Prognostic impact of metabolic syndrome in patients with primary endometrial cancer: a retrospective bicentric study.

PURPOSE: Endometrial cancer (EC) is the most common gynaecological cancer. Its incidence has been rising over the years with ageing and increased obesity of the high-income countries' populations. Metabolic syndrome (MetS) has been suggested to be associated with EC. The aim of this study was to assess whether MetS has a significant impact on oncological outcome in patients with EC. METHODS: This retrospective study included patients treated for EC between January 2010 and December 2020 in two referral oncological centers. Obesity, arterial hypertension (AH) and diabetes mellitus (DM) were criteria for the definition of MetS. The impact of MetS on progression free survival (PFS) and overall survival (OS) was assessed with log-rank test and Cox regression analyses. RESULTS: Among the 415 patients with a median age of 64, 38 (9.2%) fulfilled the criteria for MetS. The median follow-up time was 43 months. Patients suffering from MetS did not show any significant differences regarding PFS (36.0 vs. 40.0 months, HR: 1.49, 95% CI 0.79-2.80 P = 0.210) and OS (38.0 vs. 43.0 months, HR: 1.66, 95% CI 0.97-2.87, P = 0.063) compared to patients without MetS. Patients with obesity alone had a significantly shorter median PFS compared to patients without obesity (34.5 vs. 44.0 months, P = 0.029). AH and DM separately had no significant impact on PFS or OS (p > 0.05). CONCLUSION: In our analysis, MetS in patients with EC was not associated with impaired oncological outcome. However, our findings show that obesity itself is an important comorbidity associated with significantly reduced PFS.

Enhanced Diagnostic Efficiency of Endometrial Carcinogenesis and Progression in Women with Abnormal Uterine Bleeding through Peripheral Blood Cytokine Testing: A Multicenter Retrospective Cohort Study.

Objective: This study aimed to evaluate the role of plasma cytokine detection in endometrial cancer screening and tumor progression assessment in patients with abnormal uterine bleeding. Methods: In this multicenter retrospective cohort study of 287 patients with abnormal uterine bleeding, comprehensive clinical information and laboratory assessments, including cytokines, routine blood tests, and tumor markers, were performed. Associations between the clinical indicators and endometrial carcinogenesis/progression were evaluated. The independent risk factors for endometrial cancer and endometrial cancer with deep myometrial invasion were analyzed using multivariate binary logistic regression. Additionally, a diagnostic model was used to evaluate the predictive efficacy of these identified risk factors. Results: In patients with abnormal uterine bleeding, low IL-4 and high IL-8 levels were independent risk factors for endometrial cancer (p < 0.05). Combining IL-4, IL-8, CA125, and menopausal status improved the accuracy of assessing endometrial cancer risk. The area under curve of the model is 0.816. High IL-6 and IL-8 levels were independent risk factors for deep myometrial invasion in patients with endometrial cancer (p < 0.05). Similarly, combining IL-6, IL-8, and Monocyte counts enhanced the accuracy of assessing endometrial cancer risk with deep myometrial invasion. The area under curve of the model is 0.753. Conclusions: Cytokines such as IL-4, IL-8, and IL-6 can serve as markers for monitoring endometrial cancer and its progression in women with abnormal uterine bleeding.

Short-Term Outcomes After Hysterectomy for Endometrial Cancer/EIN With Concomitant Pelvic Floor Disorder Surgery.

