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Endometrial carcinoma (EC) risk stratification prior to surgery is crucial for clinical treatment. In this study, we intend to evaluate the predictive value of radiomics models based on magnetic resonance imaging (MRI) for risk stratification and staging of early-stage EC. The study included 155 patients who underwent MRI examinations prior to surgery and were pathologically diagnosed with early-stage EC between January, 2020, and September, 2022. Three-dimensional radiomics features were extracted from segmented tumor images captured by MRI scans (including T2WI, CE-T1WI delayed phase, and ADC), with 1521 features extracted from each of the three modalities. Then, using five-fold cross-validation and a multilayer perceptron algorithm, these features were filtered using Pearson's correlation coefficient to develop a prediction model for risk stratification and staging of EC. The performance of each model was assessed by analyzing ROC curves and calculating the AUC, accuracy, sensitivity, and specificity. In terms of risk stratification, the CE-T1 sequence demonstrated the highest predictive accuracy of 0.858 ± 0.025 and an AUC of 0.878 ± 0.042 among the three sequences. However, combining all three sequences resulted in enhanced predictive accuracy, reaching 0.881 ± 0.040, with a corresponding increase in the AUC to 0.862 ± 0.069. In the context of staging, the utilization of a combination involving T2WI with CE-T1WI led to a notably elevated predictive accuracy of 0.956 ± 0.020, surpassing the accuracy achieved when employing any singular feature. Correspondingly, the AUC was 0.979 ± 0.022. When incorporating all three sequences concurrently, the predictive accuracy reached 0.956 ± 0.000, accompanied by an AUC of 0.986 ± 0.007. It is noteworthy that this level of accuracy surpassed that of the radiologist, which stood at 0.832. The MRI radiomics model has the potential to accurately predict the risk stratification and early staging of EC. [ABSTRACT FROM AUTHOR]

Fully supervised medical image segmentation methods use pixel-level labels to achieve good results, but obtaining such large-scale, high-quality labels is cumbersome and time consuming. This study aimed to develop a weakly supervised model that only used image-level labels to achieve automatic segmentation of four types of uterine lesions and three types of normal tissues on magnetic resonance images. The MRI data of the patients were retrospectively collected from the database of our institution, and the T2-weighted sequence images were selected and only image-level annotations were made. The proposed two-stage model can be divided into four sequential parts: the pixel correlation module, the class re-activation map module, the inter-pixel relation network module, and the Deeplab v3 + module. The dice similarity coefficient (DSC), the Hausdorff distance (HD), and the average symmetric surface distance (ASSD) were employed to evaluate the performance of the model. The original dataset consisted of 85,730 images from 316 patients with four different types of lesions (i.e., endometrial cancer, uterine leiomyoma, endometrial polyps, and atypical hyperplasia of endometrium). A total number of 196, 57, and 63 patients were randomly selected for model training, validation, and testing. After being trained from scratch, the proposed model showed a good segmentation performance with an average DSC of 83.5%, HD of 29.3 mm, and ASSD of 8.83 mm, respectively. As far as the weakly supervised methods using only image-level labels are concerned, the performance of the proposed model is equivalent to the state-of-the-art weakly supervised methods. [ABSTRACT FROM AUTHOR]

This meta‐analysis aimed to compare laparoscopic hysterectomy (LH) and open hysterectomy (OH) in terms of surgical site wound infection, length of hospital stay, and postoperative complications in patients with endometrial cancer (EC). PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang databases were comprehensively searched for studies on OH and LH for EC published between 2008 and July 2023, in any language. The literature was screened according to the inclusion and exclusion criteria, and the quality of the included case–control studies was assessed using the Newcastle‐Ottawa Scale. Data were collated and analysed using Stata 17.0 software. A total of 1245 articles were screened according to the search strategy, and ultimately 15 studies were included in this meta‐analysis, with a total of 1606 patients with EC, of which 751 were treated with LH and 855 with OH. The results showed that the rate of postoperative wound infection was significantly higher (OR: 0.290; 95% CI: 0.169–0.496, p < 0.001), the length of hospital stay was significantly longer (SMD: −1.976, 95% CI: −2.669 to −1.283, p < 0.001), and the incidence of postoperative complications was significantly higher (OR: 0.366; 95% CI: 0.280–0.478, p < 0.001) in the OH group than in the LH group. This study showed that LH was superior to OH for the treatment of EC and is associated with a lower rate of wound infection, shorter length of hospitalisation, and a reduced risk of complications. Thus, our findings support the choice of LH over OH for EC. [ABSTRACT FROM AUTHOR]

Surgical Site Infection (SSI) is one of the common postoperative complications after hysterectomy for endometrial cancer (EC). Previous studies have investigated the risk factors for SSI in patients with EC. However, big differences in research results exist, and the correlation coefficients of different research results are quite different. A meta‐analysis was conducted to examine the risk factors related to SSI in patients with EC. We searched English databases to collect case–control studies or cohort studies published before July 20, 2023, including PubMed, Web of Science, Embase and ScienceDirect. The risk of bias in the included studies was assessed via Newcastle–Ottawa Scale. The analysis was performed using RevMan 5.4.1 tool. A total of 6 articles (n = 3647) were selected in this meta‐analysis. The following risk factors were presented to be significantly correlated with SSI in EC: laparotomy (OR = 2.66, 95% CI [1.57, 4.54]), postoperative blood sugar ≥10 mmol/L (OR = 4.38, 95% CI [2.83, 6.78]), Federation International of Gynaecology and Obstetrics (FIGO) stage‐III or IV (OR = 2.27, 95% CI [1.49, 3.46]). The occurrence of SSI is influenced by a variety of factors. Thus, we should pay close attention to high‐risk subjects and take crucial targeted interventions to lower the SSI risk after hysterectomy. Owing to the limited quality and quantity of the included studies, more rigorous studies with adequate sample sizes are needed to verify the conclusion. [ABSTRACT FROM AUTHOR]

Simple Summary: Optimum risk stratification in the early stages of endometrial cancer combines molecular and clinicopathological features. The purpose of the study was to determine the prognostic value of molecular classification and traditional pathological factors in a sample group of patients with stage I endometrial cancer according to the FIGO 2023 criteria to achieve a more personalized approach to patient care and treatment. The immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain and clinicopathological parameters, including outcomes in 139 patients, were analyzed. Our research studies confirm that molecular category corresponds to a different prognosis in clinical stage I EC according to the new 2023 FIGO classification, with POLEmut cases presenting the best outcomes and p53abn cases showing the worst outcomes. Beyond the previous routine clinicopathological assessment, the new EC staging system represents an important step toward improving our ability to stratify IC stage EC risk. Optimum risk stratification in an early stage of endometrial cancer (EC) combines molecular and clinicopathological features. The purpose of the study was to determine the prognostic value of molecular classification and traditional pathological factors in a sample group of patients with stage I EC according to the FIGO 2023 criteria, to achieve a more personalized approach to patient care and treatment. The immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain and clinicopathological parameters, including disease disease-free survival (DFS) and overall survival (OS) in 139 patients, were analyzed. It has been shown that the independent recurrence risk factors are stage IC (p < 0.001), aggressive histological types EC (p < 0.001), and the presence of p53abn protein immunoexpression (p = 0.009). Stage IC (p = 0.018), aggressive histological types EC (p = 0.025) and the presence of p53abn protein immunoexpression (p = 0.010) were all significantly associated with lower 5-year OS rates. Our research studies confirm that the molecular category corresponds to a different prognosis in clinical stage I EC according to the new 2023 FIGO classification, with POLEmut cases presenting the best outcomes and p53abn cases showing the worst outcomes. Beyond the previous routine clinicopathological assessment, the new EC staging system represents an important step toward improving our ability to stratify IC stage EC risk. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to describe the current state of the art in the field of immunotherapy applied to patients with cancer-harboring microsatellite instability, giving a comprehensive landscape of the possible therapeutical strategies in these patients. We discuss the potential of combination strategies and novel therapeutic approaches that may change the management of microsatellite-instable cancer in the future. High microsatellite instability (MSI-H) derives from genomic hypermutability due to deficient mismatch repair function. Colorectal (CRC) and endometrial cancers (EC) are the tumor types that more often present MSI-H. Anti-PD(L)-1 antibodies have been demonstrated to be agnostically effective in patients with MSI-H cancer, but 50–60% of them do not respond to single-agent treatment, highlighting the necessity of expanding their treatment opportunities. Ipilimumab (anti-CTLA4) is the only immune checkpoint inhibitor (ICI) non-targeting PD(L)-1 that has been approved so far by the FDA for MSI-H cancer, namely, CRC in combination with nivolumab. Anti-TIM3 antibody LY3321367 showed interesting clinical activity in combination with anti-PDL-1 antibody in patients with MSI-H cancer not previously treated with anti-PD(L)-1. In contrast, no clinical evidence is available for anti-LAG3, anti-TIGIT, anti-BTLA, anti-ICOS and anti-IDO1 antibodies in MSI-H cancers, but clinical trials are ongoing. Other immunotherapeutic strategies under study for MSI-H cancers include vaccines, systemic immunomodulators, STING agonists, PKM2 activators, T-cell immunotherapy, LAIR-1 immunosuppression reversal, IL5 superagonists, oncolytic viruses and IL12 partial agonists. In conclusion, several combination therapies of ICIs and novel strategies are emerging and may revolutionize the treatment paradigm of MSI-H patients in the future. A huge effort will be necessary to find reliable immune biomarkers to personalize therapeutical decisions. [ABSTRACT FROM AUTHOR]

