Racial Disparities in Endometrial Cancer Clinical Trial Representation: Exploring the Role of Eligibility Criteria.

BACKGROUND: This study aimed to determine whether Black patients with recurrent endometrial cancer were more likely than White patients to be ineligible for a recently published clinical trial due to specific eligibility criteria. METHODS: Patients with recurrent or progressive endometrial cancer diagnosed from January 2010 to December 2021 who received care at a single institution were identified. Demographic and clinicopathologic information was abstracted and determination of clinical trial eligibility was made based on 14 criteria from the KEYNOTE-775 trial. Characteristics of the eligible and ineligible cohorts were compared, and each ineligibility criterion was evaluated by race. RESULTS: One hundred seventy-five patients were identified, 89 who would have met all inclusion and no exclusion criteria for KEYNOTE-775, and 86 who would have been ineligible by one or more exclusion criteria. Patients in the ineligible cohort were more likely to have lower BMI (median 26.5 vs. 29.2, P <0.001), but were otherwise similar with regard to insurance status, histology, and stage at diagnosis. Black patients had 33% lower odds of being eligible (95% CI: 0.33-1.34) and were more likely to meet the exclusion criterion of having a previous intestinal anastomosis, but the result was not statistically significant. If this criterion were removed, the racial distribution of those ineligible for the trial would be more similar (46.4% Black vs. 42.2% White). CONCLUSIONS: Clinical trial eligibility criteria may contribute to the underrepresentation of racial groups in clinical trials, but other factors should be explored. Studies to quantify and lessen the impact of implicit bias are also needed.

No Racial Disparities Observed Using Point-of-Care Genetic Counseling and Testing for Endometrial and Ovarian Cancer in a Diverse Patient Population: A Retrospective Cohort Study.

We investigated genetic counseling and testing rates for patients with gynecologic malignancy at a tertiary care center with a large minority population. Our retrospective cohort included newly diagnosed epithelial ovarian, fallopian tube, peritoneal, or endometrial cancer patients between January 2014 and June 2022. For endometrial cancer, 373 patients were identified. A total of 207 (55%) patients were screened using mismatch repair immunohistochemistry (MMR IHC). A total of 82 (40%) had MMR deficiencies on IHC. Of these, 63 (77%) received genetic counseling. A total of 62 (98%) underwent genetic testing, and ultimately, 7 (11%) were diagnosed with Lynch syndrome (LS). The overall rate of LS was 1.9%. MMR IHC testing increased steadily, reaching 100% in 2022. For ovarian cancer, 144 patients were identified. A total of 104 (72%) patients received genetic counseling, and 99 (95%) underwent genetic testing. Rates were not influenced by race, ethnicity, insurance type, or family history of cancer. They were significantly different by cancer stage (p < 0.01). The proportion of patients who received genetic counseling increased from 47% in 2015 to 100% in 2022 (p < 0.01). Most counseling was performed by a gynecologic oncologist (93%) as opposed to a genetic counselor (6.7%). Overall, 12 (8.3%) patients were BRCA+. High rates of counseling and testing were observed with few disparities.

JAK1 promotes HDV replication and is a potential target for antiviral therapy.

BACKGROUND & AIMS: Chronic co-infection with HBV and HDV leads to the most aggressive form of chronic viral hepatitis. To date, no treatment induces efficient viral clearance, and a better characterization of virus-host interactions is required to develop new therapeutic strategies. METHODS: Using loss-of-function strategies, we validated the unexpected proviral activity of Janus kinase 1 (JAK1) - a key player in innate immunity - in the HDV life cycle and determined its mechanism of action on HDV through various functional analyses including co-immunoprecipitation assays. RESULTS: We confirmed the key role of JAK1 kinase activity in HDV infection. Moreover, our results suggest that JAK1 inhibition is associated with a modulation of ERK1/2 activation and S-HDAg phosphorylation, which is crucial for viral replication. Finally, we showed that FDA-approved JAK1-specific inhibitors are efficient antivirals in relevant in vitro models including primary human hepatocytes. CONCLUSIONS: Taken together, we uncovered JAK1 as a key host factor for HDV replication and a potential target for new antiviral treatment. IMPACT AND IMPLICATIONS: Chronic hepatitis D is the most aggressive form of chronic viral hepatitis. As no curative treatment is currently available, new therapeutic strategies based on host-targeting agents are urgently needed. Here, using loss-of-function strategies, we uncover an unexpected interaction between JAK1, a major player in the innate antiviral response, and HDV infection. We demonstrated that JAK1 kinase activity is crucial for both the phosphorylation of the delta antigen and the replication of the virus. By demonstrating the antiviral potential of several FDA-approved JAK1 inhibitors, our results could pave the way for the development of innovative therapeutic strategies to tackle this global health threat.