IMPORTANCE: Endometrial cancer and precancer are common gynecologic problems for many women. A majority of these patients require surgery as the mainstay of treatment. Many of these patients often have concurrent pelvic floor disorders. Despite the prevalence and shared risk, fewer than 3% of women undergo concomitant surgery for PFDs at the time of surgery for endometrial cancer or endometrial intraepithelial neoplasia/hyperplasia. OBJECTIVE: This study aimed to evaluate postoperative morbidity of concomitant pelvic organ prolapse (POP) and/or urinary incontinence (UI) procedures at the time of hysterectomy for endometrial cancer (EC) or endometrial intraepithelial neoplasia/endometrial hyperplasia (EIN/EH). METHODS: This retrospective analysis of women undergoing hysterectomy for EC or EIN/EH between 2017 and 2022 used the American College of Surgeons National Surgical Quality Improvement Program database. The primary outcome was any major complication within 30 days of surgery. Comparisons were made between 2 cohorts: hysterectomy with concomitant pelvic organ prolapse/urinary incontinence procedures (POPUI) versus hysterectomy without concomitant POP or UI procedures (HYSTAlone). A subgroup analysis was performed in patients with EC. A propensity score matching cohort was also created. RESULTS: A total of 23,144 patients underwent hysterectomy for EC or EIN/EH: 1.9% (n = 432) had POP and/or UI procedures. Patients with POPUI were older, were predominantly White, had higher parity, and had lower body mass index with lower American Society of Anesthesiologists class. Patients with POPUI were less likely to have EC (65.7% vs 78.3%, P < 0.0001) and more likely to have their hysterectomy performed by a general obstetrician- gynecologists or urogynecologists. Major complications were low and not significantly different between POPUI and HYSTAlone (3.7% vs 3.6%, P = 0.094). A subgroup analysis of EC alone found that the HYSTAlone subset did not have more advanced cancers, yet the surgeon was more likely a gynecologic oncologist (87.1% vs 68.0%, P < 0.0001). There were no statistically significant differences between the 2 cohorts for the primary and secondary outcomes using propensity score matching analysis. CONCLUSIONS: Concomitant prolapse and/or incontinence procedures were uncommon and did not increase the rate of 30-day major complications for women undergoing hysterectomy for EC/EH.

Analysis of Characteristics of Endometrial Carcinoma in Peri- and Postmenopausal Women with Abnormal Uterine Bleeding.

Objective: To analyze the menstrual characteristics of endometrial carcinoma and investigate whether abnormal uterine bleeding in the perimenopausal period differs from postmenopausal bleeding. Methods: We conducted a retrospective analysis of 928 cases of endometrial carcinoma in patients admitted from January 2016 to December 2022. We gathered fundamental clinical data and analyzed distinct clinical risk factors between the perimenopausal and postmenopausal groups. Furthermore, we computed the statistical variances in menarche, regular menstrual cycles, and the duration of abnormal uterine bleeding. Results: Perimenopausal patients with endometrial carcinoma exhibit similar factors to postmenopausal patients, especially if they have a history of menstrual cycles lasting more than 30 years, hypertension, abnormal uterine bleeding for over 1 year, and a high risk of endometrial carcinoma. Early intervention for abnormal uterine bleeding during the perimenopausal stage can prevent up to 80% of women from developing endometrial carcinoma. Conclusion: Perimenopause women experiencing abnormal uterine bleeding should be mindful of the risk of endometrial carcinoma, as this awareness can substantially decrease the occurrence of the disease.

Symptomatic Lymphocele After Robot-Assisted Pelvic Lymphadenectomy as Part of the Primary Surgical Treatment for Cervical and Endometrial Cancer: A Retrospective Cohort Study.

STUDY OBJECTIVES: Pelvic lymph node dissection (PLND) is part of the primary treatment for early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer. Pelvic lymphocele is a postoperative complication of PLND, and when symptomatic, lymphoceles necessitate treatment. The aim of this study was to investigate the incidence and risk factors of symptomatic lymphocele after robot-assisted laparoscopic PLND in cervical and endometrial cancer. DESIGN: Retrospective cohort study. SETTING: Single-center academic hospital. PATIENTS: Two hundred and fifty-eight patients with cervical cancer and 129 patients with endometrial cancer. INTERVENTIONS: Pelvic lymphadenectomy by robot-assisted laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: The authors retrospectively included all patients with early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer who underwent pelvic lymphadenectomy by robot-assisted laparoscopic surgery between 2008 and 2022. Medical records were reviewed for the occurrence of a symptomatic lymphocele. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for developing a symptomatic lymphocele. In total, 387 patients, 258 with cervical cancer and 129 with endometrial cancer, were included in the study. The overall incidence of symptomatic lymphoceles was 9.6% with a median follow-up of 47 months [interquartile range 23-61]. For the entire cohort, smoking was the only significant risk factor for symptomatic lymphoceles identified in univariate (OR 2.47, 95% CI 1.19-5.11) and multivariate analysis (OR 2.42, 95% CI 1.16-5.07). For cervical cancer, body mass index (BMI) (OR 1.09, 95% CI 1.00-1.17) and prior abdominal surgery (OR 2.75, 95% CI 1.22-6.17) were also identified as significant independent risk factors. For endometrial cancer, age was identified as a significant independent risk factor (OR 0.90, 95% CI 0.83-0.97). CONCLUSION: This single-center cohort study demonstrated an incidence of almost 10% of symptomatic lymphoceles after robot-assisted laparoscopic PLND for cervical cancer and endometrial cancer, with a higher risk observed among patients who smoke at the time of diagnosis. Furthermore, risk factors differ between the 2 populations, necessitating further studies to establish risk models.

