Deep Myometrial Invasion Research Articles

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.

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. 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). 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%. 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.

Cytoplasmic Keap1 Expression Is Associated With Poor Prognosis in Endometrial Cancer.

Oxidative stress is involved in several carcinogenic pathways. Nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1) and Park7 (DJ-1) are the main regulators of antioxidant enzymes eliminating reactive oxidative species (ROS). The roles of these proteins were studied as potential prognostic factors in endometrial cancer. Nrf2, Keap1 and DJ-1 expression in endometrial carcinomas was analyzed immunohistochemically. Correlations between staining patterns and clinical prognostic variables were evaluated. Extensive cytoplasmic Keap1 staining correlated to several factors associated with poor prognosis of endometrial cancer including advanced stage, poor histological differentiation, lymphovascular invasion, pelvic lymph node metastasis and deep myometrial invasion. In multivariate analysis, cytoplasmic Keap1 was a stronger predictor of poor progression-free survival than grade. Nuclear Nrf2 staining was seen in all patients with lymph node metastasis while DJ-1 staining was associated with clinically favourable disease types. Cytoplasmic Keap1 expression indicates poor prognosis in endometrial cancer.

Prognostic significance of lymphovascular space invasion in low-risk endometrial cancer.

The purpose of this study was to assess the prognostic significance of lymphovascular space invasion in women with low-risk endometrial cancer. A dual-institutional, retrospective department database review was performed to identify patients with 'low-risk endometrial cancer' (patients having <50% myometrial invasion with grade 1 or 2 endometrioid endometrial cancer according to their final pathology reports) at two gynecologic oncology centers in Ankara, Turkey. Demographic, clinicopathological and survival data were collected. We identified 912 women with low-risk endometrial cancer; 53 patients (5.8%) had lymphovascular space invasion. When compared with lymphovascular space invasion-negative patients, lymphovascular space invasion-positive patients were more likely to have post-operative grade 2 disease (p<0.001), deeper myometrial invasion (p=0.003), and larger tumor size (p=0.005). Patients with lymphovascular space invasion were more likely to receive adjuvant therapy when compared with lymphovascular space invasion-negative women (11/53 vs 12/859, respectively; p<0.001). The 5-year recurrence-free survival rate for lymphovascular space invasion-positive women was 85.5% compared with 97.0% for lymphovascular space invasion-negative women (p<0.001). The 5-year overall survival rate for lymphovascular space invasion-positive women was significantly lower than that of lymphovascular space invasion-negative women (88.2% vs 98.5%, respectively; p<0.001). Age ≥60 years (HR 3.13, 95% CI 1.13 to 8.63; p=0.02) and positive lymphovascular space invasion status (HR 6.68, 95% CI 1.60 to 27.88; p=0.009) were identified as independent prognostic factors for decreased overall survival. Age ≥60 years and positive lymphovascular space invasion status appear to be important prognostic parameters in patients with low-risk endometrial cancer who have undergone complete surgical staging procedures including pelvic and para-aortic lymphadenectomy. Lymphovascular space invasion seems to be associated with an adverse prognosis in women with low-risk endometrial cancer; this merits further assessment on a larger scale with standardization of the lymphovascular space invasion in terms of presence/absence and quantity.

Comparison of preoperative myometrial invasion on MRI with intraoperative frozen section in predicting adverse prognostic factors and survival in endometrioid endometrial cancer

Aim: There are no studies that have evaluated the accuracy of the finding of myometrial invasion in each modality in predicting adverse prognostic factors and survival. We compared the association of myometrial invasion on MRI and frozen section with presence of adverse prognostic factors and decreased disease-specific survival (DSS) in endometrioid endometrial cance. Material and Methods: A total of 149 patients diagnosed and treated surgically for endometrioid endometrial cancer at a single institution between 2010 and 2017 were included in the study. Accuracies of radiological myometrial invasion and frozen section myometrial invasion in predicting the histopathological myometrial invasion, other adverse prognostic factors and DSS were compared.Results: Frozen section had an accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 89.2%, 100.0%, 84.7%, 72.8% and 100.0%, respectively in diagnosing histopathological deep (≥50%) myometrial invasion with a kappa value of 0.876 (p<0.001). MRI had an accuracy, sensitivity, specificity, PPV and NPV of 71.3%, 55.8%, 80.6%, 63.2%, 75.3%, respectively with a kappa value of 0.392 (p<0.001) in predicting deep myometrial invasion. The accuracy of the finding of deep myometrial invasion on frozen section was higher than the finding of deep myometrial invasion on MRI in predicting the presence of adverse prognostic factors. However, the specificities and NPV’s were higher than their respective sensitivity and PPV values overall for both modalitiesd.Conclusion: Although MRI is frequently used in the preoperative evaluation of patients with endometrial cancer, the finding of deep myometrial invasion on MRI was not as accurate as that of frozen section in predicting the presence of adverse prognostic factors and poor survival. However, both test modalities demonstrated high specificity and NPV. As such both tests may provide higher efficacy in identifying patients without advanced disease who may not require complete lymph node dissection.

