Obese Endometrial Cancer Patients Research Articles

Impact of electronic medical record utilization on obesity screening and intervention for obese patients with endometrial cancer

ObjectiveTo identify the prevalence of obesity documented within the electronic medical record problem list.MethodsWe conducted a retrospective cohort study of adult patients with obesity and endometrial cancer receiving care from...

Abstract 3377: Exploring the role of obesity-induced exosome secretion and associated proteins in endometrial cancer pathogenesis: A roadmap for prevention through exosome inhibition

Abstract Introduction: Endometrial cancer (EC) is the leading gynecologic malignancy in the U.S., with obesity implicated in 57% of cases. This study explores the molecular workings of oncogenic protein expression (TMEM205, STAT5, and FAS) and their role in regulating exosome secretion. Understanding these mechanisms is crucial for unraveling pathways involved in obesity-related EC, informing the development of innovative strategies for prevention and treatment. Methods: The isolated exosomes were quantified using nanoparticle tracking analyzer (NTA) and their size measured by Transmission electron microscopy (TEM). TMEM205, STAT5, FAS and PIAS3 expression was confirmed by IHC, ELISA and RT-PCR in patient and high fat diet treated mouse tissue. Endometrial hyperplasia was developed in immunocompetent mice using high fat diet (HFD; 45 kcal% fat diet) for 16 weeks. Results: Our study investigates exosome secretion and the regulation of oncogenic proteins in adipose and uterine tissues from obese EC patients compared to non-obese EC samples. Analyzing the effects of a 45% kcal high-fat diet (HFD) on mice over 24 weeks, we observed higher body weight and increased adipose tissue in the HFD group, along with enlarged uterine horns and heightened inflammation. This correlated with elevated exosome secretion and increased expression of TMEM205, FAS and STAT5, while the tumor suppressor gene PIAS3 was downregulated. The identified small molecule inhibitor, DAP-5, selectively targeting TMEM205 and exosome secretion, demonstrated a significant reduction in body weight and adipose tissue accumulation when administered to HFD mice. Additionally, DAP-5 treatment restored normal uterine morphology and reduced the expression of exosome-related proteins. Conclusion: This study offers central insights into the mechanisms underlying obesity-mediated TMEM205 expression and exosome secretion, shedding light on their role in the pathogenesis of EC. Additionally, it provides pre-clinical evidence supporting the initiation of the first in-human studies for exosome-targeted therapies aimed at preventing obesity-mediated EC. Citation Format: Takahiko Sakaue, Kalpana Deepa Priya Dorayappan, Roman Zingarelli, Wafa Khadraoui, Muralidharan Anbalagan, John Wallbillich, Mark Wascovich, Pragyan Paramita, Adrian Suarez, Casey Cosgrove, Larry G. Maxwell, Hironori Koga, David O’Malley, David Cohn, Selvendiran Karuppaiyah. Exploring the role of obesity-induced exosome secretion and associated proteins in endometrial cancer pathogenesis: A roadmap for prevention through exosome inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3377.

MiRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy.

Endometrial cancer (EC) is the most prevalent gynecological cancer in high-income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity-related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; ≥30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI ≥30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI ≥30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR-199a-5p, miR-449a, miR-449b-5p) in normal-weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity-related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity-related pathways and that may provide novel implications for the clinical management of obese EC patients.

D&C has the best concordance between preoperative and postoperative grades among morbidly obese endometrial cancer patients.

Endometrial cancer is diagnosed by obtaining uterine biopsies by pipelle, dilatation and curettage (D&C), or hysteroscopy. In 15%-25% of the cases, the preoperative and postoperative grades do not match. This discrepancy may carry significant clinical and prognostic consequences. We aimed to assess how body mass index (BMI) affects preoperative and postoperative grade mismatches and whether biopsy methods mitigate this effect. We conducted a retrospective review of patients with endometrial cancer who underwent surgery at our center between 2014 and 2022. We stratified patients into six classes of BMI based on the WHO classification. Preoperative and postoperative grades were compared for concordance with regards to patient BMI and sampling method. A total of 158 patients were included, diagnosed by pipelle (n = 99), hysteroscopy (n = 15), or D&C (n = 44). For all methods, every unit increase in BMI increased the odds of having a gap between histology grades by 5.2%. In the pipelle group, the odds of a larger gap between the histology grades was 62% higher than that of women in the other groups. Among the D&C group, the odds of having a bigger difference between histology grades were 91.8% lower compared to the other groups. Patients with BMI over 30 had nearly 50% discrepancy when diagnosed with pipelle or hysteroscopy, but less than 10% with D&C. Increasing BMI is associated with decreasing concordance between preoperative and postoperative grades in endometrial cancer, especially when it exceeds 30. This effect is much less pronounced, however, when the diagnostic method is D&C.

