Causal association between aspirin use and risk of endometrioid carcinoma: a Mendelian randomization study.

OBJECTIVE: The aim of the study was to investigate the causal relationship between aspirin use and the risk of endometrial endometrioid cancer (EEC) using two-sample Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) study. MATERIALS AND METHODS: A TSMR analysis was conducted to estimate the potential causal relationship between aspirin use and the risk of EEC using genome-wide data from Genome-wide association study (GWAS). The causal association between aspirin use and EEC was further analyzed by MVMR analysis after adjusting for various factors such as obesity, hypertension, diabetes, and infertility. The single nucleotide polymorphism (SNP) data associated with aspirin use and EEC was obtained from the GWAS catalog database. RESULTS: A total of six SNPs were included as instrumental variables in TSMR, which showed that taking aspirin reduced the risk of EEC [OR = 0.02, 95% CI = 0-0.28, p = 0.005, inverse variance weighted (IVW) method]. Besides, the results of the weighted median (WME) method, weighted mode, and simple mode were consistent with the results shown by the IVW method. After further using the MVMR method, the causal association of aspirin use and prevention of EEC onset remained significant after adjusting for the effects of obesity, hypertension, and diabetes (OR = 0.076, 95% CI = 0.007-0.793, p = 0.031). Sensitivity analyses, including heterogeneity, horizontal multiplicity, and leave-one-out tests, showed the reliability of the instrumental variables, proving that the results were reliable and not significantly biased. CONCLUSIONS: Taking aspirin can reduce the risk of EEC morbidity, and it is expected to be of great significance for the early prevention and treatment of endometrial cancer by exploring the biological mechanism of aspirin on endometrioid cancer at a deeper level.

An analysis of clinical characteristics and prognosis of endometrioid ovarian cancer based on the SEER database and two centers in China.

PURPOSE: To assess the clinical characteristics and the risk factors related to the unfavorable prognosis of endometrioid ovarian carcinoma (EOVC) based on data from the Surveillance, Epidemiology, and End Results (SEER) database and two clinical centers in China. METHODS: Data were extracted from the SEER database and two clinical centers in China (2010 ~ 2021), 884 cases and 87 patients with EOVC were selected, respectively. Overall survival (OS) and progression-free survival (PFS) were compared among the different groups using Kaplan-Meier analysis. The Cox proportional-hazards model was used to identify independent prognostic factors related to EOVC. A nomogram was constructed based on the risk factors of the SEER database affecting prognosis and the discrimination and calibration of the nomogram were evaluated by C-index and calibration curves. RESULTS: The average age at diagnosis of patients with EOVC in the SEER database and two centers in China was 55.77 ± 12.40 years and 47.14 ± 11.50 years, 84.7% and 66.6% of them were diagnosed at FIGO stage I ~ II, respectively. In the SEER database, age over 70 years, advanced FIGO stage, tumor grade 3, only unilateral salpingo-oophorectomy were independent risk factors of unfavorable prognosis. In two clinical centers in China, 27.6% of EOVC patients were diagnosed with synchronous endometriosis. Advanced FIGO stage, HE4 > 179 pmol/L and bilateral ovarian involvement significantly correlated with poor OS and PFS in Kaplan-Meier analysis. Body mass index (BMI) < 19.34 kg/m2 was an independent risk factor relating to OS and PFS. Additionally, C-index of internal and external verification for the nomogram were 0.812 and 0.754 respectively, revealing good accuracy and clinical applicability. CONCLUSIONS: Most patients were diagnosed at early stage, low grade and had better prognosis. Asian/Pacific Islander and Chinese diagnosed with EOVC were more likely to be younger than whites and blacks. Age, tumor grade and FIGO stage (SEER database) and BMI (two centers) are independent prognostic factors. HE4 appears to be more valuable in prognostic assessment compared with CA125. The nomogram had good discrimination and calibration for predicting prognosis, providing a convenient and reliable tool for clinical decision-making for patients with EOVC.

Age-specific trend and birth cohort effect on different histologic types of uterine corpus cancers.