Risk factors for pelvic and para-aortic lymph node metastasis in endometrial cancer: A retrospective analysis of 284 patients

Aim: Hysterectomy is generally used to treat patients with endometrial cancer. Although lymphadenectomy can provide prognostic information, there are serious complications that can result from lymph node dissection. In order to avoid unnecessary surgical intervention, predictors related to both pelvic and para-aortic lymph node metastasis can be identified. In this study, we sought to define independent prognosticators for pelvic and para-aortic lymph node metastasis in women with endometrial cancer.Material and Methods: In total, 284 patients who were treated surgically between December 2009 and January 2019 were included in the study. The relationships between histopathological patient characteristics and definitive lymph node status were studied.Results: In multivariate analysis, lymphovascular space invasion (Adjusted Odds Ratio: 4.8, 95% Confidence Interval 2.4–17.5, p = 0.001) and deep myometrial invasion (Adjusted Odds Ratio 3.8, 95% Confidence Interval 1.1–14.3) were independent factors for pelvic lymph node metastasis. In multivariate analysis for para-aortic lymph node metastasis, lymphovascular space invasion (Adjusted Odds Ratio 5.9, 95% Confidence Interval 2.1–10.3) and pelvic lymph node metastasis (Adjusted Odds Ratio 20.8, 95% Confidence Interval 8.9–32.3) were independent prognostic factors significantly associated with the presence of para-aortic lymph node metastasis. Conclusion: The two independent histopathological factors identified for predicting the presence of pelvic lymph node metastasis were lymphovascular space invasion and outer half myometrial penetration of the tumor. Lymphovascular space invasion and pelvic lymph node metastasis were independently associated with the presence of para-aortic lymph node metastasis. Consideration of lymphadenectomy in patients who have evidence of outer half myometrial invasion or pelvic lymph node metastasis on preoperative imaging may be prudent. Lymphovascular space invasion and myometrial invasion findings on frozen section can be used before proceeding with lymphadenectomy in endometrial cancer.

Assessment of HER-2/neu, с-MYC andCCNE1 gene copy number variations andprotein expression in endometrial carcinomas.

To analyze copy number variations of HER-2/neu, c-MYC and CCNE1oncogenes and their protein expression in endometrioid endometrial carcinomas in relation to the degree of tumor progression and presence of a family history of cancer in cancer patients. The study was conducted on endometrial cancer (EC) samples from 68patients with I-II FIGO stages of disease. Copy number analysis of HER-2/neu, c-MYC and CCNE1genes was performed by quantitative PCR. Protein expression was analyzed using immunohistochemistry. Assessment of copy number variations of HER-2/neu, c-MYC and CCNE1genes revealed their amplification in the tumors of 18.8, 25.0and 14.3% of EC patients, respectively. High expression of corresponding proteins was detected in 14.6, 23.5and 65.6% of patients, respectively. It was established that HER-2/neu gene amplification is more common in the group of tumors of low differentiation grade than in moderate grade EC (35.7and 5.5% of cases, respectively, p < 0.05). Also, high expression of c-Myc protein was more frequently observed in low differentiated tumors compared to the moderately differentiated EC (36.6and 13.2% of cases, respectively, p < 0.05). Expression of HER-2/neu and cyclin E proteins was found to be dependent on the depth of tumor invasion into the myometrium. High expression of HER-2/neu protein was observed in 25.0and 4.1% of EC patients with tumor invasion > ½ and < ½ of the myometrium, respectively, and cyclin E- in 86.7and 46.6% of cases, respectively, p < 0.05. It was shown that among patients with a family history of cancer, a larger proportion of cases with high expression of c-Myc protein was observed compared to the group of patients with sporadic tumors (43.8and 17.3%, respectively; p < 0.05). Amplification of HER-2/neu gene, along with high expression of c-Myc, HER-2/neu and cyclin E proteins, are associated with such indices of tumor progression as a low differentiation grade and deep myometrial invasion, suggesting the potential possibility of including these markers in the panel for determining the molecular EC subtype associated with an aggressive course of the disease. In a certain category of EC patients, there is a relationship between a family history of cancer and high expression of c-Myc protein.

