Diagnostic utility of apparent diffusion coefficient in preoperative assessment of endometrial cancer: are we ready for the 2023 FIGO staging?

BACKGROUND: Although endometrial cancer (EC) is staged surgically, magnetic resonance imaging (MRI) plays a critical role in assessing and selecting the most appropriate treatment planning. We aimed to assess the diagnostic performance of quantitative analysis of diffusion-weighted imaging (DWI) in preoperative assessment of EC. METHODS: Prospective analysis was done for sixty-eight patients with pathology-proven endometrial cancer who underwent MRI and DWI. Apparent diffusion coefficient (ADC) values were measured by two independent radiologists and compared with the postoperative pathological results. RESULTS: There was excellent inter-observer reliability in measuring ADCmean values. There were statistically significant lower ADCmean values in patients with deep myometrial invasion (MI), cervical stromal invasion (CSI), type II EC, and lympho-vascular space involvement (LVSI) (AUC = 0.717, 0.816, 0.999, and 0.735 respectively) with optimal cut-off values of ≤ 0.84, ≤ 0.84, ≤ 0.78 and ≤ 0.82 mm2/s respectively. Also, there was a statistically significant negative correlation between ADC values and the updated 2023 FIGO stage and tumor grade (strong association), and the 2009 FIGO stage (medium association). CONCLUSIONS: The preoperative ADCmean values of EC were significantly correlated with main prognostic factors including depth of MI, CSI, EC type, grade, nodal involvement, and LVSI.

Preoperative Assessment of MRI-Invisible Early-Stage Endometrial Cancer With MRI-Based Radiomics Analysis.

BACKGROUND: Radiomics-based analyses have demonstrated impact on studies of endometrial cancer (EC). However, there have been no radiomics studies investigating preoperative assessment of MRI-invisible EC to date. PURPOSE: To develop and validate radiomics models based on sagittal T2-weighted images (T2WI) and T1-weighted contrast-enhanced images (T1CE) for the preoperative assessment of MRI-invisible early-stage EC and myometrial invasion (MI). STUDY TYPE: Retrospective. POPULATION: One hundred fifty-eight consecutive patients (mean age 50.7 years) with MRI-invisible endometrial lesions were enrolled from June 2016 to March 2022 and randomly divided into the training (n = 110) and validation cohort (n = 48) using a ratio of 7:3. FIELD STRENGTH/SEQUENCE: 3-T, T2WI, and T1CE sequences, turbo spin echo. ASSESSMENT: Two radiologists performed image segmentation and extracted features. Endometrial lesions were histopathologically classified as benign, dysplasia, and EC with or without MI. In the training cohort, 28 and 20 radiomics features were selected to build Model 1 and Model 2, respectively, generating rad-score 1 (RS1) and rad-score 2 (RS2) for evaluating MRI-invisible EC and MI. STATISTICAL TESTS: The least absolute shrinkage and selection operator logistic regression method was used to select radiomics features. Mann-Whitney U tests and Chi-square test were used to analyze continuous and categorical variables. Receiver operating characteristic curve (ROC) and decision curve analysis were used for performance evaluation. The area under the ROC curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. A P-value <0.05 was considered statistically significant. RESULTS: Model 1 had good performance for preoperative detecting of MRI-invisible early-stage EC in the training and validation cohorts (AUC: 0.873 and 0.918). In addition, Model 2 had good performance in assessment of MI of MRI-invisible endometrial lesions in the training and validation cohorts (AUC: 0.854 and 0.834). DATA CONCLUSION: MRI-based radiomics models may provide good performance for detecting MRI-invisible EC and MI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Significance of positive peritoneal cytology for recurrence and survival in patients with endometrial cancer.

