Diagnosis Of Endometrial Cancer Research Articles

P9 Access to gynecologic oncologist specialists for patients with a new endometrial cancer diagnosis in the United States

P9 Access to gynecologic oncologist specialists for patients with a new endometrial cancer diagnosis in the United States

The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer.

Selenium (Se) and manganese (Mn) are essential micronutrients that are important elements of cell metabolism. They are involved in the composition of enzyme systems and regulate enzyme activity. Disturbances in the homeostasis of these micronutrients affect the development of many diseases and carcinogenesis, which can be linked to increased levels of oxidative stress and impaired antioxidant properties of many enzymes. Selenium has a very important function in maintaining immune-endocrine, metabolic and cellular homeostasis. Manganese, on the other hand, is important in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activity. We review the role of selenium and manganese and their effects on tumor growth, metastasis potential and remodeling of the microenvironment. We also describe their role as potential biomarkers in the diagnosis and the potential for the use of Se- and Mn-containing compounds in composition for the treatment of cancer of the reproductive organs.

A model for predicting extrauterine tumor spread in patients with endometrial cancer

A model for predicting extrauterine tumor spread in patients with endometrial cancer
 
 Abstract
 Background: The factors predicting extrauterine spread in patients undergoing staging surgery with the diagnosis of endometrial cancer were investigated. 
 Aims: The study aimed to create a model using demographic, surgical, and pathological factors to predict extrauterine spread.
 Methods: Included in the study were 355 patients with a final diagnosis of endometrial cancer who underwent surgery for staging purposes. The effect of surgical-prognostic factors on extrauterine spread was analyzed using univariate analysis and multivariate logistic regression analysis.
 Results: Extrauterine spread was detected in 97 patients. A multivariate logistic regression model that was created to determine the factors affecting extrauterine spread identified the presence of lymphovascular invasion, cervical invasion, peritoneal cytology positivity and tumor type as independent factors. A model was created using these four independent risk factors. According to this model, the rate of extrauterine spread was 6.4% in patients who did not have the risk factors and 100% in patients who had all the risk factors (p

Serum protein N-glycome patterns reveal alterations associated with endometrial cancer and its phenotypes of differentiation.

Aberrant N-glycosylation and its involvement in pathogenesis have been reported in endometrial cancer (EC). Nevertheless, the serum N-glycomic signature of EC remains unknown. Here, we investigated serum N-glycome patterns of EC to identify candidate biomarkers. This study enrolled 34 untreated EC patients and 34 matched healthy controls (HC) from Peking Union Medical College Hospital. State-of-the-art MS-based methods were employed for N-glycans profiling. Multivariate and univariate statistical analyses were used to identify discriminative N-glycans driving classification. Receiver operating characteristic analyses were performed to evaluate classification accuracy. EC patients displayed distinct differences in serum N-glycome and had abnormal high-mannose and hybrid-type N-glycans, fucosylation, galactosylation, and linkage-specific sialylation compared with HC. The glycan panel built with the four most discriminative and biologically important derived N-glycan traits could accurately identify EC (random forest model, the area under the curve [AUC]=0.993 [95%CI 0.955-1]). The performance was validated by two other models. Total hybrid-type N-glycans significantly associated with the differentiation types of EC could effectively stratify EC into well- or poorly-differentiated subgroups (AUC>0.8). This study provides the initial evidence supporting the utility of serum N-glycomic signature as potential markers for the diagnosis and phenotyping of EC.

