Is there an increase in the incidence of uterine carcinosarcoma in north-east Scotland? A 19 years population-based cohort study.

BACKGROUND AND AIMS: The incidence of uterine carcinosarcoma and factors associated with its survival are little known and this study helps to address this question for women residing in north-east Scotland. METHODS AND RESULTS: Data were collected from women diagnosed with carcinosarcoma of the uterus residing in north-east of Scotland from 1991 to 2009. Kaplan-Meier plots and Cox regression analysis were used for analysis. A total of 43 women were analysed during this period. The median survival was 25 months. The estimated five-year survival for stage I/II disease was 52.5% (95% CI: 30.5-74.5%). The 2-year survival rate for stage III/IV disease was 46% (95% CI: 16-75%). There was an increase in the incidence during this period. Improved survival was seen in early-stage disease (FIGO stages I and II) and in the absence of lymphovascular space invasion (LVSI; p = 0.015). A total of 26% of the women had a history of tamoxifen usage with no effect seen on survival. Multivariate analysis showed that when treatment modality and LVSI were adjusted for FIGO staging, there was no statistical significance in the survival outcomes. CONCLUSION: The incidence of uterine carcinosarcomas is increasing parallel with endometrial carcinomas with no significant effect of tamoxifen on survival.

The genetic causes of the sequential occurrence of multiple primary malignancies in a young woman--5 years on.

The finding of three primary gynaecological malignancies in a young woman attending our unit was documented in 2001. We provide an update on this report as new events have prompted further discussion on the role of clinical guidelines in cancer management. The discovery of a genetic predisposition demonstrates the need for multidisciplinary input and heightened awareness in similar cases while the importance of treating each patient as an individual is emphasized.

A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium: follow up at a minimum of 10 years.

OBJECTIVE: To compare outcomes and further operations at a minimum of 10 years following microwave endometrial ablation (MEA) or transcervical resection of the endometrium (TCRE). DESIGN: Follow up of a randomised controlled trial using postal questionnaires and operative databank review. SETTING: Gynaecology department of a large UK teaching hospital. MAIN OUTCOME MEASURES: Women's satisfaction with treatment, menstrual symptoms, changes in health-related quality of life, and additional treatments received. RESULTS: One-hundred and eighty-nine of the original 263 women returned questionnaires (72%) after a minimum of 10 years post-treatment. Those totally or generally satisfied with treatment numbered 77/129 (60%) in the microwave arm and 70/134 (52%) in the resection arm, the difference is not statistically significant. Bleeding and pain scores were highly significantly reduced and similar following both MEA and TCRE, achieving amenorrhoea rates of 83 and 88% respectively. The hysterectomy rate after 10 years was significantly different with 22 (17%) in the MEA and 38 (28%) in the TCRE arm (95% CI: -0.21, -0.13). CONCLUSIONS: Both techniques achieve significant and comparable improvements in menstrual symptoms, health-related quality of life and high rates of satisfaction. With the known operative advantages, lower costs and fewer hysterectomies, it is clear that MEA is a more effective and efficient treatment for heavy menstrual loss than TCRE.

The risk of malignancy index for ovarian tumours in Northeast Scotland--a population based study.

BACKGROUND AND AIMS: The Scottish Intercollegiate Guidelines Network (SIGN) recommends the use of the Risk of Malignancy Index (RMI) for ovarian tumours, a scoring system based on ultrasound findings, menopausal status and CA 125 level, in the pre-operative evaluation of pelvic masses. The aim of this study was to investigate the accuracy of this as a predictive method of discriminating benign from malignant disease. METHODS AND RESULTS: All women who underwent oophorectomy in 2004 at Aberdeen Royal Infirmary for suspected primary ovarian pathology were evaluated. The RMI was calculated and these results were compared with the final histopathology. The sensitivity of the RMI for diagnosing malignant ovarian disease was 94% (32/34) while the specificity was 70% (76/108). CONCLUSIONS: Compared to previous studies, the RMI score was highly sensitive in detecting malignant disease, although not as specific in excluding benign lesions, particularly cystadenomas and endometriomas. This can be improved by the refinement of imaging techniques as well as the use of laparoscopy in particular cases. The RMI score may also be especially valuable in directing referrals to a specialised centre.

Treatment of advanced cervical cancer: a population-based study.

Chemoradiation is the standard treatment for locally advanced cervical cancer. We report how our population were treated over a 6-year period. Approximately 78.7% of all patients with advanced cervical cancer received chemoradiation, which appears to be well tolerated and acceptable to patients.

An audit of the quality of endometrial cancer care in a specialised unit.

