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Aims: To evaluate the sampling adequacy and diagnostic accuracy of the endometrial SAP-l sampling device in detecting endometrial lesions based on histopathological examination., Materials and Methods: In total, 182 patients who required an endometrial biopsy were enrolled in this study. All of the patients underwent endometrial biopsies with the SAP-l sampler prior to hysteroscopy (169/182) or dilatation and curettage (D&C) (13/182). Endometrial tissues were obtained at biopsy for histopathological examination., Results: Ad- equate endometrial specimens were obtained in 148 of 182 patients (81.32%). Menopause (p = 0.000), endometrial thickness (p = 0.004), and the types of endometrial diseases (p = 0.009) differed significantly between the two groups. Among the 169 patients who underwent hysteroscopy, sampling scratches were observed in the uterine cavity in 147 cases (86.98%). Compared to traditional methods, such as hysteroscopy and D&C, the sampling diagnostic sensitivity, specificity, and positive and negative predictive values were 82.35%, 100%, 100% , and 97.76% for endometrial carcinoma (n=17) and 37.5%, 100%, 100% and 97.76% for endometrial atypical hyperplasia (n=8), respectively. Those that were misdiagnosed occurred because the lesions were focal or localized in a small part of the uterine cavity. The sampling diagnostic sensitivity for polyps (n=32) was 12.5%. Two patients with submucosal leiomyoma went undiagnosed based on the sample specimens., Conclusion: Endometrial sampling using the SAP-l sampler is a minimally invasive altemative technique for obtaining adequate endometrial specimens for histopathological examination. The SAP-l sampler was useful in detecting endometrial carcinoma and atypical hyperplasia cases that were not highly suspected to be localized; however, this method was not useful in detecting endometrial polyps and submucosal leiomyomas.

Introduction: Abnormal uterine bleeding (AUB) is the most common symptom of endometrial cancer (EC) and endometrial hyperplasia with (AH) or without (EH) atypia. Risk of malignancy and hyperplasia is significantly lower in premenopausal than in postmenopausal women. Only 10% of EC occurs before menopause. Obesity and age are well-recognized risk factors of endometrial cancer. Endometrial sampling is recommended in women at high risk of endometrial malignancy. The primary objective was to determine the incidence of EC, AH and EH in premenopausal women undergoing dilation and curettage (D&C) because of AUB. Additional objective of the study was to estimate the risk of EC and AH in overweight and obese women with two types of AUB: heavy menstrual bleeding (AUB-HMB) and intermenstrual bleeding (AUB-IMB), according to PALM-COEIN classification., Material and Methods: Retrospective study in the population of women undergoing D&C in tertiary hospital because of AUB between Jan-2016 and Dec-2016. The incidence of EC, AH, EH was established. The influence of the variables: age, BMI, AUBHMB/ AUB-IMB on the occurrence of abnormal histology (EC, AH, EH) was evaluated. Finally, the model built by using backward stepwise regression and mechanism of v-fold cross-validation, showed no statistically significant relationship., Results: EC was detected in 2/213 cases (0.9%; 95% CI 0.0003 to 0.036), AH in 3/213 cases (1.4%), giving a total of 5/213 (2.3%) women with AH or EC. EH was detected in 16/213 (7.5%) women. High BMI raises the chance of AH diagnosis: OR 1.16 (95% CI 1.05- 1.28). The presence of HMB compared to IMB reduces the chance of EH: OR 0.24 (95% CI 0.07-0.9). IMB increases the chance for the diagnosis of EH 4.11 times compared to HMB (OR 4.1, 95% CI 1.1-14.9; p = 0.016)., Conclusions: EC in premenopausal women with AUB undergoing D&C is rare. There is a need to search for more effective methods of selection of patients than commonly used. Age and BMI do not seem to be factors that should be used to select patients.

Objective: We evaluated the clinical performance of liquid-based endometrial cytology (SurePath™) for detecting endometrial malignancies by comparison with the performance of suction endometrial tissue biopsy., Study Design: From November 2011 to May 2013, we consecutively collected 1,118 liquid-based endometrial cytology specimens and 674 suction endometrial tissue biopsy specimens., Results: The rate of nonpositive final histology in nonpositive liquid-based endometrial cytology (98.2%) was higher than the rate of nonpositive final histology in nonpositive suction endometrial tissue biopsy (97.0%). None of the clinical performance values of liquid-based endometrial cytology for detecting the endometrial malignancies were statistically inferior to those of the suction endometrial tissue biopsy. When the positivity threshold was more than "atypical endometrial cells of undetermined significance," the rate of positive liquid-based endometrial cytology from cases with a positive final histology (84.5%) was higher than the rate of positive suction endometrial tissue biopsy from cases with a positive final histology (69.8%). However, there were still no significant differences among all the performance values., Conclusions: Our liquid-based endometrial cytology would be more appropriate in various clinical situations as the initial detection tool for endometrial malignancies, rather than suction endometrial tissue biopsy. In addition, it could be used in screening for endometrial malignancies on a broader scale., (© 2017 S. Karger AG, Basel.)

Background: Hysteroscopic reliability may be influenced by the experience of the operator and by a lack of morphological diagnostic criteria for endometrial malignant pathologies. The aim of this study was to evaluate the diagnostic accuracy and the inter-observer agreement (IOA) in the management of abnormal uterine bleeding (AUB) among different experienced gynecologists., Methods: Each gynecologist, without any other clinical information, was asked to evaluate the anonymous video recordings of 51 consecutive patients who underwent hysteroscopy and endometrial resection for AUB. Experts (>500 hysteroscopies), seniors (20-499 procedures) and junior (≤19 procedures) gynecologists were asked to judge endometrial macroscopic appearance (benign, suspicious or frankly malignant). They also had to propose the histological diagnosis (atrophic or proliferative endometrium; simple, glandulocystic or atypical endometrial hyperplasia and endometrial carcinoma). Observers were free to indicate whether the quality of recordings were not good enough for adequate assessment. IOA (k coefficient), sensitivity, specificity, predictive value and the likelihood ratio were calculated., Results: Five expert, five senior and six junior gynecologists were involved in the study. Considering endometrial cancer and endometrial atypical hyperplasia, sensitivity and specificity were respectively 55.5 % and 84.5 % for juniors, 66.6 % and 81.2 % for seniors and 86.6 % and 87.3 % for experts. Concerning endometrial macroscopic appearance, IOA was poor for juniors (k = 0.10) and fair for seniors and experts (k = 0.23 and 0.22, respectively). IOA was poor for juniors and experts (k = 0.18 and 0.20, respectively) and fair for seniors (k = 0.30) in predicting the histological diagnosis., Conclusions: Sensitivity improves with the observer's experience, but inter-observer agreement and reproducibility of hysteroscopy for endometrial malignancies are not satisfying no matter the level of expertise. Therefore, an accurate and complete endometrial sampling is still needed.

