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.

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 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.

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.

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.

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.

Human papillomavirus 16 infection in adenocarcinoma of the cervix.

The impact of the success of organised cervical screening programme results in a steady decline of the incidence of squamous cell carcinoma of the cervix but a concomitant increase in the incidence of the less common histological subtypes, particularly adenocarcinoma of the cervix (ACC). Although Human papillomavirus (HPV) infection is believed to be a necessary cause of cervical cancer, its role in the pathogenesis of ACC is not well established. Established associations between oncogenic strains of HPV and ACC are based on molecular studies carried out on entire tumour block sections. In this study, the cervical adenocarcinoma cells of a 10-year cohort of women diagnosed with ACC were dissected using the PixCell II Laser Microdissecting System to detect the HPV 16 genome sequence using the real-time quantitative polymerase chain reaction to confirm the presence of HPV DNA within ACC cells. By coupling these two sophisticated techniques, the HPV DNA copy number cell could be calculated to investigate its role. The prevalence of HPV 16 infection in this cohort was 24%, which is significantly higher than the control group (chi(2), P=0.014). Women with ACC also had significantly higher HPV DNA copy number per cell compared to the control group (P=0.00007). Higher HPV DNA copy number is associated with risk of developing ACC.

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).

Is optimal first-line chemotherapy deliverable in all newly diagnosed ovarian cancers? A population-based study.

NICE guidance recommends the use of paclitaxel and a platinum therapy for all cases of ovarian cancer. We report our experience of treating 133 patients with ovarian cancer over a 3-year period. Where indicated, 91% received chemotherapy. A taxane/platinum combination was found to be appropriate in 63% of patients only.

A randomised trial comparing local versus general anaesthesia for microwave endometrial ablation.

OBJECTIVE: To compare the acceptability of microwave endometrial ablation using a local anaesthesia/sedation regime or general anaesthesia. To compare recovery following treatment with each type of anaesthetic. DESIGN: Prospective randomised controlled trial with follow up of women who declined randomisation. SETTING: The gynaecology department of a large teaching hospital in the UK. POPULATION: All women referred for microwave endometrial ablation at the Aberdeen Royal Infirmary between July 1999 and September 2000 without a medical reason to favour one or other type of anaesthetic. METHODS: 191 women were equally randomised to undergo microwave endometrial ablation under general or local anaesthesia. Details were also collected for women not randomised because of an anaesthetic preference. All procedures were undertaken in an operating theatre. MAIN OUTCOME MEASURES: Data collected by questionnaire including the woman's view of treatment acceptability, operative details and post-operative recovery. RESULTS: Sixty-nine percent of eligible women would consider treatment under local anaesthesia. Ninety-one percent of microwave endometrial ablation procedures that started under local anaesthesia were completed without conversion to general anaesthesia. Anaesthetic type and allocation by randomisation or preference made no significant difference to the proportion of women describing treatment as totally or generally acceptable at two weeks. Neither parity nor cavity size predicted acceptability. Women allocated general anaesthesia were more likely to describe the procedure as totally acceptable and to choose the same anaesthetic again. There was no significant difference between anaesthetic groups regarding post-operative pain, nausea or recovery time. CONCLUSIONS: Microwave endometrial ablation under local anaesthesia was acceptable to the majority of women referred for treatment. There was no recovery advantage from local anaesthesia and almost 1 in 10 women who starting treatment under local anaesthesia needed a general anaesthetic because of discomfort. The incidence of post-operative pain and nausea means that treatment with this local anaesthetic/sedation regime remains a day case rather than an outpatient procedure.

The impact of the introduction of a fast track clinic on ovarian cancer referral patterns.

The aim of this study is to review the referral patterns for ovarian cancer in the Grampian region of Scotland and assess the impact of a 'fast track' clinic on the patient journey. Population-based retrospective analysis of a gynaecological cancer database and patient case notes were used. After its inception, 13.5% of patients were referred through the fast track clinic and 83% were seen within 2 weeks. Thirty-six per cent of patients were admitted as emergencies, mainly surgical or medical. The median general practitioner-to-specialist time was 3 days (range 0-188 days). The median time to diagnosis prior to the fast track clinic was 23 days and 17.5 days after its introduction (P = 0.003). A population-based ovarian cancer referral pattern is presented. Median waiting times are short but do influence time to diagnosis as do referral through a non-cancer specialty and patient performance status. Rapid access through a gynae-oncology clinic has some impact but is underused.

Magnetic resonance imaging appearances of the uterus following microwave endometrial ablation.

AIM: Microwave endometrial ablation (MEA) is a treatment for dysfunctional uterine bleeding. It is a second generation ablative technique which is as effective as hysteroscopic methods but quicker and easier to perform. Our aim is to describe the Magnetic Resonance Imaging (MRI) appearances of the uterus following this procedure. METHODS: 15 women underwent MRI immediately before MEA, and again at one day and 4 months after treatment. T1 and T2 sequences were performed at 1.0T using a body coil. Images were assessed by 2 independent observers for quantitative and qualitative changes. Clinical questionnaires were completed before treatment and at 4 months. RESULTS: On images obtained one day post-ablation, 14 patients had a low signal intensity band subjacent to the treated area of the endometrial cavity on T2 images. Imaging at 4 months showed significant amounts of endometrial tissue in 11 patients, including 3 of the 6 patients who were amenorrhoeic. There were no changes in the appearances of myometrium or uterine dimensions and there were no haematometra. CONCLUSIONS: The detection of residual endometrium by MRI means that unopposed oestrogen hormone replacement therapy should be avoided after MEA, even in women who have amenorrhoea. Thepost-operative sub-endometrial low signal intensity zone corresponds to the region of tissue necrosis detected on vital staining of the treated uterus in in vivotesting. Depth of tissue destruction is a surrogate marker for clinical effectiveness. MRI may have a role in early assessment of patients participating in clinical research who are undergoing a modified MEA technique while retaining their uterus.