Lymphedema self-assessment among endometrial cancer survivors.

PURPOSE: Lower extremity lymphedema (LEL), which causes ankle, leg, and feet swelling, poses a significant challenge for endometrial cancer survivors, impacting physical functioning and psychological well-being. Inconsistent LEL diagnostic methods result in wide-ranging LEL incidence estimates. METHODS: We calculated the cumulative incidence of LEL based on survivor-reported Gynecologic Cancer Lymphedema Questionnaire (GCLQ) responses in addition to survivor- and nurse-reported leg circumference measurements among a pilot sample of 50 endometrial cancer survivors (27 White, 23 Black) enrolled in the ongoing population-based Carolina Endometrial Cancer Study. RESULTS: Self-leg circumference measurements were perceived to be difficult and were completed by only 17 survivors. Diagnostic accuracy testing measures (sensitivity, specificity, positive and negative predictive value) compared the standard nurse-measured ≥ 10% difference in leg circumference measurements to GCLQ responses. At a mean of ~11 months post-diagnosis, 54% of survivors met established criteria for LEL based on ≥ 4 GCLQ cutpoint while 24% had LEL based on nurse-measurement. Percent agreement, sensitivity, and specificity approximated 60% at a threshold of ≥ 5 GCLQ symptoms. However, Cohen's kappa, a measure of reliability that corrects for agreement by chance, was highest at ≥ 4 GCLQ symptoms (κ = 0.27). CONCLUSION: Our findings emphasize the need for high quality measurements of LEL that are feasible for epidemiologic study designs among endometrial cancer survivors. Future studies should use patient-reported survey measures to assess lymphedema burden and quality of life outcomes among endometrial cancer survivors.

Associations of metformin therapy treatment with endometrial cancer risk and prognosis: A systematic review and meta-analysis.

BACKGROUND: Several abstract studies have demonstrated that metformin may be beneficial for preventing and treating endometrial cancer (EC), while the results have been inconsistent and inconclusive. This systematic review and meta-analysis aimed to investigate the association between metformin use and the incidence and mortality of endometrial cancer in diabetic patients. METHODS: A systematic literature search was performed in Pubmed, EMBASE, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP from inception to November 2022. The outcome measures were hazard ratios (HRs) comparing the EC incidence and mortality in patients with type 2 diabetes mellitus (T2DM) on metformin and non-metformin. A random or fixed-effects model was applied for data analysis, and subgroup analysis was performed to look for factors of heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessed the evidence's certainty. RESULTS: Eleven studies reported data on EC incidence. The pooled results suggested that the use of metformin was associated with a significantly higher incidence of EC (HR = 1.17, 95% CI 1.09-1.26, P < 0.0001). Further, seventeen studies were included for survival analysis. The pooled data showed that metformin could significantly decrease all-cause mortality (HR = 0.62, 95% CI 0.52-0.74, P < 0.00001) and endometrial cancer-specific mortality (HR = 0.95, 95% CI 0.90, 1.00, P = 0.03). Finally, we noted that metformin was associated with significantly improving the progression-free survival (PFS) of EC patients with T2DM (HR = 0.55, 95% CI 0.44, 0.68, P < 0.00001). CONCLUSIONS: This meta-analysis did not prove that metformin was beneficial for preventing EC. However, metformin could reduce their mortality risk and prolong the progression-free survival time of EC patients with T2DM.

Abnormal preoperative haematological parameters in Endometrial cancer; reflecting tumour aggressiveness or reduced response to radiotherapy?

