OBJECTIVE: This study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database.
METHODS: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI).
RESULTS: Overall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18-1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45-0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51-0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32-4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89-1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62-1.11], p = 0.218).
CONCLUSIONS: This first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers.

BACKGROUND: The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer.
METHODS: Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure.
RESULTS: ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues.
CONCLUSIONS: These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.

OBJECTIVE: To assess the stage distribution and stage-related disease-specific survival rates for endometrial cancer using the FIGO (the International Federation of Gynecology & Obstetrics) 2009 and 2023 staging systems. Further, we sought to evaluate the prognostic utility of additional covariates beyond the FIGO 2023 stage.
METHODS: Endometrial carcinomas were molecularly classified by the Proactive Molecular Risk Classifier for Endometrial Cancer and staged according to FIGO 2009 and 2023 criteria. Disease-specific survival was calculated as the time from surgery to death from endometrial cancer.
RESULTS: Data from 604 patients were analyzed. Median follow-up time was 81 months. A total of 118 stage shifts (19.5%) occurred between the FIGO 2009 and FIGO 2023 systems, with upshifts accounting for 107 (90.7%) of these changes. Within the FIGO 2023 system, molecular classification resulted in restaging of 69 patients (11.4%). Shifts that could alter adjuvant therapy decisions were identified in 23 patients (3.8%). The FIGO 2023 system effectively categorized endometrial cancers into prognostic subgroups. The FIGO 2023 stage, tumor size, positive peritoneal cytology, and mismatch repair deficiency were associated with disease-specific survival in a multivariable analysis, whereas age and adjuvant therapy were not.
CONCLUSIONS: The FIGO 2023 staging system for endometrial cancer appears highly prognostic. Prognostic assessment of the patients can be further enhanced by readily accessible covariates. A stage shift between the FIGO 2009 and 2023 systems occurs in about one-fifth of patients. The implementation of molecular classification within the FIGO 2023 system bears implications for decisions regarding adjuvant therapy.

We examined associations between modifiable and non-modifiable cancer-related risk factors measured at endometrial cancer diagnosis and during early survivorship (~3 years post-diagnosis) with second primary cancer (SPC) risk among 533 endometrial cancer survivors in the Alberta Endometrial Cancer Cohort using Fine and Gray sub-distribution hazard models. During a median follow-up of 16.7 years (interquartile range (IQR)=12.2-17.9), 89 (17%) participants developed a SPC with breast (29%), colorectal (13%) and lung (12%) cancers being the most common. Dietary glycemic load before endometrial cancer diagnosis (≥90.4 vs. <90.4 g/day: sub-hazard ratios (sHR)=1.71, 95% confidence intervals (CI)=1.09-2.69) as well as older age (≥60 vs. <60: sHR=2.48, 95% CI=1.34-4.62) and alcohol intake (≥2 drink/week vs. none: sHR=3.81, 95% CI=1.55-9.31) during early survivorship were associated with increased SPC risk. Additionally, reductions in alcohol consumption from prediagnosis to early survivorship significantly reduced SPC risk (sHR=0.34, 95% CI=0.14-0.82). With one-in-six survivors developing a SPC, further investigation of SPC risk factors and targeted surveillance options for high-risk survivors could improve long-term health outcomes in this population. Reductions in dietary glycemic load and alcohol intake from prediagnosis to early survivorship showed promising risk reductions for SPCs and could be important modifiable risk factors to target among endometrial cancer survivors.

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.