Population Genomic Evidence of Adaptive Response during the Invasion History of Plasmodium falciparum in the Americas.

Plasmodium falciparum, the most virulent agent of human malaria, spread from Africa to all continents following the out-of-Africa human migrations. During the transatlantic slave trade between the 16th and 19th centuries, it was introduced twice independently to the Americas where it adapted to new environmental conditions (new human populations and mosquito species). Here, we analyzed the genome-wide polymorphisms of 2,635 isolates across the current P. falciparum distribution range in Africa, Asia, Oceania, and the Americas to investigate its genetic structure, invasion history, and selective pressures associated with its adaptation to the American environment. We confirmed that American populations originated from Africa with at least two independent introductions that led to two genetically distinct clusters, one in the North (Haiti and Colombia) and one in the South (French Guiana and Brazil), and an admixed Peruvian group. Genome scans revealed recent and more ancient signals of positive selection in the American populations. Particularly, we detected positive selection signals in genes involved in interactions with hosts (human and mosquito) cells and in genes involved in resistance to malaria drugs in both clusters. Analyses suggested that for five genes, adaptive introgression between clusters or selection on standing variation was at the origin of this repeated evolution. This study provides new genetic evidence on P. falciparum colonization history and on its local adaptation in the Americas.

Recurrent herpes simplex virus mimicking vulvar carcinoma in patient with Human Immunodeficiency Virus: A case report.

Patients with human immunodeficiency virus (HIV) are at increased risk for developing other gynecologic conditions, including herpes simplex virus (HSV) and vulvar intraepithelial neoplasia (VIN)/carcinoma. We describe the case of a woman with a history of microinvasive vulvar squamous cell carcinoma who presented with hypertrophic ulcerated vulvar and peri-anal masses concerning for malignancy. This case highlights the need to maintain a high index of suspicion for malignancy and herpes simplex virus, even with negative polymerase chain reaction (PCR) test, as well as the difficulty of treating this often-resistant lesion.

A stable hepatitis D virus-producing cell line for host target and drug discovery.

Chronic hepatitis D is the most aggressive form of chronic viral hepatitis. It is caused by super-infection of hepatitis B virus (HBV)-infected hepatocytes with hepatitis D virus (HDV). While the recent conditional approval of bulevirtide for HDV treatment offers a new therapeutic modality in Europe, there is an unmet medical need to further improve therapy. A more detailed characterization of virus-host interactions is needed for the identification of novel therapeutic targets. Addressing this need, we engineered a new stably-transformed cell line, named HuH7-2C8D, producing high titer recombinant HDV and allowing the study of viral particles morphogenesis and infectivity. Using this culture system, where viral propagation by re-infection is limited, we observed an increased accumulation of edited version of the viral genomes within secreted HDV viral particles over time that is accompanied with a decrease in viral particle infectivity. We confirmed the interaction of HDV proteins with a previously described host factor in HuH7-2C8D cells and additionally showed that these cells are suitable for co-culture assays with other cell types such as macrophages. Finally, the use of HuH7-2C8D cells allowed to confirm the dual antiviral activity of farnesyl transferase inhibitors, including the clinical candidate lonafarnib, against HDV. In conclusion, we have established an easy-to-handle cell culture model to investigate HDV replication, morphogenesis, and host interactions. HuH7-2C8D cells are also suitable for high-throughput antiviral screening assays for the development of new therapeutic strategies.

Dietary Behavior and Diet Interventions among Structural Firefighters: A Narrative Review.