Background: Women in Africa are experiencing a rising burden of endometrial cancer. Research and investment to improve treatment and outcomes are critically needed. We systematically reviewed and characterized endometrial cancer-related research within a clinically relevant context to help organize and assess existing endometrial cancer research in Africa. Methods: According to PRISMA guidelines, we searched online databases for published endometrial cancer articles from African countries from January 1, 2011, to July 20, 2021. Based on our inclusion and exclusion criteria, independent reviewers documented the study design, country/region, human development index, focus of research, type of interventions performed, and histologic and molecular type to illustrate the breadth of research coverage in each region. Results: A total of 18 research articles were included. With an average Human Development Index (HDI) in Africa of 0.536, the average HDI of the represented countries in this study was 0.709. The majority (88.9%) of prospective endometrial cancer research articles in Africa were from North Africa, with Egypt encompassing 83.3% of the papers. Most of these studies focused on endometrial cancer diagnosis. Research on the treatment of endometrial cancer is still emerging (33% of papers). Of all included articles, only 11.1% represented Sub-Saharan Africa, where the majority population of black Africans reside. Conclusions: Endometrial cancer research in Africa is extremely limited, with the majority being concentrated in African countries with higher HDIs. As the incidence of endometrial cancer rises in Sub-Saharan Africa, there is a pressing need for more prospective clinical research to tackle the growing disease burden and improve outcomes. [ABSTRACT FROM AUTHOR]

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener. [ABSTRACT FROM AUTHOR]

Background: Threonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear. Methods: The expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues. K-M survival analysis was also conducted to evaluate the impact of TTK on survival outcomes. Protein‒protein interaction (PPI) networks associated with TTK were explored using the STRING database. Functional enrichment analysis was performed to elucidate the biological functions of TTK. TTK mRNA expression and immune infiltration correlations were examined using the Tumor Immune Estimation Resource (TIMER) and the Tumor-Immune System Interaction Database (TISIDB). Results: TTK expression was significantly greater in EC tissues than in adjacent normal tissues. Higher TTK mRNA expression was associated with tumor metastasis and advanced TNM stage. The protein and mRNA expression of TTK was significantly greater in tumor cell lines than in normal endometrial cell lines. ROC curve analysis revealed high accuracy (94.862%), sensitivity (95.652%), and specificity (94.894%) of TTK in differentiating EC from normal tissues. K-M survival analysis demonstrated that patients with high TTK expression had worse overall survival (OS) and disease-free survival (DFS) rates. Correlation analysis revealed that TTK mRNA expression was correlated with B cells and neutrophils. Conclusion: TTK upregulation is significantly associated with poor survival outcomes and immune infiltration in patients with EC. TTK can serve as a potential biomarker for poor prognosis and a promising immunotherapy target in EC. Further investigation of the role of TTK in EC may provide valuable insights for therapeutic interventions and personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Endometrial stromal tumors (ESTs) are rare subset of mesenchymal uterine neoplasms. There are heterogeneous morphological, immunohistochemical, and genetic features. Approximately 50% of ESTs occur in perimenopausal women. In 2020, WHO sub-categorized ESTs into four groups: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS), and undifferentiated uterine sarcoma (UUS). Objective: To review the morphological spectrum of endometrial stromal tumors. Method: This retrospective study reviewed the histomorphological features of 15 endometrial stromal tumors with respect to atypia, necrosis, mitosis, collagen bands, whorling around vessels, myometrial invasion, and inflammatory cells. Immunohistochemistry markers (CD10, SMA, and ER) along with special stains (Masson's trichrome, toluidine blue) were also studied. Results: The age of the patients ranged from 32 to 60 years. Three patients were postmenopausal. The most common presenting symptom was vaginal bleeding. Five patients were operated with a clinical diagnosis of uterine fibroid. One patient presented with prolapse with no other complaint. All the 15 patients had total abdominal hysterectomy and salpingo-oophorectomy. One case showed necrosis, eight cases showed collagen bands, all the 15 cases showed whorling around vessels, one case showed vascular emboli, and seven cases showed inflammatory cells. In low-grade cases, one case showed focal atypia and one case showed focal coagulative necrosis indicating infarction. Thirteen cases were LGESS, and one case of ESN and HGESS. All cases were positive for ER and CD10. Conclusion: Endometrial stromal tumors demonstrate extensive permeation of the myometrium as irregular islands with frequent vascular invasion, whorling around vessels, collagen bands, and inflammatory cells. All these features should be observed thoroughly on microscopy by pathologists to clearly differentiate the low-grade and high-grade endometrial stromal tumors, and to understand the overlapping gray areas morphologically as it affects the prognosis of the patient. [ABSTRACT FROM AUTHOR]

OBJECTIVE We aimed to determine the effect of a Foley catheter on bladder fullness and the changes in the doses received by other critical organs (OAR) and target volumes during high-dose rate vaginal cuff brachytherapy (HDR-VBT) with an empty bladder. METHODS Twenty patients with a diagnosis of endometrial or cervical cancer underwent post-operative three-dimensional HDR-VBT between January 2020 and May 2021 and were examined dosimetrically. After the evacuation of the urine, two simulation CT scans and plans were performed with and without inserting a Foley catheter. For both plans, the volumes and doses of HRCTV and each critical organ were recorded separately. RESULTS The median age of the patients was 60 years (35-79). HDR-VBT was applied to 16 patients with endometrial cancer and 4 patients with cervical cancer diagnosis. Median 50.4 Gy (45-50.4 Gy) external RT was administered to 12 patients with a total of 15 Gy BRT boost in 3 fractions. A total of 27.5 Gy HDR-VBT in 5 fractions were administered to 8 endometrial cancer patients. No significant difference was found regarding target and critical organ volumes between the two plans with or without a Foley catheter. Also, no statistically significant difference was detected in terms of target doses such as D90, D95, and D98 of HRCTV and D0.1, D1, D2cc, and mean doses of critical organs. CONCLUSION It seems simulating and treating the patient by just emptying the urine and using the decay and treat method is sufficient in terms of OAR and HRCTV dose limits. [ABSTRACT FROM AUTHOR]

Aim: Minimally invasive surgeries for endometrial cancer are increasing worldwide. In Japan, some articles have examined surgical outcomes, but only a few have addressed oncological outcomes. This study aims to compare robot surgery, laparoscopic surgery, and laparotomy in terms of surgical and oncological outcomes within a low‐risk group for endometrial cancer recurrence. Methods: This study included patients with endometrial cancer deemed to be at low risk of recurrence and who underwent surgery between January 2011 and December 2020. We studied 99 patients who underwent robot surgery, 85 patients who underwent laparotomy, and 77 patients who underwent laparoscopic surgery. Surgical and oncological outcomes were compared retrospectively for these groups of patients. Results: The median follow‐up period was 47, 61, and 60 months in the laparotomy, laparoscopy, and robotic groups, respectively. The three groups had similar perioperative and pathological data. No significant differences in overall survival and disease‐free survival were observed among the groups. Univariate and multivariate analyses conducted on the overall study population for disease‐free survival and overall survival showed that the surgical approach did not have any influence. Minimally invasive surgery groups had longer operating times compared to the laparotomy group, but they had significantly less blood loss. The number of resected pelvic lymph nodes was similar, and the complication rate was not significant. Conclusions: Robot‐assisted surgery and laparoscopic surgery were found to be less invasive and showed similar oncologic outcomes compared to laparotomy surgery for endometrial cancer in patients with a low risk of recurrence. [ABSTRACT FROM AUTHOR]