Gastrointestinal outcomes among older women with endometrial cancer

ObjectiveTreatment for endometrial cancer may contribute to bowel dysfunction and other gastrointestinal outcomes. We investigated the risk of several gastrointestinal diagnoses among older women with endometrial cancer and matched women without a history of cancer. MethodsWomen aged 66 years and older diagnosed with endometrial cancer during 2004–2017 (N = 44,386) and matched women without a known cancer history (N = 221,219) were identified in the SEER-Medicare linked data. An index date was defined as the endometrial cancer diagnosis date in that matched set. ICD-9 and -10 diagnosis codes were used to define gastrointestinal outcomes, including constipation, abdominal pain, IBS, fecal incontinence, bowel obstruction, ileus, radiation enteritis or proctitis, colonic stricture, and vascular insufficiency of the bowel in the Medicare claims. Hazard ratios (HRs) for incident gastrointestinal diagnoses were estimated using multivariable Cox proportional hazards regression models. ResultsCompared to women without cancer, women with endometrial cancer had an increased risk of gastrointestinal symptoms after the index date, including constipation (HR = 2.27; 95% CI: 2.22–2.32), abdominal pain (HR = 2.94; 95% CI: 2.89–2.99), and fecal incontinence (HR = 1.96; 95% CI: 1.83–2.10). The risk of other gastrointestinal diagnoses was also higher among women with endometrial cancer (e.g., bowel obstruction: HR = 5.72; 95% CI: 5.47–5.98; ileus: HR = 7.22; 95% CI: 6.89–7.57). These associations were also apparent in sensitivity analyses limited to 1+ and 5+ years after the index date. ConclusionsOlder women with endometrial cancer experience an excess risk of gastrointestinal diagnoses that may persist long after cancer diagnosis. Surveillance for these conditions may be a critical part of survivorship care.

Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation?

One emerging problem for onco-gynecologists is the incidence of premenopausal patients under 40 years of age diagnosed with stage I Endometrial Cancer (EC) who want to preserve their fertility. Our review aims to define a primary risk assessment that can help fertility experts and onco-gynecologists tailor personalized treatment and fertility-preserving strategies for fertile patients wishing to have children. We confirm that risk factors such as myometrial invasion and The International Federation of Gynecology and Obstetrics (FIGO) staging should be integrated into the novel molecular classification provided by The Cancer Genome Atlas (TCGA). We also corroborate the influence of classical risk factors such as obesity, Polycystic ovarian syndrome (PCOS), and diabetes mellitus to assess fertility outcomes. The fertility preservation options are inadequately discussed with women with a diagnosis of gynecological cancer. A multidisciplinary team of gynecologists, oncologists, and fertility specialists could increase patient satisfaction and improve fertility outcomes. The incidence and death rates of endometrial cancer are rising globally. International guidelines recommend radical hysterectomy and bilateral salpingo-oophorectomy as the standard of care for this cancer; however, fertility-sparing alternatives should be tailored to motivated women of reproductive age, establishing an appropriate cost-benefit balance between childbearing desire and cancer risk. New molecular classifications such as that of TCGA provide a robust supplementary risk assessment tool that can tailor the treatment options to the patient's needs, curtail over- and under-treatment, and contribute to the spread of fertility-preserving strategies.

Impact of surgical weight loss treatments on care burden among obese endometrial cancer survivors.

5607 Background: Among obesity-related cancers globally, 40% of disability adjusted life years lost are attributed to endometrial cancer (EC). EC patients are more likely to die of obesity-related complications rather than the cancer itself. Metabolic and bariatric surgery (MBS) is an effective weight loss treatment that has been shown to reduce prevalence and severity of many obesity-related chronic conditions. However, there is limited evidence on MBS on EC survivors. We examined the burden of patient healthcare utilization among EC survivors who did and did not undergo MBS. Methods: We utilized the SEER-Medicare database to identify 31,437 patients diagnosed with endometrial cancer between 2015 and 2017. We selected 9,229 (29.4%) patients with documented obesity (ICD codes) among whom 75 (0.8%) patients underwent MBS after completing EC treatment (2017-2019). EC survivors with and without a history of MBS were matched on age at EC diagnosis. We examined annualized Medicare inpatient and provider claims payments among EC-MBS (starting 3 months after the surgery, n=66) and EC-no MBS patients (2017-2019) and used Wilcoxon Rank-Sum tests to examine differences in payments in a 1:5 matched sample. Results: EC-MBS patients were younger (59.9 years) at the time of cancer diagnosis compared to EC-no MBS patients (68.2 years, p<0.01). In an age-matched sample, annualized median inpatient and provider claim payments among EC-MBS patients ($1,824) were lower than that of EC-no MBS patients ($2,920, p<0.01). Conclusions: Surgical weight loss achieves rapid and effective weight loss and has the potential to lower healthcare utilization among EC survivors but less than 1% of eligible patients receive the surgery. Further research is needed to better understand patient, provider, and access barriers to surgical weigh loss in patients with obesity-related cancers. [Table: see text]