To evaluate the uterine corpus cancer incidence rates, age-specific trends, and birth cohort patterns by different histologic types. We conducted a retrospective cohort study of uterine cancer patients (n = 28,769) of all ages from the National Cancer Registry of Taiwan between 1998 and 2017. We estimated the incidence trends, average annual percent changes (AAPCs), and cancer-specific survival (CSS) rate for the two main subtypes (endometrioid and nonendometrioid) of uterine cancer in Taiwan. During the study period, uterine corpus cancer incidence rates increased over time from 5.3 to 15.21 per 100,000 women. Incidence trends for endometrioid carcinoma increased in all age groups (positive AAPCs > 5% for each age group), and the rise was steeper among women aged 50 years and younger. For nonendometrioid carcinomas, incidence rates increased among women over 50 years. The CSS rate improved among women with stage I (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.49-0.81) and stage III (HR 0.72, 95% CI 0.58-0.90) endometrioid carcinomas after 2013 compared with those during 2009-2012. However, the CSS rate remained unchanged for nonendometrioid carcinomas. Age, diagnostic period, stage and histologic types were significant factors associated with the 5-year CSS rate. We found that the incidences of both endometrioid and nonendometrioid carcinomas continued to increase among contemporary birth cohorts. Etiologic research is needed to explain the causes of these trends.

Quantification of Women Who Could Benefit from Hormone Therapy after Endometrial Cancer Treatment: An Analysis of SEER Data.

Our primary aim was to estimate the magnitude of stage I endometrial cancer (EC) survivors that could benefit from hormonal therapy (HT). Our secondary aims were to assess EC incidence in women below 50 and below 60 over the years, and analyze the overall survival and any influencing factors. We analyzed the endometrioid EC data from the Surveillance, Epidemiology, and End Results (SEER) program according to women's age, tumor stage, and grade. We analyzed the proportions of EC survivors below 50 and below 60 years of age and stratified those age groups by race. For age distribution and survival analysis SEER, 18 registries' research data (2000-2018) were analyzed. We analyzed the SEER 12 registries' research data (1992-2019) for incidence time trends. Our investigation found a 14% and 40% cumulative prevalence of stage I EC that occurs in women below 50 or 60 years, respectively. EC's prevalence has progressively risen in recent decades, but cancer-specific mortality remains low. The increasing number of women affected by EC in premenopause or early postmenopause face an 18 years-survival rate of 96.86% and 95.73%, respectively. A significant proportion of low-grade EC survivors can potentially benefit from HT treatment, and this requires awareness of other aspects of their health or quality of life, in addition to cancer treatments.

Endometrial cancer with concomitant endometriosis is highly associated with ovarian endometrioid carcinoma: a retrospective cohort study.

BACKGROUND: Endometriosis is assumed to be involved in ovarian cancer development, which is called endometriosis-associated ovarian cancer (EAOC). Uterine endometrial cells may be the cell of origin of EAOC. Accumulated carcinogenic changes in the uterine endometrial cells may increase the risk of developing EAOC. To further understand the pathogenesis of EAOCs, we focused on the clinicopathological characteristics of EAOCs in endometrial cancer patients with concomitant endometriosis. METHODS: We retrospectively reviewed 376 patients who were surgically treated for stage I-III endometrial cancer. Clinicopathological characteristics were compared between patients with and without endometriosis. Furthermore, the incidence of simultaneous endometrial and ovarian cancer (SEOC) and the histological characteristics of SEOC were compared between the two groups. RESULTS: Among 376 patients with endometrial cancer, 51 had concomitant endometriosis. Patients with endometriosis were significantly younger and more frequently had endometrioid G1/G2 tumors than those without endometriosis. The incidence of SEOCs was significantly higher in endometrial cancer patients with endometriosis than those without it (p < 0.0001); notably, 12 of 51 endometrial cancer patients with endometriosis (24%) had SEOCs. All of the ovarian cancers in endometrial cancer patients with endometriosis were endometrioid carcinomas. Moreover, even in those without endometriosis, endometrioid carcinoma was the most common histological type of SEOC. CONCLUSION: We revealed that endometrial cancer patients with endometriosis had a high probability of SEOC and that endometrioid carcinoma was the most common histological subtype of SEOC regardless of the presence of endometriosis. For patients with endometrial cancer and endometriosis, careful examination of ovarian endometriotic lesions may be important to detect EAOCs.

Stratified follow-up for endometrial cancer: a move to more personalized cancer care.

OBJECTIVE: Hospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses. METHODS: All patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology-European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated. RESULTS: 900 patients met the eligibility criteria. Median age was 66 years (range 28-96) and follow-up duration was 35 months (interquartile range 19-57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high-intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high-intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort. CONCLUSIONS: Relapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings.