Nodal status is one of the most important prognostic factors for patients with apparent early stage endometrial cancer. The role of retroperitoneal staging in endometrial cancer is controversial. Nodal status provides useful prognostic data, and allows to tailor the need of postoperative treatments. However, two independent randomized trials showed that the execution of (pelvic) lymphadenectomy increases the risk of having surgery-related complication without improving patients' outcomes. Sentinel node mapping aims to achieve data regarding nodal status without increasing morbidity. Sentinel node mapping is the removal of first (clinically negative) lymph nodes draining the uterus. Several studies suggested that sentinel node mapping is not inferior to lymphadenectomy in identifying patients with nodal disease. More importantly, thorough ultrastaging sentinel node mapping allows the detection of low volume disease (micrometastases and isolated tumor cells), that are not always detectable via conventional pathological examination. Therefore, the adoption of sentinel node mapping guarantees a higher identification of patients with nodal disease than lymphadenectomy. Further evidence is needed to assess the value of various adjuvant strategies in patients with low volume disease and to tailor those treatments also on the basis of the molecular and genomic characterization of endometrial tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer, the most common gynecological malignancy in developed countries, poses a growing challenge with rising incidence and mortality rates. This review explores how metabolomic technology can offer valuable insights into the molecular aspects of the disease. By identifying new possible metabolite biomarkers, it has the potential to improve the accuracy of diagnosis, prognosis, and monitoring, thereby revolutionizing the management of endometrial cancer. Endometrial cancer, the most prevalent gynecological malignancy in developed countries, is experiencing a sustained rise in both its incidence and mortality rates, primarily attributed to extended life expectancy and lifestyle factors. Currently, the absence of precise diagnostic tools hampers the effective management of the expanding population of women at risk of developing this disease. Furthermore, patients diagnosed with endometrial cancer require precise risk stratification to align with optimal treatment planning. Metabolomics technology offers a unique insight into the molecular landscape of endometrial cancer, providing a promising approach to address these unmet needs. This comprehensive literature review initiates with an overview of metabolomic technologies and their intrinsic workflow components, aiming to establish a fundamental understanding for the readers. Subsequently, a detailed exploration of the existing body of research is undertaken with the objective of identifying metabolite biomarkers capable of enhancing current strategies for endometrial cancer diagnosis, prognosis, and recurrence monitoring. Metabolomics holds vast potential to revolutionize the management of endometrial cancer by providing accuracy and valuable insights into crucial aspects. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper delves into the issue of metastatic endometrial cancer (EC), which significantly impacts treatment success and overall survival rates. The study explores various factors contributing to metastasis, including the molecular profile of EC, hormone activity (like estrogen and prolactin), and pro-inflammatory adipocytokines. It also investigates how altered microRNA expression affects gene regulation linked to the dissemination of the cancer. The paper highlights the importance of imaging techniques, particularly transvaginal ultrasound with tumor-free distance (uTFD), in detecting metastases. Additionally, it discusses how diagnostic and therapeutic methods can influence the spread of EC, with hysteroscopy potentially increasing risk in advanced stages and laparoscopic hysterectomy being safer if performed with care. This research could improve our understanding of EC and guide better diagnostic and treatment strategies. The presence of metastatic endometrial cancer (EC) is a key problem in treatment failure associated with reduced overall survival rates. The most common metastatic location is the pelvic lymph nodes, and the least common is the brain. The presence of metastasis depends on many factors, including the molecular profile of cancer (according to the TCGA—Genome Atlas), the activity of certain hormones (estrogen, prolactin), and pro-inflammatory adipocytokines. Additionally, an altered expression of microRNAs affecting the regulation of numerous genes is also related to the spread of cancer. This paper also discusses the value of imaging methods in detecting metastases; the primary role is attributed to the standard transvaginal USG with the tumor-free distance (uTFD) option. The influence of diagnostic and therapeutic methods on EC spread is also described. Hysteroscopy, according to the analysis discussed above, may increase the risk of metastases through a fluid medium, mainly performed in advanced stages of EC. According to another analysis, laparoscopic hysterectomy performed with particular attention to avoiding risky procedures (trocar flushing, tissue traumatization, preserving a margin of normal tissue) was not found to increase the risk of EC dissemination. [ABSTRACT FROM AUTHOR]

Simple Summary: The rate of concurrent endometrial cancer (EC) in women with atypical endometrial hyperplasia (AEH) is not negligible. Furthermore, among women with EC, about 12% may have a high-risk disease requiring lymph node status assessment. Given that endometrial sampling cannot exclude EC in women with AEH, knowing variables that increase the risk of malignancy can be helpful in clinical practice. Some patient characteristics were associated with this occurrence, representing possible risk factors on which to adjust treatment planning. No prediction models with internal validation showed the impact of patient characteristics in predicting EC after a preoperative diagnosis of AEH. The present study, using regressions and artificial neural networks, found recurrent patient characteristics in women with EC. However, they likely do not contain good/optimal discriminating information. Future predictive models should include other individual factors (e.g., genotypic variables) to move toward more personalized medicine. Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable. [ABSTRACT FROM AUTHOR]

Simple Summary: This study comprehensively investigated the genomic landscape of >3000 gynecological malignancies (endometrial, cervical, and ovarian cancers) in Japan. The Center for Cancer Genomics and Advanced Therapeutics database used in this study is a useful tool containing real-world data of patients with poor prognoses, as comprehensive genomic profiling tests are limited to patients with cancer who have completed standardized treatments in Japan. Genomic profiling based on histological subtypes, tumor mutational burden, and microsatellite instability highlights actionable mutations for future drug development for each gynecological cancer. This study aimed to comprehensively clarify the genomic landscape and its association with tumor mutational burden-high (TMB-H, ≥10 mut/Mb) and microsatellite instability-high (MSI-H) in endometrial, cervical, and ovarian cancers. We obtained genomic datasets of a comprehensive genomic profiling test, FoundationOne® CDx, with clinical information using the "Center for Cancer Genomics and Advanced Therapeutics" (C-CAT) database in Japan. Patients can undergo the tests only after standardized treatments under universal health insurance coverage. Endometrial cancers were characterized by a high frequency of TMB-H and MSI-H, especially in endometrioid carcinomas. The lower ratio of POLE exonuclease mutations and the higher ratio of TP53 mutations compared to previous reports suggested the prognostic effects of the molecular subtypes. Among the 839 cervical cancer samples, frequent mutations of KRAS, TP53, PIK3CA, STK11, CDKN2A, and ERBB2 were observed in adenocarcinomas, whereas the ratio of TMB-H was significantly higher in squamous cell carcinomas. Among the 1606 ovarian cancer samples, genomic profiling of serous, clear cell, endometrioid, and mucinous carcinomas was characterized. Pathogenic mutations in the POLE exonuclease domain were associated with high TMB, and the mutation ratio was low in both cervical and ovarian cancers. The C-CAT database is useful for determining the mutational landscape of each cancer type and histological subtype. As the dataset is exclusively collected from patients after the standardized treatments, the information on "druggable" alterations highlights the unmet needs for drug development in major gynecological cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Sentinel lymph node (SLN) mapping has been introduced to endometrial cancer treatment as an alternative to lymph node dissection for lymph node staging. Lymphovascular space invasion (LVSI) is a known prognostic risk factor in endometrial cancer and is associated with lymph node metastasis and worse outcomes. This study shows that LVSI is an independent predictor of recurrence in node-negative endometrial cancer patients with SLN mapping alone. The negative predictive value of sentinel lymph node mapping is significantly lower in LVSI-positive endometrial cancer patients. Due to these findings, importance should be attached to LVSI in early-stage endometrial cancer patients with negative SLN mapping, and adjuvant therapy should be discussed more thoroughly in these cases. Background: SLN mapping has emerged as a standard of care in endometrial cancer due to its high sensitivity and significant reduction in morbidity. Although lymphovascular space invasion (LVSI) is a known risk factor for lymph node metastasis and recurrence, evidence on the reliability of SLN mapping in LVSI-positive patients is scarce. The aim of this study was to determine the impact of LVSI on the diagnostic performance of SLN mapping. Methods: This retrospective cohort study included patients with endometrial cancer who underwent primary surgical treatment at the Bern University Hospital, Switzerland, between 2012 and 2022. Results: LVSI was present in 22% of patients and was significantly associated with lymph node metastasis (p < 0.001) and recurrence (p < 0.001). In node-negative patients with only SLN mapping performed, LVSI was an independent predictor of recurrence during multivariable Cox regression analysis (p = 0.036). The negative predictive value of SLN mapping was 91.5% and was significantly lower in tumors with LVSI (75.0%) compared to LVSI-negative tumors (95.6%, p = 0.004). Conclusion: The presence of LVSI was significantly associated with worse oncological outcomes. LVSI was an independent predictor of recurrence in node-negative patients with only SLN mapping performed. Furthermore, the negative predictive value of SLN mapping was significantly lower in LVSI-positive 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]

