Search Results (51)

Background: Following the results of the Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial, doubts have arisen about the safety of laparoscopy in the treatment of endometrial cancer. Methods: A retrospective multicenter cohort study which included all endometrial cancer (EC) patients who underwent a hysterectomy in Emilia Romagna hospitals from 2000 to 2019. All cases were revised and classified according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging system. The different impacts of the surgical approach on survival were stratified according to the recurrence risk from the 2016 European Society for Medical Oncology (ESMO)–European Society of Gynaecological Oncology (ESGO) classification system. The clinical characteristics and oncological outcome of patients treated by laparoscopy were compared with those treated by laparotomy. Results: A total of 2402 EC patients were included in the study. The use of laparoscopy has increased over the years, reaching 81% of procedures in 2019. Laparoscopy reduced complications and hospital stay. Laparoscopy was preferred to treat low, intermediate, and intermediate/high-risk patients. Laparoscopy showed no adverse effects on overall survival (OS) in any recurrence risk class. Particularly in high-risk EC patients, laparoscopy was associated with an increased OS in comparison with women treated by laparotomy regardless of the use of adjuvant therapy. Conclusions: Laparoscopy should always be chosen to treat EC of any risk class. The goal is to ensure correct treatment and oncological safety regardless of the surgical approach. Full article

Background/Objectives: Endometrial cancer (EC) is the sixth most common cancer among women worldwide, and its global incidence has significantly increased over the past three decades. Despite its substantial burden, comprehensive reviews of EC-related research remain limited. This study employs topic modeling to analyze and classify recent research trends in EC. Methods: We identified studies related to endometrial carcinoma published between 2019 and 2023 in PubMed, Web of Science, and the Cochrane Library. The search was conducted using the following terms: endometr* AND (neoplasm* OR cancer* OR carcinoma*) NOT endometriosis. Word clouds were constructed and topic modeling was performed to analyze research activity. Results: A total of 2188 studies were selected, and 11,552 terms were extracted. High-frequency and TF-IDF-weighted keywords included ‘cancer’, ‘risk’, ‘survival’, ‘stage’, ‘tumor’, ‘surgery’, and ‘OS.’ Topic modeling analysis identified ten clusters, categorized as follows: ‘Gynecologic cancer’, ‘Surgical staging’, ‘Therapeutic efficacy’, ‘Diagnosis’, ‘Surgical management’, ‘Multimodal treatment’, ‘Molecular treatment’, ‘Risk factors’, ‘Survival’, and ‘Hormonal regulation.’ Conclusions: This study highlights that recent research on EC has primarily focused on surgical decision making, outcome prediction, and patient survival. Future studies should place greater emphasis on multimodal treatment and prevention—particularly through the identification of risk factors—as well as on improving patients’ quality of life. Full article

Background/Objectives: High-grade endometrial cancer, including non-endometrioid and grade 3 endometrioid histologies, is associated with poor prognosis despite early-stage diagnosis. This study assessed the prognosis of early-stage high-grade endometrial cancer, identified prognostic factors, and evaluated the optimal candidates for adjuvant therapy. Methods: We retrospectively analyzed 106 patients with 2018 FIGO stage I–II high-grade endometrial cancer who underwent hysterectomies between 2008 and 2022. Adjuvant therapy was determined by a multidisciplinary team. Survival outcomes were evaluated using the Kaplan–Meier method and Cox regression model. Results: Of 106 patients, 60 had non-endometrioid, and 46 had grade 3 endometrioid carcinoma; 69 (65.1%) received adjuvant therapy. After a median follow-up of 48.8 months, 37 patients experienced disease progression, and 21 died. Non-endometrioid histology was significantly associated with worse overall survival (p = 0.002). Lack of lymph node dissection, deeper invasion, and the omission of adjuvant therapy were additional adverse prognostic factors. Adjuvant therapy improved the overall survival (p = 0.009), disease-free survival (p = 0.021), and locoregional recurrence-free survival (p = 0.034) in patients with one or two risk factors. Conclusions: Non-endometrioid histology, deep invasion, and the lack of lymph node dissection are associated with worse survival in early-stage high-grade endometrial cancer. Adjuvant therapy should be considered in patients with these risk factors. Full article

