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Introduction: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR)., Material and Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR)., Results: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m 2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m 2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth)., Conclusions: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

The risk of undertreating occult endometrial cancer is a problem faced by gynecologists when treating endometrial hyperplasia. The objective of this study is to highlight diagnostic adjuncts to endometrial sampling techniques to improve preoperative detection of co-existing cancer. A systematic search of databases till July 2021: PubMed, ISI-Clarivate Web of Science, Scopus, and CENTRAL. A search of the related literature was also carried out. Two authors screened potential studies. Studies were included if they examined the diagnostic performance of any predictors of concurrent cancer in patients diagnosed with endometrial hyperplasia. Authors charted variables related to literature characteristics (e.g., authors, year of publication), population characteristics (e.g., preoperative diagnoses), and variables related to our research questions (e.g., postoperative diagnoses, risk predictors). After screening 591 potential studies, 28 studies were included. Studies included the data of 7409 endometrial hyperplasia patients with 2377 concurrent endometrial cancer cases (32.1%). Forty potential predictors of concurrent cancer were investigated. We examined three categories of potential predictors: clinical (22 studies), histopathologic/imaging (16 studies), and molecular (six studies) predictors. The proposed predictors, age, menopausal status, diabetes, WHO and endometrial intraepithelial neoplasia histopathologic criteria, pelvic magnetic resonance imaging, and molecular profiling are promising diagnostic adjuncts., (© 2022 International Federation of Gynecology and Obstetrics.)

Objective: Dual-specificity phosphatase 6 (Dusp6) was proposed as a predictive marker of response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. However, its predictive accuracy has never been calculated. We aimed to define it in conservatively treated AEH and EEC., Methods: All patients <45 years with AEH or EEC and conservatively treated with hysteroscopic resection + LNG-IUD insertion from 2007 to 2018 were retrospectively assessed. Dusp6 immunohistochemical expression was assessed and dichotomized as "strong" vs "weak". Relative risk (RR) for "no regression" and "recurrence" or AEH/EEC was calculated. Predictive accuracy was calculated as sensitivity, specificity, positive and negative predictive values (PPV, NPV) and area under the curve (AUC) on receiver operating characteristic curve., Results: Thirty-six women were included. Weak Dusp6 immunohistochemical expression was significantly associated with increased risk of resistance to treatment, with a RR = 16 (P = 0.0074); predictive accuracy analysis showed sensitivity = 80%, specificity = 90%, PPV = 57.1%, NPV = 96.4%, AUC = 0.85. A weak Dusp6 expression was not significantly associated with the risk of recurrence after an initial regression (RR = 0.4; P = 0.53)., Conclusion: Weak Dusp6 expression appears as a significant predictor of resistance of AEH/EEC to fertility-sparing treatment, with moderate predictive accuracy. Weak Dusp6 expression is significantly associated with resistance of atypical endometrial hyperplasia or early endometrial cancer to fertility-sparing treatment, with moderate predictive accuracy., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens., Objectives: To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment., Search Methods: We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020., Selection Criteria: Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment., Data Collection and Analysis: Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods., Main Results: Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome., Authors' Conclusions: There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Endometrial cancer and atypical hyperplasia are rare in young women but create a dilemma between desire for pregnancy and oncologic outcomes., Objective: To identify remission rates and associated prognostic factors in patients undergoing fertility-sparing management for endometrial cancer and atypical hyperplasia., Search Strategy: MEDLINE was searched for studies published between January 1, 1950 and July 31, 2017 using various search terms., Selection Criteria: Studies evaluating fertility-sparing management in patients aged between 19 and 44 years with atypical hyperplasia or stage I endometrial cancer., Data Collection and Analysis: Use of PRISMA guidelines to conduct a meta-analysis of the proportion of patients in remission and meta-regression analysis to test the effect of possible prognostic factors for remission., Main Results: A total of 3673 studies were screened; 65 studies including 1604 patients met the inclusion criteria. The remission rate was 0.75 (95% CI, 0.73-0.77). Operative hysteroscopy for endometrial sampling was associated with higher remission rates (OR 2.31; 95% CI, 1.10-4.84; P=0.03). Studies with higher ratios of infertile women were associated with higher remission rates (OR 4.21; 95% CI, 1.44-12.33; P<0.01)., Conclusion: Operative hysteroscopy is the preferred endometrial sampling method for patients with atypical hyperplasia or endometrial cancer undergoing fertility-sparing management., (© 2019 International Federation of Gynecology and Obstetrics.)