Introduction: Endometrial stromal sarcoma (ESS) is a rare tumor that remains a diagnostic and therapeutic challenge to physicians worldwide. The metastatic setting implies a poor prognosis, with a 5-year survival rate below 40%. Patients with advanced-stage high-grade ESS (HG-ESS) have limited therapeutic options, often involving various chemotherapy regimens. Case Presentation: This report depicts the case of a 47-year-old female diagnosed with HG-ESS. She underwent several lines of treatment starting with radiotherapy and brachytherapy, followed by multiple lines of treatment including trabectedin over several months. After retreatment with trabectedin and achieving disease stabilization for 10 months, treatment was optimized by trabectedin combined with radiotherapy, leading to stable disease that is still ongoing and lasts for over 17 months. Conclusion: Our case underscores the challenging nature of treating patients with HG-ESS and highlights the safety of long-term retrial with trabectedin, coupled with radiotherapy administration. This approach maintained a durable stable disease response in the metastatic setting. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA‐binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region. In addition, in vivo and in vitro experiments showed that MT inhibited the proliferation and metastasis of EC cells by upregulating GATA2 expression. The protein kinase B (AKT) pathway was also affected. In conclusion, these findings suggest that MT and GATA2 play significant roles in EC development. [ABSTRACT FROM AUTHOR]

* Context.--Clinical management of endometrial carcinoma largely depends on the morphologic parameters ascertained based on the pathologic evaluation of surgical resection specimens. However, there are numerous controversial and nonstandardized aspects of both the macroscopic and microscopic assessment of surgical specimens, including grossing, adequate sampling, diagnosis, staging, reporting, and ancillary testing. Objective.--To provide a comprehensive practical review of standardized grossing, key morphologic findings for reporting and staging, and diagnostic and prognostic use of ancillary testing in endometrial carcinomas. Data Sources.--The existing literature, recommendations of the International Society of Gynecological Pathologists, and specialty consensus guidelines. Conclusions.--This review article summarizes important aspects of the grossing and sampling of surgical resection specimens for microscopic examination, key morphologic parameters that are required for reporting and staging, and morphologic features and immunoprofiles helpful in the differential diagnosis of low-grade and high-grade endometrial carcinomas, as well as the current status of the molecular classification of endometrial carcinoma and human epidermal growth factor receptor 2 testing in serous carcinoma. The information presented herein can be helpful in overcoming diagnostic challenges and issues related to the pathology reporting of endometrial carcinoma to practicing anatomic pathologists. [ABSTRACT FROM AUTHOR]

Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or antitumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1fl/flp53fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1fl/flp53fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer. [ABSTRACT FROM AUTHOR]

Introduction: Complete blood count parameters are associated with the inflammatory process in the diagnosis and prognosis of several types of cancer; thus, they have been studied as markers. In this study, the preoperative complete blood count parameters in patients with and without endometrioid type endometrial cancer were evaluated and the relationship of these biomarkers with prognostic factors in the cancer group was investigated. Methods: This study is retrospective in design. All the patients with endometrial cancer were of the endometrioid type. The cancer group involved 94 pathologically confirmed cases, and the control group comprised 96 women diagnosed with dysfunctional uterine bleeding with no signs of organic gynecological pathology. The clinicopathological features and preoperative complete blood count results of all the patients were evaluated. Results: In comparison with the controls (p<0.05), in the cancer group, hemoglobin, leucocyte, and platelet measurements were higher, whereas lymphocytes, monocytes, and mean platelet volume were lower. When subjects with endometrial cancer performed self-evaluation, the monocyte/lymphocyte ratio was higher in cases with lymph node metastasis in comparison with early-stage cases (p=0.006). Age was the only consistent factor in predictive of prognostic factors such as myometrial invasion depth, lymph node metastases, advanced stage, and grade. Discussion and Conclusion: Complete blood count parameters can be simple, readily available, and low-cost markers in endometrial cancer. Moreover, increasing monocyte/lymphocyte ratios may help predict an advanced disease. Nevertheless, to determine the actual predictive potential of these biomarkers, molecular studies that precisely examine the expression of secretory factors (cytokine/interleukin secretion of lymphocytes/macrophages, immunoglobulin secretion of plasma cells) are required. [ABSTRACT FROM AUTHOR]

Objective: To compare hysteroscopic morcellation with hysteroscopic scissors for endometrial polypectomy in terms of operating time, the need for cervical dilatation, blood loss, complications, and completeness of removal. Methods: Medical records of patients who underwent hysteroscopic polypectomy using either the Intrauterine BIGATTI Shaver (IBS) system or hysteroscopic scissors between January 2020 and August 2022 at the United Christian Hospital or Tseung Kwan O Hospital were retrospectively reviewed. Results: A total of 1063 women were operated on using the IBS (n=132) or hysteroscopic scissors (n=931). More patients in the IBS group required general/spinal anaesthesia (97.7% vs 71.1%, p<0.001) and cervical dilatation (77.3% vs 30.1%, p<0.001). The operating time was shorter in the IBS group when removing one polyp (18.6 vs 20.0 min, p=0.049) and when performed by trainees independently (17.9 vs 19.8 min, p=0.007) but was longer when performed by specialists (22.7 vs 19.7 min, p<0.001). All patients in the IBS group achieved complete removal of polyps, compared with five patients with incomplete removal of polyps in the scissors group. Conclusion: Compared with hysteroscopic scissors, hysteroscopic morcellation requires less operating time when removing one polyp and when performed by trainees independently and is more effective in achieving complete removal, but the need for cervical dilatation and anaesthesia is more for hysteroscopic morcellation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Our aim in this study is to examine the relationship of hemoglobin A1c (HbA1c) and fasting glucose with the stage, grade, and histological type of cancer and its value in predicting the prognosis of endometrial cancer in diabetic endometrial cancer patients. STUDY DESIGN: The data of 138 endometrial cancer patients with diabetes who met the study criteria were analyzed. Hemoglobin A1c levels and fasting glucose were compared with cancer stage, grade, histological type, lymphovascular invasion, chemotherapy, and radiotherapy data. RESULTS: A statistically significant difference was found between the groups in terms of HbA1c values only according to the lymphovascular invasion (p=0.02). While there was no significant correlation between endometrial thickness and HbA1c, a low positive correlation was found between the fasting glucose value (r=0.191, p=0.025) CONCLUSIONS: The higher rate of lymphovascular invasion in patients with high HbA1c values alone is insufficient in determining the prognosis when other parameters are considered. [ABSTRACT FROM AUTHOR]

