Assessment of reported uterine lesions diagnosed histologically after ovariohysterectomy in 1,928 pet rabbits (Oryctolagus cuniculus).

OBJECTIVE: To assess variations in age, breed, and clinical signs in rabbits with neoplastic or nonneoplastic uterine lesions and to investigate potential relationships between endometrial adenocarcinoma and age at ovariohysterectomy or breed in rabbits. ANIMALS: 1,928 rabbits that underwent ovariohysterectomy for treatment or prevention of possible uterine disease. PROCEDURES: With an online questionnaire distributed to 441 veterinary hospital members of the Japanese Society of Exotic Pet Medicine, data were retrospectively collected regarding age, breed, and findings on physical and histologic examinations for pet rabbits that underwent ovariohysterectomy between January 1, 2009, and April 30, 2018. Rabbits were grouped by reported age, breed, clinical signs, and uterine lesions, and results were assessed across groups. Logistic regression analysis was used to identify potential relationships between endometrial adenocarcinoma and breed or age at ovariohysterectomy in rabbits. RESULTS: The questionnaire response rate was 9.8% (43/441), with data reported for 1,928 rabbits (mixed breed, 600 [31.1%]; Netherland Dwarf, 520 [27.0%]; Holland Lop, 286 [14.8%]; or various other breeds, 522 [27.1%]). The most commonly reported neoplastic and nonneoplastic lesions were endometrial adenocarcinoma (1,035/1,928 [53.7%]) and endometrial hyperplasia (842 [43.7%]), respectively, and the most commonly reported clinical sign was hematuria or serosanguineous vaginal discharge (1,020/1,928 [52.9%]). As age at ovariohysterectomy increased, so did the odds (OR, 1.826; 95% CI, 1.640 to 2.033) of uterine adenocarcinoma. CONCLUSIONS AND CLINICAL RELEVANCE: Results supported ovariohysterectomy in rabbits before 2 years of age as a key preventative measure to mitigate uterine disease, particularly endometrial adenocarcinoma.

Assessment of the optimal age for a preventive ultrasonographic screening of the uterine health in bitches.

Studies about prevalence of uterine pathologies in bitches are scarce. Although correlation between age and uterine disorders was documented, the most suitable age for a preventive sonographic screening has not been proposed yet. Present study aimed to estimate the eligible age for an ultrasonographic screening of uterine abnormalities in dogs. Data regarding ultrasound examination and clinical records of non-pregnant intact females were retrospectively analysed. The age of each bitch was expressed as age ratio (actual/maximum age expected for the respective breed). The cut-off age ratio was determined by a ROC curve for overall uterine abnormalities. Frequencies of different abnormalities below and over the cut-off derived from the ROC curve were calculated and statistically analysed by chi-Square and OR. Prevalence of three categories of ultrasonographic findings was as follows: cystic endometrial hyperplasia (CEH) 18%; uterine collections (UC) 10.5%; masses (M) 1.3%. By the cut-off age ratio (0.325), derived by ROC curve (AUC = 0.91; SP 84.23%; SE 79.2%; PPV 83.4%; NPV 80%), 228 cases were divided into two subgroups: bitches over (exposed group: n.83) and below cut-off (control group: n.145). All abnormalities resulted more frequent in exposed group: OR was 24.96 (p < 0.0001: 71.1% over vs. 9% below cut-off) for overall abnormalities; 13.68 (p < 0.0001: 40.9% vs. 4.8%) for CEH; 6.13 (p < 0.002: 21.7% vs. 4.1%) for UC; 12.65 (p = 0.09: 3.6% vs. 0%) for M. Cystic endometrial hyperplasia represents the most common finding in adult bitches, followed by UC. A preventive sonographic screening for uterine abnormalities should start from 33% of expected longevity to preventively select animals requiring further evaluations.

Impact of body mass index and operative approach on surgical morbidity and costs in women with endometrial carcinoma and hyperplasia.

OBJECTIVE: To assess the impact of body mass index (BMI) and operative approach on surgical morbidity and costs in patients with endometrial carcinoma (EC) and hyperplasia (EH). METHODS: All women with BMI data who underwent surgery for EC or EH from 2008 to 2014 were identified from MarketScan, a healthcare claims database. Differences in 30-day complications and costs were compared between BMI groups and stratified by surgical modality. RESULTS: Of 1112 patients, 35%, 36%, and 29% had a BMI of ≤29, 30-39, and ≥40kg/m2, respectively. Compared to patients with a BMI of 30-39 and ≤29, women with a BMI ≥40 had higher rates of venous thromboembolism (3% vs 0.2% vs 0.3%, p<0.01) and wound infection (7% vs 3% vs 3%, p=0.02). This increase was driven by the subset of patients who had laparotomy and was not seen in those undergoing minimally invasive surgery (MIS). Median total costs for women with a BMI ≥40, 30-39, and ≤29 were U.S. $17.3k, $16.8k, and $16.6k respectively (p=0.53). Costs were higher for patients who had laparotomy than those who had MIS across all BMI groups, with the cost difference being highest in morbidly obese women (≥40: $21.6k vs $14.9k, p<0.01; 30-39: $18.9k vs $16.1k, p=0.01; ≤29: $19.3k vs $15k, p<0.01). Patients who had complications had higher costs compared to those who did not, with a higher cost difference in the laparotomy group ($27.7k vs $16.4k, p<0.01) compared to the MIS group ($19.9k vs $15k, p<0.01). CONCLUSIONS: MIS may increase the value of care by minimizing complications and decreasing costs. This may be most pronounced in morbidly obese women.

