Nikolaos Burbos

Predicting the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding: the Norwich DEFAB risk assessment tool

Background:This study aimed to show the longitudinal use of routinely collected clinical data from history and ultrasound evaluation of the endometrium in developing an algorithm to predict the risk of endometrial carcinoma for postmenopausal women presenting with vaginal bleeding.Methods:This prospective study collected data from 3047 women presenting with postmenopausal bleeding. Data regarding the presence of risk factors for endometrial cancer was collected and univariate and multivariate analyses were performed.Results:Age distribution ranged from 35 to 97 years with a median of 59 years. A total of 149 women (5% of total) were diagnosed with endometrial carcinoma. Women in the endometrial cancer group were significantly more likely to be older, have higher BMI, recurrent episodes of bleeding, diabetes, hypertension, or a previous history of breast cancer. An investigator best model selection approach was used to select the best predictors of cancer, and using logistic regression analysis we created a model, ‘Norwich DEFAB’, which is a clinical prediction rule for endometrial cancer. The calculated Norwich DEFAB score can vary from a value of 0 to 9. A Norwich DEFAB value equal to or greater than 3 has a positive predictive value (PPV) of 7.78% and negative predictive value (NPV) of 98.2%, whereas a score equal to or greater than 5 has a PPV of 11.9% and NPV of 97.8%.Conclusion:The combination of clinical information with our investigation tool for women with postmenopausal vaginal bleeding allows the clinician to calculate a predicted risk of endometrial malignancy and prioritise subsequent clinical investigations.

Severe metabolic acidosis as a consequence of acute starvation in pregnancy

Ketoacidosis is most often due to uncontrolled diabetes mellitus. Similar metabolic changes can occur with poor dietary intake of carbohydrates or prolonged fasting. Metabolic acidosis due to prolonged fasting is rarely described in the literature. We report a case of severe metabolic acidosis as a result of prolonged fasting in pregnancy.

Outcome of investigations for postmenopausal vaginal bleeding in women under the age of 50 years

OBJECTIVE The objective of this study is to determine the incidence of endometrial cancer in young postmenopausal women presenting with vaginal bleeding. METHODS Cross-sectional study of postmenopausal women presenting with vaginal bleeding in a gynaecological oncology centre in the United Kingdom. All women underwent transvaginal ultrasound scanning (TVS) as the initial investigation tool to evaluate the endometrium. Endometrial biopsy was performed only in cases where endometrial thickness measured equal to or greater than 5mm. The patients were divided into two groups based on their age: less than 50 years (Group A) and 50 years or older (Group B). RESULTS Over a 57-month period, 4454 women were investigated for postmenopausal vaginal bleeding. Of these, 259 (5.8%) women were diagnosed with endometrial carcinoma. 260 (5.8%) women were younger than 50 years. Endometrial biopsy was not performed in 130 women in Group A that had an endometrial thickness measurement of less than 5mm on ultrasonography. With a median follow-up period of 3 (1-5) years, we found no cases of endometrial cancer in women under the age of 50 that did not undergo endometrial biopsy at the time of initial evaluation. Overall, no cases of endometrial cancer were diagnosed in postmenopausal women under the age of 50 years. CONCLUSIONS We found no cases of endometrial cancer amongst 260 women presenting with postmenopausal vaginal bleeding under the age of 50 years. These women could be investigated on a less urgent basis depending on the available resources.

Age-related differential diagnosis of vaginal bleeding in postmenopausal women: a series of 3047 symptomatic postmenopausal women.