BACKGROUND: Endometrial cancer is the 5th most common female cancer in Scotland and though cure rates are good, 25% of women still die of their disease. Staging has been shown to be poorly performed in Scotland-wide audit and inadequate staging is a predictor of worse outcome. Only 12% of women with endometrial cancer in Scotland are operated upon by a specialist gynaecological oncologist. AIMS: To determine if the quality of staging information in endometrial cancer is improved in a region where all cases are managed by specialist gynaecological oncologists. METHODS: All 108 women diagnosed and treated with endometrial cancer in Grampian in 2002 and 2003 had a retrospective case note assessment of the completeness of staging information. This was compared to previously published Scottish results. RESULTS: Completeness of staging was high. The International Federation of Gynecology and Obstetrics (FIGO) stage was available in 100% of women. Chest X Ray was performed in 85% and peritoneal cytology in 93%. Pelvic lymphadenectomy was performed in 28%. All these results were significantly better than in the Scottish audit. CONCLUSION: Centralisation of women with endometrial cancer results in accurate staging information. However it is not yet known what effect this may have on outcome.

p53 mutation is a common genetic event in ovarian carcinoma.

Using the single-strand conformational polymorphism technique, we have screened 66 malignant ovarian tumors for p53 mutation in exons 5 to 8. Thirty-four of the tumors demonstrated a single-strand conformational polymorphism band shift in this region of the gene, including 6 in exon 5, 7 in exon 6, 12 in exon 7, and 10 in exon 8 (one of the tumors showed a shift for exons 7 and 8). All of the single-strand conformational polymorphism shifts have been further characterized by DNA sequencing, and 31 of 35 have been shown to represent genuine DNA alterations. These include 27 point mutations (23 missense, 2 nonsense, and 2 silent mutations), 3 deletions (a 2-base pair deletion introducing, by frameshift, a stop codon further downstream; a 3-base pair deletion; and an unusual 6-base pair deletion made up of separate 2-base pair and 4-base pair deletions), and a 4-base pair insertion (introducing a stop codon downstream). In total, 29 of the 66 (44%) carcinomas analyzed had mutations affecting the primary sequence of the p53 protein. p53 mutation was found in tumors of all International Federation of Gynecologists and Obstetricians stages, suggesting that it might be an earlier genetic event in the progression of epithelial ovarian tumors than previously thought. A significantly greater number of p53 mutations were seen in high-grade serous carcinomas than in those of endometrioid and mucinous types (0.02 > P > 0.01). Analysis of the distribution of point mutations showed no preference for any particular mutation type.

Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan.

PURPOSE: To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred after or didn't respond to first-line, platinum-based chemotherapy. PATIENTS AND METHODS: Patients with measurable and assessable disease were randomized to receive either PLD 50 mg/m(2) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks. Patients were stratified prospectively for platinum sensitivity and for the presence or absence of bulky disease. RESULTS: A total of 474 patients were treated (239 PLD and 235 topotecan). They comprised the intent-to-treat population. The overall progression-free survival rates were similar between the two arms (P =.095). The overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively (P =.390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan. Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival (P =.037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall survival, PLD was significantly superior to topotecan (P =.008), with a median of 108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan (P =.455). Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification, or growth factor or blood product utilization. CONCLUSION: The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.

Long-term bladder symptomatology following radiotherapy for cervical carcinoma.

The prevalence of long-term bladder symptoms 5-11 years after radiotherapy for cervical carcinoma was investigated by postal questionnaire. Sixty-six replies (68%) were received. Only 29 (44%) were asymptomatic and 17 (26%) had severe symptoms. Urgency and urge incontinence were the most common symptoms occurring in 30 women (45%). Significant frequency and nocturia occurred in 23 women (35%) but voiding problems were less common. These results suggest that long-term bladder dysfunction is a common problem following radiotherapy for cervical carcinoma.

A protective role for common p21WAF1/Cip1 polymorphisms in human ovarian cancer.

The objective of this study was to compare the frequency of two common p21WAF1/Cip1 gene polymorphisms in ovarian cancer patients with that in age-matched controls, from a population originating from Eastern Scotland. Both polymorphisms were found significantly less frequently in both the constitutive and tumour tissue DNA of ovarian cancer patients (3/65; 4.6%), than in that from geographically and age-matched controls (25/186; 13.4%) (p=0.0495, chi2). Furthermore, we found no p21WAF1/Cip1 gene mutations in any of the tumours, reflected by a relatively low degree of loss of heterozygosity (LOH) at the chromosomal region where the gene maps, providing further evidence that the p21WAF1/Cip1 gene is not mutated in ovarian cancer. The data suggest however, that there may potentially be a protective function for the two p21WAF1/Cip1 gene polymorphisms in the population under study.

Lipoprotein and apoprotein levels in postmenopausal women during treatment with norethisterone.

