Analysis of the relative inducibility of an extensive series of mutant glucocorticoid response elements (GREs) defines features critical to the constitution of an active GRE. Assuming that function as a GRE reflects binding of glucocorticoid receptor, our activity data are consistent with the recognition of the GRE as two hexamer half-sites, each half-site recognized by a single subunit of a receptor dimer, probably in a cooperative fashion. Integrity of both half-sites is necessary for an active element, and spacing of the half-sites is critical. The identity of 1 basepair within the hexamer half-site is unconstrained; the receptor probably makes no base-specific contacts at this position. In contrast, at other positions within the half-site, limited substitutions (if any) can be tolerated. These results along with data from certain insertion mutations suggest that the receptor recognizes each hexamer half-site as two separable subelements. A further implication is that the DNA-binding domain of the glucocorticoid receptor is composed of distinct subdomains, which interact with the subelements of the recognition sequence.
First published in 2019, the Ovarian-Adnexal Reporting and Data System (O-RADS) US provides a standardized lexicon for ovarian and adnexal lesions, enables stratification of these lesions with use of a numeric score based on morphologic features to indicate the risk of malignancy, and offers management guidance. This risk stratification system has subsequently been validated in retrospective studies and has yielded good interreader concordance, even with users of different levels of expertise. As use of the system increased, it was recognized that an update was needed to address certain clinical challenges, clarify recommendations, and incorporate emerging data from validation studies. Additional morphologic features that favor benignity, such as the bilocular feature for cysts without solid components and shadowing for solid lesions with smooth contours, were added to O-RADS US for optimal risk-appropriate scoring. As O-RADS US 4 has been shown to be an appropriate cutoff for malignancy, it is now recommended that lower-risk O-RADS US 3 lesions be followed with US if not excised. For solid lesions and cystic lesions with solid components, further characterization with MRI is now emphasized as a supplemental evaluation method, as MRI may provide higher specificity. This statement summarizes the updates to the governing concepts, lexicon terminology and assessment categories, and management recommendations found in the 2022 version of O-RADS US.
To evaluate whether preoperative dilation and curettage (D&C) lowers the risk of unexpected cancer at hysterectomy. Women with complex atypical endometrial hyperplasia on sampling from January 2000 to May 2008 who underwent hysterectomy within 6 months were identified using a pathology database. Patient age, sampling procedures, and hysterectomy pathology were recorded. Women were categorized as having either an office biopsy-based evaluation or a curettage-based evaluation. The proportion of women with cancer at surgery was estimated and compared for the two groups. Of 824 women with complex atypical endometrial hyperplasia on initial sampling, 48% were found to have cancer. For 100 women, cancer was diagnosed preoperatively by additional sampling before hysterectomy. For the remaining 724, 298 (41%) had unexpected cancer at hysterectomy. The diagnosis of complex atypical endometrial hyperplasia was biopsy-based for 531 (73%) and curettage-based for 193 (27%). The risk of cancer for women who had a D&C was significantly lower than for those who had biopsy, but still of concern (30% compared with 45%, P<.001), as was the risk of myometrial invasion (18% compared with 25%, P=.05). Age was strongly correlated to risk of cancer, invasive cancer, and deeply invasive or grade 3 disease. Dilation and curettage lowered the risk of unexpected cancer compared with biopsy, but 18% of women still had invasive cancer found at hysterectomy. The risk of unexpected cancer is strongly related to age. Dilation and curettage can help detect cancer preoperatively but is not reliable for excluding cancer. II.
In postmenopausal women, simple cysts greater than 1 cm in size should be described but do not need follow-up imaging unless they are greater than 3–5 cm, using the higher threshold for exceptional... This multidisciplinary consensus update aligns prior Society of Radiologists in Ultrasound (SRU) guidelines on simple adnexal cysts with recent large studies showing exceptionally low risk of cance...
Recent studies showing a protective effect of tamoxifen in women at high risk for breast cancer have expanded the indications of the drug. While acting as an estrogen antagonist in the breast, tamoxifen can have estrogenic effects on the endometrium; consensus opinion is that tamoxifen increases the risk for endometrial cancer. Because an increasing number of women are taking tamoxifen, a strategy for gynecologic surveillance is needed. Studies examining the relation between risk for endometrial cancer and tamoxifen use have conflicting results. However, because of an overall interpretation that tamoxifen use slightly increases risk for endometrial cancer, some researchers advocate routine ultrasonography and endometrial biopsy for screening asymptomatic women receiving tamoxifen. This paper reviews the literature on endometrial cancer in women taking tamoxifen and the usefulness of various screening methods in this setting. Risk factors and screening criteria for endometrial cancer in the general population are discussed, and a strategy for surveillance of women taking tamoxifen is proposed. Patients should be screened for signs or symptoms of endometrial abnormality before taking tamoxifen. This evaluation, which should include a careful history, pelvic examination, and Papanicolaou smear, should be repeated annually while the patient is receiving tamoxifen. Although transvaginal ultrasonography is not recommended for routine screening, it is indicated if an adequate pelvic examination cannot be performed or if additional risk factors are present. The likelihood of abnormality is greater for patients who have abnormal bleeding, discharge, abnormal glandular cells on Papanicolaou smear, or an endometrial measurement on ultrasonography of more than 8 mm; these findings should prompt an aggressive evaluation of the endometrium.