Objective The aim of this study is to identify the causes of vaginal bleeding in different age groups of postmenopausal women. Also, we attempt to estimate the incidence of postmenopausal vaginal bleeding and endometrial cancer in a defined geographical area. Study design The study was conducted at a gynaecological oncology centre in the United Kingdom, between February 2006 and May 2009. Patients were investigated according to established evidence-based departmental guidelines. Results During the study period 3047 women were referred with postmenopausal vaginal bleeding. In 1356 women (44.5%) the endometrial thickness measured less than 5 mm on transvaginal ultrasound scan. Benign histology was found in 1144 women (37.5%). Benign endometrial polyps were the cause of bleeding in 10.1% of the cases. The incidence of endometrial cancer in our study population was 5%. The rate of postmenopausal vaginal bleeding during the study period peaks at the age of 55–59 years (25.9/1000 postmenopausal women/year) and declines thereafter. The peak incidence of endometrial cancer during the study period (12.6/10,000 postmenopausal women/year) was seen between the ages of 60 and 64 years and similarly declines with increasing age. Conclusion To our knowledge, this is the first population-based estimation of the incidence of genital tract bleeding and endometrial cancer among postmenopausal women in the United Kingdom. The results of this study showing the age-related differential diagnosis can be used to inform clinical practice when counselling postmenopausal women with vaginal bleeding.

Comparing the performance of two clinical models in estimating the risk of endometrial cancer in symptomatic postmenopausal women

OBJECTIVE The aim of this study was to internally evaluate the accuracy measures of the two newly developed predictive models, called DEFAB and DFAB, used to estimate the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding. STUDY DESIGN Prospective study including postmenopausal women presenting with vaginal bleeding. RESULTS Over a 46-month-period, 3795 postmenopausal women presented with vaginal bleeding and were included in the study. A total of 221 (6%) women were diagnosed with endometrial carcinoma. The DEFAB predictive model incorporates known risk factors such as presence of Diabetes, Endometrial thickness measurement on transvaginal ultrasonography, Frequency of bleeding, Age, and Body mass index. The DFAB model is based on the above clinical characteristics excluding the ultrasonography result. For the recommended cut-off values, there was no evidence (p-value=0.221) of a difference in the diagnostic ability with respect to sensitivity, specificity, area under receiver operating curve, positive predictive value and negative predictive value. There was strong evidence (p-value<0.0001) to suggest that the diagnostic ability of DEFAB and DFAB agree as evidenced by the excellent Kappa statistic 0.950 (95% CI 0.940-0.960). We found strong evidence (p-value<0.0001) that the variables incorporated in both predictive models simultaneously correctly classify an individual to either having cancer or not having cancer with respect to logistic discriminant analysis. CONCLUSION We recommend that these two predictive models can be used interchangeably.

Management of postmenopausal women with vaginal bleeding when the endometrium can not be visualized

Objective. To determine the risk of endometrial cancer when endometrial thickness is not visualized using ultrasonography. Design. Cross‐sectional study. Setting. Gynecological oncology center in the United Kingdom. Population. All postmenopausal women referred with vaginal bleeding. Methods. All women were investigated using gray‐scale transvaginal ultrasonography. Women were arbitrarily stratified into four groups according to the endometrial thickness measurement. Women with endometrial thickness that was not adequately visualized on ultrasonography were included in a separate group. Main outcome measures. Endometrial cancer diagnosis. Results. Over a 50‐month period, 4454 women were investigated for postmenopausal vaginal bleeding. A total of 259 (6%) of women were diagnosed with endometrial carcinoma. Endometrial thickness measured 5–9.9mm in 1201 (27%), 10–14.9mm in 468 (11%), 15–19.9mm in 209 (5%), and equal to or greater than 20mm in 197 (4%) of women. In 174 (4%) of women, the endometrial thickness was not visualized on transvaginal ultrasonography. For women where the endometrial thickness was not adequately visualized, the final histology included benign endometrium (124), endometrial cancer (26), endometrial polyps (11), endometritis (7), and other pathology (7). The odds of endometrial cancer in women where the endometrial thickness was not visualized were found to be significantly higher than the odds of cancer for women with an endometrial thickness of 5–9.9mm (OR = 5.23, 95%CI 3.10–8.85, p‐value <0.0001). Conclusions. For women presenting with postmenopausal bleeding and where the endometrial thickness cannot be adequately visualized on ultrasonography, hysteroscopic evaluation is recommended.