Study of endometrial carcinoma on correlation between molecular typing and lymph node metastasis and construction of prediction model.

e17621 Background: TCGA molecular typing was proposed by The Cancer Genome Atlas (TCGA) in 2013 and recommended by the fifth edition of WHO, which has a strong prognositic value and is included in the risk stratification system, clinical diagnosis and treatment decision-making system of endometrial cancer (EC) patients. Meanwhile, Lymph node management in patients with EC is still controversial. Lymph node dissection (LND) and sentinel lymph node biopsy (SLNB) have their own advantages and limitations. This study attempts to establish a predictive model for lymph node metastasis (LNM) in patients with EC based on molecular typing and other clinical features and establish risk stratification, in order to provide a feasible method for predicting LNM in EC. Methods: In this study, SPSS19, R 4.2.1 and python 3.6 were used to establish a nomogram and evaluate it through a number of indicators, and the model was repeatedly verified by machine learning algorithms. With LNM as the outcome, risk stratification was set through the cut-off value of nomogram score to guide clinical treatment. Finally, an online LNM prediction website was designed to help patients. Results: A total of 325 EC patients were included, 35 (10.8%) with LNM and 290 (89.2%) without LNM. CA125 and cervical involvement were significantly correlated with LNM (p < 0.001), molecular typing, neutrophil to lymphocyte ratio (NLR), menstrual status were associated with LNM (p < 0.05). Lasso analysis screened out four independent factors: molecular typing, CA125, cervical involvement and menstrual status. The nomogram model was established by logistics regression (LR), with the prediction accuracy of the training set and validation set of 0.890 and 0.886, respectively. Machine learning algorithms in the training set also validates the model. Meanwhile, a risk stratification is established by the cut-off value of nomogram. We define high-risk group of LNM with more than the cut-off value and LND is recommended, while below the value is low-risk group and SLNB is recommended. Conclusions: We have established a nomogram clinical prediction model incorporating four factors, practicing stratified medical treatment about LND and SLNB, and formed a website for LNM prediction, genuinely providing patients recommendations.

Impact of best practice advisory on genetic counseling referral patterns for patients with endometrial cancer.

5606 Background: The National Comprehensive Cancer Network (NCCN) recommends that patients with endometrial cancer under age 50 undergo germline genetic testing. Despite this recommendation, completion rates are suboptimal for patients with gynecologic malignancies. The reasons for failure to complete testing are unknown, but oncology providers may not refer patients to genetic counselors, who frequently order this testing. Best practice advisories (BPAs) in electronic medical records can alert providers of patients who meet guideline-based treatments and testing criteria. It is unknown how oncology providers interact with a BPA indicating patients with endometrial cancer meet NCCN germline testing criteria. The objective of this study is to evaluate genetic counseling referral patterns after implementing a BPA. Methods: Our team developed a BPA to prompt oncology providers to order genetic counseling referrals for patients diagnosed with endometrial or uterine cancer under age 50. We reviewed all provider-BPA interactions between go-live (January 2022) and January 2023. Patient demographic, histopathologic, and cancer treatment data were collected. Provider actions, including BPA cancellation and order placement, were collected. The Chi-Square goodness of fit test was used to identify differences in referral rates by patient or disease characteristics. Results: The BPA displayed 1121 times for 103 patients. Attending physicians received 535 alerts, fellow physicians – 269, and advanced practice providers (APPs) – 317. The median number of alerts per patient was 7 (range 1-87). Of the 103 patients, 23 were excluded from analysis due to no diagnosis of endometrial cancer, patient declined referral, previously completed, or a lack of provider visits within the study period. Of the 80 eligible patients, 36 (45%) received referrals; 18 were placed by attending physicians, 17 by fellows, and one by an APP. Patients under age 40 versus age 40-49 were more likely to be referred (65% vs. 35%; p = 0.011). Patients with active disease were more likely to be referred than those in surveillance (65% vs. 18%; p < 0.001). There were no differences in referral rates by primary language, race, body mass index ≥40, fertility-sparing versus definitive treatment, stage I versus stage II-IV disease, or grade 1-2 versus three tumors. Conclusions: Despite implementing a BPA, only 45% of eligible patients received indicated referrals. Attending and fellow physicians frequently manage patients with active disease and often order referrals; however, APPs frequently manage patients in surveillance and infrequently place referrals, highlighting an opportunity for education. In addition, patients aged 40-49 are less likely to be referred, suggesting a need for new strategies to improve referral rates. Further research is indicated to identify referral barriers for patients undergoing active treatment.

Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer with Mismatch Repair Impairment.

The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.922 indicated good diagnostic accuracy for Nectin-4 expression in EC. Furthermore, Nectin-4 expression was associated with DNA mismatch repair (MMR) protein deficiency. Notably, the high Nectin-4 expression group of patients with MSH2/6-deficient EC had shorter progression-free survival than that of the low Nectin-4 expression group. The number of lymphovascular space invasion-positive patients in groups with MMR deficiency and high Nectin-4 expression was also increased compared with that in the low Nectin-4 expression group. Bioinformatics analysis revealed that alteration in Nectin-4 and MMR genes is associated with Nectin-4 expression in EC. To the best of our knowledge, this is the first study to show that Nectin-4 expression may be a potential biomarker for EC diagnosis and that high Nectin-4 expression in MMR-deficient patients with EC can predict short progression-free survival, thus providing clues to identify patients for adjuvant therapy.

Assessment of Cadmium (Cd) and Lead (Pb) Blood Concentration on the Risk of Endometrial Cancer.

Cadmium (Cd) and lead (Pb) are heavy metals with carcinogenic potential. Their increased concentration has been correlated with a risk of malignancies, including breast, lung, kidney, gastrointestinal, and gynecological cancers. Most of the studies have evaluated tissue heavy metal concentration. To the best of our knowledge, this is the first study to evaluate blood Cd and lead levels in different uterine pathologies and the risk of endometrial cancer. This study included 110 patients with a histopathological diagnosis of endometrial cancer, endometrial polyps, endometrial hyperplasia, uterine myoma, and normal endometrium. The patients included in the study were assessed in terms of their endometrial cancer risk factors and blood heavy metal levels. The analysis was conducted using inductively coupled plasma optical emission spectrometry. There was a significant difference in the Cd and Cd/Pb ratio among the different groups of patients (p = 0.002), with higher a median Cd concentration among the endometrial cancer patients. The differences in Pb concentration were not significant (p = 0.717). There were also no differences in the Cd and Pb concentrations based on the patients' menopausal status nor BMI index. The univariate logistic regression showed a blood cadmium concentration above the median to be associated with an increased risk of endometrial cancer (OR = 5.25; 95% CI 1.56, 17.72). No significant associations were observed between the Pb concentration or Cd/Pb ratio and endometrial cancer risk. The concentration of Cd varies in patients diagnosed with different uterine pathologies. Increased blood cadmium concentration seems to be a risk factor for endometrial studies. Further research on greater populations, accounting for environmental and lifestyle heavy metal exposure, is required to validate our findings.

Identification of Endometrial Cancer-Specific microRNA Biomarkers in Endometrial Fluid.

Abnormal uterine bleeding is a common benign gynecological complaint and is also the most common symptom of endometrial cancer (EC). Although many microRNAs have been reported in endometrial carcinoma, most of them were identified from tumor tissues obtained at surgery or from cell lines cultured in laboratories. The objective of this study was to develop a method to detect EC-specific microRNA biomarkers from liquid biopsy samples to improve the early diagnosis of EC in women. Endometrial fluid samples were collected during patient-scheduled in-office visits or in the operating room prior to surgery using the same technique performed for saline infusion sonohysterography (SIS). The total RNA was extracted from the endometrial fluid specimens, followed by quantification, reverse transcription, and real-time PCR arrays. The study was conducted in two phases: exploratory phase I and validation phase II. In total, endometrial fluid samples from 82 patients were collected and processed, with 60 matched non-cancer versus endometrial carcinoma patients used in phase I and 22 in phase II. The 14 microRNA biomarkers, out of 84 miRNA candidates, with the greatest variation in expression from phase I, were selected to enter phase II validation and statistical analysis. Among them, three microRNAs had a consistent and substantial fold-change in upregulation (miR-429, miR-183-5p, and miR-146a-5p). Furthermore, four miRNAs (miR-378c, miR-4705, miR-1321, and miR-362-3p) were uniquely detected. This research elucidated the feasibility of the collection, quantification, and detection of miRNA from endometrial fluid with a minimally invasive procedure performed during a patient in-office visit. The screening of a larger set of clinical samples was necessary to validate these early detection biomarkers for endometrial cancer.