Background: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. The levonorgestrel intrauterine device (Mirena Coil, Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown in some human studies to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain., Objectives: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia., Search Methods: We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Google Scholar, OpenGrey, Latin American Caribbean Health Sciences Literature (LILACS), and two trials registers from inception to 10 January 2017. We searched the bibliographies of all included studies and reviews on this topic. We also handsearched the conference abstracts of the European Society of Human Reproduction and Embryology (ESHRE) 2015 and the American Society for Reproductive Medicine (ASRM) 2015., Selection Criteria: We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo or no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type., Data Collection and Analysis: Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health-related quality of life, and adverse effects during treatment., Main Results: We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision.We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low-quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59) provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others.Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low-quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low-quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low-quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37, one RCT, n = 16, very low-quality evidence). Investigators provided no data on abnormal uterine bleeding or health-related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea., Authors' Conclusions: At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy - specifically, megestrol acetate - versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long-term outcome data are needed to address this clinical question.

Introduction: The aim of this study was to analyse the hospital cost of treatment with robotic-assisted laparoscopic hysterectomy and total abdominal hysterectomy for women with endometrial cancer or atypical complex hyperplasia and to identify differences in resource use and cost., Material and Methods: This cost analysis was based on two cohorts: women treated with robotic-assisted laparoscopic hysterectomy (n = 202) or with total abdominal hysterectomy (n = 158) at Copenhagen University Hospital, Herlev, Denmark. We conducted an activity-based cost analysis including consumables and healthcare professionals' salaries. As cost-drivers we included severe complications, duration of surgery, anesthesia and stay at the post-anesthetic care unit, as well as number of hospital bed-days. Ordinary least-squares regression was used to explore the cost variation. The primary outcome was cost difference in Danish kroner between total abdominal hysterectomy and robotic-assisted laparoscopic hysterectomy., Results: The average cost of consumables was 12,642 Danish kroner more expensive per patient for robotic-assisted laparoscopic hysterectomy than for total abdominal hysterectomy (2014 price level: 1€ = 7.50 Danish kroner). When including all cost-drivers, the analysis showed that the robotic-assisted laparoscopic hysterectomy procedure was 9386 Danish kroner (17%) cheaper than the total abdominal hysterectomy (p = 0.003). When the robot investment was included, the cost difference reduced to 4053 Danish kroner (robotic-assisted laparoscopic hysterectomy was 7% cheaper than total abdominal hysterectomy) (p = 0.20). Increasing age and Type 2 diabetes appeared to influence the overall costs., Conclusion: For women with endometrial cancer or atypical complex hyperplasia, robotic-assisted laparoscopic hysterectomy was cheaper than total abdominal hysterectomy, mostly due to fewer complications and shorter length of hospital stay., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Preoperative knowledge of myometrial invasion in endometrial cancer is important for surgical planning. This study aimed to assess the diagnostic efficiency of two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasonography (TVS) with and without saline infusion (SIS) and magnetic resonance imaging (MRI) for assessment of myometrial invasion in endometrial cancer., Material and Methods: 110 women with atypical endometrial hyperplasia or endometrial adenocarcinoma underwent preoperative 2D- and 3D-TVS with and without SIS and MRI. Offline 3D-TVS measurement was performed of the minimal tumor-free margin in relation to myometrial thickness expressed as deep (≥ 50%) myometrial invasion and subjective impression of cervix involvement. The quality of images was also evaluated. Diagnostic efficiencies were calculated for myometrial and cervical involvement for each method. The pathologist's final diagnosis served as the reference standard., Results: For myometrial involvement, MRI showed greater accuracy than 3D-TVS or 2D-TVS (83, 71 and 75%, respectively). The efficiency of 3D-TVS was not superior to 2D-TVS and did not improve with SIS. The sensitivities of 2D-TVS and 3D-TVS were similar to that of MRI, and the efficiency of 3D-TVS improved when volumes of inadequate quality (39%) were excluded. For evaluating cervical involvement, the accuracy of 3D-TVS was 85%, comparable to the results of 2D-TVS (80%) and MRI (85%). The results did not improve when saline was added., Conclusion: 3D-TVS or 3D-SIS was not more efficient than 2D-TVS or MRI for assessment of myometrial invasion in endometrial cancer. 3D-TVS assessment without 2D-TVS was impeded by difficulties in obtaining 3D-TVS volumes of sufficient quality., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To evaluate the accuracy of gross visual assessment of myometrial invasion in endometrial carcinoma., Design: Prospective, descriptive study., Setting: University hospital., Population: Two hundred and fourteen consecutive patients operated between 2005 and 2008. All patients were preoperatively diagnosed with endometrial carcinoma or complex atypical hyperplasia considered by the pathologist to be at the border of highly differentiated endometrial cancer., Methods: Intraoperative gross visual assessment of myometrial tumor invasion (<50 or ≥50%), cervical tumor engagement and tumor diameter in millimeters were noted for all patients., Main Outcome Measures: The collected data were compared with final histopathology., Results: Intraoperative gross visual assessment of myometrial tumour invasion correlated well with final histology, with an accuracy of 87%. Agreement between gross visual assessment and final histology was reached in 91% of grade 1 tumors. Additionally, we found that 98.5% of tumors with a diameter <20mm had <50% myometrial invasion, regardless of grade., Conclusions: Intraoperative gross visual assessment of myometrial tumor invasion and tumor size measurements are simple, fast and inexpensive methods that may provide important information for the surgeon to decide upon the extent of staging when other more accurate methods are not at hand., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