Incidence and survival of epithelial ovarian, fallopian tube, peritoneal, and undesignated abdominal/pelvic cancers in Sweden 1960-2014: A population-based cohort study.

BACKGROUND: Despite improved surgical and oncological treatment, ovarian cancer continues to be the most lethal of the gynecologic malignancies. We aimed to analyze survival trends in epithelial ovarian cancer with regard to age, tumor site, and morphology in Sweden 1960 to 2014. METHODS: A nationwide population-based study was conducted using data from the Swedish Cancer Registry on 46,350 women aged 18 or older with a diagnosis of epithelial ovarian, fallopian tube, peritoneal, or undesignated abdominal/pelvic cancer 1960 to 2014. Analyses of age-standardized incidence and relative survival (RS) were performed and time trends modelled according to age, tumor site, and morphology. RESULTS: Overall incidence of ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers declined since 1980. Median age at diagnosis increased. Serous carcinoma increased in incidence. RS at 1, 2 and 5 years from diagnosis improved since 1960, although not for the youngest and the oldest patients. Ten-year RS did not improve. The best RS was found for fallopian tube cancer and the worst RS for undesignated abdominal/pelvic cancer. Among the morphologic subgroups, endometrioid carcinoma had the best RS. CONCLUSIONS: Survival in epithelial ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers in Sweden has improved over the last six decades. Advances in epithelial ovarian cancer treatment have extended life for the first 5 years from diagnosis but 10-year survival remains poor.

A single centre experience of metabolic syndrome and endometrial carcinoma: 5 years review.

Endometrial cancer (EC) has been found to have a strong association with overweight and obesity. The aim of this study was to evaluate the link between metabolic syndrome and EC among patients. A total of 119 patients with histologically confirmed EC were recruited. About 102 cases of endometrioid carcinoma (Type I) and serous (n = 7), clear cell (n = 3) and carcinosarcoma (n = 7) were the Type II. Metabolic syndrome was significantly associated with increased risk of Type I EC (OR = 3.43, 95% CI = 1.12-10.46, p < .05) where obesity risk revealed as the main factor in Type I EC (OR = 3.88, 95% CI = 1.27-11.85, p < .05). There was no significant difference between both subtypes with other metabolic components and no impact on patients' overall survival and disease-free survival (p > .05). Metabolic syndrome was positively associated with an increased risk of Type I EC with obesity being the most influential risk factor.Impact statementWhat already known on this subject? Endometrial cancer (EC) is one of the most prevalent cancers worldwide and have a strong association with overweight and obesity of at least 40%, but there is conflicting evidence of an association of EC with metabolic syndrome (MS).What result of this study add? This study evaluated the link between EC and MS, such as high blood pressure, BMI, fasting blood sugar, triglyceride, Hyper Density Lipoprotein (HDL).What implications are of these findings for clinical practice & further research? Type I EC had and association with MS with obesity is the most potent risk factor. As the prevalence of metabolic syndrome is alarmingly high among adult Malaysians, the incidence of EC is projected to increase in the coming years. Proactive preventative measures and intervention essential for reducing the incidence of endometrial cancers. Future research to clarify the association between metabolic syndrome and endometrial cancer survival and to investigate other lifestyle factors that may affect the prognosis is needed.

[Prevalence of lymph node involvement in patients with endometrial cancer, Colombia 2009-2016: Exploratory analysis of associated factors].

OBJECTIVE: To determine the prevalence of lymph node involvement in patients with endometrial cancer and to explore factors associated with lymph node invasion. METHODS: Prevalence study with exploratory analysis. The study included patients with endometrial cancer who underwent total abdominal hysterectomy plus bilateral salpyingooophorectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy in seven oncology centers in Colombia between 2009 and 2016. Patients who had received prior radiotherapy or chemotherapy, with a histological diagnosis of neuroendocrine tumors, carcinosarcomas or synchronous or metachronous lesions were excluded. Non-probabilistic sampling. Sample size n=290. Measured variables: sociodemographic, clinical and histopathological, and pelvic or para-aortic lymph node involvement. The prevalence for the period is presented. The exploratory analysis was conducted using crude odds ratio (OR) and adjusted OR by means of a multivariate model (unconditional logistic regression). RESULTS: Overall, 467 cases were retrieved. Of them, 163 were excluded because of non-availability of all the variables. In total, 304 patients were studied. The prevalence of lymph node involvement was 15.8 % (48/304). In the crude and adjusted analysis, factors associated with lymph node involvement were lymphovascular invasion (adjusted OR: 9.32; 95 % CI 4.27-21.15) and myometrial invasion (adjusted OR: 3.95; 95 % CI 1.29-14.98). CONCLUSIONS: Of the patients undergoing lymphadenectomy, 15 % have lymph node involvement. Less invasive diagnostic options than radical surgery to ascertain lymph node invasion should be assessed.