Modifying effect of obesity on the content of sex hormones and their receptors in endometrial adenocarcinoma and its surrounding tissue

To study the effect of comorbid pathology: obesity of degree 2-3 on the level of sex steroid hormones and their receptors in the tumor and its surrounding tissue in patients with endometrial cancer (EC). Materials and methods. In 30 patients with endometrioid adenocarcinoma T1-3N0-1M0 (the main group, 15 females with obesity grade 2-3 (BMI≥35); the reference group 15 females with normal BMI) in samples of the tumor and its perifocal zone taken after surgical treatment, the levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4), androgen receptors (AR), progesterone receptors (RP4), estrogen receptors (ERα and ERβ) were determined by ELISA method. Statistical analysis was performed with STATISTICA 10.0. Results. Obese EC patients showed longer healing of postoperative wounds, slow recovery, and more frequent tumor metastasizing to regional lymph nodes. In the tumor samples in all patients, compared with the intact endometrium, the levels of estrogens, testosterone and their receptors were higher. Obesity accompanying the malignant process led to a local increase in the levels of estrogens, testosterone, progesterone and AR, ERα and ERβ in the tumor. In the tumor samples, there were no significant differences from the presence of obesity in the levels of RP4. In the perifocal zone of the tumor in patients with comorbid pathology, compared with the parameters in the reference group, the level of E2, P4 and T was also higher, but the content of all steroid receptors was lower. Conclusion. Obesity aggravates hyperestrogenism and progesterone deficiency in adenocarcinoma and increases its enrichment with the androgen and estrogen receptors with the prevalence of ERα over ERβ that may cause the autocrine-paracrine regulation of the growth and metastasizing of the malignant process in patients with endometrial cancer.

The effect of body mass index on the molecular landscape of endometrial cancer

Objectives: Obesity-associated endometrial cancers follow different clinical courses than those not associated with obesity, regardless of histology. While prior studies have examined the link between discrete molecular features and obesity in endometrial cancer, no work has performed an integrated analysis of the association of body mass index (BMI) on the full molecular landscape of endometrial cancer. Methods: Using data from The Cancer Genome Atlas (TCGA), we characterized the effect of BMI on the epigenome, genome, and transcriptome in 547 endometrial cancer samples via multivariate modeling. Results: Increasing BMI was associated with relative hypomethylation and increased RNA abundance in endometrial cancer. We identify 19 genes that show both differential methylation and RNA abundance in relation to BMI (Figure 1) and some of these predict overall survival. Amongst known cancer driver genes, DICER1 is more likely to harbor point mutations in lower BMI tumors. Increasing BMI is also positively associated with microRNA abundance. Intriguingly, there were no significant associations between copy number aberrations and BMI. Conclusions: The molecular landscape of endometrial cancer changes significantly with alterations in BMI. Some of these features may be important in explaining the prognostic differences between obese endometrial cancer patients and non-obese endometrial cancer patients, which may ultimately affect the consideration of adjuvant therapy for these patients. Obesity-associated endometrial cancers follow different clinical courses than those not associated with obesity, regardless of histology. While prior studies have examined the link between discrete molecular features and obesity in endometrial cancer, no work has performed an integrated analysis of the association of body mass index (BMI) on the full molecular landscape of endometrial cancer. Using data from The Cancer Genome Atlas (TCGA), we characterized the effect of BMI on the epigenome, genome, and transcriptome in 547 endometrial cancer samples via multivariate modeling. Increasing BMI was associated with relative hypomethylation and increased RNA abundance in endometrial cancer. We identify 19 genes that show both differential methylation and RNA abundance in relation to BMI (Figure 1) and some of these predict overall survival. Amongst known cancer driver genes, DICER1 is more likely to harbor point mutations in lower BMI tumors. Increasing BMI is also positively associated with microRNA abundance. Intriguingly, there were no significant associations between copy number aberrations and BMI. The molecular landscape of endometrial cancer changes significantly with alterations in BMI. Some of these features may be important in explaining the prognostic differences between obese endometrial cancer patients and non-obese endometrial cancer patients, which may ultimately affect the consideration of adjuvant therapy for these patients.