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.

Five-year follow up of women randomised to medical management or transcervical resection of the endometrium for heavy menstrual loss: clinical and quality of life outcomes.

OBJECTIVE: To assess clinical status, changes in health related quality of life, and subsequent management five years after medical management or transcervical resection of the endometrium for treatment of heavy menstrual loss. DESIGN: Five year follow up using postal questionnaires and operative databank review. SETTING: Gynaecology department of a large UK teaching hospital. POPULATION: Women referred to the gynaecologist for treatment of heavy menstrual loss. METHODS: Eligible women, without a treatment preference, were randomised equally to either medical treatment or transcervical resection of the endometrium. MAIN OUTCOME MEASURES: Women's satisfaction with treatment, menstrual status, changes in health related quality of life, and additional treatments received at five years. RESULTS: One hundred and forty-four patients completed questionnaires, achieving 77% follow up (medical n = 71/94; transcervical resection of the endometrium n = 73/93). At five-year follow up, 7/71 (10%) of those randomised to the medical arm still used medical treatment, while 72/94 (77%) had undergone surgical treatment and 17/94 (18%) a hysterectomy. Twenty-five (27%) women allocated to transcervical resection of the endometrium had undergone further surgery, 18/93 (19%) a hysterectomy. At five years women initially randomised to medical treatment were significantly less likely to be totally satisfied (P < 0.01, difference 21%, 95% CI -37% to -4%), or to recommend their allocated treatment to a friend (P < 0.001, difference 59%, 95% CI -73% to -45%). Bleeding and pain scores were similar in both groups and highly significantly reduced. Significantly more women in the transcervical resection of the endometrium arm had no bleeding or very light bleeding (P < 0.02, difference -22%, CI -31% to -4%), and they had significantly less days heavy bleeding (P < 0.02). Short Form 36 health survey scores were significantly improved from baseline for all eight health scales in the transcervical resection of the endometrium arm, and four in the medical arm. CONCLUSIONS: A policy of immediate transcervical resection of the endometrium for women referred to a gynaecologist for treatment of heavy menstrual loss achieves higher levels of satisfaction, better menstrual status, and greater improvements in health related quality of life than medical treatment. In addition, transcervical resection of the endometrium is safe and does not lead to an increase in the number of hysterectomies. An effective endometrial ablative technique should be offered to all eligible women seeking treatment of their heavy menses from a gynaecologist.

Invasive adenocarcinoma of the vagina following surgery for adenocarcinoma in situ of the cervix--recurrence or implantation?

A 51-year-old woman underwent cervical conization for severe glandular abnormal cells. Histology noted adenocarcinoma in situ (AIS) with incomplete excision margins. Four months later, hysterectomy revealed no residual disease. Six months subsequently she developed invasive adenocarcinoma of the upper vagina. This report documents the unusual behavior of AIS and its management difficulties.

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.

Comparison of microwave endometrial ablation and transcervical resection of the endometrium for treatment of heavy menstrual loss: a randomised trial.

BACKGROUND: Various new endometrial ablation techniques have emerged for the treatment of menorrhagia. We undertook a randomised controlled trial comparing one new technique, microwave endometrial ablation (MEA), with a proven procedure, transcervical resection of the endometrium (TCRE), for women with heavy menstrual loss. METHODS: 263 eligible and consenting women, referred for endometrial ablative surgery, were randomly assigned MEA (Microsulis plc, Waterlooville, Hampshire, UK; n=129) or TCRE (n=134). 230 participants were needed to give 80% power of demonstrating a 15% difference in satisfaction with treatment. All procedures were done under general anaesthesia 5 weeks after endometrial thinning with goserelin 3.6 mg. Questionnaires were completed at recruitment and at 12 months' follow-up. The primary outcome measures were patients' satisfaction with and the acceptability of treatment. Analysis was by intention to treat among women followed up to 12 months (n=116 MEA, n=124 TCRE). FINDINGS: At 12 months, 89 (77%) women in the MEA group and 93 (75%) in the TCRE group were totally or generally satisfied with their treatment (95% CI for difference -12 to 17) and 109 (94%) versus 112 (90%) found it acceptable (-11 to 35). Mean operating times were shorter for MEA than for TCRE (11.4 vs 15.0 min, p=0.001) and the postoperative stay slightly but not significantly shorter. One blunt perforation occurred in each study group resulting in one immediate hysterectomy (TCRE group). Of eight health-related quality of life dimensions, all were improved after MEA (six significantly) and seven were improved after TCRE (all significantly). INTERPRETATION: Both techniques achieved high rates of satisfaction and acceptability and both improved quality of life after 1 year. However, we cannot exclude a difference in satisfaction between the groups of less than 15%. MEA seems a suitable alternative to TCRE.