Lian Ulrich

Patients with atypical hyperplasia of the endometrium should be treated in oncological centers.

OBJECTIVES To examine the prevalence of undiagnosed endometrial carcinoma (EC) among women with a preoperative diagnosis of atypical endometrial hyperplasia (AEH) in correlation to age, BMI and menopause. METHODS Data extracted from the Danish Gynecological Cancer Database (DGCD) covering women diagnosed with AEH between January 1, 2005 and November 1, 2010 undergoing surgery. DGCD is a multidisciplinary, nationwide, clinical database of all cases of gynecological cancer and AEH in Denmark diagnosed after January 1, 2005. Registration is mandatory. Primary outcome was preoperative- and postoperative diagnoses. Secondary outcomes were relationship to BMI, age and menopause. RESULTS The preoperative diagnosis of AEH was retained in 41% of 773 cases and 59% had endometrial cancer. Of the cancer cases, 18% had more than Stage I disease and 3% were non-endometrioid. Cancer risk was significantly related to age (p<0.0001) and menopause (p<0.0001). The 80% who were postmenopausal had a significantly higher risk of a postoperative cancer diagnosis compared with the premenopausal group (OR 2.8). There was no significant difference regarding BMI (p=0.25). CONCLUSION More than half of the 773 Danish women primarily diagnosed with AEH had undiagnosed cancer. Failure to diagnose endometrial carcinoma preoperatively can lead to inadequate staging and potentially suboptimal treatment. We recommend that atypical endometrial hyperplasia should be treated as carcinoma in specialized gynecological-oncology centers.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy

A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained.

Childhood body mass index growth trajectories and endometrial cancer risk

Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub‐types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6–14 years and born 1930–1989 formed the analytical population. BMI was transformed to age‐specific z scores. Using linear spline multilevel models, each girls BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25–7.99, 8.0–10.99, 11.0–14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07–1.24) for all endometrial cancers, 1.12 (95% CI: 1.04–1.21) for estrogen‐dependent cancers, 1.16 (95% CI: 1.06–1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16–1.84) for non‐estrogen‐dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.

Benign leiomyoma or malignant sarcoma: The difficult differential diagnosis

April 17th 2014 the Food and Drug Administration (FDA) in he USA issued a Safety Communication on “Laparoscopic Uterine ower Morcellation in Hysterectomy and Myomectomy”, updated ovember 24th. The FDA discourages the use of laparoscopic ower morcellation during hysterectomy or myomectomy for the reatment of women with uterine fibroids because there is no relible method for predicting whether a woman with fibroids may ave a uterine sarcoma. This is based on currently available data stimating that one in 350 women undergoing hysterectomy or yomectomy for the treatment of fibroids will have an unsusected sarcoma. The FDA advises clinicians to thoroughly discuss he benefits and risks of all treatments with patients and to inform atient where morcellation is considered that their fibroid(s) may ontain unexpected cancerous tissue and that laparoscopic power orcellation may spread the cancer, significantly worsening their rognosis. Many institutions are working on bags in which to collect morellated specimens to overcome spreading of tissue, but the safety f such bags has not yet been proven. Thus morcellation may pgrade a sarcoma from stage 1 with 51% to stage 3 with close o 0% 5 year survival [1]. The same week in November the American Association of ynecologic Laparoscopists (AAGL) published a member update laiming that the figure used by the FDA was subject to publication ias, that the real risk of unsuspected sarcomas would be much ower and presented a model suggesting that the combined morality from leiomyosarcoma (LMS) and the potential dissemination hrough power morcellation would be less than the mortality from he alternative open hysterectomy. This leaves us with two questions: What is the real prevalence f sarcomas in women with fibroids, and is there a way to diagnose arcomas preoperatively. In the USA 1091 cases of morcellated presumed leiomyomata nexpectedly resulted in one case of endometrial stromal sarcoma, ne LMS and 10 cases of myomal variants like cellular leiomyomata, typical leiomyomata and stromal tumour of unknown malignant otential (STUMP) indicating a risk of 0.2% of unexpected sarcomas, ut 1% if the variants with possible malignant potential are included 2]. According to the Danish Gynaecological Cancer Database ncluding the entire Danish population of 5.6 mio, sarcomas contitute approximately 4% of uterine malignancies corresponding to pproximately 25 cases per year, 50–60% of which are LMS, and

Routine pelvic ultrasound before starting menopausal hormone therapy: Should we do it?

Routine investigations before prescription of menopausal horone therapy (MHT) differ between and within countries and ay include gynecological examination, measurement of blood ressure (BP), transvaginal ultrasound, mammography and even exa-scan or none of the above. The purpose of routine investigaions is to rule out silent pathology as opposed to investigations one on indication. The indication for MHT is relief of climacteric symptoms mainly ot flushes and night-sweats. These normally start when the eriods become irregular occurring less than monthly. MHT given equentially often regulates the bleeding pattern, and persisent bleeding irregularities during MHT indicate the need for a ransvaginal ultrasonic evaluation and possibly other investigaions, e.g. endometrial histology [1]. Likewise persistent bleeding rregularities during continuous combined MHT for more than the rst three months call for investigation. Ultrasonic evaluation may lso be a useful supplement to the gynecological examination, hen a pelvic mass is suspected (e.g. ovarian pathology or myomas nown to grown during MHT). Thus there may be several good reaons to perform pelvic ultrasonic evaluation before or soon after tart of MHT. However the question is whether ultrasonic evaluation is always equired in addition to a gynecological examination with normal ndings in a perior post-menopausal woman around 50 years, ho has had her regular cervical smears and now wishes MHT to elieve climacteric symptoms. In these cases the GP, who knows he woman’s BP and her gynecological history may prescribe MHT ithout any further examinations whereas the gynecologist may ot do a gynecological examination without a routine ultrasonic xamination. Thus investigation may depend on whether therapy is rescribed by a gynecologist or a general practitioner and whether ltrasound equipment is readily available or not. Routine ultrasonic investigation prior to prescription of MHT in normal 50 year old woman is screening of a selected population, .e. a population with a request for MHT. Screening for endometrial r ovarian cancer is currently not recommended in women withut genetic disposition. The UK endometrial cancer rate in women 5–54 years old is 20–40 per 100,000 and the equivalent ovaran cancer rate is 18–27 per 100,000 [2]. The ovarian cancer rate aries with approximately 40% over the European region and is elatively high in the UK – and also higher than in North Amerca. The rate of endometrial cancer also varies with approximately 0% across Europe, again with the UK ranking higher than averge, but with the US even higher. The rate of endometrial cancer