Lipoprotein and apolipoprotein levels were monitored in 21 postmenopausal women during 6 months' treatment with norethisterone. There was no significant change in low density lipoprotein (LDL) cholesterol but apoprotein B levels rose significantly (p less than 0.001) thus increasing the apoprotein:cholesterol ratio in LDL. High density lipoprotein (HDL) cholesterol levels decreased significantly (p less than 0.001) in the first two months and did not change significantly thereafter. The HDL2 subfraction was reduced to a greater extent than the HDL3 subfraction. Apoprotein AI and AII levels were both reduced as was the apoprotein AI:AII ratio. The ratios of apoproteins AI and AII to HDL cholesterol were increased. We conclude that norethisterone has an adverse effect on the important risk factors for cardiovascular disease.

Effects of long-term Org OD 14 administration on blood coagulation in climacteric women.

98 post-menopausal women were randomly allocated to either Org OD 14 [(7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one] 2.5 mg/day or placebo. Treatment was continued for up to 6 yr. Any thromboembolic episode that occurred was recorded. Prothrombin time (PT), partial thromboplastin time (PTT), factor VII level and factor X level were measured prior to treatment and at yearly intervals. Antithrombin III level was measured in the last two yr of the study. There was one cerebrovascular accident after 3 months of placebo therapy but no other thromboembolic episodes. No significant difference was found between the effects of Org OD 14 and placebo with regard to any clotting factors at any time interval, although factor VII and factor X levels were consistently lower in the OD 14 group than in the placebo group. Antithrombin III levels measured after 5 and 6 yr were significantly higher (P less than 0.01) in the OD 14 group, suggesting a reduced risk of thrombosis in the treatment group.

A prospective randomised study of the effects of prophylactic antibiotics on the incidence of bacteraemia following hysteroscopic surgery.

OBJECTIVE: To study the effect of prophylactic antibiotics on the incidence of bacteraemia following hysteroscopic surgery. DESIGN: Prospective randomized study. SETTING: Aberdeen Royal Infirmary. SUBJECTS: One hundred and sixteen women about to undergo either endometrial laser ablation (ELA) or transcervical resection of the endometrium (TCRE). INTERVENTION: Fifty-five women were randomised to receive 1.2 g of Augmentin (co-amoxiclav) i.v. at induction of anaesthesia. Sixty-one women received no antibiotic prophylaxis. Blood cultures were obtained at the end of the surgical procedure. RESULTS: Incidence of bacteraemia in the non-antibiotic group (16%) was significantly higher than that in the antibiotic group (2%) (95% confidence interval for difference from 5% to 25%). The majority of organisms were of dubious clinical significance and contamination could not be excluded in 7 cases out of 10. CONCLUSION: There is no convincing evidence that antibiotics are of value in this clinical setting.

Admission-discharge policies for hysteroscopic surgery: a randomised comparison of day case with in-patient admission.

OBJECTIVE: To study the effectiveness and acceptability of day case hysteroscopic surgery. DESIGN: Prospective randomised controlled trial. SETTING: Aberdeen Royal Infirmary. SUBJECTS: One hundred and ninety four consecutive women who underwent hysteroscopic endometrial ablation. INTERVENTION: Seventy three women were allocated to day case surgery and 37 to inpatient admission; 84 women though otherwise fit for day case surgery were scheduled for in-patient admission as they lived more than 20 miles away. All women completed a questionnaire 24 h after their operations. Readmission rates were obtained from case notes. Satisfaction rates 12 months after the operation were recorded by means of a follow-up questionnaire. RESULTS: Post-operative pain was absent or slight in 48 (75%) of the women in the day case group 27 (84%) of women in the in-patient group, and 55 (82%) in the non-randomised in-patient group. Post-operative analgesia was necessary in 34 (52%) women in the day case group, 24 (75%) women in the in-patient group and 36 (53%) women in the non-randomised in-patient group. Hospital costs were significantly less in the day case group. Satisfaction with stay 92% in the day case group, and 100% in the other two groups. CONCLUSION: In this setting, day care is a safe acceptable and less expensive alternative to in-patient care for hysteroscopic endometrial ablation.

Randomised trial of hysterectomy, endometrial laser ablation, and transcervical endometrial resection for dysfunctional uterine bleeding.