TITULO: PREVALENCIA DEL COMPROMISO GANGLIONAR EN PACIENTES CON CÁNCER DE ENDOMETRIO, COLOMBIA 2009-2016: ANÁLISIS EXPLORATORIO DE FACTORES ASOCIADOS. OBJETIVO: Determinar la prevalencia del compro miso ganglionar de pacientes con cáncer de endometrio y hacer una exploración de los factores asociados a la invasión ganglionar. METODOS: Estudio de prevalencia con análisis exploratorio. Se incluyeron pacientes con cáncer de endometrio llevadas a histerectomía abdominal total más salpingooforectomía bilateral y linfadenectomía pélvica, con o sin linfadenectomía paraaórtica en siete centros de oncología de Colombia, en el periodo 2009-2016. Se excluyeron pacientes con radioterapia o quimioterapia previa, diagnóstico histológico de tumores neuroendocrinos, carcinosarcomas, tumores sincrónicos o metacrónicos. Muestreo no probabilístico. Tamaño muestral n = 290. Variables medidas: sociodemográficas, clínicas e histopatológicas y compromiso ganglionar pélvico o paraaórtico. Se presenta la prevalencia de periodo; el análisis exploratorio se realizó por medio de odds ratio (OR) crudo y el ajustado mediante un modelo multivariado (regresión logística no condicional). RESULTADOS: Se obtuvieron 467 casos de los cuales se excluyeron 163 por no presentar la totalidad de las variables, se estudiaron 304 pacientes. La prevalencia del compromiso ganglionar fue del 15,8 % (48/304). Los factores asociados al compromiso ganglionar en el análisis crudo y ajustado fueron la invasión linfovascular (OR ajustado = 9,32; IC 95 %: 4,27-21,15) e invasión miometrial (OR ajustado = 3.95; IC 95 %: 1,29-14,98). CONCLUSIONES: El 15 % de las pacientes sometidas a linfadenectomía tienen compromiso ganglionar. Se deben evaluar alternativas diagnósticas menos invasivas que la cirugía radical para establecer la invasión ganglionar.

BRCA1 and BRCA2 pathogenic variant carriers and endometrial cancer risk: A cohort study.

BACKGROUND: An association between BRCA pathogenic variants and an increased endometrial cancer risk, specifically serous-like endometrial cancer, has been postulated but remains unproven, particularly for BRCA2 carriers. Mechanistic evidence is lacking, and any link may be related to tamoxifen exposure or testing bias. Hysterectomy during risk-reducing bilateral salpingo-oophorectomy is, therefore, of uncertain benefit. Data from a large, prospective cohort will be informative. METHODS: Data on UK BRCA pathogenic variant carriers were interrogated for endometrial cancer diagnoses. Standardised incidence ratios (SIRs) were calculated in four distinct cohorts using national endometrial cancer rates; either from 1/1/1980 or age 20, prospectively from date of personal pathogenic variant report, date of family pathogenic variant report or date of risk-reducing salpingo-oophorectomy. Somatic BRCA sequencing of 15 serous endometrial cancers was performed to detect pathogenic variants. RESULTS: Fourteen cases of endometrial cancer were identified in 2609 women (1350 BRCA1 and 1259 BRCA2), of which two were prospectively diagnosed. No significant increase in either overall or serous-like endometrial cancer risk was identified in any of the cohorts examined (SIR = 1.70, 95% confidence interval = 0.74-3.33; no cases of serous endometrial cancer diagnosed). Results were unaffected by the BRCA gene affected, previous breast cancer or tamoxifen use. No BRCA pathogenic variants were detected in any of the serous endometrial cancers tested. CONCLUSIONS: Women with a BRCA pathogenic variant do not appear to have a significant increased risk of all-type or serous-like endometrial cancer compared with the general population. These data provide some reassurance that hysterectomy is unlikely to be of significant benefit if performed solely as a preventive measure.

