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Introduction: Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. Methods: Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. Results: We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread (P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread (P = 0.002). Conclusion: Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence. [ABSTRACT FROM AUTHOR]

Background: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. Methods: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. Ethics and dissemination: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. Conclusions: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. Trial registration number: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022. [ABSTRACT FROM AUTHOR]

Mesonephric-like adenocarcinoma of the endometrium is a rare gynecological malignancy. Due to the low incidence, strong invasiveness, easy recurrence and metastasis, patients with this kind of disease are usually seen at an advanced stage. There is no clear treatment plan at present, and the prognosis is poor. We report the diagnosis and treatment process of a patient with mesonephric-like adenocarcinoma of the endometrium involving cervical interstitium. The patient was treated for two times of postmenopausal vaginal fluid and irregular vaginal bleeding for more than 20 days. Hysteroscopy (primary surgery) was performed on November 18, 2022, and the postoperative pathological examination results showed endometrioid adenocarcinoma. Therefore, transabdominal extrascial hysterectomy, bilateral ovarian arteriovenous high ligation, bilateral salpingo-oophorectomy, abdominal para-aortic lymphadenectomy and pelvic lymph node dissection (secondary surgery) was performed on December 1, 2022. Combined with the results of pathological examination of the two surgeries, stage Ⅱ of mesonephric-like adenocarcinoma of the endometrium was diagnosed. After surgery, the patient was given five cycles of paclitaxel combined with carboplatin chemotherapy, one course of pelvic external beam radiotherapy and one vaginal brachytherapy. No disease recurrence or metastasis was observed during follow-up until April 10, 2024. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A 19‐year‐old woman had stage IA endometrial carcinoma treated with medroxyprogesterone acetate and experienced a recurrence. This patient's experience illustrates the importance of a thorough history and endometrial assessment in younger patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify high- and low-risk subgroups of patients with lymph node (LN) metastasis in presumed early-stage endometrioid endometrial cancer (EC) patients. Methods: Clinicopathologic data of presumed early-stage endometrioid EC patients (n=361) treated with lymphadenectomy between March 2000 and July 2022 were analyzed. None of the patient had definite evidence of LN metastasis in a preoperative magnetic resonance imaging (MRI). A received operating characteristic curve analysis was conducted to define the sensitivity and specificity for the combined preoperative risk factors for LN metastasis, which was determined by multivariate analysis. Results: Nineteen patients (5.3%) had LN metastasis. Multivariate analysis identified cervical stromal invasion on MRI (odds ratio [OR]=4.386; 95% confidence interval [CI]=1.020-18.852; p=0.047), cornual location of tumor on MRI (OR=36.208; 95% CI=7.902-165.913; p<0.001), and lower uterine segment/isthmic location of tumor on MRI (OR=8.454; 95% CI=1.567-45.610; p=0.013) as independent prognostic factors associated with LN metastasis. Patients were categorized into low- and high-risk groups according to risk criteria. Significant differences in the rates of LN metastasis were observed between the two groups (0.4% vs. 22.2%, p<0.001). Conclusion: Approximately 95% of presumed early-stage endometrioid EC patients did not have LN metastasis. A model using tumor location was significantly correlated with the risk of LN metastasis. Even in presumed early-stage endometrioid EC patients, therefore, tumor location should be investigated to determine whether to perform LN assessment. [ABSTRACT FROM AUTHOR]

Simple Summary: Various diagnostic methods exist for EC, with traditional biopsy being common but invasive. Endometrial cytology using liquid specimens shows promise for non-invasive detection. Morphological features like fractal dimension, circularity, and solidity in cell clusters could potentially enhance diagnostic accuracy and predict prognosis. Circularity and fractal dimension demonstrated significant associations with EC and AEH, regardless of age and cytology results. An ROC analysis revealed improved diagnostic accuracy when combining fractal dimension with cytology, particularly in menopausal age groups. Moreover, circularity, solidity, and fractal dimension may serve as prognostic indicators for endometrial cancer. This study showed that the morphological characteristics of cell clusters in liquid-based cytology may improve endometrial cancer diagnosis and predict prognosis. Endometrial cancer (EC) in women is increasing globally, necessitating improved diagnostic methods and prognosis prediction. While endometrial histology is the conventional approach, liquid-based endometrial cytology may benefit from novel analytical techniques for cell clusters. A clinical study was conducted at the University of Fukui Hospital from 2012 to 2018, involving 210 patients with endometrial cytology. The liquid-based cytology images were analyzed using cell cluster analysis with Image J software. Logistic regression, ROC analysis, and survival analysis were employed to assess the diagnostic accuracy and prognosis between cell cluster analysis and EC/atypical endometrial hyperplasia (AEH). Circularity and fractal dimension demonstrated significant associations with EC and AEH, regardless of age and cytology results. The ROC analysis revealed improved diagnostic accuracy when combining fractal dimension with cytology, particularly in menopausal age groups. Lower circularity and solidity were independently associated with poor overall survival, while higher fractal dimension values correlated with poorer overall survival in Grades 2 and 3 endometrial cancers. The combination of circularity and fractal dimension with cytology improved diagnostic accuracy for both EC and AEH. Moreover, circularity, solidity, and fractal dimension may serve as prognostic indicators for endometrial cancer, contributing to the development of more refined screening and diagnostic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent postmenopausal bleeding (PMB) occurs in 6%–25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB. Material and Methods: A multicenter prospective cohort study was conducted over a 5‐year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode vs recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB. Results: A total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow‐up of 61 months (IQR (Interquartile range) 44–73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p‐value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p‐value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75–23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64–6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07–3.04). Conclusions: Recurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy. [ABSTRACT FROM AUTHOR]

Although several studies have been completed to investigate the effect of cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in endometrial cancer with peritoneal metastasis (ECPM), a direct comparison was not performed previously. A meta-analysis was performed to investigate the suspected additional survival benefits of CRS plus HIPEC over CRS only. Twenty-one and ten studies with a total number of 1116 and 152 cases investigating CRS only and CRS plus HIPEC were identified, respectively. When all articles were analyzed, the 1-year survival rate was 17.60% higher for CRS plus HIPEC (82.28% vs. 64.68%; p = 0.0102). The same tendency was observed for the 2-year (56.07% vs. 36.95%; difference: 19.12%; p = 0.0014), but not for the 5-year (21.88% vs. 16.45%; difference: 5.43%; p = 0.3918) survival rates. The same clinical significance, but statistically less strong observations, could be made if only the studies published after 2010 were investigated (1-year survival rate: 12.08% and p = 0.0648; 2-year survival rate: 10.90% and p = 0.0988). CRS remains one of the core elements of ECPM treatment, but the addition of HIPEC to CRS can increase the positive clinical outcome, especially in the first 2 years. [ABSTRACT FROM AUTHOR]