OBJECTIVE: To evaluate the effectiveness and safety of endometrial laser ablation and transcervical resection of the endometrium compared with hysterectomy in the surgical treatment of women with dysfunctional uterine bleeding. DESIGN: Prospective randomised controlled trial. SETTING: Gynaecology department of a large teaching hospital. SUBJECTS: 204 women who would otherwise have been undergoing hysterectomy for menorrhagia were recruited between August 1990 and March 1992 and randomly allocated to hysterectomy (n = 99) or conservative (hysteroscopic) surgery (transcervical resection (n = 52) and laser ablation (n = 53)). MAIN OUTCOME MEASURES: Operative complications, postoperative recovery, relief of menstrual and other symptoms, patient satisfaction with treatment after six and 12 months. RESULTS: Women treated by hysteroscopic surgery had less early morbidity and a significantly shorter recovery period than those treated by hysterectomy (median time to full recovery 2-4 weeks v 2-3 months, P < 0.001). Twelve months later 17 women in the hysteroscopy group had had a hysterectomy, 11 for continuing symptoms; 11 women had had a repeat hysteroscopic procedure; 45 were amenorrhoeic or had only a brown discharge; and 35 had light periods. Dysmenorrhoea and premenstrual symptoms improved in most women in both groups. After 12 months 89% (79/89) in the hysterectomy group and 78% (75/96) in the hysteroscopy group were very satisfied with the effect of surgery (P < 0.05); 95% (85/89) and 90% (86/96) thought that there had been an acceptable improvement in symptoms, and 72% (64/89) and 71% (68/96) would recommend the same operation to others. CONCLUSIONS: Hysteroscopic endometrial ablation was superior to hysterectomy in terms of operative complications and postoperative recovery. Satisfaction after hysterectomy was significantly higher, but between 70% and 90% of the women were satisfied with the outcome of hysteroscopic surgery. Hysteroscopic surgery can be recommended as an alternative to hysterectomy for dysfunctional uterine bleeding.

Randomised trial comparing hysterectomy with endometrial ablation for dysfunctional uterine bleeding: psychiatric and psychosocial aspects.

OBJECTIVE: To compare in psychiatric and psychosocial terms the outcome of hysterectomy and endometrial ablation for the treatment of dysfunctional uterine bleeding. DESIGN: Prospective randomised controlled trial. SETTING--Obstetrics and gynaecology department of a large teaching hospital. SUBJECTS: 204 women with dysfunctional bleeding for whom hysterectomy would have been the preferred treatment were recruited over 24 months and randomly allocated to hysterectomy (99 women) or to hysteroscopic surgery (transcervical resection (52 women) or laser ablation (53 women). MAIN OUTCOME MEASURES: Mental state, martial relationship, psychosocial and sexual adjustment in assessments conducted before the operation and one month, six months, and 12 months later. RESULTS: Both treatments significantly reduced the anxiety and depression present before the operation, and there were no differences in mental health between the groups at 12 months. Hysterectomy did not lead to postoperative psychiatric illness. Sexual interest after the operation did not vary with treatment. Overall, 46 out of 185 (25%) women reported a loss sexual interest and 50 out of 185 (27%) reported increased sexual interest. Marital relationships were unaffected by surgery. Personality and duration of dysfunctional uterine bleeding played no significant part in determining outcome. CONCLUSIONS: Hysteroscopic surgery and hysterectomy have a similar effect on psychiatric and psychosocial outcomes. There is no evidence that hysterectomy leads to postoperative psychiatric illness.

A reappraisal of the role of chlorambucil in patients with end stage ovarian cancer who have previously been treated with platinum regimens.

The role of chlorambucil in end stage platinum resistant epithelial ovarian cancer was evaluated in women with end stage ovarian cancer. They had received platinum based chemotherapy and all other intravenous chemotherapeutic options had been exhausted. Over a 15 year period, 30 patients were identified. The median age was 64.5 years (range 45-81). The median number of chlorambucil pulses was 4 (range 1-16). The median survival following the introduction of chlorambucil was 5.5 months (range 0.72-38.8). The 22 patients who survived for longer than three months were significantly younger than those who did not (p = 0.03). Apart from two patients who developed transient myelosupression there were no toxic side effects. Chlorambucil should be considered as a therapeutic option in end stage ovarian cancer. It is has minimal toxicity, and can be prescribed safely for long term use. In younger women, an increase in benefit may be anticipated.

A case of villoglandular papillary adenocarcinoma of the cervix with vaginal skip metastasis.

► First case of cervical villoglandular cancer with concurrent vaginal skip metastasis. ► Rapid progression to advanced stage with good response to adjuvant therapy.

The prognostic significance of micrometastases in node-negative squamous cell carcinoma of the vulva.

Nodal involvement is one of the most significant prognostic factors in squamous cell carcinoma (SCC) of the vulva. We conducted a retrospective analysis of 31 women with histologically node-negative SCC from a population-based cohort of Grampian women. Median follow-up was 42 months after radical vulvectomy with groin node dissection. In total, 13 women (42%) were found to have micrometastases on immunohistochemistry. The risk of recurrence was almost 20-fold higher in those with micrometastases compared to those without (hazard ratio=19.6 (95% CI 2.3-171).