UNASSIGNED: Over the last decade there has been a transition from traditional laparoscopy to robotic surgery for the treatment of endometrial cancer. A number of gynecological oncology surgical fellowship programmes have adopted robot-assisted laparoscopy, but the effect of training on complications and survival has not been evaluated. Our aim was to assess the impact of a proficiency-based progression training curriculum in robot-assisted laparoscopy on peri-operative and survival outcomes for endometrial cancer.
UNASSIGNED: This is an observational cohort study performed in a tertiary referral and subspecialty training center. Women with primary endometrial cancer treated with robot-assisted laparoscopic surgery between 2015 and 2022 were included. Surgery would normally include a hysterectomy and salpingo-oophorectomy with some form of pelvic lymph node dissection (sentinel lymph nodes or lymphadenectomy). Training was provided according to a training curriculum which involves step-wise progression of the trainee based on proficiency to perform a certain surgical technique. Training cases were identified pre-operatively by consultant surgeons based on clinical factors. Case complexity matched the experience of the trainee. Main outcome measures were intra- and post-operative complications, blood transfusions, readmissions < 30 days, return to theater rates and 5-year disease-free and disease-specific survival for training versus non-training cases. Mann-Witney U, Pearson\'s chi-squared, multivariable regression, Kaplan-Meier and Cox proportional hazard analyses were performed to assess the effect of proficiency-based progression training on peri-operative and survival outcomes.
UNASSIGNED: Training cases had a lower BMI than non-training cases (30 versus 32 kg/m2, p = 0.013), but were comparable in age, performance status and comorbidities. Training had no influence on intra- and post-operative complications, blood transfusions, readmissions < 30 days, return to theater rates and median 5-year disease-free and disease-specific survival. Operating time was longer in training cases (161 versus 137 min, p = < 0.001). The range of estimated blood loss was smaller in training cases. Conversion rates, critical care unit-admissions and lymphoedema rates were comparable.
UNASSIGNED: Proficiency-based progression training can be used safely to teach robot-assisted laparoscopic surgery for women with endometrial cancer. Prospective trails are needed to further investigate the influence of distinct parts of robot-assisted laparoscopic surgery performed by a trainee on endometrial cancer outcomes.

Prebiotics may influence the risk of hormone-related female cancers by modulating the gut microbiota involved in estrogens metabolism. We evaluated the association of fiber-type prebiotic intake with breast, endometrial, and ovarian cancers. Data derived from a network of Italian hospital-based case-control studies (1991-2006), including 2560 cases of cancer of the breast (2588 controls), 454 of the endometrium (908 controls) and 1031 of the ovary (2411 controls). Inulin-type fructans (ITFs), and selected fructo-oligosaccharides (FOSs, nystose, kestose and 1F-β-fructofuranosylnystose) and galacto-oligosaccharides (GOSs, raffinose and stachyose) were quantified in food products. Prebiotic intake was estimated by multiplying food frequency questionnaire intake by the foods\' prebiotic content. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were derived by multiple logistic regression models. Nystose intake was marginally directly associated with breast (OR for the 4th versus the 1st quartile 1.20, 95% CI: 1.00-1.45), ovarian (OR 1.39, 95% CI: 1.04-1.84) and endometrial cancer risk (OR 1.32, 95% CI: 0.85-2.03). High 1F-β-fructofuranosylnystose intake was inversely associated with ovarian cancer (OR 0.67, 95% CI: 0.52-0.85). ITFs, kestose, raffinose and stachyose were not associated with the three cancers. The intake of most fiber-type prebiotics was not appreciably and consistently associated with breast, endometrial and ovarian cancer risks.

OBJECTIVE: This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant chemoradiotherapy (CRT).
METHODS: Retrospective analysis of EC patients who underwent adjuvant CRT from January 2012 to June 2023 in the Department of Gynecology and Oncology of the First Affiliated Hospital of Shandong First Medical University. Neutropenia was defined as an Absolute Neutrophil Count (ANC) of peripheral blood neutrophils below 2 × 109/L. Factors affecting neutropenia in EC patients treated with CRT using Generalized Estimating Equation (GEE), and Logistic regression was used to further analyze the effect of adding radiotherapy to different chemotherapy cycles on neutropenia, so that patients receive optimal adjuvant CRT while the risk of neutropenia is appropriately controlled.
RESULTS: A total of 144 patients met the inclusion criteria. They underwent 330 cycles of adjuvant chemotherapy, of whom 96 (66.7%) developed neutropenia, which occurred 140 times. The results of one-way GEE analysis showed that before CRT, White Blood Cell (WBC) (OR = 0.827; 95%CI, 0.701-0.976), ANC (OR = 0.749; 95%CI, 0.586-0.957), Absolute Monocyte Count (AMC) (OR = 0.047; 95%CI, 0.008-0.283), Blood Urea Nitrogen (BUN) (OR = 0.857; 95%CI, 0.741-0.991), platinum and docetaxel (platinum/docetaxel) dosing regimen (OR = 2.284; 95%CI, 1.130-4.618) were associated with neutropenia with adjuvant CRT for EC (p < 0.05), results of multifactorial GEE analysis showed that before adjuvant CRT ANC (OR = 0.552; 95%CI, 0.973-2.231), AMC (OR = 0.047; 95%CI, 0.004-0.052), platinum/docetaxel (OR = 2.437; 95%CI, 1.087-5.464) were an independent influence on neutropenia in adjuvant CRT for EC (p < 0.05). Multifactorial Logistic regression shows addition of radiotherapy to the first cycle of chemotherapy (OR = 4.413; 95%CI, 1.238-18.891) was an independent influence of neutropenia (p < 0.05).
CONCLUSIONS: Patients with low pre-CRT ANC and AMC, platinum/docetaxel dosing regimens need to be closely monitored during each cycle of CRT. Also, the concurrent addition of radiotherapy should be avoided during the first cycle of chemotherapy.

