Real-world first-line treatment patterns and outcomes in recurrent/advanced endometrial cancer patients in Europe.

Background: The treatment patterns and clinical outcomes in recurrent/advanced endometrial cancer in Europe are not well known. Materials & methods: Endometrial Cancer Health Outcomes-Europe-First-Line is a multicenter, retrospective chart review study conducted in the UK, Germany, Italy, France and Spain. Patients diagnosed with recurrent/advanced endometrial cancer who initiated first-line systemic therapy between 1 July 2016 and 31 March 2020 were eligible. Results: Among 242 patients, median age was 69 years and 82.2% had stage IIIB-IV disease. In first-line, most patients received platinum-based chemotherapy (78.9%); others received endocrine therapy (6.2%), taxane monotherapy (5.8%) and nonplatinum or taxane-based chemotherapy (4.1%). Median real-world progression-free survival since first-line initiation was 10.8 months and median overall survival was 20.7 months. Conclusion: Poor prognosis with platinum-based first-line chemotherapy suggests significant unmet medical need.

Treatment patterns & survival for recurrent/advanced endometrial cancer patients in Europe who received their first treatmentThe treatments and survival for recurrent/advanced endometrial (uterus lining) cancer patients in real-life European settings are not well known. Endometrial Cancer Health Outcomes-Europe-First-Line is a multicenter study that was conducted in the UK, Germany, Italy, France and Spain and used de-identified information from existing patient medical records. Patients diagnosed with recurrent/advanced endometrial cancer who initiated a first treatment between 1 July 2016 and 31 March 2020 were included. Among 242 included patients, the average age was 69 years and 82.2% had stage IIIB-IV disease (indicating the size and extent of their cancer). As their first treatment, most patients received platinum-based chemotherapy (78.9%), which is a type of drug that kills cancer cells. Overall, patients lived for an average of 20.7 months since their first treatment. The average length of time patients lived without their disease getting worse was 10.8 months since their first treatment. We found that patients who received platinum-based chemotherapy as their first treatment had poor survival, which suggests significant unmet medical need.

Analysis of Risk Factors for Secondary Endometrial Cancer-Related Death: A SEER-Based Study.

Purpose: The aim of this study was to analyze the survival of patients with endometrial cancer diagnosed after a prior cancer and identify risk factors of endometrial cancer death in this population. Methods: Totally 1371 women diagnosed with second primary endometrial cancer (SPEC) between 2004 and 2015 were identified using the SEER database. Clinicopathological characteristics were collected, and Fine and Gray regression model was employed to assess the impact of treatment for the first primary cancer (FPC) and SPEC on the mortality of endometrial cancer patients. After propensity score matching (PSM), patients diagnosed with single primary endometrial cancer and SPEC between 2004 and 2015 were included as the second cohort. Kaplan-Meier and Cox survival risk models were used to assess the influence of previous cancer history on survival. Results: Patients previously diagnosed as lung cancer exhibited the lowest overall survival (OS). A diagnostic interval of ≥3 years was significantly associated with higher mortality from SPEC compared with that <3 years. Surgical treatment for SPEC was linked to a reduced risk of endometrial cancer-specific mortality (ECSM) and non-ECSM. Conversely, radiotherapy and chemotherapy were associated with an increased risk of ECSM. The 1-, 3-, and 5-year OS rates of patients with SPEC were significantly lower than those with single primary endometrial cancer whether before or after PSM. Univariate and multivariate analyses further demonstrated that endometrial cancer, either as FPC or SPEC, was independently associated with an increased risk for endometrial cancer-specific survival (ECSS) and OS. Conclusion: Chemotherapy and radiotherapy for SPEC can elevate the risk of ECSM. Whether as FPC or SPEC, endometrial cancer is demonstrated to be a significant independent risk factor for ECSS and OS.

Identification of Key Genes Associated with Polycystic Ovarian Syndrome and Endometrial and Ovarian Cancer through Bioinformatics.

