Single-cell profiling identifies distinct hormonal, immunologic, and inflammatory signatures of endometriosis-constituting cells.

Endometriosis consists of ectopic endometrial epithelial cells (EEECs) and ectopic endometrial stromal cells (EESCs) mixed with heterogeneous stromal cells. To address how endometriosis-constituting cells are different from normal endometrium and among endometriosis subtypes and how their molecular signatures are related to phenotypic manifestations, we analyzed ovarian endometrial cyst (OEC), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) from 12 patients using single-cell RNA-sequencing (scRNA-seq). We identified 11 cell clusters, including EEEC, EESC, fibroblasts, inflammatory/immune, endothelial, mesothelial, and Schwann cells. For hormonal signatures, EESCs, but not EEECs, showed high estrogen signatures (estrogen response scores and HOXA downregulation) and low progesterone signatures (DKK1 downregulation) compared to normal endometrium. In EEECs, we found MUC5B+ TFF3low cells enriched in endometriosis. In lymphoid cells, evidence for both immune activation (high cytotoxicity in NK) and exhaustion (high checkpoint genes in NKT and cytotoxic T) was identified in endometriosis. Signatures and subpopulations of macrophages were remarkably different among endometriosis subtypes with increased monocyte-derived macrophages and IL1B expression in DIE. The scRNA-seq predicted NRG1 (macrophage)-ERBB3 (Schwann cell) interaction in endometriosis, expressions of which were validated by immunohistochemistry. Myofibroblast subpopulations differed according to the location (OECs from fibroblasts and SPE/DIEs from mesothelial cells and fibroblasts). Endometriosis endothelial cells displayed proinflammation, angiogenesis, and leaky permeability signatures that were enhanced in DIE. Collectively, our study revealed that (1) many cell types-endometrial, lymphoid, macrophage, fibroblast, and endothelial cells-are altered in endometriosis; (2) endometriosis cells show estrogen responsiveness, immunologic cytotoxicity and exhaustion, and proinflammation signatures that are different in endometriosis subtypes; and (3) novel endometriosis-specific findings of MUC5B+ EEECs, mesothelial cell-derived myofibroblasts, and NRG1-ERBB3 interaction may underlie the pathogenesis of endometriosis. Our results may help extend pathologic insights, dissect aggressive diseases, and discover therapeutic targets in endometriosis. © 2023 The Pathological Society of Great Britain and Ireland.

The Potential of Transforming Growth Factor-beta Inhibitor and Vascular Endothelial Growth Factor Inhibitor as Therapeutic Agents for Uterine Leiomyoma.

Background: Uterine leiomyoma is the most common benign tumor in women of reproductive age, and it can cause infertility. The growth of uterine leiomyoma is mediated by various steroids and growth factors. The purpose of this study was to evaluate the expression of various growth factors in uterine leiomyoma. Additionally, comparing the effects of existing medication and specific growth factor inhibitors on leiomyoma and the normal myometrium, we aimed to see the potential of transforming growth factor-beta (TGF-ß) inhibitors and vascular endothelial growth factor (VEGF) inhibitors as therapeutic drugs for uterine leiomyoma. Methods: This in vitro study included uterine leiomyoma samples from 12 patients who underwent hysterectomy by laparoscopy or laparotomy at Seoul St. Mary's Hospital between May 2016 and March 2018. Normal myometrium and uterine leiomyoma tissue were obtained from each patient and the expression of growth factors was compared using immunohistochemical staining. After the primary culture of normal myometrial and leiomyoma cells, cell viability was evaluated following treatment with 100 nM ulipristal acetate (UPA) and mifepristone for 48 h. Western blot analysis was performed to determine the protein expression of each growth factor. Cell viability was determined following treatment with a 10-µM TGF-ß inhibitor (LY364947) and a 5-µM VEGF inhibitor (axitinib) for 24 h in cultured normal myometrium and leiomyoma cells. Results: Immunohistochemical staining revealed the significantly higher intensity of TGF-ß and VEGF in the leiomyoma tissue than in the normal myometrium (P < 0.05). Mifepristone treatment decreased VEGF expression by 62% in the leiomyoma cells (P < 0.05). According to the cell counting kit-8 (CCK-8) assay, cell viability was decreased after UPA, mifepristone, TGF-ß1 inhibitor, and VEGF inhibitor treatments in the normal myometrium and leiomyoma tissue. The effects of the TGF-ß1 inhibitor significantly differed between normal myometrium and leiomyoma tissue, with a greater decrease in cell survival in the leiomyoma tissue (P < 0.05). Post-hoc analysis showed that the TGF-ß1 and VEGF inhibitors had a greater inhibitory effect on leiomyoma tissue compared with that of UPA. Conclusion: TGF-ß and VEGF inhibitors significantly decreased the viability of uterine leiomyoma cells, showing stronger effects than the conventional drug, UPA. TGF-ß1 inhibitors affect both leiomyoma tissue and the normal uterus; thus, targeted local treatment rather than systemic treatment should be considered.