Structural firefighters (SFFs) are exposed to multiple occupational hazards that affect dietary behavior and can contribute to increased risks of cancer and cardiovascular disease compared to the United States' general population. Dietary behavior is a feasible modification for positive health outcomes. The objectives of this narrative review are to summarize the diet behavior of SFFs, review findings of diet interventions that positively modify diet behavior, identify research gaps, and suggest recommendations for addressing those gaps. PubMed, MEDLINE, Scopus, and CABI Web of Science were searched between February 2020 and June 2022 for peer-reviewed articles. The inclusion criteria were as follows: (1) study population must include SFFs; (2) investigate diet or diet intervention among SFFs; (3) report results specific to SFFs; and (4) be published in the English language. Thirty-four studies were included. Results indicate that SFFs recognize the importance of a healthy dietary pattern, but do not follow one, and that food choices are often influenced by colleagues. Diet interventions, such as the Mediterranean diet, were observed to have positive health improvements, such as improved lipid levels and lower CVD risk. Team counseling was found to be more effective for adopting healthier diets compared to one-on-one counseling; and general counseling was more effective than no counseling. A gap identified by this review is the lack of information concerning differences in dietary intake, diet quality, and dietary behaviors while on- and off-shift, and throughout the career. Diet is an important risk factor for occupational disease development; therefore, effective, consistent dietary interventions are necessary.

Fatalistic cancer beliefs and self-reported cancer screening behaviors among diverse urban residents.

Cancer fatalism-the belief that death is inevitable when cancer is present-has been identified as a barrier to cancer screening, detection, and treatment. Our study examined the relationship between self-reported cancer fatalism and adherence to cancer screening guidelines of the breasts, cervix, colon, and prostate among a diverse sample of urban-dwelling adults in Brooklyn, New York. Between May 2019 and August 2020, we conducted a cross-sectional survey of adults 40 + years of age (n = 2,341) residing in Brooklyn neighborhoods with high cancer mortality. Multivariable logistic regression models were used to assess the odds of reporting cancer screening completion across three fatalistic cancer belief categories (low, med, high). Participants' median age was 61 (IQR 51, 71) years, 61% were women, 49% self-identified as non-Hispanic black, 11% Hispanic, 4% Asian, and 6% more than one race. There were no statistically significant differences in the proportion of low, some, or high fatalistic beliefs identified among male respondents compared to women. Among women, we observed that high fatalistic cancer beliefs were associated with higher odds (OR 2.01; 95% CI 1.10-3.65) of completing breast but not cervical (1.04; CI 0.55-1.99) or colon (1.54; CI 0.88-2.69) cancer screening. Men with high fatalistic cancer beliefs had a trend towards lower odds of prostate screening (OR 0.53: 95% CI 0.18-1.57) compared to men with low fatalistic beliefs, but neither was statistically significant. Findings suggest that high fatalistic cancer beliefs may be an important factor in cancer screening utilization among women. Further examination in longitudinal cohorts with a larger sample of men may be needed in order to identify any significant effect.

Optimal cytoreduction followed by chemoradiation in stage IVB uterine serous carcinoma.