Circulating and Endometrial Tissue microRNA Markers Associated with Endometrial Cancer Diagnosis, Prognosis, and Response to Treatment.

In developed countries, endometrial cancer (EC) is one of the most common neoplasms of the female reproductive system. MicroRNAs (miRs) are a class of single-stranded noncoding RNA molecules with lengths of 19-25 nucleotides that bind to target messenger RNA (mRNA) to regulate post-transcriptional gene expression. Although there is a large amount of research focused on identifying miRs with a diagnostic, prognostic, or response to treatment capacity in EC, these studies differ in terms of experimental methodology, types of samples used, selection criteria, and results obtained. Hence, there is a large amount of heterogeneous information that makes it difficult to identify potential miR biomarkers. We aimed to summarize the current knowledge on miRs that have been shown to be the most suitable potential markers for EC. We searched PubMed and Google Scholar without date restrictions or filters. We described 138 miRs with potential diagnostic, prognostic, or treatment response potential in EC. Seven diagnostic panels showed higher sensitivity and specificity for the diagnosis of EC than individual miRs. We further identified miRs up- or downregulated depending on the FIGO stage, precursor lesions, and staging after surgery, which provides insight into which miRs are expressed chronologically depending on the disease stage and/or that are modulated depending on the tumor grade based on histopathological evaluation.

Quality of life in endometrial cancer survivors by grade of disease.

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries, with overall incidence increasing, particularly high-grade disease. There is sparse information regarding quality of life (QOL) in EC survivors with a focus on grade of disease. A total of 259 women with EC diagnosed between 2016 and 2020 were identified via the Metropolitan Detroit Cancer Surveillance System and consented to enroll in the Detroit Research on Cancer Survivors cohort study (if African American, n = 138) or completed the baseline interview (if non-Hispanic white, n = 121). Each respondent provided information about their health history, educational attainment, health behaviors, and demographics. The Functional Assessment of Cancer Therapy-General (FACT-G) and Endometrial-specific (FACT-En) were used to assess QOL. Women diagnosed with high-grade (n = 112) and low-grade (n = 147) EC participated in this study. EC survivors with high-grade disease reported significantly lower QOL compared to survivors with low-grade disease (85 vs. 91, respectively, p value = 0.025) as assessed by the FACT-G. This difference was driven by lower physical and functional subscales among women with high-grade disease compared to those with low-grade disease (p value = 0.016 and p = 0.028, respectively). Interestingly, EC-specific QOL measures, as assessed by the FACT-En, did not differ by grade. Grade of disease impacts QOL in EC survivors, as well as socioeconomic, psychological, and physical factors. Most of these factors are amenable to interventions and should be assessed in patients after an EC diagnosis.

Morbid obesity increases the failure rate of sentinel lymph node mapping for endometrial carcinoma.

The goal of this study was to examine the relationship between body mass index (BMI) and the success rate of sentinel lymph node (SLN) mapping using indocyanine green and near-infrared imaging. Sentinel lymph node mapping is recommended for patients with endometrial carcinoma to reduce the rate of full lymphadenectomy and its associated morbidity such as lymphedema. A retrospective review was conducted of robotic hysterectomy procedures for patients with a coded diagnosis of endometrial cancer and a cost code for indocyanine green discharged between March, 2016 and August, 2019. Preoperative characteristics included age, BMI, and number of prior abdominal surgeries (includes cervical, adnexal, uterine or rectal procedures, caesarian section, or appendectomy). Intra and postoperative characteristics included procedure time (incision to close), estimated blood loss, the American Society of Anesthesiologists (ASA) physical status classification, uterine weight, uterine diameter, FIGO Grade, myometrial depth, and depth of myometrial invasion. SLN and non-SLN number, location,and pathology wererecorded. The primary outcome was the bilateral success rate for SLN mapping. Patients with class III obesity (BMI > 40) were found to have a significantly lower success rate for SLN mapping when compared with all other BMI categories (54.1% vs. 76.1%, respectively, p < 0.01).