Objective: The purpose of the present study was to evaluate the reproducibility of the cytological diagnosis of endometrial lesions by the Osaki Study Group (OSG) method of new cytological diagnostic criteria using BD SurePath ™ (SP)-liquid-based cytology (LBC)., Methods: This cytological classification using the OSG method consists of six categories: (i) normal endometrium (NE), (ii) endometrial glandular and stromal breakdown (EGBD), (iii) atypical endometrial cells, cannot exclude atypical endometrial hyperplasia or more (ATEC-A), (iv) adenocarcinoma including atypical endometrial hyperplasia or malignant tumour (Malignancy), (v) endometrial hyperplasia without atypia (EH) and (vi) atypical endometrial cells of undetermined significance (ATEC-US). For this study, a total 244 endometrial samplings were classified by two academic cytopathologists as follows: 147 NE cases , 36 EGBD cases , 47 Malignant cases, eight ATEC-A cases, two EH cases and four ATEC-US cases. To confirm the reproducibility of the diagnosis and to study the inter- and intra-observer agreement further, a second review round followed at 3-month intervals, which included three additional cytopathologists., Results: The inter-observer agreement of NE classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.70 to 0.81. Both EGBD and Malignancy classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.62-0.63 to 0.84-0.95, respectively. The overall intra-observer agreement between the first and the second rounds was 'good to fair' to 'excellent', with values changing from 0.79 to 0.85. All kappa improvements were significant (P < 0.0001)., Conclusion: In this study, it seemed that the use of the OSG method as the new diagnostic criteria for SP-LBC preparation, may be a valid method to improve the precision (reproducibility) of endometrial cytology., (© 2016 John Wiley & Sons Ltd.)

Introduction: Women with postmenopausal bleeding and endometrial thickness >4 mm undergo endometrial sampling to exclude endometrial cancer. The aim of this study is to investigate the relative risk of developing endometrial cancer in a prospective cohort after initial work-up for postmenopausal bleeding showing reassuring histology or insufficient sampling., Material and Methods: All women presenting with postmenopausal bleeding were prospectively included from January 2009 to April 2011. Follow-up data were collected from patient charts and PALGA (Dutch Pathology Registry). Hazard ratios for endometrial cancer were determined by calculating standardized incidence ratios., Results: A total of 668 women were included and 568 women were available for follow-up [median follow-up time 47 (range 7-63) months]. Women who presented with postmenopausal bleeding, endometrial thickness >4 mm and hyperplasia without atypia on biopsy at the first presentation showed a significantly increased risk (standardized incidence ratio 17.15, 95% confidence interval 1.96-61.93) of being diagnosed with endometrial cancer during the first four years of follow up compared with the age-specific population. All women that developed endometrial cancer after initial reassuring histology presented with recurrent postmenopausal bleeding. None of the women with endometrial thickness >4 mm and no or insufficient sample for histology at the first presentation developed endometrial cancer during the follow up., Conclusions: Although in general, women with endometrial hyperplasia without atypia are considered to have a low risk for cancer, we observed a significant long-term risk of endometrial cancer after postmenopausal bleeding. Whether additional diagnostics or a more stringent follow-up regimen would be cost-effective, needs to be studied., (© 2016 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).)

Background: Endometrial carcinoma (EOC) is a gynecological disease with one of the highest worldwide incidences. Due to the lack of typical clinical symptoms and limited sensitive screening methods used to diagnose endometrial carcinoma, the disease is easily neglected before patients are aware of its presence. Therefore, EOC results in serious impacts on women's lives and health. We screened diagnostic biomarkers of EOC with a noninvasive method that compared healthy individuals and endometrial hyperplasia (EOH) patients., Methods: The morning urine of 25 healthy individuals, 25 patients with EOC and 10 patients with EOH were analyzed using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) platform. Metabolomics data were used to screen the different metabolites according to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) analyses. Furthermore, the screened biomarkers of the newly diagnosed EOC and EOH candidates and healthy individuals were verified using the predictive model of the support vector machine (SVM) to obtain EOC diagnostic biomarkers., Results: An EOC diagnostic biomarker group was found according to the metabolomics method. Five diagnostic biomarkers, including porphobilinogen, acetylcysteine, N-acetylserine, urocanic acid and isobutyrylglycine, were significantly changed in the EOC patients. Among them, porphobilinogen and acetylcysteine were significantly down-regulated, while N-acetylserine, urocanic acid and isobutyrylglycine were significantly up-regulated., Conclusions: Disturbances in these biomarkers have negative impacts on the body's metabolic functioning. The EOC diagnostic biomarker group can provide a clinical reference for diagnosing EOC and insight into the diagnosis of other diseases in the clinic., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Clinical guidelines recommend that women with abnormal uterine bleeding with risk factors have an endometrial biopsy to exclude hyperplasia or cancer. Given the majority of endometrial cancer occurs in postmenopausal women, it has not been widely recognized that obesity is a significant risk factor for endometrial hyperplasia and cancer in young, symptomatic, premenopausal women., Objective: We sought to evaluate the effect of body mass index on risk of endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding., Study Design: This was a retrospective cohort study in a single large urban secondary women's health service. Participants were 916 premenopausal women referred for abnormal uterine bleeding of any cause and had an endometrial biopsy from 2008 through 2014. The primary outcome was complex endometrial hyperplasia (with or without atypia) or endometrial cancer., Results: Almost 5% of participants had complex endometrial hyperplasia or cancer. After adjusting for clinical and demographic factors, women with a measured body mass index ≥30 kg/m 2 were 4 times more likely to develop complex hyperplasia or cancer (95% confidence interval, 1.36-11.74). Other risk factors were nulliparity (adjusted odds ratio, 3.08; 95% confidence interval, 1.43-6.64) and anemia (adjusted odds ratio, 2.23; 95% confidence interval, 1.14-4.35). Age, diabetes, and menstrual history were not significant., Conclusion: Obesity is an important risk factor for complex endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding who had an endometrial biopsy in a secondary gynecology service. As over half of women with the outcome in this study were age <45 years, deciding to biopsy primarily based on age, as currently recommended in national guidelines, potentially misses many cases or delays diagnosis. Body mass index should be the first stratification in the decision to perform endometrial biopsy and/or to refer secondary gynecology services., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A 9-year-old intact female mixed breed dog was presented for mammary gland tumor surgery, and preoperative radiographs showed a tubular soft tissue opacity mass with multifocal mineralization in the caudoventral abdominal cavity. Subsequent ultrasonography demonstrated uterine dilation with echogenic fluid and endometrial acoustic shadowing consistent with mineralization. Resection of mammary gland tumors and ovariohysterectomy were performed. Pyometra was diagnosed on cytologic examination of uterine fluid. Histopathology of the uterine tissue confirmed a diagnosis of cystic endometrial hyperplasia with uterine mineralization., (© 2016 American College of Veterinary Radiology.)

This study evaluated the clinical significance of endometrial cells in Papanicolaou test (Pap test). A retrospective study was performed from the cytological database of Seoul National University Hospital. The results of Pap tests of women aged 40 years or older between January 1998 and December 2007 were sorted. Medical records were reviewed to identify the presence of endometrial cells from cytology, and cytologic and histologic follow-ups were performed to determine the clinical significance of the lesions. Among 75,673 Pap cases, 832 cases presenting normal endometrial cells (nEMCs) were included in this study. Their follow-up data are as follows: 800 with nEMCs, 5 with atypical EMCs (aEMCs), and 27 with endometrial cancer cells (EMCCs) on cytologic and histologic follow-ups. Significant endometrial or cervical diseases were found in 0.5%, 40%, and 100% of the cases on the following-up the pathologic examination of the women with nEMCs, aEMCs, and EMCCs, respectively. Unlike aEMCs and EMCCs, nEMCs on Pap tests did not increase the risk of developing endometrial hyperplasia or endometrial cancer in women aged 40 years or older. There is no clinical benefit to perform routine endometrial work-up in women with nEMCs, as recommended in the 2001 Bethesda System. However, symptomatic women with nEMCs on Pap test should perform endometrial work-up regardless of menopausal status.