Introduction: Endometrial carcinoma is the second most common female genital tract malignancy in India with a incidence rising globally. Hormone receptors are positive in 35- 90% of endometrial carcinomas. Hormone therapy can be given to patients with hormone receptor positive tumours. Aim: To determine whether Progesterone and Oestrogen Receptors (PR and ER) are most often expressed in endometrial cancer cases, and to correlate this expression with histopathologic features in these cases. Materials and Methods: A cross-sectional study was conducted in the Department of Pathology, Government Medical College, Thrissur, Kerala, India, on 37 cases of endometrial carcinoma. ER and PR expression were assessed and correlated with histopathologic parameters in carcinoma endometrium. Results: 75.6% of the patients were in the 51-70 age range. Grade I endometrioid cancer accounted for 24 (77.42%) of the 31 cases, grade II for 5 (16.13%) and grade III for 2 (6.45%). 19 (51.4%) of cases had ER positivity and 21 (56.8%) had PR positivity. While all grade III tumours were PR and ER negative, grade I tumours had 70.83% and 79.17% ER and PR positivity, respectively. While ER expression did not correlate negatively with grade (p-value=0.076), PR expression did (p-value=0.043). In 29.73% of patients, lymphocytic infiltrates were seen, and they had a strong correlation with the expression of ER and PR. All cases of papillary serous carcinomas (100%), mucinous carcinomas (100%), and clear cell carcinomas (100%), showed ER negative. Hormone receptor status did not significantly correlate with FIGO (The International Federation of Gynecology and Obstetrics) stage, lymphovascular emboli, or myometrial invasion. Conclusion: Most of the endometrioid endometrial carcinomas showed ER and PR positivity, while all of the non endometrioid endometrial carcinomas were negative for both ER and PR. ER and PR were positive in most of the grade I tumours, whereas in the high-grade tumours, they were often negative. Immunoreactivity for PR had a stronger association with tumour grade, when compared to ER. [ABSTRACT FROM AUTHOR]

In 2013, the Cancer Genome Atlas (TCGA) research center completed the molecular classification endometrial carcinoma (EC), categorizing patients into POLE (DNA polymerase epsilon) mutation type, microsatellite instability-high (MSI-H) type, copy number low (CN-L) type, and copy number high (CN-H) type. Subsequently Western scholars refined this into the ProMisE and Trans-PORTEC classification to better suit clinical applications. Patients with POLE mutation EC have excellent prognosis and lower recurrence rate, allowing for a reduction in surgical scope and a deescalation of treatment. Patients with MSI-H or CN-H are still POLE mutant. MSI-H type patients have a high burden of tumor mutations and significant benefits from immunotherapy. CN-L type patients are the most common, with a prognosis second only to POLE mutant patients. These patients have a higher response rate to hormone therapy to preserve fertility. CN-H type patients have the worst prognosis, with invasive features and a high risk of recurrence. For these patients, postoperative supplementary treatment is necessary to avoid inadequate treatment. However, there are some studies have shown that targeted therapy is more effective for CN-H type patients. The TCGA molecular typing of EC has overcome the limitations of traditional pathological and histological classification for evaluating prognosis, providing new insights into the pathological characteristics, prognosis, clinical diagnosis and treatment decisions of EC. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma is the most common malignancy of the female reproductive system. Recent years have witnessed pivotal developments in the diagnosis and treatment, including the quantitative assessment of lymphovascular space invasion, the ultrastaging of sentinel lymph nodes, and the molecular stratification of endometrial carcinoma, all progressively integrated into clinical practice. These new insights have been incorporated into the 2023 version of the staging system by the International Federation of Gynecology and Obstetrics (FIGO), heralding a new era of clinical adoption. The importance of precise pathological evaluation cannot be overstated, serving as a linchpin for prognosticating patient outcomes and steering the course of adjuvant therapies. Through the lens of the updated 2023 FIGO staging for endometrial carcinoma, this discourse aims to elevate the paradigm of pathological diagnosis, promoting a benchmark of standardization and precision for pathologists, thereby empowering clinicians with a deeper and more accurate application of the staging system. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of the diagnostic superiority of systematic lymphadenectomy in endometrial cancer cases in conditions of sentinel lymph node (SLN) dissection cannot be performed. Material and Methods: The file records of 853 patients with endometrial cancer were reviewed in the gynecological oncology clinic of Kanuni Sultan Süleyman Hospital between 2008 and 2020. Thirty nine endometrial cancer patients with lymph node involvement were selected to study. Pelvic and paraaortic lymph node counts, positive lymph node ratios, metastatic lymph node sizes and percentages of tumor infiltration in lymph nodes were defined. Clinicopathological variables, including the categorical data, were analyzed as a descriptive method. Results: Grossly suspicious lymph nodes were observed in 46.2% of the patients. While 54.4% of metastatic lymph nodes were <1 cm (non-palpable), 12% of them <5 mm. In 17.9% of patients, all dissected metastatic lymph nodes were <1 cm (non-palpable). Conclusion: In clinics that can not performed SLN procedure in endometrial cancer, extent of lymphadenectomy may vary as a systemic lymphadenectomy or selective palpable lymph node excision depends on surgeon preference and patient morbidity. With comprehensive lymphadenectomy, occult lymph node metastasis can be detected and adding adjuvant chemoradiotherapy allows the patients to be given better survival rates in Stage IIIc disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer stem cells (CSCs) are responsible for tumour initiation, growth, dissemination, and resistance to therapy. In this study, we intended to evaluate the effect of inhibiting aldehyde dehydrogenase (ALDH), an enzyme found in endometrial CSCs, using N,N-diethylaminobenzaldehyde (DEAB). Our findings suggest that ALDH blockage mediated by DEAB reduces enzyme activity and expression and can modulate CSC phenotype and behaviour. Additionally, DEAB modulates the expression of certain proteins, namely, ALDH18A1, SdhA, and UBAP2L, identified in endometrial cancer, which might be promising prognostic and therapeutic targets. ALDH inhibition could be a potential strategy to prevent endometrial CSCs from growing and spreading. Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer. [ABSTRACT FROM AUTHOR]