Birth weight and the risk of histological subtypes of ovarian and endometrial cancers: Results from the Copenhagen School Health Records Register

BACKGROUND Studies of birth weight associations with ovarian and endometrial cancer risks are limited with inconsistent results, and none has evaluated associations by histologic subtype. We utilized prospectively collected birth weight information to investigate the association with risk of ovarian and endometrial cancers overall and by histologic subtype. METHODS 162,559 girls, born from 1930 to 1989, from the Copenhagen School Health Records Register (CSHRR) were followed prospectively via linkage with the Danish health registers. Ovarian (n=666) and endometrial (n=694) cancers were identified from 1978 to 2014. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS Women with lower (2.0-3.25 vs. 3.26-3.75kg) and higher (3.75-5.5 vs. 3.26-3.75kg) birth weights had increased risks of ovarian cancer overall [HR (95% CI): 1.27 (1.06-1.52); 1.51 (1.21-1.87), respectively] and serous ovarian cancers [1.54 (1.19-1.98); 1.98 (1.47-2.67), respectively]. A decreased risk of Type II endometrial tumors was suggested per kilogram increase in birth weight [HR (95% CI): 0.63 (0.40-1.00)]. CONCLUSIONS Our results suggest that both lower and higher birth weights were associated with increased ovarian cancer risk and associations were particularly strong for serous ovarian cancer, the most common subtype. Birth weight was not associated with most types of endometrial cancer.

Childhood BMI growth trajectories and endometrial cancer risk

Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub‐types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6–14 years and born 1930–1989 formed the analytical population. BMI was transformed to age‐specific z scores. Using linear spline multilevel models, each girls BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25–7.99, 8.0–10.99, 11.0–14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07–1.24) for all endometrial cancers, 1.12 (95% CI: 1.04–1.21) for estrogen‐dependent cancers, 1.16 (95% CI: 1.06–1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16–1.84) for non‐estrogen‐dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.

Childhood BMI growth trajectories and endometrial cancer risk.

Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub‐types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6–14 years and born 1930–1989 formed the analytical population. BMI was transformed to age‐specific z scores. Using linear spline multilevel models, each girls BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25–7.99, 8.0–10.99, 11.0–14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07–1.24) for all endometrial cancers, 1.12 (95% CI: 1.04–1.21) for estrogen‐dependent cancers, 1.16 (95% CI: 1.06–1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16–1.84) for non‐estrogen‐dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.

Abstract LB-375: Childhood body size at age 13 years and associations with ovarian cancer in adult life

Background: Among women, body mass index (BMI; kg/m2) and attained height are positively associated with ovarian cancer. Few studies have, however, investigated associations with childhood body size. As such, it remains largely unknown if it is body size development in early life or adult life that contributes to these associations. Therefore, we examined if childhood BMI and height at age 13 years were associated with ovarian cancer in adult life. Methods: Individuals were girls in the Copenhagen School Health Records Register who were born between 1930 and1989 and had available measures of height and weight at age 13 years. BMI and height z-scores were calculated from an internal age-specific reference. Via a personal identification number, individuals were followed up for ovarian cancer diagnosis by linkage to the Danish Cancer Registry. Cox proportional hazard regressions were performed and stratified by birth cohort. Results: Among the included 137,416 girls, 1048 cases of ovarian cancer occurred during 5.2 million person-years of follow-up with a median age of diagnosis of 57 years (range: 19-83 years). BMI tended to be non-linearly associated with ovarian cancer such that only the heaviest girls had positive associations with ovarian cancer. Compared with a 13-year-old girl of average-size (BMI z-score = 0, corresponding to a weight of 45 kg and a height of 157 cm), an equally tall girl who was at least 9 kg heavier (corresponding to a BMI z-score >1.28) had a hazard ratio (HR) for ovarian cancer of 1.33 (95% confidence interval [CI]: 1.08-1.63). In analyses adjusted for childhood height, the association was only marginally attenuated (HR = 1.30, 95% CI: 1.06-1.60). Childhood height was positively and statistically significantly associated with ovarian cancer. At age 13 years, per height z-score (corresponding to approximately 7 cm), the HR for ovarian cancer was 1.07 (95% CI: 1.01-1.14). Conclusion: Body size in early life was associated with ovarian malignancies later in life suggesting that childhood height and BMI might impact if women are later diagnosed with ovarian cancer. As ovarian cancers vary widely in their etiologies, associations with childhood body size may differ depending on the tumor type, which will be investigated. Citation Format: Julie Aarestrup, Michael Gamborg, Nicolas Wentzensen, Lian G. Ulrich, Thorkild IA Sorensen, Jennifer L. Baker. Childhood body size at age 13 years and associations with ovarian cancer in adult life. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-375.