The Estimated Prevalence and Incidence of Endometriosis With the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC): A National Population-Based Study.

BACKGROUND: The incidence and prevalence of endometriosis remain unclear due to diagnostic difficulties. Especially, there has been little information regarding the population-based epidemiology of endometriosis. The purpose of this study is to estimate the prevalence and incidence of endometriosis in Korea based on the health insurance claims data. METHODS: This study is a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort, which correspond to approximately 1 million Korean populations from 2002 to 2013. Patients aged 15-54 years were selected, and the prevalence and incidence of endometriosis were estimated by time and age groups. RESULTS: The age-adjusted prevalence rate of endometriosis also increased from 2.12 per 1,000 persons (95% confidence interval [CI], 2.01-2.24) in 2002 to 3.56 per 1,000 persons (95% CI, 3.40-3.71) in 2013. The average adjusted incidence showed no statistically significant increase. However, the age-specific incidence of the 15-19 and 20-24 years age groups increased significantly from 0.24 and 1.29 per 1,000 persons in 2003 to 2.73 and 2.71 per 1,000 persons in 2013 (R2 = 0.93 and 0.77, P < 0.001), while the incidence rate of the age group 40-44 and 45-49 years decreased from 2.36 and 1.72 per 1,000 persons in 2003 to 0.81 and 0.27 per 1,000 persons in 2013 (R2 = 0.83 and 0.89, P < 0.001). CONCLUSION: The prevalence and incidence of endometriosis in Korean women were lower than that of previous reports in high-risk population studies. Furthermore, we found a significant increase in the diagnosis of endometriosis in younger age groups.

Elevated aspartate aminotransferase and alanine aminotransferase in the torsion of ovarian mature cystic teratoma: normalised after operation for torsion.

The aim of the study was to report the elevated liver function test levels in torsion of ovarian mature cystic teratoma (MCT). A retrospective review was performed of 116 patients with MCT who underwent surgery in our hospital between 2010 and 2017. Eleven of 116 patients were with torsion of MCT. Of the 11 torsion of MCT cases, 6 of those showed abnormal elevated levels of aspartate transaminase (AST)/alanine aminotransferase (ALT). After operation, AST/ALT levels recovered to normal ranges. Elevated liver function levels require attention to complications associated with anaesthesia and emergency operation. However, the current report shows that emergency surgery should not be delayed to assess other causes of elevated liver function tests.Impact statementWhat is already known on this subject? Abnormal liver function tests require attention to complications associated with emergency surgery.What do the results of this study add: Our study shows that some patients with torsion of MCT returned to normal levels of AST/ALT after surgery without any medications to improve liver function.What are the implications of these findings for clinical practice and/or further research? This study would offer that in some cases with torsion of MCT, emergency surgery should not be delayed and the assessment of other possible causes of these elevations postponed to postoperative period. Additional studies are required to assess the correlation between elevated AST/ALT levels and torsion of MCT.

The effect of the look-back period for estimating incidence using administrative data.

BACKGROUND: The look-back period is needed to define baseline population for estimating incidence. However, short look-back period is known to overestimate incidence of diseases misclassifying prevalent cases to incident cases. The purpose of this study is to evaluate the impact of the various length of look-back period on the observed incidences of uterine leiomyoma, endometriosis and adenomyosis, and to estimate true incidences considering the misclassification errors in the longitudinal administrative data in Korea. METHODS: A total of 319,608 women between 15 to 54 years of age in 2002 were selected from Korea National Health Insurance Services (KNHIS) cohort database. In order to minimize misclassification bias incurred when applying various length of look-back period, we used 11 years of claim data to estimate the incidence by equally setting the look-back period to 11 years for each year using prediction model. The association between the year of diagnosis and the number of prevalent cases with the misclassification rates by each look-back period was investigated. Based on the findings, prediction models on the proportion of misclassified incident cases were developed using multiple linear regression. RESULTS: The proportion of misclassified incident cases of uterine leiomyoma, endometriosis and adenomyosis were 32.8, 10.4 and 13.6% respectively for the one-year look-back period in 2003. These numbers decreased to 6.3% in uterine leiomyoma and - 0.8% in both endometriosis and adenomyosis using all available look-back periods (11 years) in 2013. CONCLUSION: This study demonstrates approaches for estimating incidences considering the different proportion of misclassified cases for various length of look-back period. Although the prediction model used for estimation showed strong R-squared values, follow-up studies are required for validation of the study results.

