarian carcinoma and as a result the optimal treatment for this neoplasm is unknown. We describe here 20 patients with this ovarian tumor (15 with heterologous sarcomatous elements and five with homologous sarcomatous elements) referred to our institute. Five patients were treated with surgery alone, two patients with chemotherapy alone and 13 patients with a combination of surgery and chemotherapy. A variety of chemotherapeutic regimens were used reflecting the 10-year time span it took to accrue these patients. Forty-five per cent of all patients died within 1 year of initial surgery and there was a median survival of 14 months. Two patients achieved a complete remission following treatment with 10 cycles of intravenous cyclophosphamide and are still alive at 103 and 106 months follow-up. We suggest that a chemotherapy regimen combining cyclophosphamide and a platinum analog may be useful for the management of patients with carcinosarcoma of the ovary requiring further therapy following surgery.

Stage Ia endometrial carcinoma diagnosed on removal of an IUD.

This is a case report of a 49-year-old woman who presented with offensive vaginal discharge. Her Lippes loop IUD was removed and discovered to have suspicious material attached. Histology report was of endometrial carcinoma. This is the first report of an endometrial carcinoma being completely removed along with an IUD.

Successful pregnancy following radical trachelectomy and in vitro fertilisation with ovum donation.

This is the first known documented case of a successful pregnancy following fertility-preserving radical trachelectomy, ovum donation and in vitro fertilisation.

Immunohistochemical detection of mutant p53 protein in epithelial ovarian cancer using polyclonal antibody CMI: correlation with histopathology and clinical features.

Approximately 30-50% of cases of ovarian adenocarcinoma harbour mutations in the p53 tumour-suppressor gene associated with elevated levels of the protein detected by immunohistochemical staining. To investigate any relation between the presence of mutant p53 and clinicopathological features of disease, we examined a series of 50 cases of epithelial ovarian adenocarcinoma for expression of p53 by immunohistological staining on fixed, paraffin-embedded tissue sections using the polyclonal antibody CM1, and by direct nucleotide sequencing of polymerase chain reaction-amplified DNA from selected cases. Of the 50 cases examined, 28 (56%) were p53 positive and there was no significant correlation between p53 status and differentiation stage, clinical (FIGO) stage, multidrug resistance (mdr-1 P-glycoprotein) expression or response to treatment. However, we observed a statistically significant difference between the high prevalence of p53-positive serous tumours (18 out of 23) and the lower prevalence of p53-positive cases in mucinous tumours (3 of 12) suggesting that factors related to disease aetiology, associated with these histological subtypes, may determine the prevalence of functional inactivation of the p53 tumour-suppressor gene in ovarian adenocarcinoma.

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.

A randomised trial investigating the dose intensity of primary chemotherapy in patients with ovarian carcinoma: a comparison of chemotherapy given every four weeks with the same chemotherapy given at three week intervals.

BACKGROUND: The dose intensity of chemotherapy for patients with ovarian carcinoma remains a controversial issue. Few randomised trials have been conducted examining dose intensity using the same total dose of chemotherapy. This study was designed to investigate two schedules of chemotherapy using standard and higher dose intensity with both groups receiving the same total dose. PATIENTS AND METHODS: Patients with FIGO stage IC, II, III and IV epithelial ovarian carcinoma were randomised to receive cycles of cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with doxorubicin (50 mg/ m2) and ifosfamide (5 g/m2) at either four-weekly (n = 47) or three-weekly (n = 97) intervals (1:2 randomisation). At randomisation patients were stratified according to histological grade and amount of post operative residual tumour (greater or less than 2 cm). The two arms of the study were well balanced in terms of the major prognostic features. RESULTS: There was no difference in either progression free survival or overall survival between the two arms. The median overall survival was 730 days for the three-weekly treatment and 740 days in the four-weekly arm (progression-free survival was 500 days and 483 days, respectively). The combined overall response rate (complete and partial response) in the 114 assessable patients was 65.7% (66.7% for the three-weekly treatment and 64% for the four-weekly treatment). These differences were not statistically different. CONCLUSIONS: A modest increase in the dose intensity of chemotherapy (1:3 fold) failed to improve the response rate, progression-free survival and overall survival in patients with ovarian carcinoma.