We performed immunohistochemical analysis of estrogen (ERalpha) and progesterone receptors (PRA and PRB), phosphatase and tensin homolog (PTEN) and aromatase in endometrial hyperplasia treated with Mirena (levonorgestrel-releasing intrauterine system; LNG-IUS) and explored their prognostic significance. The baseline pre-treatment endometrial hyperplasia of a selected prospective cohort was analyzed [complex (n = 29) and atypical (n = 5)]. Study participants were categorized into those that showed endometrial regression (responders, n = 28) and those that showed non-regression or histological progression to atypia or malignancy (non-responders, n = 6). Immunohistochemical expression was expressed as a histological score (HS). Responders compared to non-responders showed significantly higher HSs for estrogen and progesterone receptors. Absence of estrogen and progesterone receptors predicted non-responder status with likelihood ratios of 9.33 (95% CI 2.19-39.81) and 2.92 (95% CI 1.47-5.79), respectively. Neither PTEN nor aromatase expression were associated with LNG-IUS therapy responsiveness. Responsiveness of endometrial hyperplasia to LNG-IUS therapy may be determined through analysis of baseline estrogen and progesterone receptors, but these exploratory findings require confirmation in a larger dataset.

Objectives: Hysterectomy represents the current routine therapy for high-risk endometrial precancers. More sophisticated methods are needed for treatment decision among women who want to preserve fertility and seriously ill patients. Among women diagnosed with high-risk hyperplasia, approximately 40% show signs of endometrial cancer in the hysterectomy specimen. Thus, more sophisticated methods are needed to select the women at risk., Setting: University Hospital of Tromsø, Regional Center for Gynecological Oncology in northern Norway., Population: From 1999 to 2004, 258 consecutive patients had endometrial hyperplasia diagnosed by D-score; 57 among these were high-risk cases (D-score < 0) and 10 had coexisting endometrial carcinoma. No further cancers were detected after long-term follow-up (4-10 years)., Design: From the initial histological specimens, material from the 10 patients with cancer and from the 13 cases without cancer (high-risk D-score < 0) was analyzed with selected histomorphometric (architectural and nuclear) and immunohistochemical (hormone receptors and apoptotic) features blinded to the investigator., Method: Original slides were used for computerized histomorphometry (4-class rule and related procedures). Serial sections from the paraffin embedded material were used for immunohistochemical investigations. Immunohistochemical expression in glands and stroma was evaluated by the semi-quantitative H-score (ER-alpha, ER-beta, PR-A, PR-B, RCAS-1, Bcl-2, BAX, and Caspase-3)., Results: The histomorphometric 4-class rule differentiates between presence and absence of cancers with a sensitivity of 80% and specificity of 77%. Several morphometric and immunohistochemical features were significantly different in cases with cancer and hyperplasia., Conclusions: Histomorphometry seems superior in predicting coexistent carcinoma in high-risk endometrial hyperplasia and should be considered for clinical use.

Background: Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH)., Methods: This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses., Results: Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens., Conclusions: The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma., (Copyright 2006 American Cancer Society.)