Hematological and biochemical markers in determining the diagnosis and stage prediction of endometrial cancer.

To establish whether there is a statistically significant difference in hematological and biochemical parameters between the patients with premalignant changes of the uterine mucosa and those with malignant changes. The aim is to establish whether hematological and biochemical parameters may be useful in predicting the stages of endometrial malignancy and in differentiating premalignant and malignant endometrial changes. A retrospective study included 100 patients (70 with endometrial carcinoma diagnosis and 30 with atypical hyperplasia). We compared hematological and biochemical parameters in both groups. CRP, granulocytes, platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) are statistically significantly higher in patients with malignant changes. Lymphocyte count is statistically significantly lower in patients with malignant changes. Platelet count is statistically significantly lower in patients with stages I and II in comparison to patients with higher disease stage. NLR and PLR have good discriminatory power for carcinoma presence. Patients with advanced changes have statistically significantly higher CRP values, higher granulocyte and platelet count, as well as higher values of NLR and PLR, and statistically significantly lower values of lymphocytes and MPV in comparison to benign changes. There is a possibility of using hematological and biochemical parameters in the assessment of endometrial changes as well as in the prediction of stages, in confirmed malignant changes of the endometrium.

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial-mesenchymal transition and stemness through Wnt/β-catenin signaling.

Endometrial cancer (EC) is one of the most common cancers among women, while the incidence of EC is rising. Many studies have found that Kinesin family member 15 (KIF15) is highly expressed in a series of cancers, but the role of KIF15 in EC is unclear. We detected the expression level of KIF15 in a microarray of EC tissues by immunohistochemical staining (IHC), and analyzed the correlation between the expression level of KIF15 and the pathological characteristics of patients. After inhibit the expression of KIF15 in EC cells with lentivirus, cell proliferation and apoptosis were detected respectively by CCK8 assay, flow cytometry and tunnel assay. Transwell assay and wound healing assay were used to examine the migration ability and invasion ability of EC cells. Spheroid formation assay was used to evaluate cell self-renewal ability. In vivo tumor xenograft model was used for validation. The expressions of epithelial-mesenchymal transition, cancer stem cells, and Wnt/β-catenin signaling molecules were detected by Western blotting. The results showed that the expression of KIF15 in EC tissues was higher than that in normal endometrial tissues, while the expression level of KIF15 in EC was positively correlated with the pathological grade of the tumor. The down-regulation of KIF15 reduced the proliferation, colony formation, invasion, migration and self-renewal ability of EC cells, while promoted cell apoptosis. Knockdown of KIF15 inactivates the Wnt/β-catenin signaling of EC cells, inhibitors of Wnt signaling can counteract the enhanced self-renewal ability caused by KIF15 overexpression. Therefore, KIF15 may be a new potential target for diagnosis and treatment of EC.

Pelvic Recovery After Endometrial Cancer Treatment: Patient-Reported Outcomes and MRI Findings

Most women with endometrial cancer (EC) have an excellent prognosis and may be cured. However, treatment-related pelvic functional impacts may affect long-term quality of life. To better understand these concerns, we explored correlations between patient-reported outcomes and pelvic magnetic resonance imaging (MRI) features in women treated for EC. Women with histologic diagnosis of EC were consented preoperatively and completed the validated Female Sexual Function Index (FSFI) and Pelvic Floor Dysfunction Index (PFDI) questionnaires at preoperative, 6-week, and 6-month follow-up visits. Pelvic MRIs with dynamic pelvic floor sequences were performed at 6 weeks and 6 months. A total of 33 women participated in this prospective pilot study. Only 53.7% had been asked about sexual function by providers while 92.4% thought they should have been. Sexual function became more important to women over time. Baseline FSFI was low, declined at 6 weeks, and climbed above baseline at 6 months. Hyperintense vaginal wall signal on T2-weighted images(10.9 vs. 4.8, p=.002) and intact Kegel function (9.8 vs. 4.8, p=.03) were associated with higher FSFI. PFDI scores trended toward improved pelvic floor function over time. Pelvic adhesions on MRI were associated with better pelvic floor function (23.0 vs. 54.9, p=.003). Urethral hypermobility (48.4 vs. 21.7, p=.01), cystocele (65.6 vs. 24.8, p<.0001), and rectocele (58.8 vs. 18.8, p<.0001) predicted worse pelvic floor function. Use of pelvic MRI to quantify anatomic and tissue changes may facilitate risk stratification and response assessment for pelvic floor and sexual dysfunction. Patients articulated the need for attention to these outcomes during ECtreatment.