Background: Polycystic ovary syndrome (PCOS), a common endocrine disorder, is linked to increased risks of endometrial cancer (EC) and ovarian cancer (OC). Our study utilises bioinformatics analysis to identify shared gene signatures and elucidate biological processes between EC and OC and PCOS. Aim: The objective of this research is to unveil the common molecular landscape shared by PCOS and EC and OC. Settings and Design: An observational computational bioinformatics analysis. Materials and Methods: Gene expression profiles for PCOS (GSE199225), EC (GSE215413) and OC (GSE174670) were obtained from the Gene Expression Omnibus database. Hub genes were identified through functional enrichment analysis and protein-protein interaction. Drug identification analyses were employed to find drugs targeting the hub genes. Results: Key hub genes linking PCOS and EC includes RECQL4, RAD54L, ATR, CHTF18, WDHD1, CDT1, PLK1, PKMYT1, RAD18 and RPL3; for PCOS and OC, they include HMOX1, TXNRD1, NQO1, GCLC, GSTP1, PRDX1, SOD1, GPX3, BOP1 and BYSL. Gene Ontology analysis revealed DNA metabolic process in PCOS and EC, while in PCOS and OC, it identified the removal of superoxide radicals. Kyoto Encyclopaedia of Genes and Genomes pathway analysis highlighted cell cycle in PCOS and EC and hepatocellular carcinoma in PCOS and OC. Potential drugs for PCOS and EC include quercetin, calcitriol and testosterone; for PCOS and OC, eugenol and 1-chloro-2,4-dinitrobenzene are identified. Conclusion: These findings offer insights into potential therapeutic targets and pathways linking PCOS with EC and OC, enhancing our understanding of the molecular mechanisms involved in these associations.

CytoGAN: Unpaired staining transfer by structure preservation for cytopathology image analysis.

With the development of digital pathology, deep learning is increasingly being applied to endometrial cell morphology analysis for cancer screening. And cytology images with different staining may degrade the performance of these analysis algorithms. To address the impact of staining patterns, many strategies have been proposed and hematoxylin and eosin (H&E) images have been transferred to other staining styles. However, none of the existing methods are able to generate realistic cytological images with preserved cellular layout, and many important clinical structural information is lost. To address the above issues, we propose a different staining transformation model, CytoGAN, which can quickly and realistically generate images with different staining styles. It includes a novel structure preservation module that preserves the cell structure well, even if the resolution or cell size between the source and target domains do not match. Meanwhile, a stain adaptive module is designed to help the model generate realistic and high-quality endometrial cytology images. We compared our model with ten state-of-the-art stain transformation models and evaluated by two pathologists. Furthermore, in the downstream endometrial cancer classification task, our algorithm improves the robustness of the classification model on multimodal datasets, with more than 20 % improvement in accuracy. We found that generating specified specific stains from existing H&E images improves the diagnosis of endometrial cancer. Our code will be available on github.

Association between chemotherapy for surgically treated rectal cancer and second primary endometrial cancer.

To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals.

Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study.

OBJECTIVE: To examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications. METHODS: Women diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student's t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type. RESULTS: A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively). CONCLUSIONS: These findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART.

High prevalence of dysfunctional uterine bleeding in candidates for metabolic/bariatric surgery: increased endometrial cancer risk?

BACKGROUND: Endometrial cancer (EC) is the strongest obesity-associated malignancy and the fastest-growing cancer in young women. Early identification of EC and other endometrial pathology (malignant and nonmalignant) in women with severe obesity may improve treatment options and uterine preservation. Screening for endometrial pathology using abnormal or postmenopausal uterine bleeding (APUB) as a surrogate in women pursuing metabolic/bariatric surgery may be clinically beneficial, but data supporting this effort are limited. OBJECTIVE: To develop and institute a screening program for APUB as a surrogate for endometrial pathology in bariatric surgery candidates. SETTING: Two, academic metabolic/bariatric surgery programs in Louisiana, United States. METHODS: The Modified SAMANTA is a 10-item questionnaire that was implemented to identify patients with APUB, specifically combining tools designed to identify anovulatory/postmenopausal and heavy menstrual bleeding. Demographic (age, race), body mass index, and questionnaire data were analyzed with respect to positive screening using data from March 2021 through May 2023. RESULTS: Of 1371 eligible women presenting for surgical evaluation, 664 (48.4%) positive screens were identified and referred for gynecologic evaluation to rule out endometrial hyperplasia/cancer or other endometrial pathology. The likelihood of positive screening for APUB was associated with increasing BMI (P = .001) and Black/African American race (P = .003), as well as increasing SAMANTA score (P < .001). In contrast, risk of positive screening was negatively associated with increasing age (P < .001). CONCLUSIONS: Women presenting for metabolic/bariatric surgery have a high prevalence of APUB and, given this dysfunctional bleeding and concurrent obesity, are at greater risk for underlying EC. Potential risk factors for APUB, given their associations with screening positive, include increased body mass index, younger age, and Black/African American race. Standardized screening with appropriate gynecologic referral should be a routine part of the overall evaluation for women with severe obesity.