Effectiveness of dienogest in improving quality of life in Asian women with endometriosis (ENVISIOeN): interim results from a prospective cohort study under real-life clinical practice.

BACKGROUND: Dienogest has been shown to substantially improve endometriosis-associated symptoms such as debilitating chronic pelvic pain, and in turn, health-related quality of life (HRQoL). To date, there is no data on patient-reported outcomes reflecting the real-world practice in Asia where endometriosis is a relevant health, social and economic burden. This non-interventional, multi-center, prospective study aims to investigate the influence of dienogest on HRQoL. METHODS: Asian women received dienogest (2 mg/daily) and were followed for 24 months. The effectiveness of dienogest to improve HRQoL and endometriosis-associated pelvic pain (EAPP) was assessed by patient-reported outcomes. HRQoL, especially the "pain" domain as primary endpoint, was evaluated with the Endometriosis Health Profile-30 (EHP-30) questionnaire. The numeric rating scale served to determine changes in the severity of EAPP. Within the presented interim analysis (data cut-off: 2017-11-27), the mean changes in EHP-30 and EAPP scores from baseline to 6 months upon availability of the data were evaluated. Treatment-emergent adverse events (TEAEs) and bleeding profiles were documented. RESULTS: Dienogest therapy decreased EHP-30 scores in all assessed domains (score 0-100, lower scores indicate better HRQoL). Primarily, the "pain" domain was improved in 78.4% of patients. EAPP was reduced (score 0-10, lower scores reflect less pain), highlighted by a mean reduction of the pain score by - 4.5 points. Patients with a higher EAPP score at baseline had an increased response to dienogest (- 6.2 points mean change) compared to patients with low baseline EAPP severity (- 1.4 points mean change). Both surgically and clinically diagnosed patients described comparable pain reduction, as well as women with or without prior treatment. Drug-related TEAEs were documented for 31.5% of patients, with amenorrhoea (5.9%) and metrorrhagia (5.1%) being the most common events. The bleeding pattern was changed upon dienogest, characterized by decreased normal bleeding (84.2 to 28.8%) and increased amenorrhea (3.2 to 42.9%) at 6 months. CONCLUSION: The data indicate an amelioration of HRQoL and EAPP upon dienogest therapy. No new safety signals were observed. Therefore, its use as first-line therapy for long-term management of debilitating and chronic endometriosis-associated pain represents an interesting option that remains to be further investigated. TRIAL REGISTRATION: Name of registry: Clinical Trials Clinicaltrials.gov registration number: NCT02425462 Registration date: 2015-04-24. Registration timing: prospective.

Multidisciplinary Approach in Large-sized Submucosal Myoma: Hysteroscopic Myomectomy after Uterine Artery Embolization.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of hysteroscopic myomectomy after uterine artery embolization (UAE) for the treatment of large-sized submucosal myomas with deep intramural invasion that are difficult to treat with 1-step hysteroscopy. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic university hospital. PATIENTS: Eight premenopausal patients with symptomatic submucosal myomas with intramural invasion. INTERVENTIONS: All of the patients after bilateral UAE underwent subsequent hysteroscopic operation 3 to 15 months after UAE. MEASUREMENTS AND MAIN RESULTS: A total of 8 patients who had a large-sized submucosal myoma with deep myometrial invasion were included. The average volume of the submucosal myomas was 87.7±39.9 cm3 as confirmed by magnetic resonance imaging, and the average patient age was 37.6 years. The mean volume reduction of the submucosal myomas was 83.3±16.4% after UAE, and no immediate complications were observed. One-step hysteroscopic myomectomy after UAE was successfully performed in all patients. Leiomyomas with hyaline degeneration were pathologically confirmed. All women showed improved symptoms, and there was no evidence of recurrence 1 year later. One patient conceived naturally and delivered a full-term baby. CONCLUSION: In premenopausal women with large-sized symptomatic submucosal myomas with deep myometrial invasion, hysteroscopic myomectomy after UAE is very effective and safe.