BACKGROUND: In endometrial cancer (EC), preoperative anaemia, thrombocytosis and leucocytosis appear to be associated with worse prognosis. It remains unclear whether these parameters solely reflect tumour aggressiveness, or also impact response to adjuvant treatment. Therefore, our primary aim is to evaluate the prognostic relevance of anaemia, thrombocytosis and leucocytosis on survival in EC. Secondary, to explore their predictive relevance in response to radiotherapy in EC. METHODS: A retrospective multicentre cohort study was performed within 10 hospitals. Preoperative haematological parameters were defined as: Anaemia - haemoglobin <7.45 mmol/L (<12 g/Dl), thrombocytosis - platelets >400 × 109 platelets/L, leucocytosis - leukocytes >10 × 109/L. The relationship of haematological parameters with clinicopathological characteristics, ESGO/ESTRO/ESP risk groups and survival were evaluated. Furthermore, the predictive value of haematological parameters was determined on the overall response to adjuvant radiotherapy and for the ESGO/ESTRO/ESP intermediate-risk group solely receiving radiotherapy. RESULTS: A total of 894 patients were included with a median follow-up of 4.5 years. Anaemia was present in 103 (11.5%), thrombocytosis in 79 (8.8%) and leucocytosis in 114 (12.7%) patients. The presence of anaemia or thrombocytosis was significantly associated with ESGO/ESTRO/ESP high-risk (respectively, P = 0.002 and P = 0.041). In the entire cohort, anaemia remained independently associated with decreased disease-specific survival (HR 2.31, 95% CI (1.19-4.50), P = 0.013) after adjusting for age, the abnormal haematological parameters and ESGO/ESTRO/ESP risk groups. In patients that were treated with adjuvant radiotherapy (n = 239), anaemia was associated with significant reduced 5-year disease-specific and recurrence-free survival (P = 0.005 and P = 0.025, respectively). In ESGO/ESTRO/ESP intermediate risk patients that received solely vaginal brachytherapy (n = 74), anaemia was associated with reduced disease-specific survival (P = 0.041). CONCLUSIONS: Current data demonstrate the importance of preoperative anaemia as independent prognostic factor in patients with EC. Moreover, anaemia seems to be associated with reduced response to radiotherapy. Prospective validation in a larger study cohort is needed to verify anaemia as predictive biomarker for radiotherapy.What is already known on this subject? In endometrial cancer, preoperative abnormal haematological parameters like, anaemia, thrombocytosis and leucocytosis appears to be associated with FIGO advanced-stage and unfavourable outcome.What do the results of this study add? It remains unclear whether anaemia, thrombocytosis or leucocytosis solely reflecting worse prognosis by advanced tumour stage, or also impact response to adjuvant treatment. Current data demonstrate that anaemia is independent associated with decreased disease-specific survival and anaemia seems related with reduced response to radiotherapy and in specific to vaginal brachytherapy in ESGO/ESTRO/ESP intermediate risk patients.What are the implications of these findings for clinical practice and/or further research? Specific applied adjuvant treatment is needed if patients with anaemia have a reduced response to radiotherapy in EC. Prospective validation in a larger study cohort is required to verify anaemia as predictive biomarker for radiotherapy and to further evaluate the prognostic/predictive impact of anaemia in addition to the molecular subgroups.

In this study we focused on three specific blood values before surgery to predict survival outcomes in endometrial cancer patients: low haemoglobin (anaemia), high platelet count (thrombocytosis) and high white blood cell count (leucocytosis). We studied 894 patients with endometrial cancer over about 4.5 years, in which 11.5% had anaemia, 8.8% thrombocytosis and 12.7% leucocytosis. Anaemia was linked to a lower chance of surviving endometrial cancer, even after we considering patients' age, thrombocytosis, leucocytosis and the endometrial cancer risk classification groups. In patients who received radiotherapy after surgery (293 patients), anaemia was linked to a lower change of surviving and cancer coming back within 5 years. In patients within the intermediate endometrial cancer risk classification group who only received specific radiotherapy (74 patients), anaemia was even linked with lower chance of survival. In conclusion, anaemia is an important factor in predicting endometrial cancer outcomes, and it might also make radiotherapy less effective for some patients.

From Infection to Malignancy: Tracing the Impact of Human Papillomavirus on Uterine Endometrial Cancer in a Nationwide Population-Based Cohort Study.

Uterine endometrial cancer (EC) is the most common gynecological malignancy in Taiwan. This study aimed to investigate the association between human papillomavirus (HPV) infection and the development of uterine EC among Taiwanese women. A nationwide population cohort research approach was employed, leveraging longitudinal health insurance databases (LHID 2007 and 2015) from the National Health Insurance Research Database alongside data from the Taiwan Cancer Registry datasets. A comparative analysis examined 472,420 female patients with HPV infection and 944,840 without HPV infection. The results demonstrated that the HPV cohort exhibited a significantly elevated risk of uterine EC, as evidenced by an adjusted hazard ratio (aHR) of 1.588 (95% CI: 1.335-1.888). Furthermore, this elevated risk extended to type 1 EC with an aHR of 1.671 (95% CI: 1.376-2.029), specifically the endometrioid adenocarcinoma subtype with an aHR 1.686 (95% CI: 1.377-2.065). Importantly, these findings were statistically significant (p < 0.001). In conclusion, this research unveils a potential association between HPV infection and an increased risk of uterine EC, particularly the type 1 endometrial cancer subtype, within the Taiwanese female population. These findings have implications for preventive measures and screening programs targeting HPV infection to reduce the risk of this prevalent gynecological malignancy in Taiwan.

