Treatment Of Endometrial Cancer Research Articles

Surgical Treatment for Endometrial Cancer, Hysterectomy Performed via Minimally Invasive Routes Compared with Open Surgery: A Systematic Review and Network Meta-Analysis

Background: Total hysterectomy with bilateral salpingo-oophorectomy via minimally invasive surgery (MIS) has emerged as the standard of care for early-stage endometrial cancer (EC). Prior systematic reviews and meta-analyses have focused on outcomes reported solely from randomised controlled trials (RCTs), overlooking valuable data from non-randomised studies. This inaugural systematic review and network meta-analysis comprehensively compares clinical and oncological outcomes between MIS and open surgery for early-stage EC, incorporating evidence from randomised and non-randomised studies. Methods: This study was prospectively registered on PROSPERO (CRD42020186959). All original research of any experimental design reporting clinical and oncological outcomes of surgical treatment for endometrial cancer was included. Study selection was restricted to English-language peer-reviewed journal articles published 1 January 1995–31 December 2021. A Bayesian network meta-analysis was conducted. Results: A total of 99 studies were included in the network meta-analysis, comprising 181,716 women and 14 outcomes. Compared with open surgery, laparoscopic and robotic-assisted surgery demonstrated reduced blood loss and length of hospital stay but increased operating time. Compared with laparoscopic surgery, robotic-assisted surgery was associated with a significant reduction in ileus (OR = 0.40, 95% CrI: 0.17–0.87) and total intra-operative complications (OR = 0.38, 95% CrI: 0.17–0.75) as well as a higher disease-free survival (OR = 2.45, 95% CrI: 1.04–6.34). Conclusions: For treating early endometrial cancer, minimal-access surgery via robotic-assisted or laparoscopic techniques appears safer and more efficacious than open surgery. Robotic-assisted surgery is associated with fewer complications and favourable oncological outcomes.

Range of Resection in Endometrial Cancer—Clinical Issues of Made-to-Measure Surgery

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

High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.

Although many recent advancements have been made in women's health, perhaps one of the most neglected areas of research is the diagnosis and treatment of high-grade endometrial cancer (EnCa). The molecular classification of EnCa in concert with histology was a major step forward. The integration of profiling for mismatch repair deficiency and Human Epidermal Growth Factor 2 (HER2) overexpression, can further inform treatment options, especially for drug resistant recurrent disease. Recent early phase trials suggest that regardless of subtype, combination therapy with agents that have distinct mechanisms of action is a fruitful approach to the treatment of high-grade EnCa. Unfortunately, although the importance of diagnosis and treatment of high-grade EnCa is well recognized, it is understudied compared to other gynecologic and breast cancers. There remains a tremendous need to couple molecular profiling and biomarker development with promising treatment options to inform new treatment strategies with higher efficacy and safety for all who suffer from high-grade recurrent EnCa.

Efficacy of Single- and Dual-Docking Robotic Surgery of Paraaortic and Pelvic Lymphadenectomy in High-Risk Endometrial Cancer

(1) The surgical method of choice for the treatment of endometrial cancer is minimally invasive surgery. In cases of high-risk endometrial cancer, completed paraaortic and pelvic lymphadenectomy are indicated. The aim of this study was to analyze the types of docking during robotic surgery assisted with the da Vinci X system while performing paraaortic and pelvic lymphadenectomy. (2) Methods: A total of 25 patients with high-risk endometrial cancer, with a mean age of 60.07 ± 10.67 (range 34.69–83.23) years, and with a mean body mass index (BMI) of 28.4 ± 5.62 (range 18–41.5) kg/m2, were included in this study. The analyzed population was divided into groups that underwent single or dual docking during surgery. (3) Results: No statistical significance was observed between single and dual docking during paraaortic and pelvic lymphadenectomy and between the type of docking and the duration of the operation. However, there was a statistically significant correlation between the duration of the operation and previous surgery (p < 0.005). The number of removed lymph nodes was statistically associated with BMI (p < 0.005): 15.87 ± 6.83 and 24.5 ± 8.7 for paraaortic and pelvic lymph nodes, respectively, in cases of single docking, and 18.05 ± 7.92 and 24.88 ± 11.75 for paraaortic and pelvic lymph nodes, respectively, in cases of dual docking. (4) Conclusions: The robot-assisted approach is a good surgical method for lymphadenectomy for obese patients, and, despite the type of docking, there are no differences in the quality of surgery.