Endometrial cancer treatment and outcomes in Argentina: ECHOS-A real-world study.

Objective: Real-world data for patients with endometrial cancer (EC) are limited, particularly in Latin America. We present treatment pattern findings from ECHOS-A - Endometrial Cancer Health Outcomes Study in Argentina. Materials and methods: A retrospective study using clinical data from privately insured patients with EC diagnosed from 2010 to 2019. Index (diagnosis proxy) was first date of an EC-related health term or treatment. Demographics, clinical characteristics, and FIGO staging were described. Disease progression and survival were assessed until study end, loss to follow-up, or death. Results: Of 805 patients with EC, 77.4 % (n = 623/805) received any treatment and 22.6 % (n = 182/805) received none. Among those treated, 31.8 % (n = 198/623) had first-line (1L) systemic therapy, and 45.5 % (n = 90/198) proceeded to second-line (2L) therapy. Mean follow-up was 33.6 (SD 31.8) months. Of those receiving any treatment, 87.3 % (n = 544/623) had FIGO stage data (I, 62.9 %; II, 18.6 %; III, 13.6 %; IV, 5.0 %). Treatment by class in 1L and 2L, respectively, were platinum chemotherapy, 73.7 %, 36.7 %; non-platinum chemotherapy, 73.7 %, 62.2 %; immunotherapy, 1.0 %, 11.1 %; hormone therapy, 17.7 %, 26.7 %. Carboplatin/paclitaxel was the most frequent 1L (52.5 %) and 2L (14.4 %) regimen. Mean time to progression was 14.1 (SD 16.3) and 8.8 (SD 8.3) months in 1L and 2L, respectively. Adjusted 1- to 5-year risk of progression/death was 46.5-77.5 % and 65.0-86.2 % in 1L and 2L, respectively. Conclusions: Approximately one-quarter of patients with EC received no treatment, and approximately two-thirds were not treated with 1L systemic therapy. Efforts to better understand the reasons for these treatment patterns are crucial for improving patient outcomes.

Is fluorometric sentinel lymph node biopsy in endometrial cancer necessary?

Objective: In this study, we collected perioperative and postoperative follow-up data from patients with endometrial cancer (EC) at different stages to evaluate the role of sentinel lymph node biopsy (SLNB) in endometrial cancer surgery. Methods: A total of 186 endometrial cancer patients undergoing radical hysterectomy from January 2018 to April 2022 were retrospectively analyzed. Patients were classified into four groups. Group A comprised patients diagnosed with stage IA grade 1 and 2 endometrioid EC who underwent SLNB. Group B comprised patients with stage IA grade 1 and 2 endometrioid EC who did not undergo SLNB. Group C comprised patients with higher-grade endometrioid EC, wherein systematic lymph node dissection was performed based on SLNB results. Group D comprised patients with higher-grade endometrioid EC who did not undergo SLNB and instead underwent direct systematic lymph node dissection. Clinical, pathological data, and follow-up information for all patients were collected. Results: In Group A and B, SLNB was performed on 36 out of 67 patients with IA stage 1 and 2 endometrial cancer, yielding a SLN positivity rate of 5.6%. There were no significant differences observed between the two groups regarding perioperative outcomes and postoperative follow-up. Conversely, among 119 patients with higher-grade endometrial cancer, 52 underwent SLNB, with 20 patients exhibiting SLN positivity, resulting in a SLN positivity rate of 38.4%. However, the decision to undergo SLNB did not yield significant differences in perioperative outcomes and postoperative follow-up among these patients. Conclusion: For stage IA grade 1 and 2 endometrioid EC, the incidence of lymph node positivity is low, omitting SLNB in this subpopulation is a feasible option. In other stages of endometrioid EC, there is no significant difference in perioperative and postoperative follow-up data between patients undergoing routine systematic lymphadenectomy and those undergoing systematic lymphadenectomy based on SLNB results. Therefore, if SLNB is not available, the standard procedure of PLND remains an option to obtain information about lymph node status, despite the surgical complications associated with this procedure.