Clinical and Ultrasound Characteristics of the Microcystic Elongated and Fragmented (MELF) Pattern in Endometrial Cancer According to the International Endometrial Tumor Analysis (IETA) criteria.

To describe sonographic features of the microcystic elongated and fragmented (MELF) pattern of myometrial invasion (MI) using the International Endometrial Tumor Analysis (IETA) criteria; to assess the effect of the MELF pattern on preoperative ultrasound evaluation of MI; and to determine the relationship of the MELF pattern to more advanced stage (≥ IB) and lymph node metastases in women with endometrioid endometrial cancer. We included 850 women with endometrioid endometrial cancer from the prospective IETA 4 study. Ultrasound experts performed all ultrasound examinations, according to the IETA protocol. Reference pathologists assessed the presence or absence of the MELF pattern. Sonographic features and accuracy of ultrasound assessment of MI were compared in cases with the presence and the absence of the MELF pattern. The MELF pattern was correlated to more advanced stage (≥IB) and lymph node metastases. The MELF pattern was present in 197 (23.2%) women. On preoperative ultrasound imaging the endometrium was thicker (p = 0.031), more richly vascularized (p = 0.003) with the multiple multifocal vessel pattern (p < 0.001) and the assessment of adenomyosis was more often uncertain (p < 0.001). The presence or the absence of the MELF pattern did not affect the accuracy of the assessment of MI. The MELF pattern was associated with deep myometrial invasion (≥ 50%) (p < 0.001), cervical stromal invasion (p = 0.037), more advanced stage (≥ IB) (p < 0.001) and lymph node metastases (p = 0.011). Tumors with the MELF pattern were slightly larger, more richly vascularized with multiple multifocal vessels and assessment of adenomyosis was more uncertain on ultrasound imaging. The MELF pattern did not increase the risk of underestimating MI in preoperative ultrasound staging. Tumors with the MELF pattern were more than twice as likely to have more advanced stage (≥ IB) and lymph node metastases.

Immunohistochemical study of folate receptor-α and mammalian target of rapamycin in endometrial hyperplasia and endometrioid endometrial carcinoma

Background Endometrioid-type endometrial carcinoma (EEC) is a common gynecologic malignancy worldwide. Folate receptor-α (FRα) is a membrane-bound glycoprotein that plays a role in cell proliferation. Mammalian target of rapamycin (mTOR) is a master regulator of the intracellular growth pathways. To date, studies about the expression of these molecules in EEC and its precursor endometrial hyperplasia (EH) are limited.Aim The aim was to examine the immunohistochemical expression of FRα and mTOR in EEC in comparison with EH and normal endometrium and correlate their expression with the clinicopathologic parameters of EEC and then assess the correlation between FRα and mTOR expression in EEC.Materials and methods FRα and mTOR expression was immunohistochemically examined in proliferative endometrium (n=30), EH (n=30), EEC (n=45), and peritumoral tissues (n=23).Results FRα and mTOR expression was significantly higher in EEC than proliferative endometrium, EH, and peritumoral tissues. FRα expression was significantly higher in postmenopausal patients, older age, higher histologic grade, deep myometrial invasion, positive vascular emboli, and higher clinical stage. mTOR expression was significantly higher in postmenopausal patients, older age, large size, and higher histologic grade. A positive correlation between mTOR and FRα in EEC was detected.Conclusion These results suggest that FRα and mTOR may contribute in the pathogenesis of EEC and its progression from EH. A positive correlation between mTOR and FRα in EEC sheds new light for a novel pathway that may modulate the cellular growth. Whether targeting these molecules could have therapeutic ramifications awaits further studies.

The added value of diffusion-weighted imaging in the preoperative assessment of endometrial cancer.