Objective: Accurate preoperative differentiation between benign endometrial conditions and malignancies is essential for guiding therapeutic interventions. However, high-quality evidence regarding the diagnostic accuracy of endometrial sampling techniques remains insufficient. This study aimed to evaluate the diagnostic efficiency of hysteroscopically directed biopsy, Pipelle suction curettage, and dilatation and curettage (D&C) for detecting endometrial hyperplasia or carcinoma in premenopausal women and to identify associated risk factors. Methods: A retrospective single-center cohort analysis was conducted on 2054 premenopausal women. Demographic, clinical, and obstetric data, along with biopsy techniques and histopathological findings, were recorded. Diagnostic accuracy of biopsy methods was compared against definitive surgical pathology. Results: The prevalence of endometrial hyperplasia and carcinoma was 5.6% and 1.0%, respectively. Hysteroscopically directed biopsy demonstrated superior diagnostic accuracy (AUC 0.957) compared to D&C (AUC 0.909) and Pipelle suction curettage (AUC 0.858). Sensitivity was highest for hysteroscopically directed biopsy (91.3%), followed by D&C (82.0%) and Pipelle suction curettage (71.7%), while specificity remained excellent across all methods (p < 0.001). Elevated BMI increased the risk of hyperplasia or carcinoma by 1.05 times per unit increase (OR = 1.054, p = 0.005), while hypertension nearly doubled the risk (OR = 1.99, p = 0.009). Multiparity showed protective effects, reducing risk with each additional delivery (OR = 0.877, p = 0.029). Conclusions: Hysteroscopically directed biopsy provides superior diagnostic accuracy for detecting endometrial hyperplasia and carcinoma in premenopausal women. Hypertension and elevated BMI increase risk, while multiparity offers protective benefits. Full article

Background/Objectives: Lipid metabolism plays a crucial role in uterine corpus endometrial carcinoma (UCEC); however, its specific mechanisms remain to be fully elucidated. This study aimed to construct a lipid-metabolism-related prognostic model and explore its association with the tumor immune microenvironment. Methods: A total of 552 UCEC and 35 normal tissue samples from The Cancer Genome Atlas (TCGA) database were analyzed to identify differentially expressed lipid-metabolism-related genes (DE-LMRGs). A prognostic risk model was established using univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression, and its clinical utility was assessed through nomogram construction. Functional enrichment analysis was performed to explore the biological pathways involved. Tumor immune infiltration patterns were evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA), Estimation of Stromal and Immune Cells in Malignant Tumors using Expression Data (ESTIMATE), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. Results: Multivariate analysis indicated that the prognostic model had robust predictive value, with AUCs of 0.701, 0.746, and 0.790 for 1-, 3-, and 5-year overall survival predictions. High-risk patients exhibited a suppressed immune microenvironment characterized by reduced immune cell infiltration, lower tumor mutation burden (TMB), and elevated TIDE scores, suggesting potential resistance to immunotherapy. Furthermore, LIPG was identified as a key hub gene through the intersection of nine machine learning algorithms, demonstrating strong associations with both cancer progression and immune infiltration. Functional validation using Cell Counting Kit-8 (CCK-8), wound healing, and transwell migration assays following small interfering RNA (siRNA) transfection demonstrated that LIPG promotes UCEC cell proliferation and migration in vitro. Conclusions: These findings highlight the critical role of lipid metabolism in UCEC progression and immune modulation, with LIPG emerging as a potential prognostic biomarker. The identified lipid-metabolism-related gene signature may provide new insights into tumor microenvironment interactions. Full article