Postmenopausal vaginal bleeding in women using hormone replacement therapy

Objective To estimate the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding using estrogen–progestogen hormone replacement therapy (HRT) regimens and to assess if the duration of HRT use has an effect on the risk of diagnosing endometrial cancer. Study design Cross-sectional study of consecutive women presenting with postmenopausal vaginal bleeding at a gynaecological oncology centre in the UK. Main outcome measures Endometrial cancer diagnosis. Results Over a 62-month period, 4847 women were investigated for postmenopausal vaginal bleeding. The majority of women (4097, 84.5%) did not use any HRT preparation at the time of initial referral and 750 (15.5%) women were using combined HRT preparations. A total of 298 (6.1%) women were diagnosed with endometrial carcinoma. Women using HRT preparations were significantly less likely to be diagnosed with endometrial cancer compared with women not using HRT (adjusted odds ratio = 0.229, 95% CI 0.116–0.452; P < 0.0001). The longer duration of HRT use did increase the risk of diagnosing endometrial cancer in women presenting with postmenopausal vaginal bleeding, but this was not statistically significant. Conclusions Postmenopausal women presenting with vaginal bleeding and using combined HRT preparations have significantly lower risk of being diagnosed with endometrial cancer when compared with women not using HRT.

Late presentation of metastatic smooth muscle neoplasm of the uterus with low malignant potential

A 48-year-old woman underwent total abdominal hysterectomy with conservation of the ovaries and tubes. Histology showed a well-circumscribed smooth muscle tumor with foci of degeneration (including infarct-type necrosis) but no coagulative tumor cell necrosis and only mild focal cytological atypia. She presented, 24 years later with shortness of breath and abdominal distension and underwent bilateral salpingo-oophorectomy, appendectomy, omental biopsy and para-aortic lymph node sampling. Histology showed bilateral ovarian smooth muscle tumors with no coagulative tumor cell necrosis or significant cellular atypia. The cells were mitotically active. The tumors in both ovaries were most likely secondary to the previous uterine smooth muscle neoplasm. To our knowledge, this case is the first in the literature to describe a benign cellular leiomyoma that subsequently behaved as a smooth muscle tumor of uncertain malignant potential, which recurred 24 years after the initial diagnosis.

The role of omental biopsy in endometrial cancer staging

Omental biopsy is not part of FIGO staging for endometrial cancer. The few studies that have looked into this matter have had conflicting results. This is the largest study in terms of the number of cases studying the incidence of omental involvement in endometrioid and non-endometrioid endometrial cancer. A retrospective study assessing 248 cases of endometrial cancer with omental biopsy at the time of primary surgical treatment for endometrial cancer at the Gynaecological Oncology Centre, Norfolk and Norwich University Hospital between January 2004 and May 2008. Demographic, clinico-pathologic and surveillance data were collected from hospital records, operative notes and histopathology results. The histology included tumour type, stage, grade and omental biopsy. All histological types were included in the study. Two hundred and forty eight patients had an omental biopsy at the time of primary surgical treatment for endometrial cancer during the study period. Of them, 187 cases were stage I, 27 stage II, 27 stage III and seven stage IV. According to histological type, 202 (81.4%) had endometrioid, 20 (8.0%) serous papillary, 20 (8.0%) malignant mixed Mullerian tumour (MMMT), three (1.2%) clear cell and three (1.2%) sarcoma. Overall, six cases (2.4%) had omental involvement, 4/202 (1.98%) with endometrioid type, 1/20 (5.0%) with serous papillary type and 1/20 (5.0%) MMMT. Eighty four percent of omental metastases (five cases) were macroscopic and noted at operation .The overall risk of omental metastases is 2.4% and in the absence of gross lesions the risk is around 0.4%. Most omental metastases can be diagnosed by careful inspection and palpation of the omentum. The possibility of missing microscopic disease is low. Based on these figures and possible increase in morbidity and operative time, omental biopsy cannot be justified as a standard procedure in endometrial cancer staging.

Ovarian cysts and ovarian cancer

Ovarian cysts and tumours are a relatively common finding among women of many ages, particularly with the wider use of regular physical examinations and ultrasound. Although the finding of an ovarian mass can be a source of considerable anxiety, most of those in younger women are not malignant and may be able to be managed entirely within primary care. However, malignant tumours of several varieties occur and many will require investigation and management by secondary care.