Background Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. Materials and Methods In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Results As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Conclusion Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications. Clinicaltrials.gov ID NCT03517449 [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of a multidisciplinary team (MDT) approach on outcomes with endometrial cancer (EC) patients, utilizing 2013–2020 data from the Reggio Emilia Cancer Registry. Recurrence rate, treatments, and outcome indicators were compared between the MDT (319 cases) and non-MDT (324 cases) groups. Among 643 cases, 52.4% were over 65 years old, 98% had microscopic confirmation, and 73% were in stage I. Surgery was performed in 89%, with 41% receiving adjuvant therapies. Recurrence rates (10%) were similar between the two groups, but MDT patients who were older and predominantly in stage I exhibited 79% recurrence within one year (21% in the non-MDT group). Disease-free survival (DFS) showed no significant difference [HR 1.1; 95% CI 0.7–1.6], while differences in overall survival (OS) were notable [HR 1.5; 95% CI 1.0–2.4]. The 5-year OS rates were 87% and 79% in the MDT and non-MDT groups. Comparing the 2013–2015 to 2016–2020 study periods, a shift towards caring for older women, more advanced-stage patients, and those residing outside the metropolitan area, along with a greater number of relapsed cases (from 16% to 76%), were accounted for. These findings underscore the impact of an MDT on EC outcomes, highlighting the evolving patient demographics over time. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study of 419 patients with endometrial cancer, we looked at two ways of checking the spread of the disease: one called 'sentinel lymph node biopsy' (SLNB) and the other, a more traditional method called 'lymph node dissection' (LND). We followed these patients for about 5.5 years. We found that both methods had similar outcomes in terms of how long patients lived without the disease coming back (known as disease-free survival) and how long they lived overall (overall survival). Whether patients had their complete lymph nodes checked or only the sentinel did not seem to change how well they did. But we did notice that the kind of treatment they received afterward could affect how they did. Overall, it seems like the newer SLNB method is just as good as the traditional LND in helping patients with endometrial cancer. Background: Recently, sentinel lymph node biopsy (SLNB) has been introduced in the surgical staging of endometrial cancer as an alternative to systematic lymph node dissection (LND). However, the survival impact of SLNB is not yet well characterised. Methods: We performed a retrospective study of 419 patients with endometrial cancer treated with SLNB alone or with pelvic and para-aortic LND. For SLNB mapping, indocyanine green was used. Results: Median follow-up was 66 months. After exclusions, 337 patients were eligible for analysis. Of them, 150 underwent SLNB and 187 LND. During the follow-up time, 27 (24.7%) of the 150 who underwent SLNB and 54 (28.9%) of the 187 who underwent LND were diagnosed with recurrent disease (p = 0.459). The estimated 5-year disease-free survival (DFS) rate was 76.7% and 72.2% for patients in the SLNB and LND group, respectively (p = 0.419). The 5-year overall survival (OS) rates were 80.7% and 77.0% in the SLNB and LND group, respectively (p = 0.895). Survival rates were similar in both groups independent of lymph node status. Multivariable analysis confirmed that the staging approach was not associated with oncological outcome. For patients without lymph node metastases, patient outcome was worsened by advanced tumour stage and non-endometrioid tumour histology. In the group of patients with confirmed lymph node metastases, advanced tumour stage and inadequate adjuvant treatment significantly reduced DFS and OS. Conclusion: Our data suggested that SLNB did not compromise the oncological outcome of patients with endometrial cancer compared to LND. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent studies have shown a negative association between prior antibiotic use and response rate to immune checkpoint inhibitors (ICIs) in solid tumors, including gynecologic cancers. In this study, use of antibiotics for >14 days prior to ICI treatment was associated with reduced survival. Restricted use and adequate duration and spectrum of antibiotics should be considered when treating patients with recurrent gynecologic cancer. The various response rates to ICI could be attributed to gut dysbiosis. A study of gut microbiota may address the ICI response in the future. Purpose: Antibiotic use preceding immune checkpoint inhibitor (ICI) treatment has been associated with a decreased efficacy of ICI in solid tumors. In this study, we evaluated the effect of antibiotic use before ICI therapy on oncological outcomes. Methods: We examined patients with recurrent gynecologic malignancies at two academic institutions. The clinical data, including antibiotic use within 60 days of ICI initiation, type of antibiotics, reasons for antibiotic use, body mass index, tumor site, chemotherapy-free interval, prior history of radiotherapy, disease control rate (DCR), and overall survival (OS), were assessed. Results: Of 215 patients, 22.9% (n = 47) received antibiotics before ICI treatment. The most common cancer was ovarian (52.1%, n = 112), followed by cervical (24.7%, n = 53) and endometrial (16.7%, n = 36). When we divided the cohort based on antibiotic use before ICIs, there were no significant differences in the DCR and baseline characteristics between the two groups. On multivariate analyses, the variables associated with poor OS were previous use of antibiotics for a cumulative duration of >14 days (HR 2.286, 95% CI 1.210–4.318; p = 0.011); Eastern Cooperative Oncology Group 2 or 3 (HR 4.677, 95% CI 2.497–8.762; p < 0.001); and chemotherapy-free interval of <6 months (HR 2.007, 95% CI 1.055–3.819; p = 0.034). Conclusion: Prior use of antibiotics for a cumulative duration of >14 days was associated with reduced survival in recurrent gynecologic malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the most common type of cancer that affects the female reproductive organs. Over 50% of women with EC present with early-stage, low-risk disease, and are treated with surgery alone. However, women diagnosed with advanced or recurrent disease have a poor prognosis and they have poor response to current therapies. However, the molecular mechanisms and the prognostic prediction for EC patients remain unclear. In this work, we identified that cancer cells utilize dysregulated nucleotide metabolism to enhance proliferation and progression. We targeted one of the dysregulated genes (DHODH) that is critical for metabolism of nucleotide biosynthesis in endometrial cancer cell. Our results provide potential clinical application to select endometrial cancer patient using "overexpression of dysregulated genes (DHODH) as the genetic markers for tailored therapeutic intervention using repurposed FDA approved drugs (Teriflunomide). Furthermore, it revealed a potential combination therapeutic strategy (Teriflunomide+ Olaparib) for the treatment of "DHODH overexpressing" endometrial cancer. Overall, this result provides preclinical data to establish future clinical therapeutic intervention to increase the efficacy of treatment response that improves overall survival of endometrial cancer patients. Endometrial carcinoma (EC) is the most common gynecological malignancy in the United States. De novo pyrimidine synthesis pathways generate nucleotides that are required for DNA synthesis. Approximately 38% of human endometrial tumors present with an overexpression of human dihydroorotate dehydrogenase (DHODH). However, the role of DHODH in cancer cell DNA replication and its impact on modulating a treatment response is currently unknown. Here, we report that endometrial tumors with overexpression of DHODH are associated with a high mutation count and chromosomal instability. Furthermore, tumors with an overexpression of DHODH show significant co-occurrence with mutations in DNA replication polymerases, which result in a histologically high-grade endometrial tumor. An in vitro experiment demonstrated that the inhibition of DHODH in endometrial cancer cell lines significantly induced replication-associated DNA damage and hindered replication fork progression. Furthermore, endometrial cancer cells were sensitive to the DHODH inhibitor either alone or in combination with the Poly (ADP-ribose) polymerase 1 inhibitor. Our findings may have important clinical implications for utilizing DHODH as a potential target to enhance cytotoxicity in high-grade endometrial tumors. [ABSTRACT FROM AUTHOR]

Objective: Prior studies comparing minimally invasive surgery with open surgery among patients with endometrial cancer have reported similar survival outcomes and improved perioperative outcomes with minimally invasive surgery (MIS). However, patients with Type II endometrial cancer were underrepresented in these studies. We sought to compare the overall survival and surgical outcomes between open surgery and MIS in a large cohort of women with Type II endometrial cancer. Methods: Using data from the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, and carcinosarcoma) between January 2010 and December 2014. The primary outcome was a comparison of the overall survival for MIS with that for the open approach. The secondary outcomes included a comparison of the length of hospital stay, readmission within 30 days of discharge, and 30- and 90-day mortality. Outcomes were compared between the cohorts using the Mann–Whitney U test, Pearson's chi-square test, or Fisher's exact test. Multivariable logistic regression with inverse propensity weighting was used to determine clinical characteristics that were statistically significant predictors of outcomes. p values < 0.05 were considered significant. Results: We identified 12,905 patients with Type II, Stage I–III endometrial cancer that underwent a hysterectomy. In total, 7123 of these women (55.2%) underwent MIS. The rate of MIS increased from 39% to 64% over four years. Women who underwent MIS were more often White, privately insured, older, and had a higher income. The laparotomy group had a higher rate of carcinosarcoma histology (30.9% vs. 23.6%, p < 0.001), stage III disease (38.4% vs. 27.4%, p < 0.001), and larger primary tumors (59 vs. 45 mm, p < 0.001). Lymph node dissection was more commonly performed in the MIS group (89.6% vs. 85.4%, p < 0.001). With regard to adjuvant therapy, subjection to postoperative radiation was more common in the MIS group (37% vs. 40.1%, p < 0.001), while chemotherapy was more common in the laparotomy group (37.6% vs. 33.9%, p < 0.001). The time interval between surgery and the initiation of chemotherapy was shorter in the MIS group (39 vs. 42 days, p < 0.001). According to the results of propensity-score-weighted analysis, MIS was associated with superior overall survival (101.7 vs. 86.7 months, p = 0.0003 determined using the long-rank test), which corresponded to a 10% decreased risk of all-cause mortality (HR 0.9; CI 0.857–0.954, p = 0.0002). The survival benefit was uniform across all three histology types and stages. MIS was associated with superior perioperative outcomes, including shorter length of stay (1 vs. 4 days, p < 0.001), lower 30-day readmission rates (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p < 0.001 for both). The increased adoption of MIS from 2010 to 2014 corresponds to a decrease in 90-day postoperative mortality (2.8% to 2.2%, r = −0.89; p = 0.04) and overall mortality (51% to 38%, r = −0.95; p = 0.006). Conclusions: In a large cohort of patients from the National Cancer Database, MIS was associated with improved overall survival and superior perioperative outcomes compared to open surgery among women with Type II endometrial cancer. A decrease in postoperative mortality and a shorter interval between surgery and the initiation of chemotherapy may contribute to the survival benefit of MIS. A racial and economic disparity in the surgical management of Type II endometrial cancer was identified, and further investigation is warranted to narrow this gap and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to report the treatment outcomes of radiation therapy for early‐stage endometrial cancer patients. In addition, this study intended to identify high‐risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate‐risk endometrial cancer patients. Methods: Patients with early‐stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age‐adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone. Results: From 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5‐year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high‐intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05–6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non‐cancer death after receiving PRT. Conclusions: Postoperative VBT alone is sufficient for early‐stage intermediate‐risk endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Germline mutations in the DNA polymerase delta 1 (POLD1) exonuclease domain cause DNA proofreading defects, tumor hypermutation, and predispose to hereditary colorectal and endometrial cancer. In this work, we used a multiprong approach to demonstrate that mutations that alter the amino acid charges in the DEDD motif of exonuclease domains could lead to proofreading deficiency. This novel mutation class, which is currently classified as a variant of uncertain significance, should be reclassified as likely pathogenic. Background: Mutations in the DNA polymerase delta 1 (POLD1) exonuclease domain cause DNA proofreading defects, hypermutation, hereditary colorectal and endometrial cancer, and are predictive of immunotherapy response. Exonuclease activity is carried out by two magnesium cations, bound to four highly conserved, negatively charged amino acids (AA) consisting of aspartic acid at amino acid position 316 (p.D316), glutamic acid at position 318 (p.E318), p.D402, and p.D515 (termed DEDD motif). Germline polymorphisms resulting in charge-discordant AA substitutions in the DEDD motif are classified as variants of uncertain significance (VUSs) by laboratories and thus would be considered clinically inactionable. We hypothesize this mutation class is clinically pathogenic. Methods: A review of clinical presentation was performed in our index patient with a POLD1(p.D402N) heterozygous proband with endometrial cancer. Implications of this mutation class were evaluated by a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review, in silico analysis with orthogonal biochemical confirmation, and whole-exome and RNA sequencing analysis of the patient's tumor and engineered cell lines. Results: Our systematic review favored a Mendelian disease mutation class associated with endometrial and colorectal cancers. In silico analysis predicted defective protein function, confirmed by biochemical assay demonstrating loss of nuclease activity. A POLD1-specific mutational signature was found in both the patient's tumor and POLD1(p.D402N) overexpressing cell. Furthermore, paired whole-exome/transcriptome analysis of endometrial tumor demonstrated hypermutation and T cell-inflamed gene expression profile (GEP), which are joint predictive biomarkers for pembrolizumab. Our patient showed a deep, durable response to immune checkpoint inhibitor (ICI). Conclusion: Charge-discordant AA substitution in the DEDD motif of POLD1 is detrimental to DNA proofreading and should be reclassified as likely pathogenic and possibly predictive of ICI sensitivity. [ABSTRACT FROM AUTHOR]