Background: Endometrial cancer is the most common gynecologic malignancy in developed countries, with obesity recognized as a major risk factor contributing to its incidence. The rising prevalence of obesity has significant implications for treatment planning, particularly in radiation therapy approaches such as high-dose-rate (HDR) vaginal cuff brachytherapy, which is commonly used as adjuvant therapy in early-stage endometrial carcinoma. Body Mass Index (BMI) is a key factor in brachytherapy, as increased adiposity may alter dosimetric parameters, affecting radiation distribution and doses received by organs at risk (OARs). Understanding the correlation between BMI and radiation dose to OARs is essential for optimizing treatment planning and minimizing adverse effects. Identifying dose variations across different BMI categories may help refine patient-specific brachytherapy approaches to ensure both efficacy and safety. Objectives: This study aims to investigate the influence of Body Mass Index (BMI) on the doses received by organs at risk (OAR) during high-dose-rate (HDR) vaginal cuff brachytherapy in patients diagnosed with early-stage endometrial carcinoma. Understanding the relationship between BMI and OAR doses could enhance treatment planning and minimize complications. Methods: We collected brachytherapy data for 242 endometrial cancer patients treated with adjuvant HDR vaginal cuff brachytherapy. The patients were categorized based on their BMI into normal weight, overweight, and obese groups. Dosimetric data were collected for OARs, including the bladder, rectum, and sigmoid colon, and also for dose fractionation, D90%, and the active length of the brachytherapy cylinder. The analysis included comparing the doses received by each organ across different BMI categories using appropriate statistical methods. Results: Preliminary findings indicated a significant variation in the doses to OARs correlating with BMI classifications. Obese patients exhibited slightly higher mean doses to the rectum and sigmoid compared to those with a normal BMI. The statistical analysis demonstrated that as BMI increased, the dose to these organs at risk also tended to increase, suggesting a need for adjusted treatment planning strategies in this population. Conclusions: Obesity is a key concern in endometrial cancer patients, with higher BMI linked to slightly increased doses to the rectum and sigmoid, though treatment remained homogeneously delivered. Future prospective clinical studies are essential to explore the relationship between these dosimetric findings, specifically the correlation between higher BMI, increased doses to organs at risk (OARs), and late treatment-related toxicities. This research is needed to better understand the long-term implications and to optimize therapeutic outcomes. Full article

Background/Objectives: Uterine carcinosarcoma (UCS) refers to a rare high-grade aggressive epithelial non-endometrioid endometrial carcinoma, with tumour cells demonstrating epithelial–mesenchymal metaplastic transition and composed of both carcinomatous epithelial and sarcomatous (homologous or heterologous) components. Methods: The aim of this study was to evaluate the epidemiology, management approach, outcomes and survival patterns of patients with UCS. Seventy-seven cases of UCS treated with primary surgery in a single tertiary centre underwent retrospective cohort analysis across a ten-year period. Observational data on clinicopathological variables and treatment pathways were reviewed and independent risk factors for relapse and mortality were analysed. Results: The 5-year disease-free and overall survival rates were 52.10% and 46.6%, respectively. Cervical stromal involvement was independently related to disease-free survival (HR = 6.26; 95%CI 1.82–21.59; p = 0.004) and overall survival (HR = 3.64; 95%CI 1.42–9.38; p = 0.007), whilst sarcomatous component type was independently related to recurrence only (HR = 3.62; 95%CI 1.38–9.51; p = 0.009) after adjusting for other pathological and treatment variables. No significant difference in recurrence or mortality was found when comparing the performance of pelvic lymph node dissection (p = 0.803 and p = 0.192 respectively) or the administration of adjuvant treatment (p = 0.546 and p = 0.627 respectively). Conclusions: Whilst our data suggests an encouraging similarity in overall survival rates compared with the literature, UCS continues to represent significant treatment challenges—with a paucity of guidelines available. Data regarding molecular analysis was not systemically available in our cohort, the more recent introduction of which (alongside the revision of endometrial cancer staging) will undoubtedly provide UCS patients with improved therapeutic options in the future. Full article