Aim: Paired boxed gene 1 (PAX1) has previously been reported to be a methylation-silenced gene in cases of cervical and ovarian cancers. We evaluated the expression of PAX1 in normal endometrium, endometrial hyperplasia and endometrial carcinoma (EC), and investigated the prognostic value of PAX1 expression in patients with EC., Methods: We conducted a hospital-based retrospective review of PAX1 distribution immunohistochemically in 201 samples of endometrium from biopsy or hysterectomy. PAX1 immunoreactivity was classified into low and high score groups based upon the extent and intensity of staining., Results: There was intense intranuclear staining for PAX1 in premalignant endometrial lesions. A high PAX1 score was observed in a high percentage of samples of normal endometrium (93.3%), in endometrial hyperplasia without atypia (97.2%) and in endometrial atypical hyperplasia (87.5%), but this level was found in only one-third of the EC samples (30.1%). The PAX1 protein score was significantly higher in samples of premalignant endometrial lesions compared with those of EC (P < 0.001). Importantly, a higher PAX1 score in EC cases was correlated with good overall survival, with a hazard ratio of 0.22 for death (95% confidence interval, 0.05-0.96)., Conclusions: PAX1 protein expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. PAX1 is also a potential prognostic marker in cases of EC., (© 2016 Japan Society of Obstetrics and Gynecology.)

Objective: The 2001 Bethesda System for Reporting Cervical Cytology includes documenting 'endometrial cells in women ≥40 years of age' (E40) to help identify endometrial carcinoma (EC) on a Papanicolaou (Pap) test. The 2014 Bethesda System for Reporting Cervical Cytology raises the threshold to ≥45 years of age (E45). As many of these women are menstruating, routine biopsy after E40, or even E45, may lead to unnecessary procedures for benign endometrial cells. Establishing a different age threshold in combination with other clinical findings may help to guide management., Methods: A retrospective chart review was performed on consecutive EC specimens and E40 Pap tests. Clinical, pathological data such as age, biopsy diagnosis, FIGO grade and the time of the last Pap test, Pap test diagnosis and resection diagnosis, depth of invasion, stage and metastases were recorded., Results: Sixty-three EC cases had prior Pap smears, with the following diagnoses: negative for an intraepithelial lesion or malignancy (n = 27), atypical glandular cells, not otherwise specified (AGC, NOS) (n = 14), adenocarcinoma (n = 10) and E40 (n = 1; 51 years). Six hundred and forty-two E40 cases had 138 (21.5%) biopsies and/or hysterectomies. Out of the 138 cases, two (1.4%) had EC (both 51 years; postmenopausal), one had complex hyperplasia with atypia (52 years; abnormal uterine bleeding), and eight had hyperplasia without atypia., Conclusions: In asymptomatic women less than 50 years, E40 correlated with benign, non-hyperplastic endometrium. However, post-menopausal women with E40 had a risk of EC. Perhaps endometrial cells should only be reported in post-menopausal women or women greater than or equal to 50 years of age., (© 2016 John Wiley & Sons Ltd.)

The purpose of the study is to assess whether a protocol for submitting clinically suspected endometrial polyps will improve the detection rate of polyps and evaluation of the background endometrium. A retrospective review from 1999 to 2015 was performed. Cases were divided into (1) polyps and curettings placed in 2 containers (separate, n=61) and (2) polyps and curettings placed in 1 container (combined, n=80). Polyps were identified in 100% of cases in the separate compared with 95% in the combined group (P=.62). The background endometrium was evaluable in 79% of cases in the combined compared to 90% in the separate group (P=.07). The frequency of hyperplasia without atypia, atypical hyperplasia, and carcinoma was 4.4%, 3.6%, and 1.5%, respectively. In conclusion, the enhanced rate of polyp detection and evaluation of the background endometrium in the separate group is minimal. This supports the recommendation of submitting endometrial polyps and curettings combined in 1 container., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Our objective was to identify the most accurate method of endometrial sampling for the diagnosis of complex atypical hyperplasia (CAH), and the related risk of underestimation of endometrial cancer. We conducted a systematic literature search in PubMed and EMBASE (January 1999-September 2013) to identify all registered articles on this subject. Studies were selected with a 2-step method. First, titles and abstracts were analyzed by 2 reviewers, and 69 relevant articles were selected for full reading. Then, the full articles were evaluated to determine whether full inclusion criteria were met. We selected 27 studies, taking into consideration the comparison between histology of endometrial hyperplasia obtained by diagnostic tests of interest (uterine curettage, hysteroscopically guided biopsy, or hysteroscopic endometrial resection) and subsequent results of hysterectomy. Analysis of the studies reviewed focused on 1106 patients with a preoperative diagnosis of atypical endometrial hyperplasia. The mean risk of finding endometrial cancer at hysterectomy after atypical endometrial hyperplasia diagnosed by uterine curettage was 32.7% (95% confidence interval [CI], 26.2-39.9), with a risk of 45.3% (95% CI, 32.8-58.5) after hysteroscopically guided biopsy and 5.8% (95% CI, 0.8-31.7) after hysteroscopic resection. In total, the risk of underestimation of endometrial cancer reaches a very high rate in patients with CAH using the classic method of evaluation (i.e., uterine curettage or hysteroscopically guided biopsy). This rate of underdiagnosed endometrial cancer leads to the risk of inappropriate surgical procedures (31.7% of tubal conservation in the data available and no abdominal exploration in 24.6% of the cases). Hysteroscopic resection seems to reduce the risk of underdiagnosed endometrial cancer., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To develop a new hysteroscopic morphologic scoring system that helps physicians, especially those who have less experience, to make a differential diagnosis among normal endometrium (NE), endometrial hyperplasia, and endometrial carcinoma., Design: A retrospective study (Canadian Task Force Classification II)., Setting: An office hysteroscopy service., Patients: A total of 435 endometrial biopsies were included in the study: 201 NE, 160 endometrial hyperplasia without atypia (EH), 30 atypical endometrial hyperplasia (AEH), and 44 endometrial cancer (EC)., Interventions: The authors retrospectively evaluated all videos of diagnostic hysteroscopies performed before endometrial biopsies to note endometrial morphologic parameters suggestive of pathology. Principal significant variables were selected by means of the chi-square test (p < .05) and integrated into an ordinal multivariate analysis. Through the estimate of the beta coefficient, a score was obtained to be appointed to each of the selected variables, and characteristic intervals of each of the endometrial lesions were created., Measurements and Main Results: The scoring system showed a sensitivity and specificity of 71.1% and 80%, 48.7% and 82.5%, 63.3% and 90.4%, and 95.4% and 98.2% regarding NE, EH, AEH, and EC, respectively. The positive predictive values and negative predictive values, respectively, were 76.8% and 80% for NE, 62% and 73.5% for EH, 32.7% and 97% for AEH, and 85.7% and 99.5% for EC., Conclusions: The proposed scoring system showed good diagnostic performance, especially in relation to endometrial cancer, and may represent a useful diagnostic tool, mainly for operators with less experience., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