AIM: This study aims to examine the association between malignant peritoneal cytology and prognosis in women with endometrial cancer. METHODS: We retrospectively analyzed the records of patients with endometrial cancer who underwent surgery with intraoperative peritoneal cytology at our hospital between January 1988 and December 2012. All results were reclassified according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) system, and the relation between intraoperative peritoneal cytology results and recurrence and prognosis was examined. RESULTS: Of the 908 patients analyzed, 205 (22.6%) had positive peritoneal cytology. Patients with positive peritoneal cytology had significantly lower rates of recurrence-free survival (RFS) and overall survival (OS) than those in the negative cytology group (both p < 0.001). Subgroup analysis of patients with FIGO stage I/II showed significantly lower RFS in the positive-cytology group (p = 0.005), but there was no significant difference in OS (p = 0.637). In the patients with FIGO stage III/IV or patients classified as "high risk," the RFS and OS were significantly lower in the positive-cytology group (both p < 0.001). Cox regression analysis identified positive peritoneal cytology as a significant predictor of recurrence in patients with FIGO stage I/II disease. CONCLUSIONS: Patients with positive peritoneal cytology for endometrial cancer have a high risk of recurrence, regardless of histopathologic type or FIGO stage. Peritoneal cytology has already been removed from the 2009 FIGO classification of endometrial cancer, but it may deserve reconsideration.

Three-dimensional transvaginal ultrasound vs magnetic resonance imaging for preoperative staging of deep myometrial and cervical invasion in patients with endometrial cancer: systematic review and meta-analysis.

OBJECTIVES: To evaluate and compare the diagnostic test accuracy (DTA) of three-dimensional transvaginal ultrasound (3D-TVS) and magnetic resonance imaging (MRI) for deep myometrial infiltration (DMI) and cervical invasion for preoperative staging and surgery planning in patients with endometrial cancer (EC). METHODS: This systematic review and meta-analysis investigated the DTA of MRI and 3D-TVS for DMI and cervical invasion in patients with EC. A literature search was performed using MEDLINE, Scopus, EMBASE, ScienceDirect, The Cochrane library, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform to identify relevant studies published between January 2000 and December 2021. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: Five studies, including a total of 450 patients, were included in the systematic review. All five studies compared the DTA of 3D-TVS vs MRI for DMI, and three studies compared the DTA of 3D-TVS vs MRI for cervical invasion. Pooled sensitivity, positive likelihood ratio and negative likelihood ratio for detecting DMI using 3D-TVS were 77% (95% CI, 66-85%), 4.57 and 0.31, respectively. The respective values for detecting DMI on MRI were 80% (95% CI, 73-86%), 4.22 and 0.24. Bivariate metaregression indicated a similar DTA of 3D-TVS and MRI (P = 0.80) for the correct identification of DMI. Pooled ln diagnostic odds ratio for detecting cervical invasion was 3.11 (95% CI, 2.09-4.14) for 3D-TVS and 2.36 (95% CI, 0.90-3.83) for MRI. The risk of bias was low for most of the four domains assessed in QUADAS-2. CONCLUSION: 3D-TVS demonstrated good diagnostic accuracy in terms of sensitivity and specificity for the evaluation of DMI and cervical invasion, with results comparable with those of MRI. Thus, we confirmed the potential role of 3D-TVS in the preoperative staging and surgery planning in patients with EC. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Endometrial serous carcinoma: A retrospective review of histological features & their clinicopathological association with disease-free survival & overall survival.