"A rare case of bladder myiasis mimicking radiation cystitis-A first case report".

Patients diagnosed with cancer post-treatment are prone to have recurrent disease. Regular follow-up of these patients enables early recognition and treatment. A tissue diagnosis before starting treatment is imperative to avoid misdiagnosis and management. Given their immunosuppression, maintaining good nutrition, body hygiene, and clean surroundings is essential to prevent the most common urinary tract infection to rare urinary myiasis infection. Cochliomyia hominivorax, Chrysomya bezziana, and Wohlfahrtia magnifica are the most prevalent flies causing myiasis in human beings. Risk factors for urinary myiasis are open or untreated wounds and debris around the genital area. Specific flies, ticks, and mosquitoes are responsible for myiasis in tropical or subtropical countries, when it is usually not transmitted from human to human. Flies lay their eggs near the urethra, and the larvae hatch and migrate to the bladder. Increased urinary frequency, haematuria, and lower abdominal pain are the most commonly found presenting symptoms. Simple preventive measures can avoid these complications. So, prevention is better than cure.

Glucagon-like peptide-1 (GLP-1) receptor agonists for weight management: A review for the gynecologic oncologist.

The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has experienced rapid growth amidst the obesity epidemic in the United States. While originally developed for glucose control in Type 2 Diabetes Mellitus, the scope of these agents now extends to encompass weight loss and cardiovascular risk reduction. GLP-1RAs have the potential to induce significant weight loss, in combination with lifestyle modifications, among adults who are overweight or obese. Furthermore, these agents demonstrate efficacy in ameliorating hyperglycemia, enhancing insulin sensitivity, regulating blood pressure, improving cardiometabolic parameters, mitigating kidney dysfunction, and potentially reducing the risk of several obesity-related cancers. Drug-related toxicity is primarily gastrointestinal and active management can prevent drug discontinuation. Obesity is associated both with an increased incidence of malignancy but also with decreased survival. More research is needed to evaluate the potential use of GLP-1RA to modify the endocrine function of adipocytes, regulate the chronic inflammatory state associated with obesity, and prospective applications in oncology. These agents can impact patients with gynecologic malignancies both through their direct mechanism of action as well as potential drug toxicity.

Association between systemic lupus erythematosus and common female reproductive system malignancies.

Lymphocytes are important for protective immunity against infections and cancers, and dysregulation of the immune system may lead to systemic lupus erythematosus (SLE). Metabolic adaptation regulates the fate of lymphocytes. The immune microenvironment is vital role in both SLE and gynecological malignancies. The disruption of the immune microenvironment in SLE is one of the key factors leading to disease occurrence. Overactive autoimmunity indices the body to attack its own tissues, leading to the formation of immune complexes that further trigger tissue damage and inflammation. This imbalance in the immune microenvironment affects the progression of SLE and may also indirectly affect the occurrence of gynecological cancers. For gynecological cancers, immune cells, cytokines, and chemokines in the tumor microenvironment jointly comprise a complex network, and their interactions determine cancer growth, invasion, and metastasis. Mendelian randomization analysis revealed that SLE does not have a statistically significant causal effect on the risk of common cancers of the female reproductive system such as cervical, endometrial, and ovarian cancers in the European population. However, the odds ratio < 1 in the inverse variance weighted results suggest the potential of SLE as a protective factor for endometrial cancer.

MRI Radiomics Data Analysis for Differentiation between Malignant Mixed Müllerian Tumors and Endometrial Carcinoma.

The objective of this study was to compare the quantitative radiomics data between malignant mixed Müllerian tumors (MMMTs) and endometrial carcinoma (EC) and identify texture features associated with overall survival (OS). This study included 61 patients (36 with EC and 25 with MMMTs) and analyzed various radiomic features and gray-level co-occurrence matrix (GLCM) features. These variables and patient clinicopathologic characteristics were compared between EC and MMMTs using the Wilcoxon Rank sum and Fisher's exact test. The area under the curve of the receiving operating characteristics (AUC ROC) was calculated for univariate analysis in predicting EC status. Logistic regression with elastic net regularization was performed for texture feature selection. This study showed that skewness (p = 0.045) and tumor volume (p = 0.007) significantly differed between EC and MMMTs. The range of cluster shade, the angular variance of cluster shade, and the range of the sum of squares variance were significant predictors of EC status (p ≤ 0.05). The regularized Cox regression analysis identified the "256 Angular Variance of Energy" texture feature as significantly associated with OS independently of the EC/MMMT grouping (p = 0.004). The volume and texture features of the tumor region may help distinguish between EC and MMMTs and predict patient outcomes.