Introduction: Pelvic organ prolapse is a common condition that can affect 50% of parous women. The surgical management can be divided into two approaches: A trans-vaginal and a trans-abdominal approach. In view of current controversies and discrepancies between guidelines, this review aims to scope the historically available data on synthetic meshes in the management of POP mainly on outcomes and complications of the trans-vaginal approach and the trans-abdominal approach. Methods: This study is a narrative review of the use of synthetic meshes in POP surgery. The different indications, the results, and comparisons to other surgical management were collected using MEDLINE and Google Scholar. Results: Regarding the trans-vaginal approach, 31 articles were included. The anatomical success rate is high, around 90%. However, this technique was recently considered cost-ineffective mostly because of high rates of erosions, ranging from 4 to 40% depending on the series. Obesity seems to be the most important risk factor of mesh erosion, followed by age and smoking. Regarding the trans-abdominal approach, 36 articles were included. In the literature, anatomical success is between 70 and 95%, with an erosion rate between 0 and 11%. Minimally invasive sacrocolpopexy and open sacrocolpopexy seem to be equally effective on anatomical outcomes and recurrence rates. Concomitant total hysterectomy might be effective but may be associated with more mesh erosions. Concomitant laparoscopic supracervical hysterectomy may be the preferred option for patients with cervical and uterine lesions but should not be performed for the sole purpose of reducing the occurrence of endometrial carcinoma, especially when uterine preservation seems effective and is associated with less blood loss and shorter operating time. Conclusion: Our review reports limited application for trans-vaginal repair because of high complications rates, leading countries to suspend their utilization. Our review reports a gold standard application for trans-abdominal sacrocolpopexy. The use of synthetic meshes in trans-abdominal sacrocolpopexy for POP repair provide durable cure rates with a lower rate of mesh-related complications and therefore may be considered the gold standard approach. Full article

Objective: Obesity is a major risk factor for endometrial cancer. In addition to hormone therapy with progestins, glucagon like peptide-1 receptor (GLP-1R) agonists such as semaglutide may be helpful to achieve weight loss during conservative treatment of endometrial hyperplasia or cancer. Methods: We theorized that the combination of semaglutide and the progestin levonorgestrel would be useful as a novel treatment or prevention regimen and tested this hypothesis using endometrial cancer cell lines and patient-derived organoids (PDOs). Results: Hec50, KLE, and Ishikawa endometrial cancer cells express GLP-1R, as determined by both qPCR and Western blotting, and GLP-1R agonist treatment induces GLP-1R mRNA transcription through positive feedback mechanisms in cell models. PDOs from six individuals with grade 1 endometrial carcinomas were treated with progesterone, levonorgestrel, semaglutide, or levonorgestrel + semaglutide. Multiple models demonstrated a significant reduction in viability in response to combinatorial treatment, and the effect was noted in models from both PR high- and PR low-expressing tumors. Most interesting was the induction not only of the membrane GLP-1R with treatment, but also the significant upregulation of nuclear and membrane progesterone receptors—PR and PGRMC1/2, respectively—indicating a potential positive feedback loop between semaglutide and progestins such as levonorgestrel. Conclusion: In summary, we identify synergistic molecular cross-talk between the GLP-1R and steroid hormone receptor pathways, with the potential to enhance the anticancer activity of levonorgestrel when combined with semaglutide. Full article

Endometrial cancer (EC) is the sixth most common cancer in women worldwide, with rising incidence, particularly in economically developed countries where obesity and type 2 diabetes are prevalent risk factors. EC comprises various histological subtypes with distinct behaviors: Type I tumors are generally estrogen-driven with favorable prognosis, while Type II tumors are hormone-independent, aggressive, and associated with poorer outcomes. Dysregulation of the cell cycle, particularly through cyclin-dependent kinases (CDKs) and their regulators like Cyclin D1 (CCND1), plays a crucial role in EC progression and recurrence. Cyclin D1 overexpression is often observed in the early stages of endometrioid carcinoma and complex hyperplasia, marking potential early carcinogenic events, while lower expression levels are common in high-grade subtypes like serous carcinoma. Although CDK inhibitors targeting Cyclin D1/CDK4/6 complexes have shown therapeutic potential in cancers such as breast and lung, their role in EC remains underexplored. This study integrates immunohistochemical evaluations of Cyclin D1 expression in EC patient samples with data from The Cancer Genome Atlas (TCGA) to assess its prognostic significance across EC subtypes. By correlating molecular, histopathological, and clinical outcomes, we aim to clarify the impact of Cyclin D1 dysregulation on EC progression and recurrence. Our findings may inform more personalized therapeutic approaches, particularly for high-grade and treatment-resistant forms of EC. Full article