Background: The purpose of this study was to evaluate the diagnostic value of transvaginal ultrasound measurement of endometrial thickness, cytology obtained by Gynoscann, and histology of the endometrium sampled by Uterine Explora Curette compared with histology of the uterine specimen as the gold standard., Methods: Consecutive patients admitted for hysterectomy had transvaginal ultrasound, sampling by Gynoscann, and Uterine Explora Curette done just before surgery, after informed consent., Results: A total of 181 women entered the study. Sixteen had endometrial cancer, seven had atypical hyperplasia and nine had complex hyperplasia. A total of 168 patients had a transvaginal ultrasound done. At a cutoff limit of 4mm (endometrial thickness of 4mm or less indicating normal endometrium), the sensitivity was 90.3%, the specificity 24.8%, the positive predictive value 21.4% and the negative predictive value 91.9%. One endometrial cancer, one atypical and one complex hyperplasia were missed. The Gynoscann method showed a sensitivity of 62.5%, a specificity of 94.0%, a positive predictive value of 69.0% and a negative predictive value of 92.1%. Two cancers, three atypical and six complex hyperplasia were missed. The Uterine Explora Curette showed a sensitivity of 90.6%, a specificity of 100.0%, a positive predictive value of 100.0% and a negative predictive value of 98.0%. One endometrial cancer and two complex hyperplasia were missed., Conclusion: Transvaginal ultrasound is a reliable method in excluding endometrial pathology. The Uterine Explora Curette was superior to Gynoscann in diagnosing neoplasia of the endometrium. It was found to have the same diagnostic accuracy as conventional dilatation and curettage.

Background: The aim of the present study was to evaluate the expression of mRNA for the keratinocyte growth factor and the keratinocyte growth factor receptor in human endometrium at different stages of the menstrual cycle. The role of estrogen and progesterone in regulating the expression of the mRNAs encoding keratinocyte growth factor and its receptor was further examined by studying the effect of continuous progestin (endometrium exposed to levonorgestrel releasing intrauterine contraceptive device), and continuous estrogen (endometrium hyperplasia) on the endometrium., Methods: The expression of mRNA in endometrial samples was evaluated using reverse transcriptase polymerase chain reaction., Results: The expression of KGF mRNA was found to vary during the menstrual cycle, with the highest levels in the progesterone-dominated late-secretory stage endometrium. Keratinocyte growth factor mRNA expression was low in both the endometrium that had been under the influence of continuous progestin (atrophic endometrium) and continuous estrogen (hyperplastic endometrium). The highest level of keratinocyte growth factor receptor mRNA expression was seen in late-proliferative stage of the menstrual cycle and in hyperplasia when the estrogen exposure to endometrium is high. A low receptor mRNA level was found in endometrium exposed to continuous progestin., Conclusion: The results suggest that keratinocyte growth factor mRNA expression is progesterone dependent, whereas keratinocyte growth factor receptor mRNA expression seems to be more estrogen than progesterone dependent.