Histopathologic assessment of the entire endometrium in asymptomatic women.

Knowledge on the nature of the endometrium in women without symptoms of endometrial disease is poor. Therefore, the aim of this prospective study was to describe the endometrium of a cohort of asymptomatic women. The entire endometrium of premenopausal and postmenopausal women was embedded for histologic examination. All included patients underwent a hysterectomy on indication of uterovaginal prolapse, from July 2011 to October 2012, in 3 hospitals in the South of the Netherlands. Exclusion criteria were symptoms of postmenopausal vaginal blood loss or premenopausal disordered vaginal bleeding. As a result, 68 women were included in the study, 48 women were postmenopausal and 20 were premenopausal. In the endometrium of 10 women, simple hyperplasia was found (15%); 1, complex hyperplasia (2%); 2, simple atypical hyperplasia (3%); 2, complex atypical hyperplasia (3%); and 2, a small focus of intramucosal endometrioid endometrial carcinoma (3%). In general, the endometrium was heterogeneous, and most lesions were not present in the entire endometrium. In conclusion, after examining the entire endometrium, a remarkable high prevalence of endometrial pathology was found in asymptomatic women. The clinical meaning of these lesions is not yet clear, but endometrial pathology may frequently exist without symptoms.

Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study.

OBJECTIVE: To evaluate the clinical safety of bazedoxifene (BZA) on the reproductive tract in postmenopausal women with osteoporosis over 7 years. STUDY DESIGN: This was a second, blinded, 2-year extension of a 3-year, randomized, double-blind, placebo (PBO)- and active-controlled phase 3 trial. In the core study, subjects were randomized to receive BZA 20 or 40mg, raloxifene 60mg, or PBO. During years 4-5, the raloxifene arm was discontinued and subjects receiving BZA 40mg were transitioned to BZA 20mg. Subjects continued to receive BZA 20mg or PBO during years 6-7. MAIN OUTCOME MEASURES: The primary endpoint was the incidence of new vertebral fractures at 7 years (reported separately). Reproductive tract safety findings at 7 years are reported here. Endometrial thickness was assessed by transvaginal ultrasonography for subjects in the endometrial safety substudy. Adverse events (AEs) were recorded throughout the study. RESULTS: At 7 years, the adjusted mean (±standard error) change in endometrial thickness was similar with BZA and PBO (-0.11 ± 0.21 and 0.07 ± 0.32 mm, respectively). The incidence of endometrial hyperplasia was low (0.1% for both groups). BZA showed significantly lower rates than PBO of endometrial carcinoma (0.1% vs. 0.4%; P=0.020) and vaginitis (6.1% vs. 7.6%; P=0.035). There were more cases of ovarian carcinoma with BZA (n=4 [0.1%]) than PBO (n=0); the difference was not statistically significant. Rates of breast-related and other gynecologic AEs were similar among groups. CONCLUSIONS: BZA was associated with a favorable reproductive safety profile in postmenopausal women with osteoporosis over 7 years.

Incidence rates of endometrial hyperplasia, endometrial cancer and hysterectomy from 1980 to 2003 within a large prepaid health plan.

Obesity strongly increases the risk of endometrial cancer and is projected to increase current and future endometrial cancer incidence. In order to fully understand endometrial cancer incidence, one should also examine both hysterectomy, which eliminates future risk of endometrial cancer, and endometrial hyperplasia (EH), a precursor that prompts treatment (including hysterectomy). Hysterectomy and EH are more common than endometrial cancer, but data on simultaneous temporal trends of EH, hysterectomy and endometrial cancer are lacking. We used linked pathology, tumor registry, surgery and administrative datasets at the Kaiser Permanente Northwest Health Plan to calculate age-adjusted and age-specific rates, 1980-2003, of EH only (N = 5,990), EH plus hysterectomy (N = 904), hysterectomy without a diagnosis of EH or cancer (N = 14,926) and endometrial cancer (N = 1,208). Joinpoint regression identified inflection points and quantified annual percentage changes (APCs). The EH APCs were -5.3% (95% confidence interval [CI] = -7.4% to -3.2%) for 1980-1990, -12.9% (95% CI = -15.6% to -10.1%) for 1990-1999 and 2.4% (95% CI = -6.6% to 12.2%) for 1999-2003. The EH-plus-hysterectomy APCs were -8.6% (95% CI = -10.6% to -6.5%) for 1980-2000 and 24.5% (95% CI = -16.5% to 85.7%) for 2000-2003. Hysterectomy rates did not significantly change over time. The endometrial cancer APCs were -6.5% (95% CI = -10.3% to -2.6%) for 1980-1988 and 1.4% (95% CI = -0.2% to 3.0%) for 1988-2003. Hysterectomy rates were unchanged, but increased endometrial cancer incidence after 1988 and the reversal, in 1999, of the longstanding decline in EH incidence could reflect the influence of obesity on endometrial neoplasia.