OBJECTIVES: The prognosis of patients presenting with stage IVB uterine serous carcinoma (USC) remains extremely poor, with a reported 5-year survival of <20%. Here were evaluate the survival impact of cytoreductive surgery and identify other prognostic factors in stage IVB USC. METHODS: A multicenter retrospective analysis of patients with stage IVB USC was conducted from 2000 to 2018. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemotherapy+/-external beam radiation therapy (EBRT). Optimal cytoreduction (R1) was defined as residual disease ≤1 cm at completion of surgery, and suboptimal cytoreduction (R2) was defined as >1 cm. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. RESULTS: Final analysis included 68 patients. There was no difference in the frequency of treatment delays between regimens (p = 0.832). 96% of patients received platinum-based chemotherapy. There was no difference in the age (p = 0.227), race (p = 0.936), type of radiotherapy (p = 0.852) or chemotherapy regimen received (p = 0.996) between R1 and R2 cohorts. The median PFS for all patients was 8 months and the median OS was 13 months. Cytoreduction to R1 was associated with a median PFS of 9 months, compared to R2 with a median PFS of 4 months (p < 0.001, HR 0.32, 95% CI 7.4-14.1). Median OS was also improved with R1 vs. R2 cytoreduction (17 months vs. 7 months, respectively) (p < 0.001, HR 0.21, 95% CI 13.7-26.4). Compared to R1, cytoreduction to R0 was not associated with a survival benefit. The R0 median OS was 17 months versus 18 months in R1 (p = 0.67). The combination of adjuvant chemoradiation was associated with improved PFS (11 months vs. 7 months) (p = 0.024, HR 0.41, 95% CI 6.5-9.4) and OS (22 months vs 13 months) (p = 0.65, HR 0.25, 95% CI 10.5-15.4) compared to chemotherapy-alone, respectively. On MVA, only the amount of residual disease (p = 0.003, HR 0.39, 95% CI 0.2-0.7) and receipt of adjuvant chemoradiation (p = 0.010, HR 0.09, 95% CI 0.01-0.58) were independent predictors of survival. CONCLUSIONS: In stage IVB USC, optimal cytoreduction should be the goal at the time of primary surgery. The combination of chemoradiation was associated with superior survival compared to chemotherapy alone and should be further investigated in this patient population.

Cell-based cccDNA reporter assay combined with functional genomics identifies YBX1 as HBV cccDNA host factor and antiviral candidate target.

OBJECTIVES: Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and hepatocellular carcinoma. A key feature of HBV replication is the synthesis of the covalently close circular (ccc)DNA, not targeted by current treatments and whose elimination would be crucial for viral cure. To date, little is known about cccDNA formation. One major challenge to address this urgent question is the absence of robust models for the study of cccDNA biology. DESIGN: We established a cell-based HBV cccDNA reporter assay and performed a loss-of-function screen targeting 239 genes encoding the human DNA damage response machinery. RESULTS: Overcoming the limitations of current models, the reporter assay enables to quantity cccDNA levels using a robust ELISA as a readout. A loss-of-function screen identified 27 candidate cccDNA host factors, including Y box binding protein 1 (YBX1), a DNA binding protein regulating transcription and translation. Validation studies in authentic infection models revealed a robust decrease in HBV cccDNA levels following silencing, providing proof-of-concept for the importance of YBX1 in the early steps of the HBV life cycle. In patients, YBX1 expression robustly correlates with both HBV load and liver disease progression. CONCLUSION: Our cell-based reporter assay enables the discovery of HBV cccDNA host factors including YBX1 and is suitable for the characterisation of cccDNA-related host factors, antiviral targets and compounds.

Treating anxiety and depression in inflammatory bowel disease: a systematic review.

OBJECTIVE: Inflammatory Bowel Disease (IBD) is associated with higher rates of clinically significant anxiety and depression than in healthy populations. Psychosocial interventions targeting anxiety and depression in IBD have variable efficacy and disparate treatment approaches, making treatment recommendations difficult. The current study aimed to identify effective treatment components across psychosocial treatment approaches for anxiety and depression in IBD. DESIGN: A systematic review of psychosocial treatments for anxiety and depression in IBD was conducted. Based on the Distillation and Matching Model, treatments were coded and data aggregated by intervention components, or practice elements (PE), to elucidate replicable clinical techniques. MAIN OUTCOME: The percentage of studies utilizing a given PE was the primary outcome. MEASURES: Among all included studies, as well as among those finding favorable, significant effects on anxiety or depression, the percentage utilizing each PE and number of PEs utilized was determined. RESULTS: The most utilized PEs among included interventions were relaxation, IBD psychoeducation, cognitive restructuring, distraction, and social skills. Examining only interventions with favorable differences on specified outcomes (HRQoL, Anxiety, Depression, and/or Coping) indicated that relaxation, education, cognitive restructuring, and mindfulness were most utilized. CONCLUSION: Implications for clinical practice are discussed, including the development and dissemination of treatment recommendations.

Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection.