Introduction: Abnormal uterine bleeding is one of the most common morbidity landing women to attend medical attention in gynecology outpatient department. This study aims to evaluate the hysteroscopy finding in diagnosis of AUB and its correlation with ultrasonography finding and histopathological reports., Methods: This was a prospective comparative study in which ultrasonography was performed in fifty patients with abnormal uterine bleeding attending OPD then hysteroscopy was performed.After removing hysteroscopy dilation and curettage was done and sample sent for histopathology.At the end reports of hysteroscopy finding were compared with sonograhic and pathological results., Results: In the study women aged from 45 to 64 years with the symptoms duration of 15 days to 6 months. Post menopausal women seek medical attention more early then the menstruating women.Common symptoms are menorrhagia, metrorrhagia and postmenopausal bleeding. Most common abnormality was menorrhagia (32%) followed by post menopausal bleeding 28 %. Ultrasonography showed 46% of abnormal finding in which 17 (47%) menstruating women and 6 (43%) women were postmenopausal women. Among 50 women 17 (34%) had negative finding and 43 (66%) had abnormal finding in which most common finding of hyperplastic endometrium. Hysteroscopy correctly diagnose atrophic endometrium, polyp and endometrial Ca which is also confirmed by histopathology finding., Conclusions: Hysteroscopy is reliable method for evaluating cases of AUB and it can be used as first line diagnostic method for benign lesions. Hysteroscopy guided biopsy has most accurate in diagnosing pathology.

Background: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions., Methods: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB., Results: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%., Conclusions: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions.

A 5-year-old female intact Mastiff dog was presented with a history of vaginal discharge for 1 day. Physical examination revealed a sanguineo-purulent vaginal discharge and systemic inflammatory response syndrome. Abdominal radiographs showed several dilated and gas- filled tubular loops. The differential diagnoses included emphysematous pyometra or small intestinal mechanical ileus. Surgical exploration of the abdomen demonstrated a severely dilated and gas-filled uterus, and emphysematous pyometra was confirmed. The patient's clinical signs resolved after ovariohysterectomy. Histopathology revealed mild endometrial cystic hyperplasia with infiltration of inflammatory cells in the superficial endometrial epithelia. Enterococcus avium, an α-hemolytic gram-positive coccus, was isolated from the uterus. This paper highlights the radiographic features of emphysematous pyometra and a pathogen that has never been reported to be associated with canine pyometra previously.

Background: Serous carcinoma arising in adenomyosis and adenomyotic cyst is very rare. Only 3 serous carcinomas and 5 serous endometrial intraepithelial carcinomas (EIC) have been reported to date., Methods: We reviewed the clinicopathological features of 2 serous carcinoma in uterine adenomyosis and 1 serous EIC in adenomyotic cyst of the cervical stump., Results: Case 1 had an endometrial serous carcinoma in the uterine myometrium and the left ovary. A minor component of benign endometrial glands with minimal endometrial stroma was found in the uterine mass and the surrounding myometrium. Case 2 showed 3 small foci of serous carcinoma, serous EIC and endometrial glandular dysplasia (EmGD) in the adenomyosis. Scanty serous carcinoma was present in the endometrium without evidence of myometrial invasion. The eutopic endometrium in both case 1 and 2 had no evidence of neoplastic changes after complete examination. Case 3 had 3 microscopic serous EICs in the adenomyotic cysts of the cervical stump. One EIC lesion coexisted with EmGD. No cancer was found in the endocervical tube although the preoperative endocervical biopsy showed a poorly differentiated endometrioid carcinoma. Immunohistochemistry demonstrated that serous carcinoma in case 1 and EIC in all 3 cases showed a characteristic pattern of p53 and p16 over expression, high Ki67 index, and lack of WT1, ER and PR staining. EmGD in case 1 and 3 had a similar staining pattern except a lower Ki67 index and the presence of ER expression., Conclusions: We believe that this case series may expand our recognition on serous carcinoma arising in uterine adenomyosis/adenomyotic cyst including extra-uterine spread and the potential synchronous growth of carcinomas in eutopic endometrium.

Introduction: Hysteroscopy is the gold standard for evaluation of uterine cavity. It can be performed either as office setting or as day care procedure under general anaesthesia. Objective of this study is to assess feasibility and acceptability of office hysteroscopy without anaesthesia., Materials and Methods: This retrospective observational study took place in the gynaecologic unit of a teaching hospital. Women who had had an office hysteroscopy from 2010 to 2013 were included., Results: Two thousand four hundred and two office hysteroscopies were carried out. Indications were menorrhagia (32.2%), postoperative evaluation (20.8%), infertility (15.8%), postmenopausal bleeding (10.9%) and other indications (20.3%). Women's mean age was 39.4 [39.0-39.9] and significantly higher among women with a failure of the office hysteroscopy (47.3 vs. 38.6, P<0.01). The failure rate was 9.5%, significantly higher in women with postmenopausal bleeding and lower in women for a postoperative evaluation. Assessment of an abnormal uterine cavity was done in 56.0% of cases with 28.7% of myomas, 27.2% of polyps, 17.7% of synechiaes, 14.7% of endometrial hypertrophies, 9.0% of trophoblastic retentions and 7.7% of uterine malformation. The complication rate of office hysteroscopy was 0.05%. Mean pain score during the examination was 3.57 out of 10 [3.48-3.66] and 0.89 [0.83-0.95] five minutes later., Conclusion: Office hysteroscopy is safe and feasible with little pain. A failure rate of 9.5% is reported, mainly for older women with postmenopausal bleeding., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The objective of this study was to assess effectiveness and safety of Depo-Provera (medroxyprogesterone acetate) in treatment of endometrial hyperplasia (EH) and to compare it with norethisterone acetate (NETA) as an oral progestogen treatment. One hundred forty six women aged 35 to 50 years with abnormal uterine bleeding and diagnosed as having EH were randomized to receive either Depo-Provera, one injection every 3 months for 6 months (2 doses), or oral cyclic NETA, 15 mg daily for 14 days per cycle for 6 months. Primary outcome measure was regression of EH. Secondary outcome variables were side effects of treatment, persistence/progression of EH during follow-up period. After 6 months of treatment, Depo-Provera was more successful in achieving regression of nonatypical EH than NETA (67 [91.8%] of 73 women vs 49 [67.1%] of 73, respectively), and the difference between the 2 groups was statistically significant (relative risk: 1.37; 95% confidence interval: 1.15-1.63, P = .048*). Adverse effects were relatively common with moderate differences between the 2 groups. This is the first randomized study comparing Depo-Provera with an oral progestogen as a treatment for EH. Depo-Provera is an effective and safe treatment for EH without atypia., (© The Author(s) 2015.)

Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with postmenopausal bleeding, the sensitivity of endometrial sampling to detect endometrial cancer and especially atypical hyperplasia and endometrial disease, including endometrial polyps, is lower than previously thought. Therefore, further diagnostic work-up for focal pathology is warranted, after a benign result of endometrial sampling., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background/aim: Fractal dimension (FD) is widely used in medicine and biology as a tool for defining features of structure. This study aimed to compare pathological endometrium (simple-complex hyperplasia and endometrial carcinoma), as well as the endometrial changes, during the phases of the menstrual cycle. The main goal was the objective measurement of fractal dimension and to refrain from subjective evaluation., Materials and Methods: Two thousand cases of endometrial tissue from patients who underwent dilatation and curettage (D&C) were reviewed. Out of these, 137 cases were eligible for the study. In each case, immunohistochemistry with cytokeratin Ae1/AE3 was performed in order to simplify the evaluation of the FD., Results: Endometria with carcinoma, simple or complex hyperplasia showed significant differences only in the immunohistochemically stained fractal dimensions. As expected, significant differences were also found between atrophic and secretory endometrium and carcinoma., Conclusion: FD is an objective, rapid and simple procedure for the differential diagnosis between complex hyperplasia and endometrial adenocarcinoma., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Sperm-associated antigen 9 (SPAG9), a recently characterized oncogene, may serve as a marker for the early diagnosis of endometrial cancer. However, whether SPAG9 can be a prognostic marker of complex atypical endometrial hyperplasia (CAEH) or grade 1 endometrioid adenocarcinoma (EA) treated with progestin is still unknown., Methods: Progestin therapy was performed in 27 women diagnosed with CAEH (19/27, CAEH group) or grade 1 EA (8/27, EA group). The expression of SPAG9 was measured in pre and post progestin-treated endometrial specimens by immunohistochemistry. The expression of SPAG9 was also examined by real-time polymerase chain reaction (PCR) and Western blot in Ishikawa cells and ECC-1 cells with or without progestin treatment., Results: (1) CAEH showed a significantly better therapeutic efficacy than EA. (2) The expression of SPAG9 was lower in CAEH than in EA. (3) SPAG9 expression significantly declined in the endometrial tissues of women responding to progestin. (4) Significant downregulations of SPAG9 were validated by reverse transcription PCR (RT-PCR) and Western blot both in Ishikawa cells and ECC-1 cells treated with progestin., Conclusion: SPAG9 may be associated with the efficacy of progestin treatment in CAEH and grade 1 EA. It may help to distinguish CAEH from grade 1 EA and serve as a new prognostic marker of CAEH or grade 1 EA treated with progestin., (© 2015 S. Karger AG, Basel.)

Aim: To compare the risk of developing endometrial carcinoma (EC) in young women with atypical endometrial hyperplasia (AEH) undergoing fertility-sparing management compared to women treated by primary hysterectomy., Patients and Methods: In this multicentric retrospective study, 111 patients with a diagnosis of AEH by endometrial biopsy were included. EC incidence was compared in two groups: 32 patients treated with fertility-sparing management and 79 older patients treated with primary hysterectomy., Results: The rates of EC diagnosed by pathology of hysterectomy specimens were comparable between the groups. The probability of developing EC at 12, 24 and 36 months were 14%, 21% and 26%, respectively, in patients managed conservatively, and 29%, 37% and 37%, respectively, in patients treated with primary hysterectomy., Conclusion: Fertility-sparing management of AEH does not increase the risk of diagnosing EC from the hysterectomy specimen., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Micronucleus (MN) is an additional, small nucleus formed due to failure of incorporation of a fragment or the whole chromosome into the main daughter nuclei during cell division. MN scoring is a useful indicator of exposure to genotoxic agents and of malignancy. This study was conducted to know whether the MN score was significantly different in cervical cytology smears of patients with endometrial carcinoma, atypical and benign cells. Three groups of cervical smears were taken up for MN scoring: Group 'A' included benign endometrial cells, Group 'B', atypical glandular cells - endometrial and Group 'C', endometrial adenocarcinoma. Post hoc analysis of variance test was used to determine significant differences between the three groups. There were 30 cases in Group 'A', 31 cases in Group 'B' and 39 cases in Group 'C'. The mean MN score was 0.67 ± 0.711 in Group A, 1.74 ± 0.930 in Group B and 4.10 ± 2.500 in Group C. MN scores were significantly different between all three groups (p < 0.05). The MN score is significantly higher in cervical smears of patients with endometrial carcinoma; as compared to smears showing atypical and benign cells and that this finding may be useful for further research., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

There are two main types of uterine cancer. Endometrial carcinoma, the most commonly diagnosed genital cancer in women, accounts for most cases (more than 95%) and sarcoma comprises the remainder. Endometrial cancer primarily occurs in postmenopausal women. Risk factors include exposure to high levels of endogenous estrogen (eg, obesity, nulliparity, late menopause) or exogenous estrogen (eg, hormone replacement therapy, tamoxifen) and pelvic radiation. Genetics are involved in a small percentage of cases, notably among women in families with hereditary nonpolyposis colorectal cancer (HNPCC). More than 80% of patients with endometrial cancers present with abnormal uterine bleeding. Endometrial biopsy and transvaginal ultrasound are the first-line tests to evaluate bleeding. If the endometrial lining is thickened on ultrasound, endometrial biopsy is indicated. If symptoms persist after negative biopsy results, or if biopsy results are inadequate, hysteroscopy is performed for tissue sampling. Most patients with endometrial cancer are diagnosed early, when cancer is confined to the uterus. Hysterectomy is the treatment of choice in such cases. Treatment of advanced disease involves radiotherapy and/or chemotherapy. Perimenopausal women should be informed that abnormal bleeding could be a sign of cancer and should be evaluated. However, no routine screening is recommended except for women with HNPCC., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

A prospective multicenter trial has been started in Korea to evaluate the diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and curettage in patients treated with progestin for endometrial hyperplasia. For conservative treatment of endometrial hyperplasia, orally administered progestins are most commonly used method with various treatment regimens and more recently, the levonorgestrel-releasing intrauterine system also has been used successfully to treat endometrial hyperplasia. However, there is no report about the accuracy of endometrial sampling during hormonal treatment for follow-up evaluation of endometrial hyperplasia. Patients with histologically confirmed endometrial hyperplasia are offered hormonal treatment with any one of the following three options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle, continuous oral medroxyprogesterone acetate 10 mg/day or insertion of levonorgestrel-releasing intrauterine system. Histological surveillance is performed at 3 months or 6 months following initial treatment. Endometrial tissues are obtained via endometrial aspiration biopsy using a pipelle and dilatation and curettage. In the case of levonorgestrel-releasing intrauterine system, endometrial aspiration biopsy will be done with levonorgestrel-releasing intrauterine system in uterus and then, after the removal of levonorgestrel-releasing intrauterine system, dilatation and curettage will be done. The biopsy findings will be compared. The primary endpoint is to compare the pathological outcome of endometrial aspiration with dilatation and curettage. The secondary endpoint is the response rate with three types of progestin treatment at 6 months., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer. Proportion of error in the detection of endometrial cancer using cytological findings was 3.4% (true false negatives). Negative rate of the cytological findings in the detection of endometrial cancer was 66.2%. PAP test is not a suitable method for detection of endometrial carcinoma due to low sensitivity (25%). The main cause of negative findings in PAP test was lack of diagnostic cells in the sample.