Objective: The standard surgery for endometrial cancer can be deferred in some situations, including morbid obesity, comorbidities, and the patient's desire for fertility. One of the options to improve patients' circumstances is bariatric surgery. Case report: This study presented two patients with stage IA, grade I endometrioid endometrial adenocarcinoma. Both patients had morbid obesity and had comorbidities. In case 1, because of fertility preservation, and in case 2, because of severe comorbidities, hormone therapy was started, followed by bariatric surgery after counseling patients. Both patients had acceptable changes in body mass index during follow-up, so cancer surgery through laparoscopy was done. Both patients did not need adjuvant therapy; months after cancer surgery, there is no recurrence, and their body mass index is also decreasing. Conclusion: Bariatric surgery can improve outcomes in patients with morbid obesity who suffer endometrial cancer. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the most lethal and endometrial cancer the most common gynaecological cancer in the UK, yet neither have a screening program in place to facilitate early disease detection. The aim is to evaluate whether online search data can be used to differentiate between individuals with malignant and benign gynaecological diagnoses. Methods: This is a prospective cohort study evaluating online search data in symptomatic individuals (Google user) referred from primary care (GP) with a suspected cancer to a London Hospital (UK) between December 2020 and June 2022. Informed written consent was obtained and online search data was extracted via Google takeout and anonymised. A health filter was applied to extract health-related terms for 24 months prior to GP referral. A predictive model (outcome: malignancy) was developed using (1) search queries (terms model) and (2) categorised search queries (categories model). Area under the ROC curve (AUC) was used to evaluate model performance. 844 women were approached, 652 were eligible to participate and 392 were recruited. Of those recruited, 108 did not complete enrollment, 12 withdrew and 37 were excluded as they did not track Google searches or had an empty search history, leaving a cohort of 235. Results: The cohort had a median age of 53 years old (range 20–81) and a malignancy rate of 26.0%. There was a difference in online search data between those with a benign and malignant diagnosis, noted as early as 360 days in advance of GP referral, when search queries were used directly, but only 60 days in advance, when queries were divided into health categories. A model using online search data from patients (n = 153) who performed health-related search and corrected for sample size, achieved its highest sample-corrected AUC of 0.82, 60 days prior to GP referral. Conclusions: Online search data appears to be different between individuals with malignant and benign gynaecological conditions, with a signal observed in advance of GP referral date. Online search data needs to be evaluated in a larger dataset to determine its value as an early disease detection tool and whether its use leads to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the sixth most common cancer among women worldwide, with an increasing mortality rate. The standard treatment of patients with advanced or recurrent endometrial cancer has not changed significantly in recent decades. However, in recent years, immunotherapy has emerged as a promising strategy that harnesses the body's immune system against cancer, particularly in advanced or recurrent cases, offering patients the possibility of better results and longer survival. Our critical review analyses recent findings in the literature in this field, focusing on the role of immunotherapy in the treatment of this disease. In particular, it focuses on the importance of molecular biology and highlights how this can change the choice of treatment, providing insights for future therapeutic strategies. The Cancer Genome Atlas (TCGA) has radically changed the history of endometrial cancer by outlining a new classification, based on its molecular characteristics. In the field of oncology, we are approaching the new era of molecular biology, particularly regarding endometrial cancer, with the increasing importance of targeted therapy. This paper is a review of phase III randomized controlled trials published in English between January 2019 and December 2023, comparing drugs of interest with standard adjuvant treatment and molecular subtypes in endometrial cancer. The use of immunotherapy alone or in combination with chemotherapy as therapy in patients with recurrent or advanced primary or metastatic endometrial cancer significantly improves the prognosis of these patients. The results show greater efficacy of all proposed treatments for mismatch repair deficiency (dMMR/MSI-H) patients compared to mismatch repair proficiency (pMMR) patients. Progression-free survival (PFS) and overall survival (OS) are better in dMMR patients in all studies analysed. Immunotherapy has the potential to revolutionize the gynaecological cancer treatment landscape, offering a new pathway and new hope for endometrial cancer patients, improving their outcomes in the future. Given the exciting results obtained in dMMR/MSI-H patients, MMR status should be investigated in every patient with advanced endometrial cancer at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: For a couple of decades, the morbidity rates for endometrial cancer (EC) have been on a constant rise. Surgery is the cornerstone in the management of this disease and may be performed for curative, staging, or palliative purposes. The type of hysterectomy, the role and extent of lymphadenectomy, the procedure of the sentinel lymph node mapping, and cytoreductive surgery in advanced or recurrent EC are discussed in detail. Most recently, the introduction of the molecular classification has changed the scene in EC treatment, and its impact on choosing the surgical strategy is outlined. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject providing an up-to-date clinical guide. Endometrial cancer (EC) poses a significant health issue among women, and its incidence has been rising for a couple of decades. Surgery remains its principal treatment method and may have a curative, staging, or palliative aim. The type and extent of surgery depends on many factors, and the risks and benefits should be carefully weighed. While simple hysterectomy might be sufficient in early stage EC, modified-radical hysterectomy is sometimes indicated. In advanced disease, the evidence suggests that, similarly to ovarian cancer, optimal cytoreduction improves survival rate. The role of lymphadenectomy in EC patients has long been a controversial issue. The rationale for systematic lymphadenectomy and the procedure of the sentinel lymph node biopsy are thoroughly discussed. Finally, the impact of the molecular classification and new International Federation of Gynecology and Obstetrics (FIGO) staging system on EC treatment is outlined. Due to the increasing knowledge on the pathology and molecular features of EC, as well as the new advances in the adjuvant therapies, the surgical management of EC has become more complex. In the modern approach, it is essential to adjust the extent of the surgery to a specific patient, ensuring an optimal, made-to-measure personalized surgery. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject, providing an up-to-date clinical guide. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is related to the higher incidence and the increased invasiveness of endometrial cancer (EC). Hyperglycemia, hyperinsulinemia, insulin resistance and obesity in patients with T2DM have been widely studied as potential pathogenesis of EC, and the imbalance of intestinal flora may be the key factor of T2DM-related EC. This paper summarizes the relationships between T2DM and EC, T2DM and intestinal flora, T2DM-related EC and intestinal flora, including the abnormal expression of microRNA, mitochondrial dysfunction, inflammation and adiponectin level, and the progress of intestinal flora in treating T2DM-related EC, in order to provide a reference for the prevention and treatment of T2DM-related EC from the perspective of intestinal flora. [ABSTRACT FROM AUTHOR]

Objectives We aimed to differentiate endometrial cancer (EC) between TP53mutation (P53abn) and Non-P53abn subtypes using radiological-clinical nomogram on EC body volume MRI. Methods We retrospectively recruited 227 patients with pathologically proven EC from our institution. All these patients have undergone molecular pathology diagnosis based on the Cancer Genome Atlas. Clinical characteristics and histological diagnosis were recorded from the hospital information system. Radiomics features were extracted from online Pyradiomics processors. The diagnostic performance across different acquisition protocols was calculated and compared. The radiological-clinical nomogram was established to determine the nonendometrioid, high-risk, and P53abn EC group. Results The best MRI sequence for differentiation P53abn from the non-P53abn group was contrast-enhanced T1WI (test AUC: 0.8). The best MRI sequence both for differentiation endometrioid cancer from nonendometrioid cancer and high-risk from low- and intermediate-risk groups was apparent diffusion coefficient map (test AUC: 0.665 and 0.690). For all 3 tasks, the combined model incorporating all the best discriminative features from each sequence yielded the best performance. The combined model achieved an AUC of 0.845 in the testing cohorts for P53abn cancer identification. The MR-based radiomics diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). Conclusion In the present study, the diagnostic model based on the combination of both radiomics and clinical features yielded a higher performance in differentiating nonendometrioid and P53abn cancer from other EC molecular subgroups, which might help design a tailed treatment, especially for patients with high-risk EC. Advances in knowledge (1) The contrast-enhanced T1WI was the best MRI sequence for differentiation P53abn from the non-P53abn group (test AUC: 0.8). (2) The radiomics-based diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). (3) The proposed model derived from multi-parametric MRI images achieved a higher accuracy in P53abn EC identification (AUC: 0.845). [ABSTRACT FROM AUTHOR]