Association of Bariatric Surgery with Risk of Incident Obesity-Associated Malignancies: a Multi-center Population-Based Study.

INTRODUCTION: Obesity has a known association with certain types of malignancy, and we aimed to determine whether bariatric surgery has a protective effect against de novo obesity-associated cancer development in adult patients. METHODS: We performed a multi-center retrospective cohort studying utilizing TriNetX national database. Patients were identified utilizing ICD-10-CM coding, and propensity score matching was performed. We compared patients with obesity who underwent bariatric surgery to patients with obesity who did not undergo bariatric surgery. RESULTS: We initially identified 60,285 patients in the bariatric surgery group and 1,570,440 patients in nonsurgical control group. After propensity score matching, we included 55,789 patients in each patient cohort. The cumulative incidence of de novo obesity-associated cancers at 10 years was 4.0% (2206 patients) in the bariatric surgery group and 8.9% (4,960 patients) in the nonsurgical control group (HR 0.482 [95% CI 0.459-0.507]). The bariatric surgery group had lower incidence proportions for de novo breast cancer (HR 0.753 [CI 0.678-0.836]), colon cancer (HR 0.638 [CI 0.541-0.752]), liver cancer (HR 0.370 [CI 0.345-0.396]), ovarian cancer (HR 0.654 [CI 0.531-0.806]), and endometrial cancer (HR 0.448 [CI 0.362-0.556]) when compared to the nonsurgical control group. CONCLUSION: We noted that bariatric surgery is associated with a significantly lower cumulative incidence of de novo obesity-associated cancer compared to a nonsurgical matched control group. Incidence proportions of de novo breast, colon, liver, ovarian, and endometrial cancer were significantly lower in adult patients with obesity in the bariatric surgery group compared to the nonsurgical group.

The interplay of obesity, microbiome dynamics, and innovative anti-obesity strategies in the context of endometrial cancer progression and therapeutic approaches.

Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, and its incidence and mortality are rising. Obesity is more tightly associated with EC than any other cancer. Thus, the rising prevalence of obesity and associated risk factors, including diabetes and insulin resistance, cause alarm. The metabolic derangements of obesity increase the bioavailability of estrogen, hyperinsulinemia, and inflammation in a complex system with direct and indirect effects on the endometrium, resulting in proliferation and, ultimately, carcinogenesis. In addition, the gut dysbiosis associated with obesity helps contribute to these metabolic derangements, priming an individual for developing EC and perhaps affecting treatment efficacy. More recent studies are beginning to explore obesity's effect on the local tumor microbiome of EC and its role in carcinogenesis. Significant and sustained weight loss in individuals can considerably decrease the risk of EC, likely through reversal of the altered metabolism and dysbiosis resulting obesity. Bariatric surgery is the gold standard for successful weight loss and highlights how reversing of the systemic effects of obesity can reduce EC risk. However, the current limited availability, knowledge, and imposed stigma of bariatric surgery prohibits population-level reductions in EC. Therefore, effective and maintainable non-surgical dietary and pharmacologic interventions are needed.

Adherence to ESGO guidelines and impact on survival in obese patients with endometrial cancer: a multicentric retrospective study.