Omitting lymphadenectomy in obese endometrial cancer patients undergoing sentinel lymph node mapping: when more is less

<h3>Objectives:</h3> Obese patients present unique surgical and technical challenges to their surgeons and anesthesiologists given their multiple comorbidities, difficult anatomy, and excessive weight. Thus, any surgical procedure that prolongs surgical time and potentially increases risk for complications in this population, needs to be carefully evaluated and minimized.The aim of this study is to evaluate the feasibility of sentinel lymph node (SLN) mapping in obese endometrial cancer patients, and to determine whether omitting lymph node dissection (LND) from surgical staging where SLN sampling is performed, impacts oncologic outcomes. <h3>Methods:</h3> Between December 2007 and August 2017, 722 patients with uterine cancer underwent surgical staging in our institution. We excluded patients with sarcomas (n=32), patients with stage 4 disease (n=9), patients who received neoadjuvant therapy (n=5) and patients whose body mass index (BMI) was below 35.0 kg/m² (n=453). The approach for LND at our center changed over the years: all surgeries from January 2008 to August 2014 included bilateral pelvic LND, with para-aortic LND at the surgeon's discretion (LND±SLN cohort). In addition to LND, all consecutive patients from December 2010 to August 2014 underwent SLN mapping with a cervical injection. With the establishment of SLN mapping algorithm feasibility, patients operated from August 2014 to August 2017 went through SLN mapping without LND (SLN cohort). <h3>Results:</h3> Out of 223 patients with a median BMI of 40.6 kg/m², 140 patients underwent LND (± SLN) and 83 patients underwent SLN. The median operative time for surgical staging in SLN only group was shorter in 47.5 minutes than for patients in the LND±SLN group (190.5 minutes (108-393) vs. 238 minutes (131-440), respectively, (p<0.001)), and they had reduced estimated blood loss (EBL) compared to the LND±SLN group (30 ml (0-300) vs. 40 ml (0-800ml), P=0.03). At a 24 months' follow-up cut-off, 98% of the patients were alive and 95.5% were free of disease, without significant differences in OS, DSS and PFS between the two groups (p=0.7, p=0.8 and p=0.4, respectively).Overall, 171 patients underwent SLN biopsy (±LND) and stratified by the tracer used for mapping (ICG versus blue dye). The ICG injected group had higher successful mapping and bilateral detection rates (92.8% vs 71.7%, p<0.001 and 80.2% vs 43.3%, p<0.001, respectfully). <h3>Conclusions:</h3> The obese population is at increased risk for intraoperative and postoperative complications associated with prolonged operative time from secondary to challenges in the surgical and anesthesia process. The advantage of minimizing the surgery towards SLN approach, as reflected in our results by shorter operative time and minimal bleeding is of particular importance in this set of patients. Omitting LND from surgical staging where SLN is performed was not associated with inferior survival outcomes. Given the higher successful detection and metastatic nodes rates with ICG and NIR fluorescence imaging compared to previously reported rates with blue dye based SLN, ICG should be the dye of choice in obese and morbid obese EC patients. Future studies should focus on molecular stratification of obese EC patients into risk groups for nodal disease, selecting patients for LND in cases of failed mapping.

The role of adiposity in enhancing LIF/LIFR signaling pathway in endometrial cancer