Port Site Metastasis in Women with Low- or Intermediate-Risk Endometrial Carcinoma: A Systematic Review of Literature.

Background: Port site metastasis (PSM) has been reported as a rare metastasis in women with endometrial carcinoma (EC). However, even more rarely, it has also been described in patients with low- or intermediate-risk EC. Unfortunately, knowledge appears limited on the topic. Objectives: Our objective was to systematically review the literature on PSM in low- or intermediate-risk EC. Search Strategy: A systematic review of the literature was performed by searching six electronic databases from their inception to January 2023. Selection Criteria: We included in our research all peer-reviewed studies which reported PSM in low- or intermediate-risk EC women. Data Collection and Analysis: Data on PSM were collected from the included studies and compared. Results: Seven studies with 13 patients (including our case) were included in the systematic review. PSM was reported in patients with low- or intermediate-risk EC independently from tumor histologic characteristics, endoscopic approach, lymph node staging type, number and site of the port, route of specimen removal, prevention strategies for PSM, and concomitant metastases. Among several proposed treatments, local resection and radiotherapy with or without chemotherapy might be the most appropriate ones. Nevertheless, the prognosis appears poor. Conclusions: In patients with low- or intermediate-risk EC, PSM can occur as a rare metastasis, regardless of tumor characteristics or surgical strategy. Unfortunately, no consensus has been reached regarding treatment, and the prognosis appears poor. Additional cases are needed in order to confirm and further explore this rare EC metastasis.

A 10-Year Retrospective Cohort Study of Endometrial Cancer Outcomes and Associations with Lymphovascular Invasion: A Single-Center Study from Germany.

This 10-year retrospective cohort study at a single-center clinic in Germany aimed to analyze the outcomes of endometrial cancer patients and explore the impact of lymphovascular invasion (LV) on patient outcomes and disease-free survival (DFS). Identifying correlations among demographic data, tumor characteristics, treatment modalities, and survival outcomes could enhance patient management and improve survival rates. The study encompassed patients diagnosed and treated for endometrial cancer from January 2010 to December 2020. Clinical and pathological data were extracted from medical records for 311 patients, focusing on variables such as age, histological type, tumor grade, type of surgical treatment, and adjuvant therapies. Survival analysis was conducted using the Kaplan-Meier method and multivariate Cox proportional hazard models to identify factors independently associated with survival. The study demonstrated that lymphovascular invasion significantly impacted survival outcomes on Kaplan-Meier analysis (log-rank p-value = 0.0058). Patients with LV showed a marked decrease in DFS compared to those without LV invasion, with a median DFS of 3.2 years and a hazard ratio of 2.18 (95% CI: 1.56-3.04, p < 0.001). Furthermore, high-grade tumors and p53 positivity were strongly associated with reduced DFS, with hazard ratios of 1.93 (p = 0.001) and 2.11 (p < 0.001), respectively. Patients with distant metastasis exhibited the most significant decline in survival, with a hazard ratio of 5.56 (95% CI: 2.45-10.18, p < 0.001). Despite comprehensive surgical and adjuvant therapies, these high-risk factors dictated poorer outcomes. The presence of lymphovascular invasion, high-grade tumors, and genetic markers like MSI and p53 are pivotal in predicting the course of endometrial cancer. This study underscores the necessity for aggressive management strategies in patients exhibiting these high-risk features to potentially improve prognosis and survival outcomes. The findings advocate for enhanced therapeutic strategies tailored to the biological behavior of the tumor, thereby aiming to elevate the overall survival rates for women diagnosed with endometrial cancer.

Comprehensive molecular characterization of early stage grade 3 endometrioid endometrial adenocarcinoma.

OBJECTIVE: The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes. METHODS: Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures. RESULTS: 46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%). CONCLUSIONS: This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.

"The optimal endometrial thickness threshold for prediction of endometrial cancer in postmenopausal women without bleeding remains uncertain - Systematic review and meta-analysis".