Effect of mistletoe on endometrial stromal cell survival and vascular endothelial growth factor expression in patients with endometriosis.

Research Question: To evaluate the effect of mistletoe on the cell viability of patients with endometriosis, the expression levels of vascular endothelial growth factor (VEGF) were measured, and the change in the expression level of VEGF following mistletoe treatment was recorded. Design: Forty reproductive-aged women with endometriosis (stage I/II [group 1, n=20], and stage III/IV [group 2, n=20]) were prospectively enrolled. Twenty women who underwent gynaecologic operations for benign conditions were selected as the control group. Both eutopic and ectopic endometrial tissues were obtained from the endometriosis patients. The endometrial tissues were cultured and the stromal cells were separated. The cells were cultured for 24 hours with peritoneal fluid from patients and controls with and without mistletoe supplementation (200 ng/mL), respectively. The MTT assay was used to assess cell viability, and VEGF expression was analysed by Western blotting and ELISA. Results: Using peritoneal fluid from endometriosis patients treated with mistletoe, we found that both eutopic and ectopic endometrial stromal cell viability increased after treatment with peritoneal fluid from patients with early-stage (I and II) endometriosis. After mistletoe treatment, the cell viability was decreased, in both eutopic and ectopic endometrial stromal cells in all stages of endometriosis. These findings were verified consistently by evaluating the expression and concentration of VEGF, a marker of angiogenesis. Conclusions: The present study showed that mistletoe can reduce the cell viability of endometrial stromal cells and the peritoneal fluid-induced elevation of VEGF in eutopic and ectopic endometrial stromal cells obtained from endometriosis patients, especially in the early stage. Mistletoe might have anti-angiogenic activity on endometrial stromal cells and thus is a potential candidate for the treatment of endometriosis.

Development of a Model for the Prediction of Treatment Response of Uterine Leiomyomas after Uterine Artery Embolization.

Background: Uterine artery embolization (UAE) is one of the minimally-invasive alternatives to hysterectomy for treatment of uterine leiomyomas. There are various factors affecting the outcomes of UAE, but these have only been sporadically studied. Study Objective: To identify factors associated with the efficacy of UAE for the treatment of uterine leiomyoma, and to develop a model for the prediction of treatment response of uterine leiomyomas to UAE. Study design: A retrospective cohort study (Canadian Task Force Classification II-2) Patients: One hundred ninety-eight patients with symptomatic uterine leiomyomas. Intervention: UAE Measurements and Main Results: Among 198 leiomyoma patients who were treated with UAE, 104 who underwent pelvic magnetic resonance imaging (MRI) with diffusion-weighted imaging were selected for developing prediction model. Variables that were statistically significant from the univariate analysis were: location of leiomyoma, total number of lesions, sum of leiomyomas diameters, T2 signal intensity of largest leiomyoma, and T2 leiomyoma:muscle ratio. After a logistic regression analysis, leiomyoma location and T2 signal intensity of the largest leiomyoma were found to be statistically significant variables. Using intramural myomas defined as controls, submucosal leiomyomas showed a greater response to UAE with an odds ratio of 7.6904. The odds ratio of T2 signal intensity with an increase in signal intensity of 10 was 1.093. Using these two variables, we developed a prediction model. The AUC in the prediction model was 0.833, and the AUC in the validation set was 0.791. Conclusion: We identified that submucosal leiomyomas and those leiomyomas that show high signal intensity on T2-weighted imaging will exhibit a greater response to UAE. Prediction models are clinically helpful in selecting UAE as an appropriate treatment option for managing uterine leiomyoma.

Analysis of MED12 Mutation in Multiple Uterine Leiomyomas in South Korean patients.

Uterine leiomyomas are one of the most common benign gynecologic tumors, but the exact causes are not completely understood. In 2011, through DNA sequencing, MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several recent studies confirmed the high frequency of MED12 mutation in uterine leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of patients with multiple leiomyomas in a patient. The purpose of this study was to investigate the frequency of MED12 mutations in uterine leiomyomas of South Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas in the same patients. Uterine leiomyoma tissues were obtained from symptomatic women who underwent hysterectomy or myomectomy for medically indicated reasons. We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to 12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years. Of the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14 patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three of them had the same mutations. Five of them, each leiomyoma had a different mutation. Two of them did not have mutation. Four of them had both mutation-positive and mutation-negative leiomyomas. In conclusion, we confirmed the high frequency of the MED12 mutation in uterine leiomyomas of South Korean patients. We also identified various MED12 mutation status in patients with multiple leiomyomas. This suggests that in a given patient, different tumors may have arisen from different cell origins and therefore it is supposed that occurrence of multiple leiomyoma in a single patient may not be caused by intrauterine metastasis or dissemination.