Objectives: The incidence of endometrial cancer (EC) is estimated to increase by 1-2% annually. More than half of all EC diagnoses are currently attributable to obesity, which is an independent risk factor for this cancer. Obesity is suspected to function as a potent inducer of leukemia inhibitory factor (LIF), the most pleiotropic member of the interleukin-6 family of cytokines. Our recent studies utilizing public databases revealed high levels of LIF and its receptor LIFR are associated with poor survival in EC patients (KM plotter). The objective of this study is to determine whether alterations in the LIF/LIFR signal cascade occur in EC cells under conditions of adiposity; and whether this pathway could be a target for therapy. Methods: All patient samples, EC tissue, serum, and adipose tissue, were collected through the UT Health San Antonio tumor registry under IRB approval. Expression of LIF in EC patient samples was analyzed using immunohistochemistry (IHC) using a UT Health generated tumor tissue array (TMA) and scored by UT Health Pathology. Primary EC tissue derived cells and established EC cell lines were treated with primary adipocyte conditioned medium and non-obese patient serum or obese patient serum. The effect of adiposity on EC cells was determined using MTT cell viability assay and colony formation assay, in addition to utilization of organoids derived from primary EC tissue. Mechanistic studies were conducted using Western blotting, RT-qPCR, and reporter assays thus confirming the activation of LIF/LIFR downstream pathways including STAT3, mTOR, Akt, and MAPK. The recently developed LIFR inhibitor, EC359, was used to elucidate the therapeutic utility of targeting the enhanced LIF/LIFR pathway generated by high adiposity. Results: Treatment of established and primary EC cells with adipose environment increased the expression of LIFR protein, enhanced LIFR reporter activity, and increased cellular proliferation. Western blot and RT-qPCR analyses confirmed that increased expression of LIFR correlated with enhanced downstream LIFR signaling and subsequent activation of LIFR target genes. Treatment of EC cells with the LIFR inhibitor EC359 significantly reduced cell viability under adipose conditions. EC359 treatment also decreased adipose environment mediated organoid growth. IHC results using TMA that contained normal tissue (n=33) and EC tumors (n=45) with BMI >30 showed significantly increased expression of LIF in EC compared to normal endometrium. Further, LIF expression was upregulated in EC from obese patients compared to non-obese EC control patients. Conclusions: Collectively, our results suggest that increased adiposity contributes to accelerated EC cell growth via upregulation of the LIF/LIFR pathway. The LIF/LIFR axis represents a potential therapeutic target for adiposity driven EC and the LIFR inhibitor EC359 may be useful in modulating LIF/LIFR signaling in obese EC patients.

Metabolic and bariatric surgery among endometrial cancer survivors: Are we missing an opportunity to help?

5591 Background: Multiple studies have delineated a clear link between the estrogenic effects of obesity and the incidence of endometrial cancer (EC). Obese EC patients are less likely to receive guideline-recommended surgical treatment (ST) relying instead on chemotherapy and radiation therapy. Furthermore, EC patients are more likely to die from obesity-related complications than from cancer-related causes. Several small-scale studies have demonstrated that metabolic and bariatric surgery (MBS) could offer EC patients fast, safe and effective weight loss, which provides an opportunity to improve survival. This is the first population-based study that examines uptake and outcomes of MBS among EC survivors in New York State (NYS). Methods: This study was based on the all-payer longitudinal data from the NYS’s Statewide Planning and Research Cooperative System and included inpatient and ambulatory surgeries performed between 2006 and 2012. Using ICD and CPT diagnostic and procedure codes, we identified patients diagnosed with EC for the first time, and we further examined whether they received ST within one year of their initial EC diagnosis. We followed EC patients with ST for 4 years to examine the rates of MBS, and we assessed long-term patient outcomes through 2019. We conducted bivariate and multivariate analyses to evaluate all-cause mortality and identify risk factors for poor surgical outcomes and readmissions. Results: Among 24,950 EC patients (2006-2012), 16,156 (65%) of them underwent ST within 1 year of EC diagnosis. Compared to those who did not receive ST, patients who underwent ST were younger, less likely to be White and more likely to be from urban counties, had private insurance, diagnosed with diabetes and hypertension, and had lower Elixhauser scores for readmission and mortality ( p &lt; 0.01 for all). Within 4 years following ST, 136 (0.8%) EC patients underwent MBS. Those who underwent MBS were younger ( p &lt; 0.01), predominantly white, privately insured, morbidly obese ( p &lt; 0.01) and diabetic ( p = 0.01) compared to those who did not undergo MBS. Conclusions: Despite having higher risk of mortality from obesity-related complications such as diabetes and cardiovascular disease, the proportion of EC patients obtaining MBS (0.8%) was similar to that seen among the US population eligible for MBS (1.0%). More research is needed to understand barriers to MBS among eligible women with EC.

Assessing the Effectiveness of a Weight Reduction Program in Hospitalized Obese Patients Undergoing Laparoscopic Surgery.