ERBB2 Targeting Reveals a Significant Suppression of Tumorigenesis in Murine Endometrial Cancer with Pten Mutation.

Endometrial cancer is the most common gynecologic malignancy. PTEN is a negative regulator of PI3K signaling and is deficient in > 50% of primary human endometrial cancer. Amplification of ERBB2 promotes tumorigenesis and pathogenesis of several human cancers. However, the effect of ERBB2 targeting has not been studied in endometrial cancer with PTEN mutations. The murine model Pgrcre/+Erbb2f/fPtenf/f (Erbb2d/d Ptend/d) was developed to evaluate the effect of ERBB2 targeted therapy in endometrial cancer with PTEN deficiency. Histopathological and molecular analysis was performed for Ptend/d and Erbb2d/dPtend/d mice. Histopathological analysis revealed that Erbb2d/dPtend/d mice significantly reduced development and progression of endometrial cancer compared to Ptend/d mice. Furthermore, percentage of proliferative cells in Erbb2d/dPtend/d mice revealed anti-tumorigenic effect of Erbb2 ablation compared to Ptend/d mice. Our results demonstrate that Erbb2 ablation reveals a significant suppression of tumorigenesis on endometrial cancer of Ptend/d mice. Our results suggest that Erbb2 functions as an oncogene in endometrial cancer of Ptend/d mice implying that Erbb2 targeting can be used as an effective therapeutic approach for treatment of endometrial cancer with PTEN deficiency to hinder cancer development.

Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

ObjectivesNodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition.Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. MethodsClinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. ResultsFifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case.Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT.Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. ConclusionsIn this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

VNOTES retroperitoneal sentinel lymph node dissection for endometrial cancer staging: First multicenter, prospective case series.

The current standard treatment for endometrial cancer is a laparoscopic hysterectomy with adnexectomies and bilateral sentinel node resection. A retroperitoneal vNOTES sentinel node resection has several theoretical potential advantages. These include being less invasive, leaving no visible scars, operating without Trendelenburg, and therefore offering the anesthetic advantage of easier ventilation in obese patients and following the natural lymph node trajectory from caudally to cranially and therefore a lower risk of missing the sentinel node. The aim of this study is to determine the feasibility of a retroperitoneal vNOTES approach to sentinel lymph node dissection for staging of endometrial cancer. A prospective multicenter case series was performed in four hospitals. A total of 64 women with early-stage endometrial carcinoma suitable for surgical staging with sentinel lymph node removal were operated via a transvaginal retroperitoneal vNOTES approach. The paravesical space was entered through a vaginal incision after injecting the cervix with indocyanine green. A vNOTES port was placed into this space and insufflation of the retroperitoneum was performed. Sentinel lymph nodes were identified bilaterally using near-infrared light followed by endoscopic removal of these nodes. A total of 64 women with early-stage endometrial cancer underwent sentinel lymph node removal by retroperitoneal vNOTES technique. All patients also underwent subsequent vNOTES hysterectomy and bilateral salpingo-oophorectomy. The median age was 69.5 years, median total operative time was 126 min and the median estimated blood loss was 80 mL. In 97% of the cases bilateral sentinel nodes could be identified. A total of 60 patients had negative sentinel nodes, three had isolated tumor cells and one had macroscopically positive sentinel nodes. No complications with sequel occurred. This prospective multicenter case series demonstrates the feasibility of the vNOTES approach for identifying and removing sentinel lymph nodes in women with endometrial carcinoma successfully and safely. vNOTES allows sole transvaginal access with exposure of the entire retroperitoneal space, following the natural lymph trajectory caudally to cranially, and without the need for a Trendelenburg position.

EnBloc Resection of Sentinel Lymph Nodes with the Hysterectomy Specimen in Endometrial Cancer.