Effect of helixor A on natural killer cell activity in endometriosis.

BACKGROUND AND AIM: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosis MATERIALS AND METHODS: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker. RESULTS: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p=0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p=0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p=0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p=0.014) in stage III/IV. CONCLUSIONS: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results open new role of helixor A as an imune modulation therapy, or in combination with hormonal agents, for the treatment of endometriosis.

Association between osteocalcin and metabolic syndrome in postmenopausal women.

OBJECTIVES: Undercarboxylated osteocalcin (ucOC) has been proved as a regulator of glucose and fat mass in an animal model. This study examined the association between osteocalcin and metabolic syndrome (MetS) in postmenopausal women. METHODS: We selected 135 postmenopausal women and determined anthropometric values [waist-hip ratio (WHR), visceral fat area (VFA), body fat mass (BFM), and skeletal muscle mass (SMM)], the lipid profile, fasting plasma glucose (FPG), insulin, high-sensitivity C-reactive protein (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR), serum leptin and adiponectin level, and serum tOC and ucOC level. RESULTS: There were 52 postmenopausal women in the MetS group. After adjusting for age and years since menopause, ucOC was negatively correlated with WHR, VFA, BFM, triglyceride, fasting insulin, HOMA-IR, and serum leptin and was positively correlated with serum adiponectin. The odds ratio for MetS was significantly lower in the highest quartile than the lowest quartile after adjusting for age, years since menopause, and BMI. In multiple regression analysis, serum leptin and HOMA-IR were the most important predictors of the independent variables that affect serum ucOC. CONCLUSION: ucOC showed an inverse correlation with markers of insulin resistance, central obesity, and the presence of MetS in postmenopausal women and appears to protect against MetS. Further large-scale clinical and experimental studies are needed to clarify the potential of ucOC as a predictor of MetS in postmenopausal women.

Comparison of the inhibitory effect of gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM), antiprogesterone on myoma cell proliferation in vitro.

Uterine myomas are the most common gynecologic tumor in women of reproductive age. Treatment options of uterine myomas consist of surgical, medical and interventional therapy such as uterine artery embolization or myolysis. Given that it is the most common type of tumor in women of reproductive age, the treatment of uterine myomas must prioritize uterine conservation. There are several drugs for medical treatment of uterine myoma such as gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM) and antiprogesterone. The objective of this study was to compare the effect of GnRH agonist, SERM, and antiprogesterone in the treatment of uterine myomas in vitro. The effect of drugs was evaluated through the cell viability assay in cultured leiomyoma cells, western blot analysis of proliferating cell nuclear antigen (PCNA), and BCL-2 protein expression. As a result, mifepristone single-treated group represents the most significant reduction in myoma cell viability and proliferation. When pretreated with leuprolide acetate, raloxifene shows more significant reduction in myoma cell viability and proliferation than mifepristone. This study suggests one of the possible mechanisms how medications act on uterine myoma, especially at the molecular level.

Outpatient multimodality management of large submucosal myomas using transvaginal radiofrequency myolysis.

STUDY OBJECTIVE: To evaluate the safety and efficacy of transvaginal radiofrequency myolysis (RFM) with or without combined hysteroscopy for treatment of large submucosal leiomyomas with a substantial intramural portion. DESIGN: Retrospective observational study (Canadian Task Force classification III). SETTING: Hospital outpatient department. PATIENTS: Twenty-four patients with large submucosal leiomyomas with a substantial intramural portion. INTERVENTIONS: Transvaginal RFM with or without combined hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients with large submucosal leiomyomas with a substantial intramural portion were enrolled to undergo stepwise RFM. Additional hysteroscopic myomectomy was performed in 6 patients at 3 to 6 months after RFM. Myoma volumes were measured via 3-dimensional ultrasonography before RFM and at 1, 3, 6, 12, and 24 months postoperatively. Symptom severity was assessed using the Uterine Fibroid Symptom and Quality of Life questionnaire and the Health-Related Quality of Life questionnaire. The total volume reduction rate 24 months postoperatively was 84.2%. Symptom severity and health-related quality of life scores demonstrated substantial improvements at 12 months after RFM. CONCLUSIONS: RFM with or without hysteroscopy is an effective treatment for large myomas with deep intramural positioning, and it seems safe for use in all patients with submucosal myoma-related symptoms.