OBJECTIVE: The significant global burden of endometrial cancer (EC) and the challenges associated with predicting EC recurrence indicate the need for a dynamic prediction model. This study aimed to propose nomograms based on clinicopathological variables to predict recurrence-free survival (RFS) and overall survival (OS) after surgical resection for EC.
METHODS: This single-institution retrospective cohort study included patients who underwent surgical resection for EC. Web-based nomograms were developed to predict RFS and OS following resection for EC, and their discriminative and calibration abilities were assessed.
RESULTS: This study included 289 patients (median age, 56 years). At a median follow-up of 51.1 (range, 4.1-128.3) months, 13.5% (39/289) of patients showed relapse or died, and 10.7% (31/289) had non-endometrioid tumors (median size: 2.8 cm). Positive peritoneal cytology result (hazard ratio [HR], 35.06; 95% confidence interval [CI], 1.12-1095.64; P = 0.0428), age-adjusted Charlson comorbidity index (AACCI) (HR, 52.08; 95% CI, 12.35-219.61; P < 0.001), and FIGO (Federation of Gynecology and Obstetrics) stage IV (HR, 138.33; 95% CI, 17.38-1101.05; P < 0.001) were predictors of RFS. Similarly, depth of myometrial invasion ≥ 1/2 (HR, 1; 95% CI, 0.46-2.19; P = 0.995), AACCI (HR, 93.63; 95% CI, 14.87-589.44; P < 0.001), and FIGO stage IV (HR, 608.26; 95% CI, 73.41-5039.66; P < 0.001) were predictors of OS. The nomograms showed good predictive capability, positive discriminative ability, and calibration (RFS: 0.895 and OS: 0.891).
CONCLUSIONS: The nomograms performed well in internal validation when patients were stratified into prognostic groups, offering a personalized approach for risk stratification and treatment decision-making.

OBJECTIVE: To evaluate the impact of a four-month training program on radiology residents\' diagnostic accuracy in assessing deep myometrial invasion (DMI) in endometrial cancer (EC) using MRI.
METHODS: Three radiology residents with limited EC MRI experience participated in the training program, which included conventional didactic sessions, case-centric workshops, and interactive classes. Utilizing a training dataset of 120 EC MRI scans, trainees independently assessed subsets of cases over five reading sessions. Each subset consisted of 30 scans, the first and the last with the same cases, for a total of 150 reads. Diagnostic accuracy metrics, assessment time (rounded to the nearest minute), and confidence levels (using a 5-point Likert scale) were recorded. The learning curve was obtained plotting the diagnostic accuracy of the three trainees and the average over the subsets. Anatomopathological results served as the reference standard for DMI presence.
RESULTS: The three trainees exhibited heterogeneous starting point, with a learning curve and a trend to more homogeneous performance with training. The diagnostic accuracy of the average trainee raised from 64 % (56 %-76 %) to 88 % (80 %-94 %) across the five subsets (p < 0.001). Reductions in assessment time (5.92 to 4.63 min, p < 0.018) and enhanced confidence levels (3.58 to 3.97, p = 0.12) were observed. Improvements in sensitivity, specificity, positive predictive value, and negative predictive value were noted, particularly for specificity which raised from 56 % (41 %-68 %) in the first to 86 % (74 %-94 %) in the fifth subset (p = 0.16). Although not reaching statistical significance, these advancements aligned the trainees with literature performance benchmarks.
CONCLUSIONS: The structured training program significantly enhanced radiology residents\' diagnostic accuracy in assessing DMI for EC on MRI, emphasizing the effectiveness of active case-based training in refining oncologic imaging skills within radiology residency curricula.