Perioperative outcomes of women with and without class III obesity undergoing hysterectomy for endometrioid endometrial cancer: A population-based study.

OBJECTIVE: Population-based data on perioperative complications among women with endometrial cancer and severe obesity are lacking. We evaluated 30-day complication rates among women with and without class III obesity (body mass index ≥ 40 kg/m2) undergoing primary surgical management for endometrioid endometrial cancer (EEC), and how outcomes differed according to surgical approach (open vs. minimally invasive). METHODS: We performed a retrospective population-based cohort study of women with EEC undergoing hysterectomy in Ontario, Canada, between 2006 and 2015. We evaluated perioperative complications in the whole cohort, and in a 1:1 matched analysis using hard and propensity score matching to ensure similar distributions of patient, tumour, provider and institution-level factors between women with and without class III obesity (identified using a surgical billing code). The primary outcome of interest was the 30-day perioperative complication rate. RESULTS: 12,112 women met inclusion criteria; 2697 (22.3%) had class III obesity. We matched 2320 (86%) women with class III obesity to those without. The composite complication rate was significantly higher among women with class III obesity (23.2% vs. 18.4%, standardized mean difference [SMD] = 0.12), primarily due to wound infection/disruption (12.1% vs. 6.2%). There was no difference in outcomes for women with and without class III obesity when a minimally invasive approach was used. CONCLUSIONS: Wound infection/disruption was increased for women with class III obesity compared to women without. Otherwise, perioperative complications were similar between the matched pairs. When minimally invasive approaches were used, women with class III obesity had a similar risk of complications as women without obesity.

Clinical patterns and genomic profiling of recurrent 'ultra-low risk' endometrial cancer.

OBJECTIVE: Despite good prognosis for patients with low-risk endometrial cancer, a small subset of women with low-grade/low-stage endometrial cancer experience disease recurrence and death. The aim of this study was to characterize clinical features and mutational profiles of recurrent, low-grade, non-myoinvasive, 'ultra-low risk' endometrioid endometrial adenocarcinomas. METHODS: We retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA endometrioid endometrial cancers who underwent primary surgery at our institution, between January 2009 and February 2017, with follow-up of ≥12 months. 'Ultra-low risk' was defined as FIGO tumor grade 1, non-myoinvasive, and lacking lymphovascular space invasion. Tumor-normal profiling using massively parallel sequencing targeting 468 genes was performed. Microsatellite instability was assessed using MSIsensor. DNA mismatch repair (MMR) protein proficiency was determined by immunohistochemistry. RESULTS: A total of 486 patients with ultra-low risk endometrioid endometrial cancers were identified: 14 (2.9%) of 486 patients developed a recurrence. Median follow-up for non-recurrent endometrioid endometrial cancers: 34 (range 12-116) months; for recurrent endometrioid endometrial cancers: 50.5 (range 20-116) months. Patients with recurrent disease were older, had lower body mass index, and were most commonly non-White (p=0.025, p<0.001, and p<0.001, respectively). Other clinical characteristics did not differ. MMR immunohistochemistry was obtained for 211 (43%) tumors: 158 (75%) MMR-proficient and 53 (25%) MMR-deficient. Primary tumors of 9 recurrent and 27 non-recurrent endometrioid endometrial cancers underwent mutational profiling. Most were microsatellite stable (6/9, 67% recurrent; 25/27, 93% non-recurrent). Recurrent PTEN and PIK3CA mutations were present in both groups. Exon 3 CTNNB1 hotspot mutations were found in 4/9 (44%) recurrent and 8/27 (30%) non-recurrent (p=0.44). CONCLUSIONS: Patients diagnosed with ultra-low risk endometrioid endometrial cancers have an overall excellent prognosis. However, in our study, 2.9% of patients with no identifiable clinical or pathologic risk factors developed recurrence. Further work is warranted to elucidate the mechanism for recurrence in this population.