Differentiating Uterine Sarcoma From Atypical Leiomyoma on Preoperative Magnetic Resonance Imaging Using Logistic Regression Classifier: Added Value of Diffusion-Weighted Imaging-Based Quantitative Parameters.

OBJECTIVE: To evaluate the added value of diffusion-weighted imaging (DWI)-based quantitative parameters to distinguish uterine sarcomas from atypical leiomyomas on preoperative magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 138 patients (age, 43.7 ± 10.3 years) with uterine sarcoma (n = 44) and atypical leiomyoma (n = 94) were retrospectively collected from four institutions. The cohort was randomly divided into training (84/138, 60.0%) and validation (54/138, 40.0%) sets. Two independent readers evaluated six qualitative MRI features and two DWI-based quantitative parameters for each index tumor. Multivariable logistic regression was used to identify the relevant qualitative MRI features. Diagnostic classifiers based on qualitative MRI features alone and in combination with DWI-based quantitative parameters were developed using a logistic regression algorithm. The diagnostic performance of the classifiers was evaluated using a cross-table analysis and calculation of the area under the receiver operating characteristic curve (AUC). RESULTS: Mean apparent diffusion coefficient value of uterine sarcoma was lower than that of atypical leiomyoma (mean ± standard deviation, 0.94 ± 0.30 10-3 mm²/s vs. 1.23 ± 0.25 10-3 mm²/s; P < 0.001), and the relative contrast ratio was higher in the uterine sarcoma (8.16 ± 2.94 vs. 4.19 ± 2.66; P < 0.001). Selected qualitative MRI features included ill-defined margin (adjusted odds ratio [aOR], 17.9; 95% confidence interval [CI], 1.41-503, P = 0.040), intratumoral hemorrhage (aOR, 27.3; 95% CI, 3.74-596, P = 0.006), and absence of T2 dark area (aOR, 83.5; 95% CI, 12.4-1916, P < 0.001). The classifier that combined qualitative MRI features and DWI-based quantitative parameters showed significantly better performance than without DWI-based parameters in the validation set (AUC, 0.92 vs. 0.78; P < 0.001). CONCLUSION: The addition of DWI-based quantitative parameters to qualitative MRI features improved the diagnostic performance of the logistic regression classifier in differentiating uterine sarcomas from atypical leiomyomas on preoperative MRI.

Prevalence, incidence, and treatment trends of adenomyosis in South Korean women for 15 years: A national population-based study.

OBJECTIVE: Adenomyosis is associated with female infertility worldwide. With improvements in imaging methods, such as pelvic magnetic resonance imaging, the diagnosis and treatment of adenomyosis have changed. This study aimed to evaluate the overall prevalence, incidence, and treatment trends of adenomyosis in South Korea using data from the Korean National Health Insurance Service Database (NHIS). METHODS: Data were collected from the Korean NHIS, a population-based complete enumeration database. A total of 678 641 women aged 11-55 years diagnosed with adenomyosis (N80.0 ICD-10 code) from the database from 2002 to 2016 were enrolled. After applying a one-year look-back method, 629 592 patients were analyzed to estimate the prevalence, incidence, and treatment trends of adenomyosis. RESULTS: The overall prevalence during the study period was 3.86 per 1000 people. The prevalence of adenomyosis has increased from 1.42 per 1000 individuals in 2002 to 7.50 per 1000 individuals in 2016. The crude annual incidence rate of adenomyosis was 1.62 per 1000 people in 2003, which increased to 4.12 per 1000 people in 2016. In addition, the proportion of uterus-preserving surgeries in adenomyosis treatments has increased from 7.51% to 21.29% over 15 years. CONCLUSION: The prevalence and incidence of adenomyosis in South Korea increased between 2002 and 2016. Furthermore, the proportion of uterus-preserving surgeries and progestin prescriptions for adenomyosis treatment has increased. We expect that our findings will raise awareness of the necessity for fertility preservation through earlier diagnosis and proper management of patients with adenomyosis.