Endometriosis is a common but an enigmatic disease in which endometrial glands and stroma are found outside the uterus. Worldwide, 80 million women are affected by the disease. It has generally been accepted as a problem of reproductive ages and affects 6-10% of those women. It is more common in women with infertility. Moreover, since it is an estrogen dependent problem, it is generally believed that endometriosis connotes 'active ovarian function' and is 'healed' after the menopause. However, there are reports on endometriosis beyond the reproductive ages. In this article, endometriosis after the menopause will be discussed.

Objective: This study investigated the in vitro fertilization (IVF) outcome of levonorgestrel-releasing intrauterine system (LNG-IUS) pretreatment for simple endometrial hyperplasia (EH) in patients with polycystic ovary syndrome (PCOS) undergoing IVF embryo transfer (IVF-ET)., Methods: One hundred ninety patients with PCOS and simple EH without cytologic atypia were allocated randomly to 2 independent arms, that is, the LNG-IUS group (90 patients) and the non-LNG-IUS group (100 patients). Four hundred fourteen patients with PCOS without endometrial disease comprised the control group. Each patient was reevaluated by transvaginal ultrasonography (TVS) and endometrial biopsy after 6 months. For each patient, IVF outcome measures, such as number of recombinant follicle-stimulating hormone, endometrial thickness on human chorionic gonadotropin (HCG) day, hormone levels (progesterone, luetinizing hormone, and serum estradiol) on HCG day, number of oocytes, fertilization rate, clinical pregnancy rate, and miscarriage rate were compared among the 3 groups., Results: In general, the 3 groups did not differ with respect to the main clinical and biochemical data. After 6 months, patients in LNG-IUS group had an EH resolution rate of 87.77%. In the non-LNG-IUS group, the resolution rate was 15.00%, and 3% of these patients showed progression of EH. The clinical pregnancy rates in the non-LNG-IUS group were significantly lower (28.04%) than that in the LNG-IUS group (46.06%) and the control group (44.65%). The miscarriage rate was highest in the non-LNG-IUS group, but no significant difference in miscarriage rate existed among the 3 groups., Conclusion: The study illustrates that the LNG-IUS can be safely used for 6 months as a treatment for patients with PCOS and simple EH. Additionally, use of the LNG-IUS can increase the clinical pregnancy rates and implantation rates of patients with PCOS and simple EH who undergo gonadotropin-releasing hormone agonist IVF-ET protocols., (© The Author(s) 2014.)

Purpose: To determine the accuracy of hysteroscopy in diagnosing endometrial cancer, hyperplasia, polyps and submucous myomas., Methods: Relevant articles were retrieved from the MEDLINE and the Cochrane Library (1986-2011). Studies were selected blindly. Results for diagnostic accuracy were extracted to form separate 2 × 2 tables (for endometrial cancer, hyperplasia, polyps and submucous myomas). A summary sensitivity and specificity point reflected the average accuracy observed. Summary ROCs (SROCs) were also calculated according to the HSROC model., Results: For endometrial cancer, the estimated sensitivity was 82.6% (95% CR 66.9-91.8%) and the specificity was 99.7% (95% CR 98.1-99.9%). For endometrial hyperplasia, sensitivity was 75.2% (95% CR 55.4-88.1 %), while specificity was 91.5% (95% CR 85.7-95.0%). For endometrial polyps, sensitivity was 95.4% (95% CR 87.4-98.4%) and specificity was 96.4% (95% CR 93.7-98.0%). Finally, for submucous myomas, sensitivity was estimated to 97.0% (95% CR 89.8-99.2%) and specificity to 98.9% (95% CR 93.3-99.8%)., Conclusions: Diagnostic accuracy for hysteroscopy is high for endometrial cancer, polyps and submucous myomas, but only moderate for endometrial hyperplasia.

Endometrial carcinoma ranks the seventh most common malignant tumor worldwide. The distinction between atypical endometrial hyperplasia (AEH) and endometrial carcinoma, especially the well-differentiated grade, is particularly difficult with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino acid peptide that is synthesized by gastric mucosa and is expressed in a variety of normal and tumor tissues. In endometrial tissue, it is expressed during the menstrual cycle, involved in the uterine development and cyclic growth. Data regarding role of Ghrelin in endometrial carcinoma are contradictory. In the present study, immunohistochemical expression of Ghrelin was evaluated in 55 endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The relationship between Ghrelin expression and clinicopathologic features of endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression was significantly related to endometrioid carcinoma, especially the well-differentiated type, compared with AEH and EIN (p = 0.000 and 0.006, respectively). Ghrelin loss was also related to poorly differentiated histologic grades of endometrioid carcinoma (p = 0.04). Ghrelin loss is helpful in differentiation between AEH and EIN from endometrioid adenocarcinoma, especially the well-differentiated grade. It could be also related to poor differentiation.

Objectives: To compare the diagnostic accuracy of brush endometrial sampling with conventional dilatation and curettage in women with abnormal uterine bleeding., Patients and Methods: Two hundred and twenty (220) women with abnormal uterine bleeding were included in this comparative study; endometrial sampling was done before cervical dilatation using Tao Bruch followed by conventional dilatation and curettage (D&C). The histopathology report of the Tao Bruch samples was compared with that of the D&C samples and the D&C results were considered as the gold standard., Results: 100% of samples obtained by conventional D&C, while 98.2% of the samples obtained by Tao Brush were adequate for histopathology examination. In this study; Tao Brush had 100% sensitivity, 100% specificity, 100% predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium, also, it had 86.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99% negative predictive value (NPV) and accuracy for diagnosing endometritis (no significant difference compared to conventional D&C), while, it had 77.8% sensitivity, 100% specificity, 100% PPV and 99% NPV and accuracy for diagnosing endometrial polyps (no significant difference compared to conventional D&C) CONCLUSION: Endometrial sampling using endometrial brush cytology (EBC) is safe, accurate, cost-effective outpatient procedure, avoids general anesthesia with high sensitivity and specificity for detection of endometrial hyperplasia and endometrial carcinoma. EBC could be used as complementary diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted or not available.

Background: Endometrial pathology risk has been linked to obesity; however, little is known of its prevalence in severely obese women not seeking care for endometrial pathology associated symptoms. This pilot study was designed to explore the frequency and risk factors associated with endometrial pathology in cancer-free, severely obese, bariatric surgery candidates using the Pipelle endometrial sampling technique (SureFlex Preferred Curette, Bioteque America, Inc, New Taipei City, Taiwan)., Methods: Twenty-nine severely obese bariatric surgery candidates with intact uteruses and no history of endometrial cancer or endometrial ablation were included in this subanalysis from a larger cohort of 47. Endometrial samples were obtained using a Pipelle endometrial suction curette at a single time point before surgery. Logistic regression was used to assess the relationship between body mass index and endometrial pathology when adjusting for age and race., Results: Of the 29 successful biopsies, 8 (27.6%) were classified as abnormal endometrium: 1 was classified as complex atypical hyperplasia, 1 was classified as hyperplasia without atypia, 4 samples were identified with endometrial polyps, and 2 samples were identified with metaplasia. None presented with cancer. Increasing body mass index was significantly associated with higher risk of abnormal endometrium (OR = 1.19, 95% CI [1.03-1.36], P = .01)., Conclusions: The findings in this sample suggest that obesity may be associated with increased risk of having undiagnosed endometrial pathology. More thorough examination of relationships between levels of obesity and endometrial pathology are needed to better characterize high cancer risk groups who may benefit from introducing new screening measures., (Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.