We demonstrate the surgical technique of removing the sentinel lymph nodes with its afferent lymphatic vessels attached to the hysterectomy specimen. Stepwise demonstration of the technique with narrated video footage. Sentinel lymph node sampling has been established as an acceptable staging method in endometrial cancer cases.1 Lymphatic anatomy has been described according to three consistent channels for endometrial cancer dissemination: (1) an upper paracervical pathway draining external or obturator lymph nodes; (2) a lower pathway draining internal iliac lymph nodes; and (3) the infundibulo-pelvic pathway with a course along the broad ligament.2 A study in patients with cervical cancer identified tumor cells in the afferent lymphatic vessels of the upper pathway, even when the corresponding sentinel node was negative (3/20 patients).3 This could be an important prognostic factor in patients with cervical cancer. Since the typical position of sentinel nodes is the same in both endometrial and cervical cancers, we aimed to assess the feasibility of removing 'enbloc' the sentinel node with its afferent lymphatic vessels, and the uterus.4 INTERVENTIONS: The Da Vinci Xi surgical system was used. Indocyanine green was injected cervically, the pelvic surgical spaces were developed, and the sentinel lymph nodes, along with the afferent lymphatic vessels, were identified using the Firefly infrared camera. The lymphovascular tissue was mobilized and separated from the uterine artery, which was skeletonized and ligated. Colpotomy was performed and the specimen was retrieved vaginally. Emerging evidence regarding diagnosis, characterization, and treatment of endometrial cancer has introduced a new era, based on minimally invasive techniques for staging through sentinel lymph node biopsy, molecular classification, and personalized treatment algorithms that include immune checkpoint inhibitors and targeted therapies.5 Lymph node staging is one of the most significant prognostic factors in endometrial cancer patients and is a guide for adjuvant treatment. Sentinel lymph node biopsy is not inferior to conventional lymphadenectomy and is in fact a better way of identifying low-volume cancer through the use of ultrastaging, as part of the sentinel node algorithm.6 The dissection technique described in this video could offer an improvement in the staging of endometrial cancer, ensuring that the true sentinel lymph node is identified and that potential cancer cells inside the afferent lymphatic vessels are also excised. Therefore, it could be utilized as a more accurate way of planning adjuvant treatment and consequently improving recurrence and survival; however more studies are needed to further evaluate the feasibility and sensitivity of identifying disease in the afferent lymphatic vessels. This novel surgical technique emphasizes the importance of anatomical knowledge and offers inspiration for studies with potential clinical benefit that should follow.

Daily Online Adaptive Radiation Therapy of Postoperative Endometrial and Cervical Cancer With PTV Margin Reduction to 5 mm: Dosimetric Outcomes, Acute Toxicity, and First Clinical Experience

PurposeThis study evaluated the first clinical implementation of daily iterative cone-beam computed tomography (iCBCT)-guided online adaptive radiotherapy (oART) in the postoperative treatment of endometrial and cervical cancer. Methods and MaterialsSeventeen consecutive patients treated with daily iCBCT-guided oART were enrolled in this prospective study, with a reduced uniform three-dimensional PTV margin of 5 mm. Treatment plans were designed to deliver 45 or 50.4 Gy in 1.8 Gy daily fractions to PTV. Pre- and posttreatment ultrasound and iCBCT scans were performed to record intrafractional bladder and rectal volume changes. The accuracy of contouring, oART procedure time, dosimetric outcomes and acute toxicity were evaluated. ResultsThe average time from first iCBCT acquisition to completion of treatment was 22 min and 26 s. During this period, bladder volume increased by 44 cm3 using iCBCT contouring, while rectal volume remained stable (62.9 cm3 pretreatment vs. 61.9 cm3 posttreatment). A total of 91.6% of influencers and 88.1% of CTVs required no or minor edits. The adapted plan was selected in all (434) fractions and significantly improved the dosimetry coverage for CTV and PTV, especially the vaginal PTV coverage by nearly 7% (p<0.05). The adapted bladder Dmean was 104.61 cGy, and the rectum Dmean was 123.67 cGy, significantly lower than the scheduled plan of 108.24 and 128.19 cGy, respectively. The bone marrow, femur head left and right dosimetry were also improved with adaptation. Grade 2 acute gastrointestinal and genitourinary toxicities were 24% and 0, respectively. There was a Grade 3 acute toxicity of decreased white blood cell count in one patient. ConclusionsDaily oART was associated with favourable dosimetry improvement and low acute toxicity, supporting its safety and efficacy for postoperative treatment of endometrial and cervical cancer. These results need to be validated in a larger prospective randomized controlled cohort.

Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment

ObjectiveBrachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session.Study design: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. ResultsThis analysis included 250 patients, of whom 208 were considered to be at high–intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8–8.3] and 7.8% at 5 years (95% CI 4.8–12.6). The 5-year OS rate was 86.2% (95% CI 80.6–90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1–82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. ConclusionThese findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

RELEVANCE OF OVARIAN PRESERVATION&#x0D; IN YOUNG WOMEN WITH EARLY-STAGE&#x0D; ENDOMETRIAL CANCER AFTER HORMONAL&#x0D; AND SURGICAL TREATMENT:&#x0D; A COMPREHENSIVE LITERATURE REVIEW

Relevance: Ovarian preservation in young women with early-stage endometrial cancer after surgical treatment has been conventionally associated with complications. Nevertheless, recent randomized studies suggest a different perspective.&#x0D; The study aimed to clarify the occurrence of complications, in particular relapses, associated with ovarian preservation in young&#x0D; women after hormonal and surgical treatment for early-stage endometrial cancer.&#x0D; Methods: The analysis included articles published in full text over the past 10 years. We identified relevant observations from studies using a comprehensive search in the following databases: PubMed, Medline, Embase, and Cochrane Library. The search strategy&#x0D; included terms related to endometrial cancer: premenopausal, young woman, endometrial cancer, ovarian conservation. The study&#x0D; followed the PRISMA guidelines for systematic reviews.&#x0D; Results: A total of 178 articles were studied, of which 111 articles (literature reviews and meta-analyses) (62%) described the&#x0D; cases of ovarian preservation. Of these, 84 were excluded for various reasons; 29 eligible articles were included in this analysis.&#x0D; Notably, factors such as younger age (P&lt;0.0001), later year of diagnosis (P=0.03), residence in Central and Southern Europe and&#x0D; the United States (P=0.02), and lower-grade tumors in Asian countries (P&lt;0.002) correlated with the desire of women to preserve&#x0D; their ovaries. The conducted literature review showed that ovarian preservation did not significantly affect cancer-specific survival&#x0D; (risk ratio (HR) =0.78, 95% CI 0.17-2.74) or overall survival (HR=0.78, 95% CI 0.24-1.75).&#x0D; This study’s results remained practically unchanged even after excluding women after radiation and hormone therapy.&#x0D; Conclusion: This literature review revealed no statistically significant difference in relapse-free survival between patients after&#x0D; ovarian preservation at stage IA and partially at stage II com-pared to those after bilateral salpingo-oophorectomy.

Advances in research on autophagy mechanisms in resistance to endometrial cancer treatment.

Administering medication is a crucial strategy in improving the prognosis for advanced endometrial cancer. However, the rise of drug resistance often leads to the resurgence of cancer or less-than-ideal treatment outcomes. Prior studies have shown that autophagy plays a dual role in the development and progression of endometrial cancer, closely associated with drug resistance. As a result, concentrating on autophagy and its combination with medical treatments might be a novel approach to improve the prognosis for endometrial cancer. This study explores the impact of autophagy on drug resistance in endometrial cancer, investigates its core mechanisms, and scrutinizes relevant treatments aimed at autophagy, aiming to illuminate the issue of treatment resistance in advanced endometrial cancer.

Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers.

The development of endometrial cancer (EC) is closely related to the abnormal activation of the estrogen signaling pathway. Effective diagnostic markers are important for the early detection and treatment of EC. We downloaded single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) data of EC from public databases. Enrichment scores were calculated for EC cell subpopulations using the "AddModuleScore" function and the AUCell package, respectively. Six predictive models were constructed, including logistic regression (LR), Gaussian naive Bayes (GaussianNB), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and neural network (NK). Subsequently, receiver-operating characteristics with areas under the curves (AUCs) were used to assess the robustness of the predictive model. We classified EC cell coaggregation into six cell clusters, of which the epithelial, fibroblast and endothelial cell clusters had higher estrogen signaling pathway activity. We founded the epithelial cell subtype Epi cluster1, the fibroblast cell subtype Fib cluster3, and the endothelial cell subtype Endo cluster3 all showed early activation levels of estrogen response. Based on EC cell subtypes, estrogen-responsive early genes, and genes encoding Stage I and para-cancer differentially expressed proteins in EC patients, a total of 24 early diagnostic markers were identified. The AUCs values of all six classifiers were higher than 0.95, which indicates that the early diagnostic markers we screened have superior robustness across different classification algorithms. Our study elucidates the potential biological mechanism of EC response to estrogen at single-cell resolution, which provides a new direction for early diagnosis of EC.