Simple Summary: Previous studies have shown that women with endometriosis have an increased risk of ovarian cancer. However, it is unclear whether endometriosis is associated with a risk of developing endometrial cancer. Therefore, this study was designed to retrospectively assess the clinicopathological relationship between endometrial cancer and endometriosis using the medical records of patients with endometrial cancer who underwent surgery at our institution. Endometriosis is known to be associated with an increased risk of endometrioid and clear cell ovarian cancer. However, the association between endometriosis and endometrial cancer is controversial. Therefore, we retrospectively analyzed the medical records of women with endometrial cancer who had undergone surgery at our institution to evaluate the clinicopathological relationship between endometrial cancer and endometriosis. The study included 720 women pathologically diagnosed with endometrial cancer at our hospital between 2000 and 2020. The participants were allocated to two groups of patients with endometrial cancer: patients with endometriosis (n = 101) and patients without endometriosis (n = 619). Endometrial cancer patients with endometriosis were significantly younger (median age 54.0 vs. 58.0; p = 0.002). In addition, endometrial cancer patients with endometriosis had fewer pregnancies and deliveries (median pregnancy 1.58 vs. 1.99; p = 0.019, median delivery 1.25 vs. 1.56; p = 0.012). The percentage of patients classified as stage IA was significantly higher in those with endometrial cancer with endometriosis (68.3% vs. 56.4%; p = 0.029). In the analysis of synchronous ovarian cancer, the percentage of dual primary cancer was higher in patients with endometriosis (14.9% vs. 1.6%; p < 0.001). The association of young-onset early-stage endometrial cancer with endometriosis is an important finding that cannot be ignored clinically. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the most common gynecological malignancy, and its incidence is still on the rise. Surgical treatment is the most important step in patient treatment protocols and consists of hysterectomy, bilateral salpingo-oophorectomy and lymph node assessment. This retrospective single-center study analyzes the influence of pelvic lymphadenectomy on the disease-free and overall survival of endometrial cancer patients. The role of pelvic lymphadenectomy in endometrial cancer remains unclear. In this study, we aimed to investigate the influence of lymphadenectomy on progression-free and overall survival among patients diagnosed with endometrial carcinoma. This retrospective single-center study included 1532 patients operated on in a Polish reference center for gynecologic oncology at Holy Cross Hospital, Kielce, between 2002 and 2020. A total of 1004 patients underwent systematic lymphadenectomy as a part of their surgical procedure. The median number of collected lymph nodes was seven. In total, 11.6% of patients were found to have lymph node invasion. The number of lymph nodes removed correlated with patient survival. In patients in whom the number of removed lymph nodes was above the median (>7), the risk of death was reduced (HR 0.68, p = 0.002). The risk of death correlated with the presence of lymph node metastasis (HR 4.12, p < 0.001). The risk of cancer progression was associated with the number of lymph nodes removed (HR 0.54, p = 0.006), and the risk of EC recurrence was greater in patients with lymph node metastasis (HR 1.94, p = 0.016). Our study provides additional evidence that systematic lymphadenectomy may influence the disease-free and overall survival of patients with endometrial cancer. The number of lymph nodes removed correlated with patient prognosis. Further studies are needed to evaluate the use of lymphadenectomy in endometrial cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic value of tumor volume on preoperative MRI in endometrial cancer (EC) patients and its association with adverse prognostic factors and survival. Methods: A retrospective observational study with 127 consecutive patients with endometrioid EC was carried out between 2016 and 2021 at Juan Ramón Jiménez University Hospital, Huelva (Spain). All patients underwent preoperative magnetic resonance imaging (MRI) for local staging. The tumor volume was analyzed on MRI by two different methods: by measuring the three maximum diameters of the tumor according to an ellipse formula and by manual region of interest in different sections; the ratio between tumor volume and uterus volume was also calculated as a third tool. The relationships between volume, prognostic factors, and survival were analyzed. Results: A total of 127 patients with endometroid EC underwent preoperative MRI and were included in the study. Tumor volume was significantly higher for deep myometrial invasion, cervical stromal involvement, infiltrated serosa, lymph node metastases, high‐grade EC, and lymphovascular space involvement, advanced FIGO stage, and High Recurrence Risk Group (P < 0.001). ROC curves showed that tumor volume greater than 25 cm3 predicts lymph node metastases. Volume index greater than 17 cm3 was associated with reduced disease‐free survival (P < 0.001) and overall survival (P < 0.003). Multivariate analysis showed that the greatest tumor volume had an independent impact on recurrence (odds ratio [OR]1.019, 95% confidence interval [CI] 1.005–1.032) and survival (OR 1.027, 95% CI 1.009–1.046). Conclusions: This study shows an important correlation between tumor volume on MRI and poor prognostic factors. Preoperative tumor volume on MRI is a valuable biomarker to be considered for management of EC. Synopsis: Tumor volume of EC measured on preoperative MRI is associated with reduced disease‐free survival and overall survival and can be considered an independent prognostic factor. [ABSTRACT FROM AUTHOR]

The article explores the association between obesity, measured by body mass index (BMI), and the age at the time of diagnosis of endometrial intraepithelial neoplasia (EIN), a precursor to endometrial endometrioid adenocarcinoma. The retrospective cohort study, spanning a decade and including 503 patients, reveals a significant linear association in premenopausal patients, indicating that higher BMI correlates with a decrease in the age at EIN diagnosis.