Investigate the efficacy of a hospitalized weight reduction program before laparoscopic surgery among high body mass index (BMI) patients with endometrial cancer. The patients were housed in a shared room, received exercise guidance, and restricted to a total caloric intake of 1200 kcal. A physiotherapist and a dietitian provided pedometer and nutritional guidance, respectively. The primary outcome was weight reduction. Among the 16 patients included, 12 (75%) had Stage I endometrial cancer and 10 (62.5%) underwent laparoscopic surgery. Weight and BMI at first consultation were 88.4±10.4 kg and 34.8±3.9 kg/m2, respectively. The rate of weight reduction was 6.5%±2.5%; on average, BMI decreased by 2.1±1.0 kg/m2. The duration from initial consultation to surgery was 39.1±11.4 days. Hospitalization duration until weight reduction was 20.8±8.0 days; there were no surgical complications. Our hospitalized weight reduction program may be effective for obese endometrial cancer patients.

Omitting Lymphadenectomy in Obese Endometrial Cancer Patients Undergoing Sentinel Lymph Node Mapping: More Is Less

Study Objective To evaluate the feasibility of sentinel lymph node (SLN) mapping in obese endometrial cancer patients. Design A retrospective study of obese patients (BMI ≥35 kg/m2), diagnosed with endometrial carcinoma between 2007 and 2017, comparing surgical and oncological outcomes of two patient's cohorts. Setting Tertiary gynecology oncology center. Patients or Participants 223 patients with median BMI of 40.6 kg/m2 including: 140 patients that underwent LND (with or without SLN) and 83 patients that underwent SLN. Interventions Lymph node dissection (LND) with or without SLN versus only SLN for endometrial cancer staging. Measurements and Main Results Patients that had only SLN seemed to have more metastatic pelvic nodal disease (13.3% vs. 7.1%), though this difference did not reach statistical significance (p=0.2). Patients from the SLN only group had significantly higher rate of successful mapping (92.8% vs. 78.4%, p=0.009), bilaterally detected SLN (80.7% vs. 54.5%, p Conclusion Omitting LND from surgical staging where SLN is performed was associated with shorter operative time and minimal bleeding without affecting survival. ICG should be the dye of choice in obese endometrial cancer patients.

Challenges on the morbidly obese endometrial cancer surgery: Laparotomy or laparoscopy, lymphadenectomy or no lymphadenectomy?

A considerable proportion of endometrial cancer patients are morbidly obese. Management of these cases is a serious dilemma. The aim of this study was to investigate the relevance of laparoscopic route and omission of lymphadenectomy as morbidity-reducing strategies in this special population. Endometrial cancer patients' archival records were retrospectively reviewed and cases with body mass index ≥ 40 kg/m2 were selected. A comparative evaluation of their characteristics and survival rates were performed. Firstly, according to the surgical approach; laparoscopy or laparotomy, and then regarding to performing lymphadenectomy or not. There were 146 patients enrolled in this study. Whereas, significantly higher postoperative complications and longer hospital stays were determined in the laparotomy compared to laparoscopy groups. Five years disease-free and overall survival were not significantly different (83.6% vs 70.7%, p = 0.184 and 83.9% vs 86.6%, p = 0.571, respectively). On the other hand, operation length, postoperative hospitalization time, both intraoperative and postoperative complications were significantly lower in the non-lymphadenectomy compared to the lymphadenectomy groups. However, five-years disease-free and overall survival were not significantly different (77.3% vs 81.3%, p = 0.586 and 87.5% vs 78%, p = 0.479, respectively). Laparoscopic approach and omission of lymphadenectomy are worthy policies in the morbidly obese endometrial cancer patients.

Abstract 642: Increasing BMI is associated with tumor volume and uterine weight in endometrial cancer