Oncologic and Pregnancy Outcomes of a Fertility Sparing Treatment in Endometrial Cancer: A Single Center Experience

Oncologic and Pregnancy Outcomes of a Fertility Sparing Treatment in Endometrial Cancer: A Single Center Experience

Lenvatinib plus pembrolizumab in the patients with advanced previously treated endometrial cancer: A cost-effectiveness analysis in the United States and in China.

To investigate the cost-effectiveness of lenvatinib plus pembrolizumab (LP) compared to chemotherapy as a second-line treatment for advanced endometrial cancer (EC) from the United States and Chinese payers' perspective. In this economic evaluation, a partitioned survival model was constructed from the perspective of the United States and Chinese payers. The survival data were derived from the clinical trial (309-KEYNOTE-775), while costs and utility values were sourced from databases and published literature. Total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were estimated. The robustness of the model was evaluated through sensitivity analyses, and price adjustment scenario analyses was also performed. Base-case analysis indicated that LP wouldn't be cost-effective in the United States at the WTP threshold of $200 000, with improved effectiveness of 0.75 QALYs and an additional cost of $398596.81 (ICER $531392.20). While LP was cost-effective in China, with improved effectiveness of 0.75 QALYs and an increased overall cost of $62270.44 (ICER $83016.29). Sensitivity analyses revealed that the above results were stable. The scenario analyses results indicated that LP was cost-effective in the United States when the prices of lenvatinib and pembrolizumab were simultaneously reduced by 61.95% ($26.5361/mg for lenvatinib and $19.1532/mg for pembrolizumab). LP isn't cost-effective in the patients with advanced previously treated endometrial cancer in the United States, whereas it is cost-effective in China. The evidence-based pricing strategy provided by this study could benefit decision-makers in making optimal decisions and clinicians in general clinical practice. More evidence about budget impact and affordability for patients is needed.

[Prevention and treatment of endometrial cancer].

Endometrial cancer is rising in incidence, especially in young women. This rise in incidence has implications for both primary prevention and screening in high-risk population. In the past several years, our understanding of the integration of clinically related genomic and pathologic data optimized the management of endometrial cancer. The updated 2023 FIGO staging includes the histological and molecular classification to better reflect the improved understanding of the heterogenous nature of endometrial carcinoma. Standard primary treatment is quite essential, however, selection of patients for adjuvant radiation or chemotherapy remains in controversy. Molecular characterization of endometrial cancer is becoming critical in directing treatment for advanced and recurrent disease, and the addition of immunotherapy to frontline chemotherapy is becoming the standard of care. More attention should be given to increase awareness of survivorship issues and improve patient quality-of-life.

A Comparative Cohort Study of Laparoscopy Versus Laparotomy for the Treatment of Iranian Endometrial Cancer Patients

Background: In recent decades, laparoscopy and robotic surgery are mostly used for the treatment of endometrial cancer. Laparoscopic surgery's popularity has grown due to rapid postoperative recovery and reduced post-surgical morbidity and complications compared with open surgery. Objectives: This study aimed to compare laparoscopic surgery and laparotomy in terms of their advantages and disadvantages for treating early-stage endometrial cancer in a population of Iranian patients in a referral center of gyneco-oncology. Methods: In this cohort study at Imam Hossein Medical Center in Tehran, Iran, from 2019 to 2022, early-stage endometrial cancer patients were included. Advanced disease, patients with medical comorbidity not suitable for laparoscopy, previous surgery for endometrial cancer, and prior chemotherapy or radiotherapy for treatment of the endometrial cancer were excluded from the study. The study compared two groups regarding operative findings, including FIGO stage, grade, postoperative complications, and hospitalization days. Results: The study included 17 patients in the laparoscopic group with a mean age of 56(+ 12.5) years old and 44 patients in the laparotomy group with a mean age of 57(+ 10.2) years old. Two groups were well-matched in terms of body mass index and menopausal status. The median intraoperative blood loss was significantly in terms of statistical less in the laparoscopic group (200 ml versus 500 ml, P = 0.001). Four (23.5%) patients in the laparoscopic group needed intraoperative blood transfusion versus 22 (50.0%) in the laparotomy group, P = 0.061. Hospital stay days were shorter in the laparoscopic group, with a median of three versus six days (P &lt; 0.001). Conclusions: In conclusion, the minimally invasive operation caused less blood loss, hospital stay, and blood transfusion in comparison to laparotomy in Iranian endometrial cancer patients, confirming the preferred method of laparoscopy in these patients.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