The incidental finding of endometrial thickness (ET) >4 mm in the absence of postmenopausal bleeding (PMB) is a common cause of referring women to secondary care. However, there is lack of consensus amongst gynecologists as regards the management. It is estimated that up to 15% of endometrial cancers occur in women without PMB. The aim this study was to determine the optimal ET threshold, on trans-vaginal ultrasound scan, that discriminates normal endometrium from endometrial hyperplasia and cancer in this cohort. On using a thorough search strategy, a total 16 studies including 4088 women were deemed eligible. However, the data were not amenable to meta-analysis. There were wide variations in the thresholds reported with potential bias given the retrospective nature of the majority of the studies. Despite contacting authors, we could not obtain the primary data to generate a Receiver Operating Characteristic (ROC) Curve. No linear or curvilinear association was found between ET thresholds and the percentage of women diagnosed with endometrial hyperplasia and cancer using either Pearson's correlation, linear or curvilinear regression, or a simple visual scan/scatter diagram. The result of this study reveals the lack of evidence to inform clinical practice in this area, and there is a need for a well-designed multi-center prospective study.

Lymphovenous anastomosis and complex decongestive therapy for severe deformed lymphedema with recurrent infection: A case report.

BACKGROUND: Lower extremity lymphedema is a common complication following treatment for gynecological malignancies. Its incidence rate can reach up to 70%, affecting ~20 million people worldwide. However, specialized treatment centers are scarce, and there is a lack of consensus on treatment approaches. Furthermore, there are even fewer reports on the systematic and effective treatment of severe lymphedema with malformations. Effective management of this condition remains a significant challenge for clinicians. CASE SUMMARY: A 40-year-old woman developed bilateral leg swelling 6 years after receiving treatment for endometrial cancer. Since August 2018, she experienced > 30 episodes of lymphangitis. Upon presentation, she exhibited bilateral leg swelling and deformation, with four large swellings in the posterior thigh that impeded movement, and pain in the limbs. Skin manifestations included lichenoid lesions and features of deep sclerosis. Radionuclide lymphoscintigraphy confirmed the diagnosis of lower limb lymphedema. After 6 mo of complex decongestive therapy (CDT) and three lymphaticovenous anastomosis (LVA) treatments, the patient lost 49 kg in weight. She also experienced a maximum circumference reduction of 35.2 cm in the left lower limb and 37.5 cm in the right lower limb. The leg pain disappeared, her swelling significantly decreased, and she regained the ability to walk, cycle, and run normally. CONCLUSION: The combined application of CDT and LVA therapy demonstrates significant positive effects in the treatment of severe, deformed stage III lymphedema.

Economic Burden of Endometrial Cancer Associated With Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged females, and women with PCOS are at increased risk for endometrial cancer (EndoCA), the most common gynecological malignancy. Our study sought to assess the economic burden associated with EndoCA in PCOS. METHOD: Using PRISMA systematic review guidelines, we evaluated studies on EndoCA rates in patients with PCOS. Excluded studies were reviews and case reports, non-human subjects, without controls, without full text available, or reporting solely on other conditions. Selected studies were assessed for quality using the Newcastle-Ottawa Scale (NOS). Meta-analysis used DerSimonian-Laird random effects model to assess pooled risk ratio (RR). Excess cost was assessed in U.S. dollars (USD). RESULT: Of 98 studies screened, nine were included. Pooled RR for EndoCA in PCOS was 3.46 (95% CI 2.28-5.23), p=<0.001. In the US, prevalence of EndoCA in patients with PCOS in 2020 was 1.712%, compared with a baseline estimated prevalence in all women of 0.489%. The excess prevalence of EndoCA attributable to PCOS was 1.223%, approximately 98,348 affected women. A population-attributable fraction of EndoCA for PCOS was 24.4%. Given estimated cost of EndoCA exceeds $1.9 billion (in 2023 USD), the economic burden of EndoCA attributable to PCOS exceeds $467 million/year. CONCLUSION: The excess annual healthcare cost for EndoCA attributable to PCOS exceeds $467 million/year (2023 USD) for the US. Although a concerning morbidity of PCOS, it is notable that the economic burden of EndoCA attributable to the disorder represents only a small fraction of its total healthcare burden.

Individuality and generality of intratumoral microbiome in the three most prevalent gynecological malignancies: an observational study.

Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = -0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = -0.4451) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = -0.3868) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.