Objectives: To build preoperative prediction models with and without MRI for regional lymph node metastasis (r-LNM, pelvic and/or para-aortic LNM (PENM/PANM)) and for PANM in endometrial cancer using established risk factors. Methods: In this retrospective two-center study, 364 patients with endometrial cancer were included: 253 in the model development and 111 in the external validation. For r-LNM and PANM, respectively, best subset regression with ten-time fivefold cross validation was conducted using ten established risk factors (4 clinical and 6 imaging factors). Models with the top 10 percentile of area under the curve (AUC) and with the fewest variables in the model development were subjected to the external validation (11 and 4 candidates, respectively, for r-LNM and PANM). Then, the models with the highest AUC were selected as the final models. Models without MRI findings were developed similarly, assuming the cases where MRI was not available. Results: The final r-LNM model consisted of pelvic lymph node (PEN) ≥ 6 mm, deep myometrial invasion (DMI) on MRI, CA125, para-aortic lymph node (PAN) ≥ 6 mm, and biopsy; PANM model consisted of DMI, PAN, PEN, and CA125 (in order of correlation coefficient β values). The AUCs were 0.85 (95%CI: 0.77–0.92) and 0.86 (0.75–0.94) for the external validation, respectively. The model without MRI for r-LNM and PANM showed AUC of 0.79 (0.68–0.89) and 0.87 (0.76–0.96), respectively. Conclusions: The prediction models created by best subset regression with cross validation showed high diagnostic performance for predicting LNM in endometrial cancer, which may avoid unnecessary lymphadenectomies. Clinical relevance statement: The prediction risks of lymph node metastasis (LNM) and para-aortic LNM can be easily obtained for all patients with endometrial cancer by inputting the conventional clinical information into our models. They help in the decision-making for optimal lymphadenectomy and personalized treatment. Key Points: •Diagnostic performance of lymph node metastases (LNM) in endometrial cancer is low based on size criteria and can be improved by combining with other clinical information. •The optimized logistic regression model for regional LNM consists of lymph node ≥ 6 mm, deep myometrial invasion, cancer antigen-125, and biopsy, showing high diagnostic performance. •Our model predicts the preoperative risk of LNM, which may avoid unnecessary lymphadenectomies. [ABSTRACT FROM AUTHOR]

In recent years the progress of targeted therapy and immunotherapy has developed rapidly, such as poly (ADP-ribose) polymerase inhibitor (PARPi) and immune checkpoint inhibitors (ICI) have changed the traditional treatment pattern of gynecologic tumors, but some patients have limited efficacy or develop drug resistance. Preclinical studies have found that PARPi damages DNA repair process, results in increasing tumor mutation burden and tumor -specific antigen neoantigens, modulates the tumor microenvironment, and stimulates the production of tumor infiltrating lymphocytes (TIL) and promotes anti-tumor immune response, which providing a theoretical basis for the combination treatment of PARPi and ICI. Recently, many clinical studies have found that the combination of PARPi and ICI can significantly improve the prognosis of patients with gynecological malignant tumors. [ABSTRACT FROM AUTHOR]

Background: The incidence of endometrial cancer is globally increasing. Aotearoa New Zealand is no exception with a 59% increase in cases over that last ten years. Aims: We report a sub‐set of themes which pertain to provider reflections of rising endometrioid‐type endometrial cancer incidence in individuals with high weight. Materials and Methods: Fifteen semi‐structured interviews with healthcare professionals experienced in providing care to women with endometrial cancer were audio‐recorded and transcribed. Interviews were analysed using reflexive thematic analysis. Results: Two main themes emerged: (1) concerns for the future; and (2) impact on fertility and treatment options. Healthcare professionals discussed rising incidence in younger people and a need for increased awareness about the association of excess weight as a risk factor for developing the disease. The concern extended to workforce and equipment shortfalls of meeting the needs of individuals with higher weight, which subsequently influenced treatment options, health outcomes and survivorship. Conclusions: Rising incidence of endometrial cancer in individuals with high weight presents multiple chances for inequitable access and health outcomes over the care continuum for endometrial cancer. Action is required to address incidence, awareness, access to equitable and inclusive treatment, and survivorship. [ABSTRACT FROM AUTHOR]

Aim: The effectiveness of hysteroscopy in diagnosing endometrial lesions has been demonstrated, showing high diagnostic accuracy for malignant endometrial lesions. Although the characteristic appearances of atypical and malignant endometria have been reported, they are not definitive and sometimes complicated. This study aimed to identify a small number of characteristic features to detect endometrial abnormalities using a simple judgment system and analyze the diagnostic characteristics and their accuracy in endometrial malignancy diagnosis. Methods: We performed a retrospective analysis of hysteroscopy video data of 250 patients, of which we selected for analysis based on pathology examination 152 cases with benign changes, 16 with atypical endometrium, and 18 with carcinoma in situ or endometrial cancer. Endometrial characteristics assessed included protrusion, desquamation, extended vessel, atypical vessel, and white/yellow lesion. Results: Multivariable analysis revealed that desquamation (p = 0.001, odds ratio [OR] 5.28), atypical vessels (p < 0.001, OR 8.50), and white/yellow lesions (p = 0.011, OR 1.37) were significant predictors for endometrial malignancy. From their contribution status, scoring points of 4, 6, and 1 were settled according to the odds ratio proportions. When scores ≥5 (at least both desquamation and white/yellow lesions or only atypical vessels) were used to define endometrial malignancy, sensitivity and specificity were 100% and 92%, respectively. When detecting cancer, atypical, and benign cases, sensitivity and specificity were 88% and 90%, respectively. Conclusion: Our characteristics hysteroscopic findings showed a higher predictive ability in detecting endometrial malignancies. However, further examination with more cases would be needed to accurately diagnose endometrial malignancy by hysteroscopy. [ABSTRACT FROM AUTHOR]