Background & objectives: Endometrial serous carcinoma (ESC) is a high-grade epithelial neoplasm with increased risk for metastasis and recurrence. This study was aimed to assess various histomorphological features of ESC and their clinicopathological association with disease-free survival (DFS) and overall survival (OS). Methods: A total of 205 slides (belonging to 120 patients) diagnosed as ESC from January 2009 to December 2015 were reviewed. Receiver operating characteristics (ROC) curves were established for the diagnostic performance of depth of invasion (DOI), tumour-free distance (TFD) to serosa and percentage myometrial invasion (MI%). OS and DFS were generated by Kaplan-Meier curves and prognostic significance by Cox regression analysis. Results: The mean age at diagnosis was 61.8 yr and the mean tumour size was 4.01 cm. Majority of the females were multiparous (84%; n=94) and postmenopausal (89.2%; n=107). On histopathology, <50 per cent of MI was identified in 37 of the 104 (35%), while 62/104 (59.61%) patients had ≥50 per cent MI. Seven (6.7%) patients had full-thickness invasion with serosal involvement, while five (4.8%) patients had no microscopic MI (minimal uterine serous carcinoma). Information about MI was not available in 16 patients. TFD ≥7.0 mm, DOI ≥6.0 mm and MI% ≥40 were significant variables in univariate analyses for OS; however, on multivariate analysis; none of these turned out to be an independent predictor in terms of OS. For DFS, DOI (≥6.0 mm) and MI% (≥40%) showed a significant association, in univariate as well as multivariate analysis; however, TFD (≤7.0 mm) did not show any significant association with DFS. Follow up data were available in 111 of the 120 (92.5%) patients with a five-year OS and DFS of 22.2 and 17.2 per cent, respectively. Interpretation & conclusions: Conventionally calculated DOI (less than or more than half thickness) did not show significance in the present study. Thus, calculating the actual myometrial DOI, MI% and TFD to serosa have the potential for contributing meaningfully to prognostication of ESC.

Ovarian insufficiency and CTNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities.

Endometrioid endometrial carcinomas (EECs) carry multiple driver mutations even when they are low grade. However, the biological significance of these concurrent mutations is unknown. We explored the interactions among three signature EEC mutations: loss-of-function (LOF) mutations in PTEN, gain-of-function (GOF) mutations of phosphoinositide 3-kinase (PI3K), and CTNNB1 exon 3 mutations, utilizing in vivo mutagenesis of the mouse uterine epithelium. While epithelial cells with a monoallelic mutation in any one of three genes failed to propagate in the endometrium, any combination of two or more mutant alleles promoted the growth of epithelium, causing simple hyperplasia, in a dose-dependent manner. Notably, Ctnnb1 exon 3 deletion significantly increased the size of hyperplastic lesions by promoting the growth of PTEN LOF and/or PI3K GOF mutant cells through the activation of neoadenogenesis pathways. Although these three mutations were insufficient to cause EEC in intact female mice, castration triggered malignant transformation, leading to myometrial invasion and serosal metastasis. Treatment of castrated mice with progesterone or estradiol attenuated the neoplastic transformation. This study demonstrates that multiple driver mutations are required for premalignant cells to break the growth-repressing field effect of normal endometrium maintained by ovarian steroids and that CTNNB1 exon 3 mutations play critical roles in the growth of preneoplastic cells within the endometrium of premenopausal women and in the myometrial invasion of EECs in menopausal women.

Is microcystic, elongated, and fragmented pattern of myometrial invasion in endometrioid endometrial carcinoma associated with survival?

BACKGROUND: Microcystic, elongated, and fragmented (MELF) pattern is one of the myometrial invasion patterns in endometrioid endometrial carcinoma (EEC), and it has been associated with poor prognostic parameters, especially lymphovascular space invasion (LVSI) and lymph node metastasis (LNM). This study aims to represent the frequency of MELF pattern in EEC and the relationship between MELF pattern with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS). METHODS: In this retrospective cohort study, we examined 233 patients with EEC diagnoses with the result of a total hysterectomy and bilateral salpingo-oophorectomy between 2009 and 2014. The association of MELF pattern with risk factors such as stage, recurrence, and survival was analysed statistically with the comparison of MELF positive and negative cases. RESULTS: MELF pattern was seen in 21.8% of all cases (51/233) and 23% of grade 1-2 cases (50/217). The MELF pattern showed a significant difference among patients when they were compared according to advanced age (≥60) (p = 0.022), LVSI (p = 0.021), deep myometrial invasion (p < 0.01), LNM (p = 0.027), and advanced FIGO stage (p = 0.043). MELF pattern was a predictive factor of LNM in univariate logistic regression analysis but did not show significance in multivariate analysis. The Kaplan-Meier survival analysis showed that MELF positive cases had reduced OS (66.7% vs 79.7% p = 0.003) and DFS (66.7% vs 77.5% p = 0.017) rates. In the univariate analyses, MELF pattern was an independent prognostic factor on OS and DFS along with other parameters, while it was not observed to maintain this effect in the multivariate analyses. DISCUSSION: This study is one of the largest series examining the relationship between MELF pattern of myometrial invasion and survival, and our results represented that the MELF pattern is associated with the worse clinical outcome since it is associated with lymphovascular space invasion, deep myometrial invasion, lymph node metastasis, and reduced overall survival and disease-free survival rates. Although the presence of MELF pattern is not reported in routine practice, it may be used as an indicator that will help predict a worse outcome.

Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer-A Swedish Gynecologic Cancer Group (SweGCG) study.

INTRODUCTION: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice. MATERIAL AND METHODS: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I-III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard. RESULTS: In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively. CONCLUSIONS: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI.

Preoperative Magnetic Resonance Imaging versus Intraoperative Frozen Section Diagnosis for Predicting the Deep Myometrial Invasion in Endometrial Cancer: Our Experience and Literature Review.

AIM: The present study was designed to directly compare the diagnostic performance of preoperative magnetic resonance imaging (MRI) and intraoperative frozen section (FS) diagnoses in predicting deep myometrial invasion (MI) of endometrial cancer. METHODS: Using MRI findings and FS diagnoses, 194 patients with surgically staged endometrial cancer were evaluated for deep MI between 2006 and 2018. Definitive histological diagnosis of paraffin sections of excised tissues was used as the gold standard approach. RESULTS: Of 194 cases, 53 (27.3%) cases were finally diagnosed as having deep MI (≥50%). There was 82% total agreement between MRI and FS diagnoses in predicting deep MI, with a kappa value of 0.54 (95% confidence interval [CI] = 0.40-0.67, moderate agreement). The sensitivity of FS diagnosis (0.66, 95% CI = 0.52-0.78) for predicting deep MI was lower than that of MRI (0.77, 95% CI = 0.63-0.87; p = 0.21), while the specificity of FS (0.98, 95% CI = 0.93-0.99) was significantly higher than that of MRI (0.88, 95% CI = 0.81-0.93; p = 0.001). Overall, the accuracy of FS (0.89, 95% CI = 0.84-0.93) was higher than that of MRI (0.85, 95% CI = 0.79-0.90), although the difference did not reach statistical significance (p = 0.23). The accuracy (0.95, 95% CI = 0.90-0.97) was very high in cases with concordant MRI and FS results. CONCLUSIONS: MRI and FS showed different diagnostic characteristics for predicting deep MI, with a higher specificity observed for FS and the greatest accuracy obtained in concordant cases. Thus, our findings recommend the addition of FS diagnosis, either alone or in conjunction with MRI, to MI evaluation.

COMPARISON OF TVUS, MRI, AND FROZEN SECTION METHODS IN PREOPERATIVE DETECTION OF MYOMETRIAL INVASION IN PATIENTS WITH ENDOMETRIAL CANCER.

We aimed to evaluate the depth of myometrial invasion preoperatively with transvaginal ultrasound, magnetic resonance imaging, and frozen section examination techniques in patients diagnosed with endometrial cancer. Our study included 65 patients. Transvaginal ultrasound and magnetic resonance imaging were performed in study patients in the preoperative period. Frozen section examination was performed in all hysterectomy samples obtained from all study patients. Data were analyzed with SPSS Statistics 22.0 program. The sensitivity of transvaginal ultrasound in determining the depth of myometrial invasion was 88.64%, specificity 90.48%, positive predictive value 95.12%, and negative predictive value 79.17%. For magnetic resonance imaging, the sensitivity was 63.64%, specificity 95.24%, positive predictive value 96.55%, and negative predictive value 55.56%. In addition to the frozen section examination, which is the gold standard in determining the myometrial invasion depth, transvaginal ultrasound and magnetic resonance imaging have become commonly used methods for this purpose in recent years. Ultrasound examination performed by an experienced specialist is superior to magnetic resonance imaging as it is fast, inexpensive, and associated with higher sensitivity.

Influence of uterine corpus invasion on prognosis in stage IA2-IIB cervical cancer: A multicenter retrospective cohort study.