Objective: Our primary objective was to evaluate the oncologic outcomes of patients with abnormal p53 FIGO grade 3 (high-grade) endometrioid endometrial cancer. As secondary objectives, we determined the global prevalence of abnormal p53 in grade 3 endometrioid endometrial carcinomas and the geographical variations. Methods: The following electronic databases were searched: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. We followed the Meta-Analysis for Observational Studies in Epidemiology guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This review was preregistered with PROSPERO (no: CRD42023495192). Bias was assessed using the Quality in Prognosis Studies tool. For time-to-event data, the effect of p53 status on grade 3 endometrial cancer was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Overall survival and progression-free survival were analyzed using one- and two-stage approaches, the Kaplan–Meier method, and Cox proportional hazards models. Results: Fifty-seven studies with 2528 patients were included. Patients with abnormal p53 had an increased risk of death (HR, 1.29 (95% CI, 1.11–1.48); I² = 88%) and disease progression (HR, 1.63; 95% CI, 1.42–1.88; I² = 2%) compared with patients with wildtype p53 G3 endometrial cancer. The global pooled prevalence of abnormal p53 was 30% (95% CI, 25–34%; tau² = 0.02; I² = 74%), with the highest prevalence being found in studies conducted in Asia (95% CI, 27–41%; tau² = 0.01; I² = 52%). Conclusions: Abnormal p53 grade 3 endometrioid endometrial cancer is more common in Asia, and it is associated with decreased overall survival and progression-free survival. Full article

Background/Objectives: This study investigates which demographic, clinical and pathological factors of women with early-stage presurgical EC could be considered risk factors for the presence of different subtypes of metastases in sentinel lymph nodes (SLNs). Methods: This is a retrospective single-center study that collected data between December 2015 and April 2024. EC patients who underwent total hysterectomy with salpingo-oophorectomy and SLN mapping with indocyanine green (ICG) were recorded. Results: Data from 98 women with EC were analyzed. The endometrioid histotype was present in 85 (86%) women, and the non-endometrioid histotype was present in 13 (13%) women. High-grade EC (G3) was present in 21 (21.4%) patients, and low-grade EC (G1-G2) was present in 77 (78.6%) patients. The total number of women with SLN metastasis was 21/98 (21%). Of 21 women, 5 had MAC, 6 had MIC and 10 had ITCs. Conclusions: Preliminary analysis identified three risk factors for nodal involvement: age greater than 67 years, high-grade endometrial carcinomas and myometrial invasion greater than or equal to 50%. Lymphovascular space invasion, histotype 2 and p53 mutation showed a slight, but not statistically significant, tendency to be risk factors for SLN positivity. A deeper analysis with univariate uninominal logistic regression showed that high-grade EC is related to a greater probability of MACs, as shown in other studies, and that low-grade EC (grades 1 and 2) had a strong relationship with low-volume metastasis (LVM); further studies are needed to confirm these results. Full article