Lymph node metastasis probability in young patients eligible for conservative management of endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is a rare condition in young women. The objective of this study was to evaluate the risk of pelvic lymph node (LN) metastasis in young women with EC who are candidates for conservative management. METHODS: Using the SEER database, a population-based analysis was conducted to identify women <45 years with grade 1, 2, or 3 endometrioid adenocarcinoma stage IA (FIGO 2009) who underwent pelvic lymphadenectomy with at least ten LNs removed. The LN macrometastases rate based on conventional histological diagnosis was analyzed according to tumor grade and myometrial invasion (MI) on final histology. RESULTS: A cohort of 1284 women was analyzed. The LN metastasis rates were: 2/414 (0.5%) grade 1 EC without MI, 5/239 (2.1%) grade 2 or 3 EC without MI, 5/308 (1.6%) grade 1 EC with MI, and 14/323 (4.3%) grade 2 or 3 EC with MI. Tumor size was not correlated with LN metastasis probability. CONCLUSIONS: Young patients eligible for conservative management have a low rate of LN macrometastasis, especially in stage IA without MI grade 1 EC. A systematic lymphadenectomy should not be performed in these patients. Prospective study evaluating the sentinel LN mapping in conservative management of EC could be performed to assess the LN micrometastasis rate.

A modern assessment of the surgical pathologic spread and nodal dissemination of endometrial cancer.

OBJECTIVE: To examine the risk of nodal metastases in a contemporary cohort of women based on pathologic risk factors including histology, depth of invasion, tumor grade, and lymphovascular space invasion. METHODS: Women with endometrial cancer who underwent hysterectomy from 2004 to 2016 who were registered in the National Cancer Database were analyzed. Patients were stratified by T stage: T1A (<50% myometrial invasion), T1B (>50% myometrial invasion) and T2 (cervical involvement). Lymph node metastases were assessed in relation to tumor T stage and grade, and further stratified by lymphovascular space invasion. RESULTS: We identified 161,960 patients. The rate of nodal metastases within the endometrioid histology cohort was 2.2% for T1A cancers, 12.8% for T1B cancers and 19.9% for T2 cancers. For stage TIA cancers, the percent of patients with positive nodes increased from 1.1% for grade 1 cancers, to 2.9% for grade 2 cancers to 4.8% for grade 3 cancers. The corresponding rates of nodal metastases for stage T1B cancers were 8.6%, 13.7%, and 16.9%, respectively. For T1A cancers without lymphovascular space invasion, nodal metastases ranged from 0.6% in those with grade 1 cancers to 3.0% for grade 3 cancers. The corresponding risk of nodal disease ranged from 11.8% to 13.9% for T1A cancers with lymphovascular space invasion. CONCLUSIONS: There was a sequential increase in the risk of lymph node metastases based on depth of uterine invasion, tumor grade, and the presence of lymphovascular space invasion. The overall rate of nodal metastasis is lower than reported in the original GOG 33.

Incidence and potential predictors of thromboembolic events in epithelial ovarian carcinoma patients during perioperative period.

OBJECTIVE: To assess the incidence and the risk factors of venous thromboembolism (VTE) in patients with epithelial ovarian carcinoma (EOC) during the perioperative period. METHODS: A retrospective analysis was conducted on the patients with epithelial ovarian cancer treated in our hospital, between January 2017 and July 2019, and a comprehensive review of the medical documentation was performed to collect relevant data. We then analyzed the related factors of the thrombosis in the EOC patients, using univariate and multivariate analysis to identify significant risk factors for VTE, and bootstrap resampling method was used to verify the multivariate analysis results. The ROC curve methods were conducted to evaluate the diagnostic value for the prediction of VTE. RESULTS: We analyzed 233 cases of patients with EOC, of whom the incidence of VTE was 11.16%. According to multivariate and 5000 bootstrap samples analysis, preoperative D-dimer levels (>4.215 µg/ml, p = 0.041 and p = 0.032) and comorbid of cerebral infarction (p < 0.001 and p < 0.001) had statistical significance in predicting VTE events; bootstrap analysis also found the Alb, CA125, OCCC had statistical significance. While According to multivariate and 5000 bootstrap samples analysis, age (>50.5 years old, p = 0.019 and p = 0.002) and nonoptimal debulking surgery (p = 0.007 and p = 0.002) showed significance in predicting VTE after surgery; bootstrap analysis also found the D-dimer levels (>4.215 µg/ml) and tuberculosis had statistical significance. CONCLUSION: More effective thromboprophylaxis and pre-test assessment is necessary for EOC patients. For prediction VTE events, D-dimer levels (>4.215 µg/ml) were the independent predictors before operation. Age and debulking surgery were the independent predictors post operation.

Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study.

BACKGROUND: Several studies have suggested that endometriosis is associated with an increased risk of ovarian cancer, especially for the clear-cell and endometrioid subtypes. However, previous studies lack sufficient power or diagnostic certainty. OBJECTIVE: The objective of the study was to assess the association between histologically proven endometriosis and ovarian cancer in a large population-based cohort study. STUDY DESIGN: We identified 131,450 women with a histological diagnosis of endometriosis between 1990 and 2015 from the Dutch nationwide registry of histopathology and cytopathology (PALGA). For the control cohort 132,654 women with a benign dermal nevus were matched on age and inclusion year with the endometriosis cases. Histological diagnoses of ovarian, fallopian tubes, and peritoneal cancers between January 1990 and July 2017 were retrieved. Incidence rate ratios were estimated for ovarian cancer and its subtypes for the whole follow-up period as well as for women with more than 1 person-year at risk. RESULTS: We found a crude incidence rate ratio of 4.79 (95% confidence interval, 4.33-5.31) and an age-adjusted incidence rate ratio of 7.18 (95% confidence interval, 6.17-8.36) for ovarian cancer overall. Endometrioid and clear-cell ovarian cancer had the highest age-adjusted incidence rate ratio of 29.06 (95% confidence interval, 20.66-40.87) and 21.34 (95% confidence interval, 14.01-32.51), respectively. Median age at ovarian cancer diagnosis was 56 years (interquartile range, 49-63) for the endometriosis cohort and 60 years (interquartile range, 53-67) for the nevus cohort, (P < .05). After excluding women with less than 1 person-year at risk following an endometriosis diagnosis, we found a crude incidence rate ratio of 1.04 (95% confidence interval, 0.91-1.19) and an age-adjusted incidence rate ratio of 1.08 (95% confidence interval, 0.87-1.35) for ovarian cancer overall. However, statistically significant age-adjusted incidence rate ratios of 2.29 (95% confidence interval, 1.24-4.20) for clear-cell ovarian cancer and 2.56 (95% confidence interval, 1.47-4.47) for endometrioid ovarian cancer were found. CONCLUSION: A significantly higher incidence of clear-cell and endometrioid ovarian cancer was found in women with histologically proven endometriosis. Additionally, we found an increased incidence of all ovarian cancer subtypes in histologically proven endometriosis; however, in many of these women, endometriosis and ovarian cancer were diagnosed synchronously after the average menopausal age, which may suggest that the risk of ovarian cancer in endometriosis patients remains, even when clinical endometriosis symptoms are no longer present.

Serum HSP70 level in patients with endometrial cancer with and without diabetes.

Diabetes mellitus (DM) is associated with an increased risk of endometrial carcinoma (EC). Heat shock proteins have a role in the modulation of both diseases. The aim of this study was to investigate extracellular HSP70 (eHSP70) level alternations in patients with two different types of EC (endometrioid and non-endometrioid) with and without type 2 diabetes. In a case-control study, 88 participants were enrolled in four groups including: 18 EC patients with DM, 19 EC patients without DM, 29 patients with DM, and 22 healthy individuals. Blood samples were taken before surgery in cancer patients. Estradiol, eHSP70, sex hormone-binding globulin (SHBG), FBS, and HbA1c were assessed. Serum HSP70 level was higher in patients with diabetes (52.24 ± 14.2 ng/ml) compared to healthy controls (39.04 ± 6.96) (p < .05). It was lower in EC (26.05 ± 12.28) compared to healthy controls (39.04 ± 6.96) (p < .05). eHSP70 was also lower in endometrioid-type carcinoma (22.57 ± 11) compared to non-endometrioid type (31.55 ± 12.38) (p < .05). Further analysis showed increased levels of eHSP70 in patients having both endometrioid-type carcinoma and diabetes (27.23 ± 11.41) compared to the same patients without DM (17.08 ± 7.78) (p < .05). Presence of diabetes in patients with endometrioid type carcinoma resulted in an increase in eHSP70 approaching the level of eHSP70 in patients with non-endometrioid histology.

Minimally Invasive Surgery Rate as a Quality Metric for Endometrial Cancer.