OBJECTIVE: To determine the associations between the presence and depth of uterine corpus invasion and survival in patients with cervical cancer. METHODS: Clinical data of patients with stage IA2-IIB cervical cancer who underwent radical hysterectomy between 2004 and 2016 were retrospectively reviewed. Uterine corpus invasion was identified from a review of uterine pathology. Independent prognostic factors for 5-year disease-free survival (DFS) and overall survival (OS) were identified using multivariate forward stepwise Cox proportional hazards regression models. RESULTS: A total of 1414 patients with stage IA2-IIB cervical cancer from 11 medical institutions in China were included. Retrospective review of the original pathology reports revealed a missed diagnosis of uterine corpus invasion in 38 (13.4%) patients and a misdiagnosis in 20 (1.8%) patients. Therefore, 284 patients with cervical cancer and uterine corpus invasion (90 [31.7%] patients had endometrial invasion, 105 [37.0%] patients had myometrial invasion <50%, and 89 [31.3%] patients had myometrial invasion ≥50%), and 1130 patients with cervical cancer without uterine corpus invasion were included in the analysis. The 5-year DFS and OS were significantly shorter for patients with uterine corpus invasion compared to patients with no uterine corpus invasion. Myometrial invasion ≥50% was an independent prognostic factor associated with decreased 5-year DFS (aHR, 2.307, 95% CI, 1.588-3.351) and 5-year OS (aHR, 2.736, 95% CI, 1.813-4.130), while myometrial invasion <50% or endometrial invasion had no effect on patient outcomes. CONCLUSIONS: Diagnosis of uterine corpus invasion is frequently missed. Myometrial invasion ≥50% within the uterine corpus was an independent factor associated with worse prognosis in patients with cervical cancer, while myometrial invasion <50% or endometrial invasion had no effect on outcomes.

The apparent diffusion coefficient (ADC) on 3-T MRI differentiates myometrial invasion depth and histological grade in patients with endometrial cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) with apparent diffusion coefficient (ADC) measurement provides additional information about tumor microstructure with potential relevance for staging and predicting aggressive disease in patients with endometrial cancer (EC). PURPOSE: To determine whether ADC values in EC diverge according to the tumor's histologic grade and myometrial invasion depth. MATERIAL AND METHODS: A sample of 48 pathologically confirmed cases of EC were reviewed retrospectively. The sample was distributed as follows: G1 (n = 9); G2 (n = 18); G3 (n = 21); with myometrial invasion <50% (n = 31); and with myometrial invasion ≥50% (n = 17). DW images were performed at 3.0T with b factors of 0-1000/mm2. The region of interest (ROI) was defined within the tumor with T1-weighted and T2-weighted imaging and copied manually to an ADC map. The tumor's grade and myometrial invasion's depth were determined by postoperative histopathological tests. RESULTS: The means of ADCmin and ADCmean values were significantly lower for patients with G2 and G3 endometrial tumors than G1. The same tendency was observed in myometrial invasion, as both ADCmin and ADCmean values were lower for patients with deep than for those with superficial myometrial invasion. The cut-off values of the ADCmin and ADCmean that predicted high-grade tumors were 0.69 × 10-3 mm2/s and 0.82 × 10-3 mm2/s, respectively, while those for myometrial infiltration were 0.70 × 10-3 mm2/s (ADCmin) and 0.88 × 10-3 mm2/s (ADCmean). CONCLUSION: ADCmin and ADCmean values correlated with histologic tumor grade and myometrial invasion depth; therefore, it is suggested that ADC on MRI may be a useful indicator to predict malignancy of ECs.

Endometrial Tumour Microenvironment.