Objective: The purpose of this study was to assess prognostic factors correlated with recurrence and decreased oncologic outcomes, as well as the role of adjuvant treatment on survival in women with stage I and II endometrioid endometrial cancer without lymphovascular space invasion (LVSI). Material and Methods: Patients with LVSI negative, early-stage endometrioid endometrial cancer patients were retrospectively reviewed. Multivariable logistic regression models were used for identifying predictors of recurrence. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and survival curves were compared by log-rank test. Univariable and multivariable analyses were performed to establish factors affecting OS and DFS. Hazard ratios with 95% confidence intervals were calculated. Results: A total of 289 patients were included, with a mean age of 58 years and the median surveillance time of 45 (6-147) months. The majority of the patients (54%) had grade 1 tumors. Adjuvant therapy was administered to 68 (23.5%). A total of 13 (4.5%) recurred with median time to recurrence of 52 months. Patients receiving adjuvant treatment were more likely to recur (p=0.015), and grade was the only independent predictor of recurrence (p=0.029). Five-year OS and DFS were 95.8% and 97.9%, respectively. While tumor size (p=0.018) and grade 3 histology (p=0.045) were related with shorter DFS, age (p<0.001) was the only related factor for decreased OS. Conclusion: Recurrence rate was low among LVSI negative, early-stage endometrioid endometrial cancer patients. Although recurrences were seen more frequently in patients who received adjuvant treatment, it wasn't an independent prognostic factor. Neither recurrence nor adverse uterine risk factors were associated with shorter OS. While age was the only prognostic factor for decreased OS, grade 3 histology and tumor size were associated with decreased DFS. [ABSTRACT FROM AUTHOR]

Background: Cyclin-dependent kinase inhibitor 3 (CDKN3) has been studied in many cancers. However, the comprehensive and systematic pancancer analysis of CDKN3 genes is still lacking.Methods: Data were downloaded from online databases. R was used for analysis of the differential expression and gene alteration of CDKN3 and of the associations between CDKN3 expression and survival, signaling pathways, and drug sensitivity. Clinical samples and in vitro experiments were selected for verification.Results: CDKN3 expression was higher in most types of cancers, and this phenotype was significantly correlated with poor survival. CDKN3 showed gene alterations and copy number alterations in many cancers and associated with some immune-related pathways and factors. Drug sensitivity analysis elucidated that CDKN3 could be a useful marker for therapy selection. Clinical samples elucidated CDKN3 expressed high in endometrial cancer tissue. In vitro studies showed that CDKN3 induced pro-tumor effect in immune environment and facilitated endometrial cancer cell proliferation and G1/S phase transition.Conclusion: CDKN3 has been shown to be highly expressed in most types of cancers and promoted cancer cell progression. CDKN3 may serve as a novel marker in clinical diagnosis, treatment, and prognosis prediction in future. [ABSTRACT FROM AUTHOR]

Background/Aim: Breast cancer is the leading cause of cancer-related fatalities in women. Tamoxifen, a selective estrogen receptor modulator (SERM), is frequently employed for chemoprevention in hormone receptor (HR)-positive breast cancer patients due to its anti-estrogenic impact on breast tissue. Nevertheless, tamoxifen exhibits agonistic effects on the endometrium, particularly in postmenopausal women. This study aims to assess gynecological issues and endometrial pathologies that emerge during the treatment and follow-up phases of women diagnosed with HR-positive/negative breast cancer. Methods: This cohort study involved a data review from 857 breast cancer patients diagnosed over a decade at a tertiary center. Histopathological endometrial findings were evaluated for 166 patients who underwent gynecological consultations before breast cancer treatment with normal examination results and underwent invasive assessments due to gynecological symptoms that arose during treatment and followup. The study encompassed cases culminating in total abdominal hysterectomy and bilateral salpingooophorectomy (TAH+BSO). Results: The study analyzed 166 cases meeting the inclusion criteria. The mean age at breast cancer diagnosis was 48 years with a standard deviation of 8.4 years, and the average follow-up duration was 4.1 (3.8) years. The predominant histopathological type was invasive ductal carcinoma (75.3%). Of the cases, 68.6% occurred during premenopausal and 31.4% during postmenopause. HR positivity was identified in 136 cases (81.9%), while 30 (18.1%) exhibited negative HR status. Among HR-positive cases, 113 (83.0%) received tamoxifen treatment, while 23 (17.0%) were treated with letrozole. Common clinical findings during and after treatment encompassed increased endometrial thickness (ET) and abnormal uterine bleeding (AUB). Histopathological evaluation of invasive procedures prompted by increased ET indicated the following frequent endometrial findings: proliferative endometrium (33.1%), endometrial polyp (20.5%), and endometrial hyperplasia (EH) without atypia (9%). The histopathological outcomes of invasive procedures prompted by AUB included atrophic endometrium (11.4%), proliferative endometrium (3.6%), and endometrial cancer (1.8%). Among the endometrial malignancies, three occurred in the premenopausal phase and four in the postmenopausal phase. Notably, three of the seven endometrial malignancies were observed in the tamoxifen hormone therapy group, all HR-positive. Four cases were from the non-tamoxifen hormone therapy group with negative HR status. Conclusion: Globally, breast cancer ranks as the most prevalent malignancy in women. Tamoxifen, a frequently utilized adjuvant therapy post breast cancer surgery, can exert diverse effects on gynecological organs, encompassing benign pathologies like increased ET and malignant pathologies like uterine neoplasia. There is a rising suspicion that etiopathogenetic factors contributing to breast cancer progression might also precipitate uterine cancer, irrespective of tamoxifen use. Vigilant patient monitoring is paramount for detecting uterine neoplasia and other gynecological pathologies. [ABSTRACT FROM AUTHOR]

Background: Preclinical models suggest synergy between anti-angiogenesis therapy, mammalian target of rapamycin (mTOR), and histone deacetylase inhibitors to promote anticancer activity. Methods: This phase I study enrolled 47 patients between April 2012 and 2018 and determined safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) when combining bevacizumab, temsirolimus, and valproic acid in patients with advanced cancer. Results: Median age of enrolled patients was 56 years. Patients were heavily pretreated with a median of 4 lines of prior therapy. Forty-five patients (95.7%) experienced one or more treatment-related adverse events (TRAEs). Grade 3 TRAEs were lymphopenia (14.9%), thrombocytopenia (8.5%), and mucositis (6.4%). Grade 4 TRAEs included lymphopenia (2.1%) and CNS cerebrovascular ischemia (2.1%). Six patients developed DLTs across 10 dose levels with grade 3 infection, rash, mucositis, bowel perforation, elevated lipase, and grade 4 cerebrovascular ischemia. The MTD was dose level 9 (bevacizumab 5 mg/kg days 1 and 15 intravenously (IV) plus temsirolimus 25 mg days 1, 8, 15, and 22 IV and valproic acid 5 mg/kg on days 1-7 and 15-21 per orally (PO)). Objective response rate (ORR) was 7.9% with confirmed partial response (PRs) in 3 patients (one each in parotid gland, ovarian, and vaginal cancers). Stable disease (SD) ≥+6 months was seen in 5 patients (13.1%). Clinical benefit state (CBR: PR + SD ≥+6 months) was 21%. Conclusion: Combination therapy with bevacizumab, temsirolimus, and valproic acid was feasible, but there were numerous toxicities, which will require careful management for future clinical development (ClinicalTrials.gov Identifier: NCT01552434). This is the first study to evaluate the combination of bevacizumab, temsirolimus, and valproic acid in patients with advanced malignancies. This combination demonstrated modest efficacy among various solid tumors, but at the expense of toxicity. [ABSTRACT FROM AUTHOR]

Thyroid metastasis from cervical carcinomas is an extremely rare disease; therefore, only a few cases have so far been reported in the literature. Due to the lack of data and the heterogeneity of clinical cases, the percentage of patients affected by thyroid metastases eligible to undergo surgery is not easily predictable. This report describes a rare case of endometrioid adenocarcinoma metastasized to the thyroid gland. A 72-year-old woman was referred to the ENT department of our hospital (Ospedale Degli Infermi di Biella, Italy) presenting with dyspnea and rapidly worsening condition, in need of emergency surgery. The peculiarity of this case lies in the metastasis isotype rarity, in its voluminous dimension, and in its mediastinal localization, which required the intervention of a multidisciplinary team to establish successful treatment planning. [ABSTRACT FROM AUTHOR]