Background: The aim of this study was to compare specimen adequacy of SAP-1 provided for cytology with that of dilation and curettage (D & C) or hysteroscopy for histology, and evaluate the accuracy of combining endometrium sampling by SAP-1 and liquid-based cytology using SurePath preparation for screening endometrial carcinoma and its precursor., Methods: Endometrial specimens from women (n = 1514) with risk factors were obtained using an SAP-1 device for cytological analysis; histological samples were obtained from 375 of these women who underwent D & C or hysteroscopy. Cytological specimens were prepared to liquid-based smear using SurePath technology and stained by Papanicolaou. Histological samples were processed in routine pathology and stained by hematoxylin and eosin., Results: Adequate specimens for cytology were obtained from 1458/1541 patients (96.3%), while adequate samples for pathology were obtained from 285/375 patients (76%). However, for postmenopausal women, 1006 of 1045 cytology (86.3%) were adequate, 153 of 238 histology (64.3%) were adequate, it was easier to collect cytological specimens than histological specimens (P < 0.05). The accuracy of endometrial cytology for detecting endometrial carcinoma and its precursor was 92.4% (sensitivity, 73%; specificity, 95.8%; positive predictive value, 75%; and negative predictive value, 95.3%)., Conclusions: Endometrial cytology using SAP-1 sampling and SurePath preparation may be a reliable approach for screening patients with endometrial carcinoma and its precursor.

Objective: To compare the efficacy and safety of the levonorgestrel-releasing intrauterine device (LNG-IUD) with dydrogesterone applied for the same duration in patients having endometrial hyperplasia (EH) without atypia., Materials and Methods: One hundred thirty eight women aged between 30 and 50 years with abnormal uterine bleeding and diagnosed as EH by transvaginal ultrasound were randomized to receive either LNG-IUD or dydrogesterone for 6 months. Primary outcome measures were regression of hyperplasia after 6 months of therapy. Secondary outcome measures were occurrence of side effects during treatment or recurrence of hyperplasia during follow-up period., Results: After 6 months of treatment, regression of EH occurs in 96% of women in the levonorgestrel-releasing intrauterine system (LNG-IUS) group versus 80% of women in the oral group (P < .001). Adverse effects were relatively common with minimal differences between the 2 groups. Intermenstrual vaginal spotting and amenorrhea were more common in the LNG-IUD group (P value .01 and .0001). Patient satisfaction was significantly higher in the LNG-IUS group (P value .0001). Hysterectomy rates were lower in the LNG-IUS group than in the oral group (P = .001). Recurrence rate was 0% in the LNG-IUD group compared to 12.5% in the oral group., Conclusion: In management of EH without atypia, LNG-IUS achieves a higher regression and a lower hysterectomy rate than oral progesterone and could be used as a first-line therapy., (© The Author(s) 2014.)

Although the incidence of uterine disorders in pet rabbits is high there are only a few retrospective studies and case reports on genital tract disease in female rabbits. Uterine disorders were assessed in 50 pet rabbits. In 31 pet rabbits with suspected clinical uterine disease, medical records were further reviewed regarding clinical signs, diagnostic workup, treatment as well as the outcome itself. Uterine adenocarcinoma (54%) was most frequently diagnosed, followed by endometrial hyperplasia (26%). Serosanguineous vaginal discharge was the predominant clinical sign observed by the rabbit owners. In approximately 50% of the rabbits with suspected uterine disorders, abdominal palpation revealed enlarged and/or irregular masses in the caudoventral abdomen indicating uterine lesions. Out of 23 rabbits undergoing ovariohysterectomy, four were either euthanized or died shortly after surgery because they were clinically unstable. Overall, 80% of the ovariohysterectomized animals were still alive 6 mo after surgery. In female pet rabbits that are not breeding, either ovariohysterectomy should be performed at an early age or routine checks including ultrasonography of the abdomen are recommended on a regular basis.

The study compared ultrasound and ambulatorial hysteroscopy as diagnostic methods detecting endometrial polyps in postmenopause women. 281 women aged 41-82 years who underwent ambulatorial hysteroscopy were analyzed for presence of uterine bleeding and/or altered transvaginal ultrasound (endometrial thickness ≥5 mm). Ultrasonography detected endometrial polyps in 22.8% of patients and endometrial thickening in the other 59.8%. Hysteroscopy diagnosed endometrial polyps in 80.8%. Ultrasonography showed sensitivity of 88.7%, specificity of 25.4%, positive predictive value of 81.7%, negative predictive value of 37.5% and accuracy of 75.4% in diagnosing endometrial polyps. Hysteroscopy showed 96.4% sensitivity, 74.6% specificity, 93.4% positive predictive value, 84.6% negative predictive value and 91.8% accuracy. Hysteroscopy demonstrated more accuracy than ultrasonography, which is not sufficient for accurate diagnosis.

Progesterone inhibits the proliferative growth effects of estrogen in the endometrium and prevents the development of endometrial hyperplasia and Type I adenocarcinoma. The exact mechanism of this action is unknown. The progesterone-induced helix-loop-helix transcription factor Heart and Neural Crest Derivatives Expressed 2 (Hand2) was recently shown to suppress production of growth factors in the endometrium. In Hand2 knockout mice, continuous proliferation of the endometrium was observed. In this study, archival paraffin-embedded tissue from 56 hysterectomy specimens was examined by immunohistochemistry for the expression and localization of Hand2, estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Diagnoses included disordered proliferative endometrium, simple and complex hyperplasia with or without atypia, and endometrioid adenocarcinoma. Hand2 expression is localized to endometrial stromal nuclei. In benign endometrium, Hand2 expression was moderate to strong (10/11; 91%), with weak Hand2 expression in only 1 case (1/11; 9%). Similar Hand2 expression patterns were observed in disordered proliferative endometrium and simple hyperplasia without atypia, with moderate to strong expression in 91% of cases (10/11) and weak expression in 9% of cases (1/11). In contrast, simple and complex hyperplasia with atypia exhibited moderate to strong Hand2 expression in 8% of cases (1/12) and a loss of expression or weak expression in 92% of cases (11/12). In endometrioid adenocarcinomas, Hand2 expression was absent in all cases (22/22). Hand2 is expressed in the stroma of benign endometrium, but expression is significantly reduced or lost in atypical hyperplasia and endometrioid carcinoma. Thus, the absence of Hand2 expression may be a useful biomarker for atypical hyperplasia and endometrioid carcinoma.