Recurrent bleeding occurred in a premenopausal breast cancer woman during tamoxifen therapy. This bleeding required three curettages. Atypical hyperplasia and carcinoma were excluded, and the patient was prepared for endometrial ablation with two GnRH agonist injections. An endometrial ablation using the roller ball technique was carried out without complications. Tamoxifen therapy was continued postoperatively. During 24 months' follow-up the patient experienced no bleeding and no endometrium was seen by sonography.

Endometrial curettings from 204 patients containing severe forms of atypical hyperplasia, carcinoma in situ, and well-differentiated carcinoma were compared with subsequent hysterectomy specimens to evaluate and identify the most useful histologic criteria for predicting the presence of invasive carcinoma. Endometrial stromal invasion, increased degrees of nuclear atypism, mitotic activity, cellular stratification, and epithelial necrosis in curettings were associated with a greater likelihood of carcinoma in the uterus. Of these, stromal invasion was the most significant feature. When stromal invasion was absent, carcinoma was present in the uterus in only 17%, and the carcinomas were well differentiated and confined to the endometrium or only superficially invasive. When stromal invasion was present in curettings, residual carcinoma was present in the uterus in half, and of these, one third were moderately or poorly undifferentiated and a quarter invaded deeply into the myometrium. The criteria for invasion are 1) an irregular infiltration of glands associated with an altered fibroblastic stroma or desmoplastic response; 2) a confluent glandular pattern in which individual glands are uninterrupted by stroma and merge to form a cribriform pattern of stromal replacement; 3) an extensive papillary pattern; and 4) replacement of stroma by masses of squamous epithelium. To qualify as invasion, 2, 3, and 4 must occupy at least one half (2.1 mm) of low power field 4.2 mm in diameter. Because of the important role of stromal invasion in predicting prognosis, future classifications of endometrial neoplasia should utilize this feature in distinguishing atypical hyperplasia from well differentiated adenocarcinoma.

Endometrial curettings from 170 patients with all grades of endometrial hyperplasia, who did not undergo a hysterectomy for at least 1 year were evaluated in order to correlate the histopathologic features with behavior. Follow-up ranged from 1 to 26.7 years (mean, 13.4 years). Cytologic and architectural alterations were analyzed separately in order to assess their respective roles in predicting the likelihood of progression to carcinoma. Classification of proliferative lesions based solely on the presence of cytologic atypia revealed that atypia was a discriminant factor. Proliferations lacking cytologic atypia were designated hyperplasia and those displaying atypia were designated atypical hyperplasia. Only 2 (1.6%) of 122 patients with hyperplasia progressed to carcinoma compared with 11 (23%) of women with atypical hyperplasia (P = 0.001). Subclassification of the two forms of hyperplasia (those with cytologic atypia and those without) was performed using the degree of architectural abnormalities. Hyperplasia and atypical hyperplasia displaying marked glandular complexity and crowding producing a back-to-back appearance were designated complex hyperplasia (CH) and complex atypical hyperplasia (CAH), respectively. Hyperplasia and atypical hyperplasia with lesser degrees of glandular complexity and crowding were designated simple hyperplasia (SH) and simple atypical hyperplasia (SAH), respectively. Progression to carcinoma occurred in 1 (1%) of 93 patients with SH, in 1 (3%) of 29 patients with CH, in 1 (8%) of the patients with SAH, and in 10 (29%) of the patients with CAH. The differences between the four subgroups suggest a trend but are not statistically significant. The findings in this study provide a rationale for classifying noninvasive endometrial proliferations primarily on the basis of cytologic atypia since this is the most useful criterion in predicting the likelihood of progression to carcinoma. In addition, the presence of concommitant architectural alterations appears to identify a particularly high-risk subgroup.