Endometrial cancer (EC) is the most common gynaecological tumour in developed countries, and its incidence is increasing in part due to the prevalence of obesity and its related hormone dysregulation. As described in this chapter, the tumour microenvironment plays a principal role in unopposed oestrogen stimulation promoting tumour cell proliferation. Factors and cytokines secreted by the different cell types defining the reactive tumour stroma also determine the invasive abilities of the tumour cells. Cancer-associated fibroblasts and tumour-associated macrophages actively participate through SDF-1, TGF-b or HGF to promote epithelial-to-mesenchymal transition or to generate an appropriate tumour niche. Likewise, endothelial cells facilitate lymph node and vascular infiltration through VEGF. Finally, the possibility to balance the immunosuppressive phenotypes in advanced endometrial cancer through the tumour microenvironment will probably represent a main therapeutic strategy in the near future.

Diagnostic performance of intraoperative assessment in grade 2 endometrioid endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Grade 2 carcinoma is associated with pelvic lymph-node metastasis, depending on selected risk factors. Intraoperative assessment (IOA) can identify patients at risk for lymph node metastasis who should undergo staging surgery. Our objective was to establish the diagnostic precision of IOA in determining the need for surgical staging in grade 2 endometrioid endometrial carcinoma. METHODS: Two hundred twenty-two patients underwent IOA. Results were compared to the final pathology report. The accuracy of the IOA parameters was calculated. Variables were evaluated in patients with positive versus negative IOA. Overall and disease-free survivals were calculated according to IOA, lymphadenectomy, and nodal metastasis. RESULTS: IOA was positive in 80 patients. It showed an accuracy of 76.13% when compared with the postoperative assessment. The best individual parameter was myometrial invasion. Nodal metastasis was observed in 16 patients in the positive IOA group and 7 patients in the negative group. Patients with lymph node metastasis had a 5-year overall survival rate of 80.9%, whereas patients without metastasis had a 5-year overall survival rate of 97.9%. CONCLUSIONS: IOA is an adequate tool to identify high-risk patients in grade 2 endometrial carcinoma. Myometrial invasion is the individual parameter that yields the highest diagnostic precision.

The value of MRI in management of endometrial hyperplasia with atypia.

BACKGROUND: The value of the magnetic resonance imaging (MRI) in the assessment of women with endometrial hyperplasia and its role in diagnosis of myometrial invasion or coexistence of cancer is not known. This study aimed to evaluate the accuracy and usefulness of MRI in the management of patients diagnosed on endometrial biopsy with complex endometrial hyperplasia with atypia (CEHA). METHODS: A retrospective study of 86 cases diagnosed with endometrial hyperplasia with atypia on the initial endometrial biopsy in a tertiary university teaching hospital between 2010 and 2015 was carried out. The MRI accuracy in predicting malignant changes and influence the clinical management was compared among women who had either pelvic MRI, transvaginal ultrasound (TVUS), or no additional imagistic studies. RESULTS: MRI was performed in 24 (28%) and TVUS in 11 (13%)cases, while 51 (59%) women had no additional imagistic studies. In the group of women with no imaging studies, 26/51 (51%) were surgically treated and 8/26 (31%) were diagnosed with endometrial cancer (EEC) stage 1a. In the group of women who had TVUS, 5/11 (45%) were surgically treated and none was diagnosed with EEC. In the group of women who underwent an MRI examination, 20/24 (83%) were surgically treated. Among these, 11/20 (55%) were diagnosed with EEC, 7 had EEC stage 1a, and 4 had EEC stage 1b. Although MRI was able to identify malignant changes with a good sensitivity (91.7%), it had a low specificity in characterisation of malignant transformation (8%). MRI correctly identified 31% of the stage 1a and 33% of the stage 1b endometrial cancer. CONCLUSION: In this study, we found a potential diagnostic value of MRI for identifying malignant transformation in patients with CEHA. However, pelvic MRI has a rather weak predictive value of myometrial invasion in women with CEHA and concurrent EEC. The diagnostic and therapeutic benefits of MRI assessment in patients with CEHA need further validation.

Assessment of thiol disulfide balance in early-stage endometrial cancer.