The purpose of this study was to evaluate diagnostic efficiency of methods of diffusion-weighted imaging (DWI) in the diagnosis of diseases of the body the uterus at the high and ultra high field MRI (1,5T1, 3,OT1). In total we examined 150 patients. In 72 patients (48%) there were histologically verified malignant changes; of these 70 patients (46.7%) had endome- trial cancer (EC), 2 (1.3%)--uterine sarcoma. 40 EC patients (57.2%) had of Stage I, 15 patients (21.4%)--Stage II, 11 patients (15.7%)--Stage III, and 4 patients (5.8%) of--stage IV. 48 patients (32%) had benign processes of the endometrium (uterine fibroids--27 patients, endometrial hyperplasia--12 patients, endometrial polyps--9 patients). The control group consisted of 30 (20%) healthy patients. All patients underwent MRI examination of the pelvic organs into high and ultra-high MRI (1,5T1, 3,0T1). All patients were required performance of SP DWI (diffusion-weighted images) in 2 projections (Ax and Sag) with different diffusion factors (50-500-1100). MRI data using DWI were compared with surgical material. To our opinion modern MRI techniques allow to reliably determine the size of the pathological process, its location, the extent of the parameters for endometrial cancer, as well as the degree of involvement in the pathological process of the bladder and rectum, to assess the condition of the pelvic lymph nodes. MRI, supplemented DWI, allowed differentiating benign and malignant lesions of the uterus. MRI data corresponded to a post mortem conclusion in the case, specificity 86%, sensitivity of 92% and a diagnostic accuracy of 91%, which significantly improved the diagnostic accuracy of a standard MRI. Thus the method DWI MRI using modern software improves the differential diagnosis of diseases of the body uterus, can reliably assess the extent of the pathological process, to fully assess the invasion of parametrial tissue, provide a comprehensive assessment of the status of the lymph nodes.

Objective: This study compares hysteroscopic and histopathological results in postmenopausal women with abnormal uterine bleeding (AUB) and asymptomatic postmenopausal women with a thickened endometrium., Materials and Methods: This is a retrospective study of 570 cases hysteroscopically examined between January 2008 and July 2012. The patients were followed up at the Istituto Tumori 'Giovanni Paolo II', Bari, Italy., Results: A total of 320 of the 570 cases were selected. The inclusion criteria were transvaginal ultrasound, hysteroscopy and endometrial biopsy. In the AUB group, if the hysteroscopy results were normal, a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100, 95, 71 and 100%, respectively, were achieved, while in the asymptomatic group these values were 100, 97, 90 and 100%, respectively. For both the group with polyps and that with myomas, the sensitivity, specificity, PPV and NPV were 100%. For endometrial hyperplasia, hysteroscopy showed a sensitivity, specificity, PPV and NPV of 81, 96, 87 and 93%, respectively, in the AUB group, while in the asymptomatic group, the sensitivity was 60%, the specificity and PPV were 100%, and the NPV was 98%. The sensitivity of hysteroscopy for endometrial cancer was 63%, the specificity 97%, the PPV 77%, and the NPV 95%., Conclusions: In postmenopausal women with a thickened endometrium with or without AUB, hysteroscopy allows for an accurate diagnosis in benign endometrial pathology. Hysteroscopy also allows directed biopsies of suspicious lesions, which is useful in malignant endometrial pathology., (© 2015 S. Karger AG, Basel.)

PAX2 has been cited as a technically robust biomarker which nicely delineates precancerous lesions of the endometrium when the endometrial intraepithelial neoplasia (EIN) classification scheme is used. Its utility in distinguishing between atypical and nonatypical hyperplasia when applied within the 1994 World Health Organization classification system is questionable. The purpose of this study was to evaluate PAX2 in a side by side comparison of its staining patterns in a series of endometrial samples that were classified using both systems. A total of 108 precancerous endometrial cases were identified, of which 30 cases were deemed nonhyperplastic by consensus agreement and 11 cases lost the tissue of interest on deeper sections. The remaining 67 cases were categorized according to the 1994 World Health Organization criteria and EIN scheme by 2 gynecologic pathologists. PAX2 staining was scored in lesional tissue as normal or altered (lost, increased, or decreased) compared with nonlesional background. The most common pattern of alteration was complete loss of nuclear PAX2 staining (86.3%) followed by decreased staining (11.3%) and markedly increased staining (2.3%). PAX2 alterations correlated well with EIN diagnoses (33/36, 92%) compared with benign hyperplasia (2/13, 15%) but were less useful when the 1994 World Health Organization classification system was applied (PAX2 alteration in 22/25 (88%) of atypical hyperplasia cases versus 16/25 (64%) of nonatypical hyperplasia cases). Forty-five percent of follow-up hysterectomies with a previous PAX2-altered biopsy case harbored adenocarcinoma. In conclusion, PAX2 may be a helpful adjunct stain and training tool when the features of atypical hyperplasia/EIN are in question.

The aim was to evaluate the prevalence of concomitant somatic pathology in patients with endometrial hyperplasia. It is shown that the incidence of endometrial hyperplastic processes of combination and somatic pathology is 50%. The main types of comorbid diseases are obesity, metabolic syndrome, gastrointestinal and cardiovascular disorders.

Objective: To establish a risk model for predicting the probability of endometrial carcinogenesis while diagnosed as AEH preoperatively., Study Design: 149 patients with AEH diagnosed by D&C specimens or hysteroscopy undergoing total hysterectomy were enrolled in this retrospective study. Patients were divided into two groups: 51 cases in AEH to AEH group and 98 cases in AEH to EC group. The clinical pathological characteristics were compared between the two groups. With the use of ROC curves, cutoff values of age, CA199, CA125 and uterine height were determined. The relationships of these evaluators with endometrial carcinogenesis were investigated by multivariate analysis with a logistic regression model., Results: 65.8% (98/149) of preoperative AEH patients become EC after confirmed by paraffin hysterectomy specimens. The cutoff values were 51.5 years of age, 14.06U/ml of CA199, 14.30U/ml of CA125 and 45mm of uterine height, respectively. Logistic regression analysis demonstrated age (OR=0.58, 95% confidence interval [95%CI]: 0.08-3.94), CA199 (OR=7.27, 95%CI: 1.43-36.92), CA125 (OR=13.97, 95%CI: 2.49-78.37), uterine height (OR=0.49, 95%CI: 0.08-3.08) and abnormal uterine bleeding (OR=4.27, 95%CI: 0.53-34.52) were associated with endometrial carcinogenesis. However, only CA199 (p=0.017) and CA125 (p=0.003) revealed significant differences. Therefore, when entered into the risk model, CA199≥14.06U/ml and CA125≥14.30U/ml were considered as cogent predictors of endometrial carcinogenesis., Conclusions: This risk model may well predict the probability of endometrial carcinogenesis when preoperatively diagnosed as AEH., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To compare the safety and regression rates of conservative treatments for complex atypical hyperplasia (CAH) between pre- and postmenopausal women., Methods: Historical cohort study of pre- and postmenopausal women with CAH managed conservatively at one center (Royal Women's Hospital, Melbourne, Australia) between September 1999 to June 2012., Results: Of the 153 women with CAH, 92 (60%) underwent hysterectomy and the remaining 61 were managed conservatively with oral or intrauterine progestogen: 42 were premenopausal and 19 were postmenopausal. Within 12 months, 32 (76%) premenopausal women demonstrated regression of CAH and none developed endometrial cancer. In contrast, only 4 (21%) postmenopausal women showed disease regression and 4 (21%) progressed to endometrial cancer. Over a median of 24 months, 3 premenopausal women relapsed with CAH and 2 developed endometrial cancer. Four premenopausal women had successful pregnancies., Conclusion: Conservative treatment with progestogen in premenopausal women with CAH leads to high regression rates within the first 12 months. In contrast, postmenopausal women have high rates of ongoing disease and cancer progression and conservative therapy should be avoided., (© The Author(s) 2014.)