A novel predictive model of lymphovascular space invasion in early-stage endometrial cancer.

To predict lymphovascular space invasion (LVSI) positivity in early-stage (stage 1-2) endometrial cancer (EC) using a predictive model with prognostic factors of EC. We included 461 patients who underwent total hysterectomy and bilateral salpingo-oophorectomy with pelvic-paraaortic lymphadenectomy as the primary treatment for presumed early-stage EC at our clinic between 2010 and 2020. Moreover, all surgical specimens were examined histopathologically for the positivity or negativity of LVSI, and the patients were divided into two groups based on these pathologic outcomes. Age, menopausal status, histological type (type 1-2), histological grade (grades 1-2-3), depth of myometrial invasion, and peritoneal cytology results were recorded and analyzed as clinicopathological and demographic characteristics of the patients. The Loess algorithm determined the relationship between the observed and predicted outcomes. The distinction between the algorithms was evaluated by calculating the C-index. LVSI positivity was significantly associated with advanced age, menopause, type 2 EC, advanced histological grade, malignant peritoneal cytology, cervical involvement, and a tumor exceeding 50% of the myometrial depth (p<0.001, respectively). Remarkably, LVSI was most strongly associated with three explanatory variables: 1- More than 50% myometrial invasion [odds ratio (OR): 3.78; 95% confidence interval (CI): 1.80-7.60], 2- Advanced histological grade [OR=1.98 (1.20-3.20) 95% CI], 3- Malignant peritoneal cytology [OR= 3.06 (1.40-6.30) 95% CI]. The penalized maximum likelihood estimation model correctly classified 87% of the included patients (C-index: 0.876). Our predictive model may help predict LVSI based on different prognostic factors. The prognostic factors included in the nomogram were significantly associated with LVSI, particularly myometrial invasion depth of more than 50%, advanced histological grade, and malignant peritoneal cytology.

Potential bioactive compound and hub gene identification of endometrial carcinoma using systems biology

Endometrial carcinoma is a frequent cancer of the female genital tract. Endometrial carcinoma accounts for 97% of all uterine malignancies and 3 % of sarcomas that develop from the endometrium’s glands. Endometrial cancer is frequently found in its early stages since most women quickly report postmenopausal vaginal hemorrhage. The need for more advanced medications to improve survival in such situations is still unfulfilled. As a result, there is growing interest in employing an herbal treatment to treat endometriosis, which seems to be an effective strategy. We have discovered a few unintended targets (ligands) in our investigation that are active components of common therapeutic herbs. The differentially expressed genes (DEG - target protein) for endometrial cancer were found using the NCBI and CIViC databases. In our investigation, the protein used for docking and simulation was PDB ID: 3THW. Using the Cytoscape server, the gene-encoding protein network has been identified. It was discovered that the Protein 3THW's binding energy to the bioactive substance (Asarone) was −7.15 Kcal/mol. It was discovered that the crucial interacting amino acid residues were ILE648, PHE650, ILE651, VAL802, TYR815, VAL817. The properties of the pharmaceutical target are further investigated by employing a molecular simulation study for 100 ns with NAMD software. Low RMSD and SASA (Solvent accessible surface area), high RMSF, High hydrogen bonds, between Asarone and MSH2 demonstrated their potency as endometrial cancer inhibitor compounds. Based on these analyses we infer that the bioactive substances originating from medicinal plants may be an effective treatment for endometrial cancer. Communicated by Ramaswamy H. Sarma