Objectives: To assess the ability of the International Endometrial Tumor Analysis (IETA)‐1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. Methods: This was a retrospective study, in which we validated the IETA‐1 model on the IETA‐3 study cohort (n = 1745). The IETA‐3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow‐up of non‐endometrial pathology, in the work‐up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow‐up of at least 1 year if endometrial sampling was not performed. The IETA‐1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non‐uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver‐operating‐characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). Results: The median age of the women in the IETA‐3 cohort was 51 (range, 20–85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA‐1 model had an AUC of 0.81 (95% CI, 0.73–0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32–0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62–0.73) (n = 1532). The IETA‐1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95–0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75–0.91), compared with 0.62 (95% CI, 0.52–0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08–0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA‐1 model gave an AUC of 0.81 (95% CI, 0.71–0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60–0.81) (difference in AUC, 0.11; 95% CI, 0.01–0.20). Conclusion: The IETA‐1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China’s real world. Methods This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤45 years old) and non-young (>45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT)±VBT. Results The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT±VBT and those who received VBT alone. Conclusions In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the most lethal and endometrial cancer the most common gynaecological cancer in the UK, yet neither have a screening program in place to facilitate early disease detection. The aim is to evaluate whether online search data can be used to differentiate between individuals with malignant and benign gynaecological diagnoses. Methods: This is a prospective cohort study evaluating online search data in symptomatic individuals (Google user) referred from primary care (GP) with a suspected cancer to a London Hospital (UK) between December 2020 and June 2022. Informed written consent was obtained and online search data was extracted via Google takeout and anonymised. A health filter was applied to extract health-related terms for 24 months prior to GP referral. A predictive model (outcome: malignancy) was developed using (1) search queries (terms model) and (2) categorised search queries (categories model). Area under the ROC curve (AUC) was used to evaluate model performance. 844 women were approached, 652 were eligible to participate and 392 were recruited. Of those recruited, 108 did not complete enrollment, 12 withdrew and 37 were excluded as they did not track Google searches or had an empty search history, leaving a cohort of 235. Results: The cohort had a median age of 53 years old (range 20–81) and a malignancy rate of 26.0%. There was a difference in online search data between those with a benign and malignant diagnosis, noted as early as 360 days in advance of GP referral, when search queries were used directly, but only 60 days in advance, when queries were divided into health categories. A model using online search data from patients (n = 153) who performed health-related search and corrected for sample size, achieved its highest sample-corrected AUC of 0.82, 60 days prior to GP referral. Conclusions: Online search data appears to be different between individuals with malignant and benign gynaecological conditions, with a signal observed in advance of GP referral date. Online search data needs to be evaluated in a larger dataset to determine its value as an early disease detection tool and whether its use leads to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: Endometrial cancer is diagnosed by obtaining uterine biopsies by pipelle, dilatation and curettage (D&C), or hysteroscopy. In 15%–25% of the cases, the preoperative and postoperative grades do not match. This discrepancy may carry significant clinical and prognostic consequences. We aimed to assess how body mass index (BMI) affects preoperative and postoperative grade mismatches and whether biopsy methods mitigate this effect. Methods: We conducted a retrospective review of patients with endometrial cancer who underwent surgery at our center between 2014 and 2022. We stratified patients into six classes of BMI based on the WHO classification. Preoperative and postoperative grades were compared for concordance with regards to patient BMI and sampling method. Results: A total of 158 patients were included, diagnosed by pipelle (n = 99), hysteroscopy (n = 15), or D&C (n = 44). For all methods, every unit increase in BMI increased the odds of having a gap between histology grades by 5.2%. In the pipelle group, the odds of a larger gap between the histology grades was 62% higher than that of women in the other groups. Among the D&C group, the odds of having a bigger difference between histology grades were 91.8% lower compared to the other groups. Patients with BMI over 30 had nearly 50% discrepancy when diagnosed with pipelle or hysteroscopy, but less than 10% with D&C. Conclusions: Increasing BMI is associated with decreasing concordance between preoperative and postoperative grades in endometrial cancer, especially when it exceeds 30. This effect is much less pronounced, however, when the diagnostic method is D&C. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether multiparametric magnetic resonance imaging (MRI) radiomics-based machine learning methods can improve preoperative local staging in patients with endometrial cancer (EC). Methods: Data of patients with histologically confirmed EC who underwent preoperative MRI were retrospectively analyzed and divided into a training or test set. Radiomic features extracted from multiparametric MR images were used to train and test the prediction of deep myometrial invasion (DMI) and cervical stromal invasion (CSI). Two radiologists assessed the presence of DMI and CSI on conventional MR images. A combined model incorporating a radiomic signature and conventional MR images was constructed and presented as a nomogram. Performance of the predictive models was assessed using the area under curve (AUC) in the receiver operating curve analysis and pairwise comparison using DeLong's test with Bonferroni correction. Results: This study included 198 women (training set = 138, test set = 60). Conventional MRI achieved AUCs of 0.837 and 0.799 for detecting DMI and 0.825 and 0.858 for detecting CSI in the training and test sets, respectively. The nomogram achieved AUCs of 0.928 and 0.869 for detecting DMI and 0.913 and 0.937 for detecting CSI in the training and test sets, respectively. The ability of the nomogram to detect DMI and CSI in the two sets was superior to that of conventional MRI (adjusted p < 0.05), except for the ability to detect CSI in the test set (adjusted p > 0.05). Conclusion: A nomogram incorporating radiomics signature into conventional MRI improved the efficacy of preoperative local staging of EC. [ABSTRACT FROM AUTHOR]

Cervical cancer, endometrial cancer and ovarian cancer are the three most common malignant tumors in gynecology, and the incidences are on the rise in all ages in recent years. The gynecological malignant tumors have become a serious threat to women's health in China. Although the application of a variety of targeted drugs has significantly prolonged the survival of patients, cervical cancer, endometrial cancer and ovarian cancer are still a group of diseases that cannot be accurately diagnosed and treated. MiR-17-92 gene cluster, as the earliest identified miRNA family of oncogene, has been widely concerned about its mechanism. As a member of the miR-17-92 gene cluster, miR-20a can play a post-transcriptional regulatory role by reducing or increasing the expression, thus affecting the downstream gene pathway, regulating the proliferation, invasion, and metastasis of malignant tumor cells, and finally achieving the occurrence and progress of malignant tumors. According to the current research progress, the specific increase of miR-20a expression in cervical cancer, endometrial cancer and ovarian cancer is usually related to the malignant progress of the disease. This article reviews the research progress of miR-20a in the pathogenesis of three common gynecological malignant tumors. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the current investigation is to compare the efficacy of different diffusion models and diffusion kurtosis imaging (DKI) in differentiating stage IA endometrial carcinoma (IAEC) from benign endometrial lesions (BELs). Methods: Patients with IAEC, endometrial hyperplasia (EH), or a thickened endometrium confirmed between May 2016 and August 2022 were retrospectively enrolled. All of the patients underwent a preoperative pelvic magnetic resonance imaging (MRI) examination. The apparent diffusion coefficient (ADC) from the mono-exponential model, pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) from the bi-exponential model, distributed diffusion coefficient (DDC), water molecular diffusion heterogeneity index from the stretched-exponential model, diffusion coefficient (Dk) and diffusion kurtosis (K) from the DKI model were calculated. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency. Results: A total of 90 patients with IAEC and 91 patients with BELs were enrolled. The values of ADC, D, DDC and Dk were significantly lower and D* and K were significantly higher in cases of IAEC (p < 0.05). Multivariate analysis showed that K was the only predictor. The area under the ROC curve of K was 0.864, significantly higher compared with the ADC (0.601), D (0.811), D* (0.638), DDC (0.743) and Dk (0.675). The sensitivity, specificity and accuracy of K were 78.89%, 85.71% and 80.66%, respectively. Conclusion: Advanced diffusion-weighted imaging models have good performance for differentiating IAEC from EH and endometrial thickening. Among all of the diffusion parameters, K showed the best performance and was the only independent predictor. Diffusion kurtosis imaging was defined as the most valuable model in the current context. [ABSTRACT FROM AUTHOR]

Endometrial lesions are common and prevalent gynecological diseases. Endometrial histopathology is the ′gold standard′ for diagnosis, the traditional method of endometrial sampling is dilatation and curettage, which is a blind procedure that can causes missed diagnosis and severe pain. Other methods of endometrial sampling include endometrial tissue sampler, endometrial cytology sampler, microscale endometrial sampler and hysteroscopic-guided biopsy, etc. These various methods of endometrial sampling are commonly used to diagnose abnormal uterine bleeding or chronic endometritis, and some can be used for screening endometrial cancer. Endometrial tissue sampler and microscale endometrial sampler are suitable for screening lesions, but not for patients with focal lesions and atrophy endometrium. Endometrial cytology sampler is also used for screening lesions, especially for patients with atrophy endometrium, but cytology has no diagnostic value. Hysteroscopic-guided biopsy can diagnose focal lesions and is the ′gold standard′ in endometrial sampling, but is not used for screening. The appropriate methods of endometrial sampling should be used for different kinds of condition. [ABSTRACT FROM AUTHOR]