Abstract Obesity and diabetes is associated with increased risk and worse outcomes in endometrial cancer (EC). Our previous work has found that obesity leads to more aggressive tumor behavior and a doubling of tumor size in EC mouse models. Thus, we explored the association between endometrial tumor volume (TV) and uterine weight (UW) as a function of BMI in EC patients. We performed a retrospective review of EC patients diagnosed and treated from 2005-2010 at a single tertiary care center. Tumor histology, dimensions, stage, grade, and UW were extracted from surgical pathology reports. Patient age, BMI, and diabetic status were also collected. TV was determined using the formula TV=l*d*w*pi/6. Independent variables include obesity classification, BMI, and diabetic status. Univariable and multivariable regression models were used to assess strength of association. A total of 564 EC patients were evaluated, with either endometrioid (n=522) or serous (n=42) histologies (Table 1). Within the endometrioid subgroup, associations were noted for both increased TV and UW with obesity (TV p=0.02; UW p&amp;lt;0.001) and BMI (TV p=0.007; UW p&amp;lt;0.001). Within the serous subgroup, increased TV was associated with obesity and BMI (p&amp;lt;0.001; p=0.007), but UW was only associated with obesity (p=0.005) and not BMI (p=0.07). Controlling for stage and grade, multivariable models demonstrated similar patterns with obesity status and BMI within both subgroups. Multivariable analyses also demonstrated that having diabetes (n=160) was associated with both higher TV and UW in the endometrioid subgroup (TV p=0.004; UW p=0.02), but not in the serous subgroup (TV p=0.71; UW p=0.12). Obesity and increasing BMI appear to be associated with both increased TV and UW in EC patients, consistent with our previously described findings in murine models. Diabetes was also associated with higher TV and UW, but was only significant in patients with endometrioid ECs. Our results may partially account for the worse outcomes seen in obese EC patients. Table 1EC HistologyMedianIQREndometrioid (n=522)Uterine Weight (g)Non-obese118.183.0-157.5Obese140.0103.8-200.0Tumor Volume (cm3)Non-obese3.6950.927-9.664Obese4.3591.419-14.216Serous (n=42)Uterine Weight (g)Non-obese116.667.4-166.6Obese189.8127.6-252.6Tumor Volume (cm3)Non-obese3.2490.601-9.382Obese23.8247.356-59.494 Citation Format: Yingao Zhang, Nerlyne Desravines, Dominic T. Moore, Paola A. Gehrig, Leslie H. Clark, Victoria L. Bae-Jump. Increasing BMI is associated with tumor volume and uterine weight in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 642.

Assessing disease-related outcomes in morbidly obese endometrial cancer patients

Assessing disease-related outcomes in morbidly obese endometrial cancer patients

Disease-related outcomes in morbidly obese endometrial cancer patients

Objective: We sought to evaluate the impact of morbid obesity on disease outcomes in women with low-risk and high-risk endometrial cancer (EC).

Hysterectomy utilization among newly diagnosed endometrial cancer patients by body mass index category: A real-world analysis using a claims and electronic health record database.

e17112 Background: For endometrial cancer (EC), laparoscopic hysterectomy (LH) is an effective, minimally invasive surgical treatment; however, this approach may not be recommended for obese patients due to increased risk for complications. Methods: This retrospective study utilized insurance claims linked to electronic health record (EHR) data contained in the IBM MarketScan Explorys Claims-EHR Data Set. Newly diagnosed EC patients (1/1/2007 - 6/30/2017) with continuous enrollment during a 12-month baseline and 6-month follow-up period were selected. Patients were stratified into four BMI subgroups based on baseline BMI on the EHR: normal or underweight (BMI &lt; 25), overweight (BMI 25- &lt; 30), obese (BMI 30- &lt; 40), morbidly obese (BMI &gt; 40), and were required to have had a hysterectomy within the follow-up period. Emergency room visits and rehospitalization within 30 days of hysterectomy were measured. Results: A total of 1,090 newly-diagnosed EC patients met the selection criteria, of whom, 16% were normal/underweight, 19% were overweight, 39% were obese, and 26% were morbidly obese. The proportion of patients receiving LH increased as BMI category increased (Table 1). Among those with LH between 6% and 15% had an ER visit or rehospitalization in 30 days, and rates were higher among other hysterectomy modalities. Conclusions: This real-world analysis shows that LH is utilized in a high proportion of morbidly obese EC patients, despite that it is frequently deemed infeasible in this patient population. Although the rate of ER visits and rehospitalization is lower among LH patients than those undergoing traditional hysterectomy across all BMI strata, further research is needed to determine the optimal patient population to receive LH.[Table: see text]

A pilot study of gonadotropin-releasing hormone agonist combined with aromatase inhibitor as fertility-sparing treatment in obese patients with endometrial cancer.