AIM: We carried out this research to assess thiol disulfide balance in patients with early-stage endometrial cancer. METHODS: Fifty-seven endometrial cancer patients and 60 age-matched healthy subjects volunteered for this study. Thiol disulfide parameters and the ratios of these parameters were examined using a colorimetric system. We also evaluated total antioxidant capacity, total oxidant capacity and oxidative stress index. RESULTS: Subjects with endometrial cancer had statistically significantly lower serum native thiol and total thiol levels (224.2 [122.8-267.5] and 270.5 [171.6-323.2], respectively) than healthy subjects (281.35 [213.45-358.9] and 339.55 [274.1-425.95], respectively) (P = 0.001, P < 0.001). Subjects with endometrial cancer had statistically significantly higher serum disulfide/native thiol and disulfide/total thiol ratios (12.22 [8.77-17.61] and 9.82 [7.46-13.02], respectively) than healthy subjects (8.9 [6.79-16.35] and 7.36 [5.9-12.32], respectively) (P = 0.038, P = 0.028). Disulfide/native thiol ratio appeared to be strongly and positively correlated with the stage of endometrial cancer (r = 0.827, P < 0.001). CONCLUSION: This is an initial report related to thiol disulfide balance in endometrial cancer patients. We believe that oxidative stress contributes both to the evolution and to the progression of the disease. We conclude that deterioration of thiol disulfide balance due to oxidative stress is likely to contribute to the etiopathogenesis of endometrial cancer.

The diagnostic performance of ADC value for tumor grade, deep myometrial invasion and lymphovascular space invasion in endometrial cancer: a meta-analysis.

BACKGROUND: Disputes exist regarding whether the apparent diffusion coefficient (ADC) can differentiate the tumor grade, deep myometrial invasion and lymphovascular space invasion (LVSI) in endometrial cancer. The aim of this review was to assess the diagnostic performance of the ADC value in endometrial cancer. MATERIAL AND METHODS: The PubMed, Web of Science, Embase and Cochrane Library databases were searched for studies that used the ADC value to assess tumor grade, deep myometrial invasion and LVSI in endometrial cancer. We used forest plots to analyze the heterogeneity and generate the pooled sensitivity (SEN) and specificity (SPE). We used summary receiver operating characteristic (SROC) curves to work out the area under the SROC curve (AUC). Likelihood ratios (LRs) were also obtained. RESULTS: Of the 460 identified studies, 11 studies met our inclusion criteria and were included. Overall, nine studies (491 patients) aimed at differentiating high tumor grade had a pooled SEN, SPE and AUC of 77%, 73% and 81%, respectively; three studies (181 patients) for differentiating deep myometrial invasion had a pooled SEN, SPE and AUC of 71%, 67% and 77%, respectively; and two studies (106 patients) for differentiating LVSI had a pooled SEN and SPE of 66% and 74%, respectively. The positive and negative LRs were 2.77 and 0.35 for the tumor grade, 2.08 and 0.45 for deep myometrial invasion, and 2.48 and 0.45 for LVSI. CONCLUSION: This meta-analysis showed that the ADC value had a moderate diagnostic performance for the tumor grade, deep myometrial invasion and LVSI in endometrial cancer.

Comparison of the determination of the local tumor extent of primary endometrial cancer using clinical examination and 3 Tesla magnetic resonance imaging compared to histopathology.

PURPOSE: The aim of this study is to analyze the correct staging of primary endometrial cancer (EC) using clinical examination and 3 Tesla (T) magnetic resonance imaging (MRI) results compared to histopathology. METHODS: In this prospective, non-randomized, single-center study, 26 women with biopsy-proven EC were evaluated. All women underwent clinical examination including transvaginal ultrasound (CE/US) and 3T MRI (T2-weighted, diffusion-weighted and dynamic contrast-enhanced sequences) prior to surgery. Spearman's correlation coefficient was employed to analyze the correlation between both staging methods and histopathology and generalized estimation equation analysis to compare their staging results. Main outcome measures are determinations of local tumor extent for EC on CE/US and 3T MRI compared to histopathology (gold standard). RESULTS: Sixteen women had an early-stage pT1a tumor, 10 a locally advanced ≥ pT1b tumor. The early stage was correctly diagnosed at CE/US in 100%, by MRI in 81%. Spearman's correlation coefficient was r = 1.0 (p < 0.001) for correlation of CE/US and histopathology, r = 0.93 (p < 0.001) for correlation of MRI and pathology. A locally advanced tumor stage was exactly diagnosed by MRI in 70% and at CE/US in 50%. CONCLUSIONS: CE/US is sufficient for staging T1a endometrial cancer, while MRI provides higher sensitivity in detecting locally advanced tumors. Based on our results, combining CE/US and 3T MRI in patients with at least suspected deep myometrial invasion offers a more reliable workflow for individual treatment planning.