OBJECTIVES: Obesity is known to be both a major risk factor for endometrial cancer and associated with surgical complexity. Therefore, the management of patients with obesity is a challenge for surgeons and oncologists. The aim of this study is to assess the adherence to European Society of Gynaecological Oncology (ESGO) guidelines in morbidly obese patients (body mass index (BMI) >40 kg/m2). The secondary objectives were the impact on overall survival and recurrence-free survival. METHODS: All the patients who were treated for an endometrial cancer in the 11 cancer institutes of the FRANCOGYN group were included and classified into three weight groups: morbid (BMI >40 kg/m2), obese (BMI 30-40), and normal or overweight (BMI <30). Adherence to guidelines was evaluated for surgical management, lymph node staging, and adjuvant therapies. RESULTS: In total, 2375 patients were included: 1330 in the normal or overweight group, 763 in the obese group, and 282 in the morbid group. The surgical management of the morbid group was in accordance with the guidelines in only 30% of cases, compared with 44% for the obese group and 48% for the normal or overweight group (p<0.001); this was largely because of a lack of lymph node staging. Morbid group patients were more likely to receive the recommended adjuvant therapy (61%) than the obese group (52%) or the normal or overweight group (46%) (p<0.001). Weight had no impact on overall survival (p=0.6) and morbid group patients had better recurrence-free survival (p=0.04). CONCLUSION: Adherence to international guidelines for surgical management is significantly lower in morbid group patients, especially for lymph node staging. However, morbidly obese patients had more often the adequate adjuvant therapies. Morbid group patients had a better recurrence-free survival likely because of better prognosis tumors.

Effect of coexisting adenomyosis on tumour characteristics and prognosis of endometrial cancer: A systematic review and meta-analysis.

To compare clinicopathological features and survival outcomes in patients with endometrial cancer, with and without associated adenomyosis. PubMed, Embase and Scopus databases were systematically searched for relevant observational studies. The pooled effect sizes were reported as either hazards ratio (HR) for survival-related outcomes or as odds ratio (OR) for other categorical outcomes. Weighted mean difference (WMD) was reported for continuous outcomes. All the analyses used the random effects model. A total of 21 studies (N = 46,420) were included. Compared to endometrial cancer patients without adenomyosis, patients with associated adenomyosis had improved overall 5-year survival (OS) (HR 0.62, 95% CI: 0.50, 0.79) and disease-free survival (DFS) (HR 0.60, 95% CI: 0.44, 0.82). Disease-specific survival was statistically similar in patients with and without adenomyosis (HR 0.60, 95% CI: 0.35, 1.05). Among patients with adenomyosis, the risk of having an advanced tumour grade (Grade 2 or 3) was lower (OR 0.51, 95% CI: 0.42, 0.62) and a risk of having International Federation of Gynaecology and Obstetrics (FIGO) stage I or II was higher (OR 2.23, 95% CI: 1.65, 3.01). Patients with adenomyosis had lower risk of tumour invasion of adnexa, cervical stromal invasion, deep myometrial involvement (DMI), lympho-vascular space invasion (LVSI) and peritoneal invasion. Presence of adenomyosis in patients with endometrial cancer is associated with favourable tumour characteristics and may improve the survival.

Risk of endometrial polyp and surgical intervention in postmenopausal women with proliferative endometrium.

OBJECTIVE: To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and requiring future gynecological interventions, and to compare them with women with atrophic endometrium. DESIGN: Retrospective cohort study of all women aged 55 or over who underwent endometrial biopsy between 1/1997 and 12/2008. Outcome data were available through to 2/2018. Women with proliferative endometrium were compared with those with atrophic endometrium for the presence of endometrial polyps, uterine fibroids, future endometrial biopsy for recurrent vaginal bleeding, and future hysteroscopy or hysterectomy. Logistic regression models were used to evaluate the association of endometrial histology and other covariates with the risk of morbidities. MAIN FINDINGS: Postmenopausal women with proliferative endometrium are at higher risk of developing endometrial polyps, uterine fibroids and need for surgical intervention. Of 1808 women who underwent endometrial biopsy during the study period, 962 met inclusion criteria: 278 had proliferative and 684 had atrophic endometrium. Length of surveillance was similar in the two groups (11.9 vs. 11.5 years, p = 0.2). Compared with women with atrophic endometrium, women with proliferative endometrium had significantly higher rates of endometrial polyps (17.3 % vs 9.7 % p = 0.001). Multivariable logistic regression confirmed that women with proliferative endometrium had more fibroids on ultrasound (62.1 % vs 50.3 % 3 = 0.02), and had increased risks of developing endometrial polyps (aOR 1.9, 95 % CI 1.28-3.07, p = 0.002), repeat endometrial biopsy (34.9 % vs. 16.8%p < 0.001) and future hysterectomy or hysteroscopy (26.6 % vs 16.2 % p < 0.001). CONCLUSIONS: In addition to the long-term increased risk of cancer, postmenopausal women with proliferative endometrium are more likely to have future bleeding, surgical interventions and diagnosis of endometrial polyps. Medical management to reduce estrogenic activity and associated risks may be considered in these cases.