ObjectiveThis study aims to evaluate the effects and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH agonist) combined with aromatase inhibitor (AI) in preserving the fertility of obese women with grade 1 endometrial cancer (EC).MethodsThis study recruited obese EC patients who wished to preserve their fertility. The treatment regimen consisted of intramuscular GnRH agonist 3.75 mg every 4 weeks and oral AI 2.5 mg daily. The maintenance regimen was the same as the initial treatment regimen. Primary outcomes included response rate, time to complete response (CR), and time to recurrence; pregnancy outcomes included the time to pregnancy, pregnancy rate and live birth rate.ResultsSix obese patients with EC were included in this study, with the age (mean±standard deviation [SD]) of 30.5±3.3 years and body mass index (mean±SD) of 35.0±1.4 kg/m2. CR rate was 100%, and time to CR was 3–6 months. None of the patients had recurrence after a median follow-up of 4.0 years (range, 1.3–7.0 years). The most common side effects were menopause-like symptoms. Among these patients, no weight gain was observed during treatment. The pregnancy rate and live birth rate was 50.0% and 75.0%, respectively, with a median time to pregnancy of 2.4 years (range, 1.0–5.5 years).ConclusionThe combination of GnRH agonist and AI demonstrated promising long-term effect in young obese EC patients who wished to preserve their fertility. No weight gain side effects were observed. Further studies with a larger sample size are needed to fully evaluate this novel treatment regimen.

Anesthetic and surgical outcomes in obese endometrial cancer patients undergoing robotic hysterectomy

Objective: To determine the effect of obesity, pneumoperitoneum, and steep Trendelenburg positioning on respiratory system mechanics during robot surgery for endometrial cancer (EC).

PTEN negative correlates with miR-181a in tumour tissues of non-obese endometrial cancer patients

The effects of microRNAs on PTEN levels are characteristic for many types of cancer. However, the picture of the correlation between the expression levels of PTEN and its targeting microRNAs in endometrial cancer is not fully presented. Our study investigated and analysed the expression levels of PTEN and PTEN-targeting miR-21, miR-181a, miR-214, miR-301a, and miR-1908 in total of 78 samples, out of which 26 samples were from normal endometrium, whereas the 52 samples were from endometrial cancer samples. Our results demonstrated a high variability of individual endometrial cancer samples in the levels of PTEN. The level of miR-181a showed significant increment in endometrial cancer tissues in comparison with normal endometrium. We did not observe any statistically significant correlation between levels of microRNAs and PTEN in a heterogeneous cohort of patients. At the same time, in samples collected from endometrial cancer patients, it was found out that the relationship between PTEN expression and body mass index had significant positive correlation. Moreover, our data demonstrated that the expression of PTEN was significantly decreased, whereas expression of miR-181a was significantly over-expressed in non-obese compared to obese endometrial cancer patients. Additionally, we observed the relationship between PTEN levels and miR-181a related to the cancerous tissues for non-obese patients was established to be negatively correlated. Our findings suggest that decrease of PTEN via increase of miR-181a may be important contributor to endometrial cancer in non-obese patients.

Adipose-Derived VEGF-mTOR Signaling Promotes Endometrial Hyperplasia and Cancer: Implications for Obese Women.

Obesity is responsible for increased morbidity and mortality in endometrial cancer. Despite the positive correlation of body mass index (BMI) or obesity in endometrial carcinogenesis, the contribution of adipose tissue to the pathogenesis of endometrial hyperplasia and cancer is unclear. This study clarifies the role of adipocytes in the pathogenesis of endometrial cancer by demonstrating that adipocyte-conditioned medium (ACM) increases proliferation, migration, and survival of endometrial cancer cells compared with preadipocyte-conditioned medium (PACM). Comparative cytokine array analysis of ACM and PACM reveal upregulation of a group of cytokines belonging to the VEGF signaling pathway in ACM. VEGF protein expression is upregulated in visceral adipose tissue (VAT) in obese patients, which is correlated with increased tumor growth in an in vivo xenograft model. The increased tumor size is mechanistically associated with the activation of the PI3K/AKT/mTOR pathway, a downstream target of VEGF signaling, and its suppression decreased the growth-promoting effects of VAT on endometrial cancer cells. Similar to the human model systems, pathologic changes in endometrial cells in a hyperphagic obese mouse model are associated with increased body weight and hyperactive mTOR signaling. Analysis of human tissue specimens depicts increased in tumor vasculature and VEGF-mTOR activity in obese endometrial cancer patients compared with nonobese patients. Collectively, these results provide evidence that VEGF-mTOR signaling drives endometrial cell growth leading to hyperplasia and cancer.Implications: Adipocyte-derived VEGF-mTOR signaling may be an attractive therapeutic target against endometrial cancer in obese women. Mol Cancer Res; 16(2); 309-21. ©2017 AACR.