Accuracy of frozen section at early clinical stage of endometrioid endometrial cancer: a retrospective analysis in Germany.

PURPOSE: The aim of this study was to estimate the accuracy of intra-operative frozen section (FS) diagnosis during hysterectomy for early-stage endometrial cancer (EC). METHODS: At the Department of Obstetrics and Gynecology, University of Luebeck, between 2009 and 2014, the intra-operative FS pathology of 164 patients with pre-operative endometrial curettage, showing G1 or G2 endometrioid EC at an early clinical stage (FIGO I-II), was compared retrospectively with the final paraffin section reports. The accuracy of myometrial invasion (MI) in all patients and separately in stage FIGO I patients was calculated and the under- or overtreatment of the patients was analyzed. A subgroup analysis was performed focusing on the percentage of inadequate staging by FS with clinical consequences. RESULTS: Concordance of FS and final pathology results in terms of FIGO stage was 85.2%, with an under-diagnosis rate of 14% and an over-diagnosis rate of 0.8%. The subgroup analysis rate of patients who were inappropriately operated using FS was 6.6%, while 3.3% underwent a secondary operation. The overall accuracy of FS in predicting MI was 93.3% and in patients with stage FIGO I, 92.7%. Sensitivity, specificity, PPV and NPV were 98.25%, 89.06%, 88.89% and 98.28%, respectively, and in stage FIGO I, 98.25%, 84.62%, 90.32% and 97.06%, respectively. CONCLUSION: The authors consider that intra-operative FS is a reliable diagnostic method to identify the clinical stage of EC and especially MI, to determine the necessity of lymphadenectomy. Further development of diagnostic techniques is essential to maximize diagnostic accuracy.

Clinicopathological and prognostic significance of blood microvessel density in endometrial cancer: a meta-analysis and subgroup analysis.

OBJECTIVE: The study aimed to systematically review the association between angiogenesis and clinicopathological characteristics and its prognostic value in patients with endometrial cancer. METHODS: Eligible studies were searched in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang database. Studies that assessed blood microvessel density (BMVD) and correlated with clinicopathological features and/or overall survival (OS) were included. Geometric mean values and hazard ratio with 95% confidence interval were pooled to examine the risk or hazard association. Subgroup analyses were conducted based on populations, BMVD criteria, BMVD markers, and type of survival analysis. RESULTS: A total of 29 studies of 2517 patients were included. BMVD was associated with depth of myometrial invasion (MI) [standard mean difference (SMD) 1.24; 95% CI 0.53-1.95; P = 0.0006], lymphovascular space invasion (LVSI) (SMD 0.75; 95% CI 0.3-1.21; P = 0.001), and lymph node metastasis (LNM) (SMD 0.99; 95% CI 0.46-1.52; P = 0.0003). BMVD was also significantly associated with poor OS (HR 2.65; 95% CI 1.86-3.77; P < 0.00001). The association remained significant in the subgroups Asian population, BMVD criteria using Weidner method, BMVD marker CD34 for MI, LVSI, and LNM, CD105 for MI, and factor VIII for MI and LNM, respectively. For OS, either Asian or non-Asian population, BMVD criteria using Weidner or non-Weidner method, BMVD marker CD31, or factor VIII antibody and analysis using univariate or multivariate were all significantly associated. CONCLUSIONS: BMVD was associated with deeper MI, positive LVSI, positive LNM, and poor OS in patients with endometrial cancer. Therefore, angiogenesis is a useful measure for poor clinicopathological outcomes and prognosis in patients with endometrial cancer.