Objective: This study aimed to evaluate the efficacy of a new biomarker, termed SIR-En, in identifying patients at risk of endometrial carcinoma among those presenting with abnormal uterine bleeding during menopause. Material and Methods: A retrospective case–control analysis was conducted on 242 women with menopausal abnormal uterine bleeding and endometrial thickness ≥ 4 mm. Peripheral blood samples were collected within 7 days before histological diagnosis. systemic inflammatory reaction (SIR) indices were calculated, including NLR, MLR, PLR, and SII. SIR-En was derived by multiplying SII and endometrial thickness. Statistical analyses, including multivariate linear regression and ROC curve analysis, were performed to assess the diagnostic capability of SIR-En. Results: Patients were categorized into endometrial hyperplasia (50 patients) and endometrial cancer (192 patients) groups. The SIR-En index was significantly higher in the carcinoma group (8710 vs. 6420; p = 0.003). The ROC curve for SIR-En had an AUC of 0.6351 (95% CI: 0.5579–0.7121). Using Youden’s method, the optimal SIR-En cutoff was 13,806, showing a specificity of 0.940 and a positive predictive value of 0.957. Conclusions: Combining systemic inflammatory indices with endometrial thickness, the SIR-En index can effectively distinguish between endometrial hyperplasia and carcinoma in menopausal women with abnormal uterine bleeding. Despite the retrospective design, the identified cutoff’s high specificity and positive predictive value support its potential utility in clinical practice. Further prospective studies are required to validate these findings and optimize clinical application. Full article

Background: According to epidemiological studies, endometrial carcinoma is one of the most frequently diagnosed malignancies of the female reproductive system, with an increasing incidence. Currently, the risk stratification of this neoplasm takes into account the stage, degree of tumor differentiation, histological type and depth of myometrial invasion. Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, numerous reports have appeared on the molecular characteristics of different types of endometrial carcinoma. Taking this into account, the FIGO Committee determined in 2023 that changes and updates to the staging system are justified to reflect new information about this tumor. Due to the high prevalence of the disease and mortality from endometrial cancer, an in-depth study of the molecular genetic characteristics of tumor cells is relevant; the results of such studies can be used to improve the efficiency of diagnosis, assess the risk of metastasis and prognosis of the disease. Lymph node assessment is crucial for the choice of treatment strategy for endometrial cancer, since metastatic lymph node involvement is one of the main factors affecting prognosis. At the same time, the criteria for the appropriateness of lymphadenectomy in low-differentiated malignant tumors are not clearly defined. Various molecular methods have been proposed to assess the status of lymph nodes; candidate genes are being studied as potential diagnostic biomarkers, as well as microRNA. The aim of the study was to analyze the literature data on numerous studies of molecular risk factors for progression in endometrioid carcinoma, as well as to preserve the most important marker changes in relation to the prognostic development of this disease. Methods: A literature review was conducted using data from the electronic databases PubMed, Google Scholar, and Wiley Cochrane Library for the period from 2018 to 2023 using the specific keywords. Results: The current scientific genetic studies on metastasis and prognostic factors in uterine cancer were analyzed, and a systematization of the reviewed data from the modern literature was done. Conclusions: To select the most effective treatment - intraoperative, adjuvant or combination therapy, minimize postoperative risks of lymphadenectomy and clearly predict the results - further study of the molecular genetic features of endometrial cancer is necessary. Full article

(1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we collected data on 51 patients diagnosed with NSMP EC following the introduction of molecular profiling at our institution. Patients were retrospectively analyzed for estrogen receptor (ER) status, histotype, and grade to identify potential prognostic subgroups. (3) Results: Our analysis identified two distinct subgroups within NSMP EC: low-risk and high-risk, based on ER status, histotype, and grade. The low-risk NSMP group demonstrated significantly better survival outcomes compared to the high-risk group. With a median follow-up time of 16 moths (IQR 13.0–29.7), the disease-free survival (DFS) and overall survival (OS) for the low-risk group were 100%. For the high-risk group, the DFS and OS were 71.4% and 78.6%, respectively, which showed a statistically significantly difference (Log-Rank Mantel-Cox < 0.001). In the high-risk group, four patients experienced recurrence, and three of these patients died. (4) Conclusions: Stratifying NSMP EC into low-risk and high-risk categories based on ER status, histotype, and grade can lead to more accurate prognostic assessments. In time, it may require tailored adjuvant therapies and a personalized treatment. Full article