Metastatic skull base malignancies infrequently occur but, when present, typically arise from breast malignancies. Pterygopalatine fossa (PPF) metastasis of any malignancy is further seldom reported, and metastasis of gynecologic malignancies to the PPF has not been previously described in the literature. We present a single case of a 42-year-old female with the first likely case of high-grade endometrial sarcoma metastatic to the PPF. The patient presented with facial pain and numbness in the V2 distribution presented for evaluation. History was significant for several months of dysmenorrhea and metrorrhagia. Computed tomography, magnetic resonance imaging, and positron emission tomography imaging revealed a PPF mass with local extension and bony metastases. Endoscopic biopsy was performed, and final pathology was most consistent with metastatic high-grade endometrial stromal sarcoma. This is the first reported case of likely metastatic endometrial sarcoma to the PPF. This case report highlights the possibility of rare distant metastasis of gynecologic malignancy to this area of the skull base. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are involved in the pathogenesis and progression of various cancers, but their roles in endometrial cancer (EC) are largely unknown. Methods: The expressions of LINC00478 and PTBP1 in EC tissues were determined by RT-qPCR. Cell counting kit-8, flow cytometry and Transwell assays were executed for detecting the roles of LINC00478 in EC cells proliferation, migration and invasion. The mouse–xenograft models were established by subcutaneous injection in vivo. The interaction between LINC00478 and PTBP1 was confirmed by RNA pull-down assay and RNA-binding protein immunoprecipitation assay. Results: LINC00478 was significantly down-regulated in EC tissues while compared to that in their paracancerous samples, and a higher expression level of LINC00478 was negatively correlated with clinical progress of EC patients. Functional experiments in vivo and in vitro revealed that LINC00478 overexpression could dramatically retard the proliferation of EC cells, decrease the rate of colony formation, suppress the migration and invasion abilities of EC cells in vitro and inhibit tumor growth in vivo. Mechanistically, LINC00478 regulated the expression of PTBP1, a key factor in the Warburg effect, and affected the metabolic process of EC cells. Conclusions: LINC00478 acts as a tumor suppressor in EC by negatively controlling PTBP1 expression and influencing the Warburg effect, providing a potential biomarker and therapeutic target for patients with EC. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the second most common tumor of the female reproductive organs in the world. Taking into account the immunological mechanisms of defense against cancer, an important role is attributed to cytokines. In this case-control study, we aimed to identify the possible associations between selected single nucleotide polymorphisms (SNPs), localized in the CCL2, CCL5, CXCL8, and CXCR2 genes, and the onset and progression of endometrial cancer. We found that CCL5 and CXCR2 polymorphisms were associated with increased cancer risk, while the relationships remained significant after adjustments for age, diabetes, hypertension, or endometrial thickening. The selected haplotypes for CCL5 and CCL2 SNPs also correlated with an increased risk of cancer. We concluded that the four polymorphisms studied were significantly associated with an increased risk of endometrial cancer. The obtained results may be useful for identifying the signaling pathways involved in observed genetic changes, which is important for the tumorigenesis of endometrial cancer. Significant relationships with endometrial cancer were demonstrated, both for CCL2, CCL5, and CXCL8 chemokines and for the chemokine receptor CXCR2. The reported case-control study of genetic associations was designed to establish the role of selected single nucleotide polymorphisms (SNPs) of the CCL2, CCL5, CXCL8, and CXCR2 genes in the onset and progression of endometrial cancer. This study was conducted on 282 women, including 132 (46.8%) patients with endometrial cancer and 150 (53.2%) non-cancerous controls. The genotypes for CCL2 rs4586, CCL5 rs2107538 and rs2280789, CXCL8 rs2227532 and −738 T>A, and CXCR2 rs1126580 were determined, using PCR-RFLP assays. The AA homozygotes in CCL5 rs2107538 were associated with more than a quadruple risk of endometrial cancer (p ≤ 0.050). The GA heterozygotes in the CXCR2 SNP were associated with approximately threefold higher cancer risk (p ≤ 0.001). That association also remained significant after certain adjustments, carried out for age, diabetes mellitus, arterial hypertension, or endometrial thickness above 5 mm (p ≤ 0.050). The A-A haplotypes for the CCL5 polymorphisms and T-A-A haplotypes for the CCL2 and CCL5 SNPs were associated with about a twofold risk of endometrial cancer (p ≤ 0.050). In conclusion, CCL2 rs4586, CCL5 rs2107538 and rs2280789, and CXCR2 rs1126580 demonstrated significant associations with an increased risk of endometrial cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic reprogramming, especially fatty acid metabolism, is very strongly associated with carcinogenesis and progression of endometrial cancer. Increasing evidence revealed that oleic acid exhibited pro- and anti-tumor effects in different types of tumors, yet the mechanism underlying this dual effect on tumor growth remains unknown. In this study, we found that oleic acid significantly inhibited cell proliferation and tumor growth in endometrial cancer cells and a transgenic mouse model of endometrial cancer. Oleic acid increased lipogenesis and lipid droplets, and inhibition of the formation of lipid droplets resulted in an enhanced effect of oleic acid on inhibiting endometrial cancer cells. Importantly, oleic acid enhanced the expression of wild-type PTEN, while knockdown of PTEN or targeting AKT by ipatasertib partially reversed or amplified the effect oleic acid on cell proliferation and formation of lipid droplets, respectively. Thus, our results confirm that oleic acid inhibits cell growth depending on PTEN/AKT/mTOR pathway in endometrial cancer. Reprogramming of fatty acid metabolism promotes cell growth and metastasis through a variety of processes that stimulate signaling molecules, energy storage, and membrane biosynthesis in endometrial cancer. Oleic acid is one of the most important monounsaturated fatty acids in the human body, which appears to have both pro- and anti-tumorigenic activities in various pre-clinical models. In this study, we evaluated the potential anti-tumor effects of oleic acid in endometrial cancer cells and the LKB1fl/flp53fl/fl mouse model of endometrial cancer. Oleic acid increased lipogenesis, inhibited cell proliferation, caused cell cycle G1 arrest, induced cellular stress and apoptosis, and suppressed invasion in endometrial cancer cells. Targeting of diacylglycerol acyltransferases 1 and 2 effectively increased the cytotoxicity of oleic acid. Moreover, oleic acid significantly increased the expression of wild-type PTEN, and knockdown of PTEN by shRNA partially reversed the anti-proliferative and anti-invasive effects of oleic acid. Inhibition of the AKT/mTOR pathway by ipatasertib effectively increased the anti-tumor activity of oleic acid in endometrial cancer cells. Oleic acid treatment (10 mg/kg, daily, oral) for four weeks significantly inhibited tumor growth by 52.1% in the LKB1fl/flp53fl/fl mice. Our findings demonstrated that oleic acid exhibited anti-tumorigenic activities, dependent on the PTEN/AKT/mTOR signaling pathway, in endometrial cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: This study compared the long-term surgical outcomes of single-port laparoscopy with other surgical methods (multi-port laparoscopy, robot-assisted laparoscopy, and laparotomy) in endometrial cancer (EC) surgical staging. After conducting propensity score matching, all surgical methods demonstrated comparable survival outcomes with respect to disease-free survival and overall survival. Consequently, single-port laparoscopy is deemed a viable option for surgical staging in EC. This single-institution, retrospective study aimed to compare the surgical outcomes of single-port, multi-port, and robot-assisted laparoscopy, as well as laparotomy, in patients with endometrial cancer who underwent surgical staging between January 2006 and December 2017. This study evaluated various parameters, including disease-free survival (DFS), overall survival (OS), recurrence rate (RR), recurrence site, and intra- and postoperative complications. Propensity score matching was performed to account for baseline characteristics, and a total of 881 patients were included in the analysis. The 3-year DFS of single-port laparoscopy was similar to that of the other groups, but laparotomy exhibited a lower 3-year DFS compared to multi-port (p = 0.001) and robot-assisted (p = 0.031) laparoscopy. Single-port laparoscopy resulted in a significantly higher 3-year OS than laparotomy (p = 0.013). After propensity score matching, the four groups demonstrated similar survival outcomes (3-year DFS: p = 0.533; 3-year OS: p = 0.328) and recurrence rates (10.3%, 12.1%, 10.3%, and 15.9% in the single-port, multi-port, and robot-assisted laparoscopy and laparotomy groups, respectively, p = 0.552). Recurrence most commonly occurred in distant organs. The single-port laparoscopy group had the longest operative time (205.1 ± 76.9 min) but the least blood loss (69.5 ± 90.8 mL) and the shortest postoperative hospital stay (5.2 ± 2.3 days). In contrast, the laparotomy group had the shortest operative time (163.4 ± 51.0 min) but the highest blood loss (368.3 ± 326.4 mL) and the longest postoperative hospital stay (10.3 ± 4.6 days). The transfusion rate was 0% in the single-port laparoscopy group and 3.7% in the laparotomy group. Notably, the laparotomy group had the highest wound complication rate (p = 0.001), whereas no wound hernias were observed in the three minimally invasive approaches. In conclusion, the survival outcomes were comparable between the methods, with the benefit of lower blood loss and shorter hospital stay observed in the single-port laparoscopy group. This study suggests that single-port laparoscopy is a feasible approach for endometrial cancer surgical staging. [ABSTRACT FROM AUTHOR]