Asymptomatic endometrial thickening.

OBJECTIVE: To formulate clinical recommendations for the assessment of endometrial thickening when it is found on ultrasound in a postmenopausal patient without bleeding. OUTCOMES: Ensure that women with asymptomatic thickening and endometrial polyps found on ultrasound are managed appropriately. EVIDENCE: Published literature was retrieved through searches of English language articles from the EMBASE, Cochrane, and PubMed databases for relevant peer-reviewed articles dating from 1970 to 2009, using appropriate controlled vocabulary (e.g., "asymptomatic endometrial thickness," "endometrial cancer," "postmenopausal bleeding," "transvaginal ultrasonography," "endometrial biopsy" and "endometrial polyp"). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to April 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The level of evidence was determined according to the criteria established by the Canadian Task Force on Preventative Health Care (Table). Recommendations are ranked according to this method. BENEFITS, HARMS, AND COSTS: It is anticipated that the adoption of these recommendations would save postmenopausal women unnecessary anxiety, pain, and risk of procedural complication. It is also expected to decrease the cost to the health system by eliminating unnecessary interventions.

Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia.

PURPOSE The severity of endometrial hyperplasia (EH)-simple (SH), complex (CH), or atypical (AH)-influences clinical management, but valid estimates of absolute risk of clinical progression to carcinoma are lacking. Materials and METHODS We conducted a case-control study nested in a cohort of 7,947 women diagnosed with EH (1970-2002) at one prepaid health plan who remained at risk for at least 1 year. Patient cases (N = 138) were diagnosed with carcinoma, on average, 6 years later (range, 1 to 24 years). Patient controls (N = 241) were matched to patient cases on age at EH, date of EH, and duration of follow-up, and they were counter-matched to patient cases on EH severity. After we independently reviewed original slides and medical records of patient controls and patient cases, we combined progression relative risks (AH v SH, CH, or disordered proliferative endometrium [ie, equivocal EH]) from the case-control analysis with clinical censoring information (ie, hysterectomy, death, or left the health plan) on all cohort members to estimate interval-specific (ie, 1 to 4, 5 to 9, and 10 to 19 years) and cumulative (ie, through 4, 9, and 19 years) progression risks. Results For nonatypical EH, cumulative progression risk increased from 1.2% (95% CI, 0.6% to 1.9%) through 4 years to 1.9% (95% CI, 1.2% to 2.6%) through 9 years to 4.6% (95% CI, 3.3% to 5.8%) through 19 years after EH diagnosis. For AH, cumulative risk increased from 8.2% (95% CI, 1.3% to 14.6%) through 4 years to 12.4% (95% CI, 3.0% to 20.8%) through 9 years to 27.5% (95% CI, 8.6% to 42.5%) through 19 years after AH. CONCLUSION Cumulative 20-year progression risk among women who remain at risk for at least 1 year is less than 5% for nonatypical EH but is 28% for AH.

Benign and hyperplastic endometrial changes associated with tamoxifen use.

For nearly 20 years, tamoxifen has been successfully used in the management of breast cancer. Tamoxifen is a mixed estrogen agonist/antagonist that has a proliferative effect on the endometrium. The drug has been associated with a higher percentage of endometrial polyps and hyperplasia than in control patients as well as slightly increased risk of endometrial cancer. Although patients need to undergo annual gynecologic exams and abnormal vaginal bleeding needs to be aggressively followed up, the utility of routine gynecologic screening of tamoxifen patients has not been established and requires further study. Transvaginal sonography is a useful tool for detecting endometrial proliferation; however, an appropriate cut-off point for further intervention must be established. A cut-off point that is too low for abnormal endometrial thickness would result in a large number of unnecessary endometrial biopsies. Routine office endometrial biopsy needs further study as a screening method for breast cancer patients on tamoxifen.

Endometrial hyperplasia and neoplasia. Cytologic screening with the Endopap endometrial sampler.

A new endometrial sampling device, the Endopap, was tested in a series of 851 patients. This sampler is of simple design, without moving parts, inexpensive and easy to use. Cellular samples proved adequate in 90% of the cases, usually with very abundant material. Endometrial cancer shed atypical cells in all 20 cases studied. However, only about half the patients with adenomatous hyperplasia were correctly identified by the endometrial sample. This fact seems to reflect the lack of adequate morphologic criteria for the recognition of endometrial hyperplasia; this situation prevails with all types of endometrial cell samplers.