STUDY OBJECTIVE: To determine the frequency with which Commission on Cancer-accredited hospitals met a metric of ≥80% minimally invasively performed hysterectomies for endometrial cancer and to compare the clinical outcomes of hospitals meeting this metric with those that did not. DESIGN: Retrospective cohort study. SETTING: Hospitals caring for ≥20 endometrial cancer patients per year recorded in the National Cancer Database in 2015 were included. PATIENTS: Women who had undergone hysterectomy for endometrial cancer and had an epithelial histology, a Charlson comorbidity score of 0, and stage I to III disease. INTERVENTION: Patient characteristics, patterns of care, and outcomes were compared between hospitals performing ≥80% minimally invasive hysterectomies and hospitals not meeting this metric. MEASUREMENTS AND MAIN RESULTS: The hospitals (n = 510) treated 20 670 women with endometrial cancer. In 283 (55%) hospitals ≥80% of hysterectomies were minimally invasively performed (high-minimally invasive surgery [MIS] hospitals, overall MIS rate 89%). In the 227 hospitals that did not meet this metric, 61% of hysterectomies for endometrial cancer were performed using a minimally invasive approach. In high-MIS hospitals, patients were more likely to be white (87% vs 82%, p<.001), privately insured (53% vs 49%, p <.001), and have stage I disease (84% vs 82%, p = .002) and an endometrioid histology (79% vs 76%, p <.001). Surgery was more often performed robotically (80% vs 71%), and conversion to laparotomy was less likely (1.5% vs 3.2%, adjusted odds ratio [aOR], 0.47; 95% confidence interval [CI], 0.39-0.57) (both p <.001). Patients treated at high-MIS hospitals were more likely to have undergone lymph node assessment at the time of surgery (76% vs 69%; aOR, 1.43; 95% CI, 1.35-1.53) and been discharged on the same or next day (74% vs 57%; aOR, 2.27; 95% CI, 2.13-2.42) and were less likely to have an unplanned 30-day readmission (1.8% vs 2.9%; aOR, 0.64; 95% CI, 0.53-0.77). CONCLUSION: An MIS rate of ≥80% for endometrial cancer is feasible on a national scale and is associated with other hospital-level measurements of high-quality care.

Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia.

BACKGROUND: Endometrial intraepithelial neoplasia, also known as complex atypical hyperplasia, is a precancerous lesion of the endometrium associated with a 40% risk of concurrent endometrial cancer at the time of hysterectomy. Although a majority of endometrial cancers diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low risk and low stage, approximately 10% of patients ultimately diagnosed with endometrial cancers will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, few data exist regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology. OBJECTIVE: To determine whether preoperative factors can predict the presence of concurrent endometrial cancer at the time of hysterectomy in patients with endometrial intraepithelial neoplasia; and to describe the ability of preoperative characteristics to predict which patients may be at a higher risk for lymph node involvement requiring lymph node assessment at the time of hysterectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring lymphadenectomy. Unadjusted associations between covariates and progression to endometrial cancer were estimated by 2-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation. RESULTS: Of the 1055 charts reviewed, 169 patients were eligible and included. Of these patients, 87 (51.5%) had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease, whereas 82 (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at the time of hysterectomy (15.7 mm; standard deviation, 9.5) versus 12.5 mm; standard deviation, 6.4; P = .01). An endometrial stripe of ≥2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% confidence interval, 1.5-10.0), controlling for age. In all, 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe of ≥2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe of <2 cm. CONCLUSION: Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment.

Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients.

We explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes in major histological types of ovarian cancer. We performed targeted sequencing to assess germline and somatic mutations of 16 HR-associated genes and 4 mismatch repair (MMR) genes among 207 ovarian cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell carcinomas (CCC), 39 endometrioid carcinomas (EC), 13 mucinous carcinomas (MC), and 6 low-grade serous carcinomas (LGSC)). Germline or somatic mutations of HR-associated genes were detected in 44% of HGSC, 28% of CCC, 23% of EC, 16% of MC, and 17% of LGSC patients. The profile of HR-associated gene mutations was remarkably different among each histological type. Germline BRCA1/2 mutations were frequently detected in HGSC and were rarely observed in CCC, EC, and MC patients. ATM somatic mutation was more frequently detected in CCC (9%) and EC patients (18%) than in HGSC patients (4%). There was a positive correlation between MMR gene mutations and HR-associated gene mutations (p = 0.0072). Our findings might be useful in selection of ovarian cancer patients that should be treated with PARP inhibitors.