Chronic hepatitis D is one of the most severe and aggressive forms of chronic viral hepatitis with a high risk of developing hepatocellular carcinoma (HCC). It results from the co-infection of the liver with the hepatitis B virus (HBV) and its satellite, the hepatitis D virus (HDV). Although current therapies can control HBV infection, no treatment that efficiently eliminates HDV is available and novel therapeutic strategies are needed. Although the HDV cycle is well described, the lack of simple experimental models has restricted the study of host-virus interactions, even if they represent relevant therapeutic targets. In the last few years, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key cellular entry factor for HBV and HDV has allowed the development of new cell culture models susceptible to HBV and HDV infection. In this review, we summarize the main in vitro model systems used for the study of HDV entry and infection, discuss their benefits and limitations and highlight perspectives for future developments.

Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases.

BACKGROUND: We seek to evaluate the difference in recurrence patterns and survival among stage IIIC high-grade endometrial cancer treated with surgery followed by adjuvant chemotherapy alone, radiation therapy alone, or both (chemoradiation). METHODS: A multicenter retrospective analysis of surgically staged IIIC HGEC receiving adjuvant therapy was conducted. HGEC was defined as grade 3 endometrioid adenocarcinoma, serous, clear cell and carcinosarcoma. Differences in the frequency of recurrence sites and treatment delays were identified using Pearson's χ2 test. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates. RESULTS: A total of 155 patients were evaluable: 41.9% carcinosarcoma, 36.8% serous, 17.4% grade 3 and 3.9% clear cell. Of these, 67.1% received chemoradiation, 25.8% received chemotherapy and 7.1% received radiation therapy. There was no difference in the frequency of treatment delays between regimens (p = 0.571). There was a trend towards greater retroperitoneal recurrence with chemotherapy (25.9%) versus chemoradiation (8.4%) and radiation therapy (7.7%) (p = 0.252). Grade 3 tumors had improved progression-free and overall survival (26 and 42 months, respectively) versus serous (17 and 30 months, respectively), carcinosarcoma (14 and 24 months, respectively) and clear cell (24 and 30 months respectively) (p = 0.002, p < 0.001). Overall, chemoradiation was superior to chemotherapy and radiation therapy in PFS (p < 0.001) and OS (p < 0.001). Upon multivariate analysis, only histology and receipt of chemoradiation were independent predictors of survival. CONCLUSION: The majority of stage IIIC high-grade endometrial carcinomas recurred. Chemoradiation was associated with improved survival and less retroperitoneal recurrence. Grade 3 tumors demonstrated improved survival versus other histologies regardless of adjuvant treatment modality.

Risk models for predicting the health-related quality of life of caregivers of youth with gastrointestinal concerns.

PURPOSE: To determine the usefulness of cumulative and additive risk models in predicting the healthy-related quality of life (HRQOL) of caregivers of youth with chronic gastrointestinal conditions. METHODS: 203 caregivers (82.8% mothers; 77.3% white) of youth (M = 11.27 years; 44.3% female; 78.8% White) completed self-report questionnaires focused on potential environmental, child health, and family risk factors that could impact caregiver HRQOL. Cumulative risk models, evaluating overall combined risk level, as well as an additive risk model, exploring individual risk variables, were evaluated. RESULTS: Higher levels of cumulative risk were associated with poorer caregiver HRQOL after controlling for child and caregiver sex. A linear cumulative risk model was a better fit than a quadratic cumulative risk model for predicting caregiver HRQOL, while an additive model identified child HRQOL, child pain interference and family functioning as the most individually impactful risk variables. CONCLUSION: This study illustrates the usefulness of both additive and cumulative risk approaches in identifying caregivers at risk for poor HRQOL. Provision of appropriate referrals and interventions based on the caregiver's risk factors can help protect caregiver quality of life and, in turn, benefit the care children with chronic conditions receive at home.

Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid arthritis: a sub-analysis of the international, observational ACTION study.

Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.

Relations between disease status and body composition in pediatric inflammatory bowel disease.