Primary bronchial lung cancer, commonly known as lung cancer, is one of the malignant tumors with high morbidity and mortality in the world. In recent years, the incidence of lung cancer in women has increased, and most of them are lung adenocarcinoma. Because the early symptoms of lung cancer are occult, it is often detected when metastasis has already occurred. We report a case of endometrial metastasis of lung adenocarcinoma. The patient presented with abnormal vaginal bleeding, and the pathology after curettage indicated adenocarcinoma. After immunohistochemical examination and imaging examination were combined to exclude the possibility of tumor origin in other sites, the diagnosis was confirmed as lung adenocarcinoma metastasis to the endometrium. Metastasis of lung cancer to the endometrium is extremely rare and is likely to be missed or misdiagnosed. In this paper, the data of a case of endometrial metastasis of lung adenocarcinoma were retrospectively analyzed and the relevant literatures were reviewed in order to enhance the clinical vigilance of endometrial metastasis of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Fatty acid synthase (FASN) is a key enzyme in the fatty acid synthesis that catalyzes the de novo synthesis of lipids. Most of the fatty acids are of food origin in normal tissues, while fatty acids are dependent on the de novo synthesis of lipids in endometrial cancer cells. Previous studies have shown that FASN expression is associated with the development, progression and poor prognosis of endometrial malignancies. The overexpression of FASN is correlated with mitogen extracellular kinase (MEK)/ extracellular signal -regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathways. Specific blockade of its activity can significantly inhibit the growth and proliferation of tumor cells. We review the action of FASN and mechanism in endometrial malignancies and the progress of FASN inhibitors such as C75, C93, orlistat and so on, in endometrial cancer or other tumors, with the aim of providing new ideas for the treatment of endometrial tumors [ABSTRACT FROM AUTHOR]

Endometrial cancer is a common gynecological malignant tumor, which seriously threatens the quality of life and health of women. Recent studies have shown that in the immune microenvironment of endometrial cancer, the interaction between immune cells such as dendritic cells and immune-enhancing factors can enhance the anti -tumor immune effect, while immune cells such as tumor -associated macrophages and immunosuppressive factors can exert tumor-promoting immune effects by inhibiting immune responses. This article reviews the research progress on the effects of some immune cells, immunosuppressive factors and immune enhancing factors in the immune microenvironment of endometrial cancer, and provides new ideas for further study of the pathogenesis and immunotherapy of endometrial cancer. [ABSTRACT FROM AUTHOR]

Copper ion as an important coenzyme participates in a wide range of metabolic processes, including aerobic respiration, peptide amidation, iron transport, superoxide dismutase and extracellular matrix biosynthesis. Copper homeostasis is an important mechanism to maintain cell activity. Cuproptosis is a form of cell death caused by the accumulation of copper ions, which is characterized by the imbalance of copper homeostasis, the accumulation of copper in cells, the selective disturbance of tricarboxylic acid cycle, the aggregation of fatty acylated mitochondrial enzymes and the loss of iron -sulfur protein, the protein stress of mitochondria, the cell membrane cracking, and finally the cell death. Gynecological malignant tumors are important causes of cancer death in women. It is found that cuproptosis is closely related to the occurrence, development, prognosis and drug resistance of gynecological malignant tumors. Some cuproptosis regulators can inhibit tumor metastasis and recurrence by inhibiting angiogenesis and regulating drug resistance of cancer cells. Therefore, cuproptosis is a valuable research direction for the treatment of gynecological malignant tumors. [ABSTRACT FROM AUTHOR]

In this study, we conducted a comparative analysis of demographic, histopathological, and sonographic characteristics between pre- and postmenopausal women diagnosed with endometrial cancer, while also examining sonographic and anthropometric features in 'low' and 'intermediate/high-risk' cases, stratified by menopausal status. Our analysis, based on data from the International Endometrial Tumor Analysis (IETA) 4 cohort comprising 1538 women (161 premenopausal, 1377 postmenopausal) with biopsy-confirmed endometrial cancer, revealed that premenopausal women, compared to their postmenopausal counterparts, exhibited lower parity (median 1, IQR 0–2 vs. 1, IQR 1–2, p = 0.001), a higher family history of colon cancer (16% vs. 7%, p = 0.001), and smaller waist circumferences (median 92 cm, IQR 82–108 cm vs. 98 cm, IQR 87–112 cm, p = 0.002). Premenopausal women more often had a regular endometrial–myometrial border (39% vs. 23%, p < 0.001), a visible endometrial midline (23% vs. 11%, p < 0.001), and undefined tumor (73% vs. 84%, p = 0.001). Notably, despite experiencing a longer duration of abnormal uterine bleeding (median 5 months, IQR 3–12 vs. 3 months, 2–6, p < 0.001), premenopausal women more often had 'low' risk disease (78% vs. 46%, p < 0.001). Among sonographic and anthropometric features, only an irregular endometrial–myometrial border was associated with 'intermediate/high' risk in premenopausal women. Conversely, in postmenopausal women, multiple features correlated with 'intermediate/high' risk disease. Our findings emphasize the importance of considering menopausal status when evaluating sonographic features in women with endometrial cancer. [ABSTRACT FROM AUTHOR]

Objectives: The role of lymphadenectomy in the management of early endometrial cancer remains controversial. The aim of our study was to evaluate risk factors associated with nodal metastases in endometrial cancer and to devise a predictive risk model based on the significant risk factors in predicting node metastasis. Materials and Methods: A retrospective study was conducted on women diagnosed with uterus-confined endometrial cancer, and who underwent surgical staging with pelvic and/or paraaortic lymphadenectomy from our center during July 1, 2017 to June 30, 2019. Clinical details, Magnetic Resonance imaging (MRI)-detected myometrial invasion, and pre and post-operative histological details of tumor were correlated with pelvic and/or para-aortic lymph node metastasis. Risk factors were assessed using logistic regression model and risk models devised. Results: 128 patients were included in the study. Paraaortic lymphadenectomy was done in 72.7% patients. Nodal metastasis was seen in 14.8% of patients. Logistic regression analyses revealed lymphovascular invasion (P = 0.002), parametrial involvement (P = 0.017) and nonendometrioid histology (P = 0.004) to be significant risk factors. Tumor size >2 cm, grade 3 and deep myometrial invasion had higher risk for nodal metastasis, although non-significant. Risk models were derived with sensitivity of 79-89.5%, specificity of 58.7-69.7%, Negative predictive value (NPV) of 95-97% and accuracy of 63-71%. Conclusion: Lymphovascular invasion, nonendometrioid histology and parametrial involvement are independent predictors of lymph node metastasis in endometrial cancer. Risk models using these risk factors can better predict the risk of nodal metastasis and thus avoid lymph node dissection in low risk patients. Our risk models had reasonably good sensitivity in nodal metastasis prediction and require further validation. [ABSTRACT FROM AUTHOR]