Frequencies, clinicopathological features, and risk factors of type I and type II endometrial cancer; a retrospective observational study at a tertiary care hospital in Pakistan

Background: Endometrial cancer (EC) is the most common gynecological malignancy worldwide. The death rates for EC have increased by more than 100% over the past 2 decades. EC is subdivided into two types based on distinct histological and clinical features: type I and type II. Our study aims to determine the risk factors and clinicopathological features of both type I and type II EC and draw a comparison between the two types based on frequency, risk factors and clinicopathological features. Methods: It was a retrospective observational study including patients of a single tertiary care center. The study included Patients diagnosed, treated, and followed up for type I and type II endometrial cancer at the study center over the past 19 years from 1st January 2000 to 31st December 2018. All the patients with metastatic endometrial cancer were excluded from the study. SPSS version 26 was used for statistical analysis. Results: A total of 376 patients were included in this study. Among these 343 (91.7) patients had endometroid adenocarcinoma (Type I) and 32 (8.3) had serous and clear cell tumor (type II). Type I EC had a mean age of 57.56 (SD±10.42) while patients with type II EC presented with a mean age of64.97 (SD±6.59). Hypertension and Diabetes were the most common comorbid in EC patients. HRT prior to EC was found to have an association with risk of EC. Compared to patients who were on HRT, patients who were not on HRT prior to diagnosis of EC had 80% less chance of developing endometrial cancer. (Confidence interval: 0.056-0.114, p=0.016). Conclusions: In summary our study demonstrates that both sub types of endometrial cancer have many risk factors that are similar to each other. Despite the difference between the population of both subgroups we were able to prove associations between risk factors and endometrial cancer. However further research is needed at provincial and national level with larger and relatively comparable sample sizes for both subgroups to recognize risk factors and numerically associate them to EC for Pakistani population.

Germline multigene panel testing of patients with endometrial cancer.

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. The present study aimed to determine the frequency of germline pathogenic variants (PV) in patients with EC. In this multicenter retrospective cohort study, germline genetic testing (GGT) was performed in 527 patients with EC using a next generation sequencing panel targeting 226 genes, including 5 Lynch syndrome (LS) and 14 hereditary breast and ovarian cancer (HBOC) predisposition genes, and 207 candidate predisposition genes. Gene-level risks were calculated using 1,662 population-matched controls (PMCs). Patients were sub-categorized to fulfill GGT criteria for LS, HBOC, both or none. A total of 60 patients (11.4%) carried PV in LS (5.1%) and HBOC (6.6%) predisposition genes, including two carriers of double PV. PV in LS genes conferred a significantly higher EC risk [odds ratio (OR), 22.4; 95% CI, 7.8-64.3; P=1.8×10-17] than the most frequently altered HBOC genes BRCA1 (OR, 3.9; 95% CI, 1.6-9.5; P=0.001), BRCA2 (OR, 7.4; 95% CI, 1.9-28.9; P=0.002) and CHEK2 (OR, 3.2; 95% CI, 1.0-9.9; P=0.04). Furthermore, >6% of patients with EC not fulfilling LS or HBOC GGT indication criteria carried a PV in a clinically relevant gene. Carriers of PV in LS genes had a significantly lower age of EC onset than non-carriers (P=0.01). Another 11.0% of patients carried PV in a candidate gene (the most frequent were FANCA and MUTYH); however, their individual frequencies did not differ from PMCs (except for aggregated frequency of loss-of-function variants in POLE/POLD1; OR, 10.44; 95% CI, 1.1-100.5; P=0.012). The present study demonstrated the importance of GGT in patients with EC. The increased risk of EC of PV carriers in HBOC genes suggests that the diagnosis of EC should be included in the HBOC GGT criteria.