To evaluate the effect of remission status on physical activity and body composition in pediatric patients with inflammatory bowel disease (PIBD) and healthy peers. Single-center cohort study, including 54 PIBD patients and 33 healthy peers. During the initial study visit, a brief demographic questionnaire, physical activity questionnaire completed by participants, and instructions on recording dietary intake were given. Physicians completed the Physician Global Assessment (PGA) for disease severity. Medical chart abstraction was done to obtain disease variables of interest. DEXA scan completed 1 week later to obtain information on body composition. Variables of interest were compared between the three groups (IBD-Remission, IBD-Active, and healthy controls) using an ANOVA or Chi-square test as appropriate. IBD patients were older than controls, reported lower quality of life (73.9 vs. 80.9), and engaged in less MVPA (195.4 versus 361.1). The IBD-Active group had a significantly lower lean body mass, bone mineral density, and time spent in MVPA compared to the IBD-Remission group and healthy controls. IBD-Remission group had a significantly lower percentage of biologic use (55% vs. 87%) and comorbidities (26% vs. 44%) compared to IBD-active group. IBD-remission group also had a lower fat mass percentage. In this study, we report significantly favorable LBM, BMD, and time spent in MVPA in patients with IBD in remission compared to those not in remission with the former demonstrating a body composition resembling that of healthy peers.Conclusion: While an improvement in BMD was observed with remission, the scores were still lower than controls. What is Known: • Body composition deficits in pediatric inflammatory bowel disease are common and some persist despite achievement of remission leading to long term outcomes including osteopenia and osteoporosis. • Weight restoration in patients with pediatric IBD is primarily explained by gains in fat mass without similar gains in lean mass. What is New: • While an improvement in bone mineral density was observed, the achievement of remission significantly improves affects physical activity and body composition in pediatric inflammatory bowel disease. • However, some parameters of body composition do not reach levels comparable to healthy peers.

Breast metastases: A rare manifestation of advanced uterine serous carcinoma.

Metastasis of non-mammary tumors to the breast are uncommon, representing <1% of all breast tumors. Breast metastasis are associated with advanced disease and poor prognosis regardless of the origin of the primary tumor. Uterine cancer metastasis to the breast is an extremely rare finding and has not been reported in the case of serous histology. Here, we review two cases of uterine serous carcinoma metastatic to the breast. Both patients presented with breast-specific complaints including pain and palpable mass and were found to have widely metastatic disease. Tissue biopsy and immunohistochemistry consistent with primary uterine serous carcinoma confirmed the diagnosis of metastasis in both cases. Our findings suggest hematogenous metastasis to the breast is a late phenomenon in the course of endometrial carcinoma and associated with the development of disease at multiple sites. This emphasizes the importance of complete evaluation in patients presenting with breast complaints and known history of malignancy, as this may be the only presenting symptoms in patients with widely metastatic disease.

Clinical comparison between neuroendocrine and endometrioid type carcinoma of the uterine corpus.

OBJECTIVE: To compare the clinicopathologic features and survival outcomes of neuroendocrine tumor of the uterine corpus (NET-U) to endometrioid type endometrial carcinoma (EC). METHODS: From 1993 to 2012, the Surveillance, Epidemiology and End Results cancer registry was queried for women diagnosed with EC or NET-U. Data regarding stage, grade, presence of extra-uterine disease, lymph node metastasis, receipt of adjuvant radiation, surgical intervention and overall survival (OS) was extracted. Chi-square tests, t-tests and Kaplan Meir curves were used for statistical analysis. RESULTS: A total of 98,363 patients were identified: 98,245 with EC and 118 with NET-U. The mean age at diagnosis for EC was 61.7 years and 64.8 years for NET-U (p=0.01). NET-U cases were more likely to be poorly differentiated (97.0% vs. 15.6%; p≤0.01) and have nodal metastasis (56.4% vs. 11.1%; p≤0.01) when compared to EC. Presence of extrapelvic disease at the time of diagnosis was observed more frequently in NET-U compared to EC, 49.1% vs. 4.8%, respectively (odds ratio=18; 95% confidence interval=13.1-27.2; p≤0.01). Significant improvement in OS was observed in NET-U patient who received radiation (OS: 7.7 vs. 3.3 years; p≤0.01) or underwent surgical management (5.6 vs. 0.9 years; p≤0.01). The OS for EC was 14.4 vs. 4.6 years for NET-U (p≤0.01). CONCLUSION: NET-U represents an aggressive form of uterine malignancy. When compared to EC, patients with NET-U present at more advanced stage, have more frequent extra-uterine disease and lower OS.