Association of mismatch repair deficiency in endometrial cancer with 18F-FDG PET/CT and clinicopathological features and their prognostic value.

PURPOSE: Identification of the mismatch repair (MMR) deficiency in endometrial cancer (EC) may aid in the screening of patients who may benefit from immunotherapy. Our goal was to investigate the relationship between MMR status and 18F-FDG PET/CT metabolic parameters and clinicopathological features in patients with EC, as well as to explore their prognostic value. METHODS: This retrospective study included 106 EC patients who were classified as MMR deficient (dMMR) or MMR proficient (pMMR) group based on MMR protein expression status evaluated by immunohistochemistry. Clinicopathological characteristics and PET metabolic parameters were compared between the dMMR and pMMR groups, and their relationships with MMR status and prognosis were evaluated. RESULTS: Of 106 EC patients, 30 patients (28.1%) had dMMR, while 76 (71.7%) had pMMR. Compared with the pMMR group, the dMMR group showed a lower prevalence of overweight (BMI ≥ 25) (17.2% vs. 43.9%, P = 0.019) and more lymph vascular space invasion (43.3% vs. 21.1%, P = 0.029). Although no relationship between glucometabolism parameters and MMR status was observed in all enrolled patients, higher SUVmax was observed in the endometrioid type of EC with MMR deficiency (P = 0.047). Additionally, SUVmax related to MMR status was found in EC patients with advanced FIGO stage (P = 0.026) or deep myometrial invasion (P = 0.026). Multivariate Cox regression analysis revealed that lymph node metastasis was independently predictive of PFS, while advanced FIGO stage was an independent predictor of OS. No significant association between MMR status and prognosis was found in EC. CONCLUSION: Higher SUVmax was associated with MMR deficiency in EC patients with endometrioid type, advanced stage, or deep myometrial invasion, which may be useful for predicting the MMR status and thus aiding in determination of immunotherapy for patients with EC.

The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer.

OBJECTIVE: The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. METHODS: We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. RESULTS: The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29-5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18-8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31-10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage. CONCLUSIONS: The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.

EXPRESSION OF PROGRAMMED CELL DEATH RECEPTOR IN ENDOMETRIAL CANCER PATIENTS WITH METABOLIC DISORDERS.

AIM: To study the expression of the programmed cell death receptor (PD-1) and its ligand (PD-L1) by immunocompetent cells in endometrial cancer patients with metabolic disorders. MATERIALS AND METHODS: Populations and subpopulations of lymphocytes were analyzed by flow cytometry. Antibodies against CD279 were used to detect PD-1 on the CD4+ and CD8+ T cells. Antibodies against CD14 and CD274 were used to detect PD-L1 on monocytes. RESULTS: In patients with severe metabolic disorders, the expression of PD-1 on CD8+ and CD4+ lymphocytes and the expression of the corresponding PD-L1 on CD14+ cells before treatment and after radiation therapy were higher than in the control group. CONCLUSION: Theincreased expression of PD-1 and PD-L1 receptors by immunocompetent cells can be considered a new prognostic marker in endometrial cancer patients with morbid obesity.

Effect of bariatric surgery on endometrial cancer regression as part of fertility sparing treatment.

INTRODUCTION: Obesity is a major risk factor in the development of endometrial cancer (EC) in young patients of reproductive age. Fertility sparing treatment is a viable option for a select group of patients with early EC, and involves systemic and intra-uterine hormonal therapy. Weight loss has been associated with improved outcomes in this group. Bariatric surgery (BS) has been shown to be the most efficient and durable method of weight loss in obese patients. However, there is a paucity of data studying the benefit of BS as part of fertility sparing treatment. METHODS: We present a retrospective case series of five patients who are undergoing fertility sparing treatment for early EC, who also underwent BS for treatment of obesity and related comorbidities. We aim to show early regression of EC for all the patients and also report on the other health benefits of BS. RESULTS: All five patients in the series achieved regression of EC within 6 months of undergoing BS. They also achieved significant weight loss consistent with previous studies, and three patients who had comorbidities related to obesity had remission of these conditions. One of the patients with EC regression also managed to conceive with IVF (In-vitro Fertilisation). CONCLUSION: Patients on fertility sparing treatment for early EC who underwent BS was associated with early regression within 6 months, significant weight loss and resolution of comorbidities. BS could be a promising component of fertility sparing treatment. Long term, prospective studies are required to confirm the benefits reported in this case series.