High -grade neuroendocrine carcinoma of the uterus is a rare malignant tumor of the uterus with high malignancy and poor prognosis. Due to its low incidence rate, there is no standard treatment at present. Therefore, this paper reports the diagnosis and treatment of a 56 -year -old patient with stage Ⅳ uterine high -grade neuroendocrine carcinoma accompanied by endometrioid adenocarcinoma. The patient has undergone surgery, followed by 1 intraperitoneal chemotherapy and 6 courses of systemic chemotherapy (paclitaxel + platinum), then the patient′s outcome was close to complete response. Subsequently, 2 courses of consolidation chemotherapy were performed, and the patient′s condition was evaluated as stable. Currently followed up for 2 years and 10 months, the patient recovered well and did not show obvious signs of recurrence on imaging examination. With retrospective analysis of the clinical characteristics, diagnosis, and treatment of this case as well as relevant literature analysis, this paper aim to improve clinician′s understanding of this type of disease [ABSTRACT FROM AUTHOR]

Gynecological diseases are one of the causes that threaten women′s health. The incidence and mortality rate of gynecological malignant tumors are in the forefront among various systemic diseases in women, and the prognosis of the disease is poor due to tumor recurrence and drug resistance. Sphingolipids are important substances that make up plasma lipoproteins and are essential for various cellular functions and signaling. Sphingolipid metabolism is involved in regulating inflammatory responses and the proliferation, migration, invasion and metabolism of cancer cells. Studies have confirmed that there are differences in the levels of sphingolipids and their metabolites in benign and malignant gynecological diseases, including ceramides, sphingomyelin, sphingosine-1-phosphate and sphingosine. Abnormalities in sphingolipid levels can affect disease progression and sensitivity to chemoradiotherapy, analyzing sphingolipid metabolism may predict the outcome of disease. The review summarizes the research progress of sphingolipid metabolism in benign and malignant gynecological diseases to gain an in-depth understanding of the characteristics and functions of sphingolipids, which can provide new insights for exploring and discovering the pathogenesis, diagnosis, treatment and prognosis of benign and malignant gynecological diseases, in order to improve the treatment prospects and prolong the survival of patients. [ABSTRACT FROM AUTHOR]

Vimentin is an important type Ⅲ intermediate filament protein, mainly derived from mesenchymal cells. Vimentin is expressed in various types of tumors, and up -regulated expression of Vimentin is related to the migration and invasion ability of tumor cells, suggesting poor prognosis. Vimentin is a typical marker of epithelial-mesenchymal transition of tumor cells and a potential drug target. Studies have shown that Vimentin is abnormally expressed in cervical cancer, ovarian cancer and endometrial cancer, and is related to prognosis, tumormetastasis and recurrence, which has potential clinical application value. This article reviews the relationship between Vimentin as well as gynecological malignancy and its possible mechanism. [ABSTRACT FROM AUTHOR]

Endometrial cancer is one of the three major gynecological cancers, and the proportion of endometrial cancer among women of childbearing age is increasing yearly. How to achieve effective, safe and economical prevention and control of endometrial cancer through early diagnosis and screening has become a major topic. At present, there are still huge challenges in the early diagnosis and screening of endometrial cancer, including inadequate methods and programs, uncertain screening objects, and lack of efficient and minimally or non-invasive methods. In recent years, the molecular and imaging protocols are gradually alleviating these difficulties, which are expected to become efficient and safe screening programs for endometrial cancer. This article is aimed to review the current status of endometrial cancer screening and the research progress of emerging molecular and imaging regimens of early screening and diagnosis of endometrial cancer, and explore the implementation of future screening strategies. [ABSTRACT FROM AUTHOR]

Objective(s): The prognosis of endometrial cancer (EC) is significantly affected by tumor infiltration and metastasis. Cortactin (CTTN) regulates infiltration and metastasis in other tumors. Studies on the role and mechanism of CTTN in EC are limited and further studies are needed. Materials and Methods: Quantitative PCR and immunohistochemistry were used to detect Rasassociated C3 botulinum toxin substrate 1 (Rac1) and CTTN in EC and normal tissues. The relationship between the expression of these two genes and their prognostic factors was analyzed. A CTTNRNAi lentiviral system was constructed and transfected into EC cells. Migration and invasion were evaluated by scratch assay, transwell migration, and invasion assays. Pseudopodia formation was observed by immunofluorescence staining. Western blotting was performed to detect the expression of Rac1. Results: The expression levels of Rac1 and CTTN in EC tissues were significantly higher than those in normal tissues. In the EC group, Rac1 and CTTN levels were correlated. The protein expression levels of Rac1 and CTTN were related to myometrial invasion and stage. After CTTN knockdown, the migration rate, invasiveness, and migratory ability of EC cells decreased significantly. Lamellipodia was observed to disappear with the appearance of blebs. Rac1 protein expression was decreased after CTTN knockdown. Conclusion: CTTN may promote the invasion and migration of EC by lamellipodia. This effect may be related to the regulation of Rac1 by CTTN. [ABSTRACT FROM AUTHOR]

Background: The 2019 European Society of Urogenital Radiology (ESUR) guidelines for endometrial cancer recommend performing either dynamic contrast-enhanced magnetic resonance imaging (CE MRI) or single-phase CE MRI. However, no study has directly compared these options. Therefore, this study compared dynamic versus single-phase CE MRI for the evaluation of myometrial invasion in women with endometrial cancer. Methods: This retrospective, single-institution comparative study was conducted among women with surgically proven endometrial cancer, including 30 consecutive women with single-phase CE MRI and 30 age- and pathologic stage-matched women with dynamic CE MRI. Three readers independently compared dynamic and single-phase CE MRI in terms of the tumor-myometrium signal intensity (SI) difference ratio, depth of myometrial invasion, image quality, and image number. Pathologic findings served as a reference standard for the depth of myometrial invasion. Results: The estimated mean SI difference ratios of dynamic CE MRI and single-phase CE MRI fell within an equivalence margin of 0.05 (90% confidence intervals [CIs] = [−0.0497 to −0.0165], [−0.0226 to −0.0403], and [−0.0429 to −0.0433], respectively, for readers A, B, and C). The area under the receiver operating characteristic curve for the detection of deep myometrial invasion was not significantly different between the acquisitions (P =.3315, P =.3345, and P =.8593, respectively). Single-phase CE MRI showed significantly better image quality than dynamic CE MRI (P =.0143, P =.0042, and P =.0066, respectively), while the median number of images for dynamic CE MRI was 2.4 times higher than that for single-phase CE MRI. Conclusion: Single-phase acquisition may be a better option for CE MRI in women with endometrial cancer than dynamic acquisition. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the oncologic outcomes of patients with endometrial cancer who underwent sentinel lymph node (SLN) biopsy without ultrastaging compared with that of those who underwent lymphadenectomy (LND). Methods: Patients with endometrial cancer who underwent staging with SLN biopsy or LND during 2006 - 2021 were analyzed using propensity score matching (PSM). SLN metastasis was examined using hematoxylin and eosin staining, without ultrastaging. Progressionfree survival (PFS) was compared between the two groups before and after PSM using age, histology, and stage as covariates. Clinical variables such as recurrence patterns and lymphatic complications, were assessed. Results: After excluding 213 patients who underwent validation LND with SLN biopsy, 902 were identified. The demographics of the remaining patients differed according to histology, myometrial invasion depth, and stage. Lymph node metastasis was less frequent in the SLN group than in the LND group (9.4% vs. 3.8%, p=0.004). The recurrence rates within 2 years were lower in the SLN group. The SLN group exhibited significantly superior 2-year and overall PFS than the LND group. Among patients with uterus-confined disease, overall PFS was favorable for SLN biopsy. After matching, differences in PFS were no longer observed, although the lymphocele and lymphedema rates were significantly lower in the SLN group. Conclusion: In patients with endometrial cancer, SLN biopsy without ultrastaging did not compromise survival outcomes and was associated with significantly reduced lymphatic complication rates compared with LND. Therefore, SLN biopsy can be recommended for patients with endometrial cancer without definitive preoperative evidence of distant metastasis. [ABSTRACT FROM AUTHOR]

Aim: Minimally invasive surgery (MIS) has been introduced as an alternative to more radical surgical procedures. The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy conducted a cross‐sectional questionnaire survey to ascertain the status of MIS for endometrial cancer. Methods: The survey was conducted between May 10 and June 30, 2022. The questionnaire included information on personal attributes, academic affiliations, qualifications, hysterectomies, and intraoperative procedures performed. Results: The total number of questionnaire respondents was 436 (9.2% of the membership). The hysterectomy methods and percentage performed were as follows: simple total hysterectomy (equivalent to benign surgery), 3%; simple total hysterectomy with care to avoid shaving the cervix, 31%; extended total hysterectomy, 48%; and modified radical hysterectomy, 15%. An analysis of hysterectomies performed using MIS for endometrial cancer by qualified gynecologists of endoscopy or board‐certified gynecologic oncologists showed a tendency not to choose simple total hysterectomy compared to the gynecologists who did not hold certification (p = 0.019, p = 0.045, and p = 0.010, respectively). Additionally, 67% of respondents did not use uterine manipulators, and 59% of the respondents did not perform lymph node dissection following the guidelines for treating endometrial cancer in Japan. Conclusion: This study provided the current status of MIS for endometrial cancer in Japan. The hysterectomy method, use of uterine manipulators, and criteria for omitting lymph node dissection were generally in agreement with the guidelines. Currently, an extra‐fascial simple hysterectomy, including at least not shaving the cervix, was a major method for early invasive endometrial cancer using MIS. [ABSTRACT FROM AUTHOR]

Endometrial cancer is one of the most widely known gynaecological malignancies that lacks a prognostic prediction model. This study aimed to develop a nomogram to predict progression-free survival (PFS) in patients with endometrial cancer. Information for endometrial cancer patients diagnosed and treated from 1 January 2005 to 30 June 2018 was collected. The Kaplan–Meier survival analysis and multivariate Cox regression analysis were carried out to determine the independent risk factors and a nomogram was constructed by R based on analytical factors. Internal and external validation were then carried out to predict the probability of 3- and 5-year PFS. In total, 1020 patients with endometrial cancer were included in the study and the relationship between 25 factors and prognosis was analysed. Postmenopause (hazard ratio = 2.476, 95% confidence interval 1.023–5.994), lymph node metastasis (hazard ratio = 6.242, 95% confidence interval 2.815–13.843), lymphovascular space invasion (hazard ratio = 4.263, 95% confidence interval 1.802–10.087), histological type (hazard ratio = 2.713, 95% confidence interval 1.374–5.356), histological differentiation (hazard ratio = 2.601, 95% confidence interval 1.141–5.927) and parametrial involvement (hazard ratio = 3.596, 95% confidence interval 1.622–7.973) were found to be independent prognostic risk factors; these factors were selected to establish a nomogram. The consistency index for 3-year PFS were 0.88 (95% confidence interval 0.81–0.95) in the training cohort and 0.93 (95% confidence interval 0.87–0.99) in the verification set. The areas under the receiver operating characteristic curve for the 3- and 5-year PFS predictions are 0.891 and 0.842 in the training set; the same conclusion also appeared in the verification set [0.835 (3-year), 0.803(5-year)]. This study established a prognostic nomogram for endometrial cancer that provides a more individualised and accurate estimation of PFS for patients, which will help physicians make follow-up strategies and risk stratification. • A retrospective study included 1020 EC patients and 25 prognostic factors. • A nomogram to predict 3-year and 5-year PFS in patients with EC. • The AUC of nomogram＞0.8 in the training set and verification set. [ABSTRACT FROM AUTHOR]

Muir–Torre syndrome (MTS) is a rare subtype of hereditary nonpolyposis colorectal cancer syndrome caused by a defect in DNA mismatch repair leading to microsatellite instability. It is characterized by the presence of at least one sebaceous gland tumor and one internal malignancy, most commonly colorectal and endometrial tumors. These patients have a high propensity for tumorigenesis, and while strict screening protocols are in place, there are only two cases that describe the management approach to recurrent colon cancer. Here, we present a case of recurrent colorectal cancer in a patient with MTS, and describe how it was managed at our facility by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Background: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. Methods: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). Results: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3–5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. Conclusion: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. Trial registration: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139). [ABSTRACT FROM AUTHOR]

Organoids are three-dimensional cellular models cultured in vitro that retain the histological, physiological, and genetic characteristics of original tissues in vivo. They have the advantages of short culture time and high proliferative efficiency. In recent years, organoids have been widely applied in the field of life sciences, particularly in the endometrial research. By overcoming the limitations of conventional cell and animal models, organoids provide a more accurate simulation of the cyclic physiological changes of the endometrium and the characteristics of embryo implantation. Additionally, they show significant potential in disease modeling, precision medicine, drug screening for endometrium -related diseases such as endometriosis, endometrial tumors, and infertility. This review summarizes the progress in the application of organoids in translational research of basic endometrial and related diseases. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between ProMisE molecular typing and lymph node metastasis and other clinical features in endometrial cancer. Methods: 74 patients with endometrial cancer who underwent surgical treatment at Cancer Hospital Affiliated of Dalian University of Technology from December 2014 to December 2018 were selected. Clinical data were collected and molecular typing was performed using the ProMisE method. The clinical characteristics of patients with different subtypes were compared, and the influencing factors of lymph node metastasis in endometrial cancer were analyzed. Results: Among 74 patients with endometrial carcinoma, 20 patients (27.0%) were mismatch repair defective, 2 patients (2.7%) were POLE mutant, 34 patients (46.0%) were p53 wild-type, and 18 patients (24.3%) were p53 mutated. There were statistically significant differences in lymph node metastasis (P=0.004), clinical stage (P=0.018), and pathological grading (P=0.036) among the four molecular subtypes of patients. Binary Logistic regression analysis revealed that p53 mutated (OR=27.669, 95%CI: 3.224-237.480, P=0.002) and muscle infiltration≥1/2 (OR=22.046, 95%CI: 4.185-116.146, P＜0.001) as risk factors for lymph node metastasis. Conclusions: Molecular typing can provide an important reference for preoperative decision-making, that is, ProMisE molecular typing is performed on preoperative diagnostic uterine curettage specimens. If p53 mutant is found, the risk of lymph node metastasis is high and may need to be expanded intraoperatively. [ABSTRACT FROM AUTHOR]