ObjectiveTo evaluate the added value of diffusion-weighted imaging (DWI) in the preoperative assessment of myometrial invasion in endometrial cancer, in comparison with T2-weighted imaging (T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Materials and MethodsThis was a retrospective study involving 44 women with endometrial cancer who underwent preoperative 1.5 T MRI. Two radiologists, both of whom were blinded to the histopathology reports, performed a consensus interpretation of the depth of myometrial invasion and of the stage of the cancer, considering three sets of sequences: T2WI, DCE-MRI+T2WI, and DWI+T2WI. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each set. The accuracy was compared with p-value adjustment by the Benjamini-Hochberg procedure. ResultsAmong the 44 patients evaluated, DWI+T2WI demonstrated better diagnostic performance in assessing deep myometrial invasion and correctly staged more patients (n = 41) than did DCE-MRI+T2WI (n = 34) and T2WI (n = 22). The superior diagnostic accuracy of DWI+T2WI was statistically significant in comparison with T2WI (p < 0.05) but not in comparison with DCE-MRI+T2WI (p > 0.05).ConclusionThe addition of DWI apparently improves the diagnostic accuracy of MRI in the preoperative assessment of the depth of myometrial invasion in endometrial cancer, which may be particularly helpful in patients for whom contrast agents are contraindicated.

Does lymphadenectomy improve survival in patients with intermediate risk endometrial cancer? A multicentric study from the FRANCOGYN Research Group.

The role of lymphadenectomy in intermediate risk endometrial cancer remains uncertain. We evaluated the impact of lymphadenectomy on overall survival and relapse-free survival for patients with intermediate risk endometrial cancer. We retrospectively reviewed patients from the FRANCOGYN database with intermediate risk endometrial cancer, based on pre-operative and post-operative criteria (type 1, grade 1-2 tumors with deep (> 50%) myometrial invasion and no lymphovascular space invasion), who received primary surgical treatment between November 2002 and August 2013. We compared overall survival and relapse-free survival between staged and unstaged patients. From 1235 screened patients, we selected 108 patients with intermediate risk endometrial cancer. Eighty-two (75.9%) patients underwent nodal staging (consisting of pelvic +/- para-aortic lymphadenectomy). Among them, 35 (32.4%) had lymph node disease. The median follow-up was 25 months (range 0.4 to 155.0). The overall survival rates were 82.5% for patients staged (CI 64.2 to 91.9) vs 77.9 % for unstaged patients (CI 35.4 to 94.2) (P = 0.73). The relapse-free survival rates were 68.9% for staged patients (CI 51.2 to 81.3) vs 68.8% for unstaged patients (CI 29.1 to 89.3) (P=0.67). Systematic nodal staging does not appear to improve overall survival and relapse-free survival for patients with IR EC but could provide information to tailor adjuvant therapy. Sentinel lymph node dissection may be an effective and less invasive alternative staging technique and should provide a future alternative for this population.

Role of Positron Emission Tomography/Computed Tomography in Preoperative Assessment of Carcinoma Endometrium-a Retrospective Analysis.

PET/CT has made significant inroads into routine oncological practice in recent times. In our study, we aim to determine its value in preoperative assessment of endometrial carcinoma. A retrospective study between January 2011 and March 2016 was conducted; we included all cases of carcinoma endometrium with a preoperative PET/CT scan. PET/CT images were analyzed and correlated with histological findings after surgical staging. A total of 46 cases were analyzed, mean age was 59.8years, BMI 30.8kg/m2, and most common histology endometrioid type (69.5%). We correlated PET/CT findings with histopathology as reference standard. PET/CT had a sensitivity of 40%, moderate specificity (75%) and accuracy (71.7%), good NPV (91.2%), but poor PPV (16.7%) for lymph node involvement. A total of 10 (21.7%) cases were detected to have distant metabolically active lesions on PET/CT, seven out of these were positive for malignancy. And 90% of them were either non-endometrioid type or grade two and higher. We found that SUV of primary tumor was significantly higher in patients with deep myometrial invasion (p = 0.018), and high-risk histological type of tumor (p = 0.022), though not statistically significant when lymph nodal involvement (p = 0.9), cervical involvement (p = 0.56), or histological grade (p = 0.84) were considered. Sensitivity and specificity of PET/CT in staging endometrial cancer is not high enough to reliably tailor lymphadenectomy. Although SUV of the primary tumor was significantly higher in patients with deep myometrial invasion and high-risk histological type, it's usefulness in classifying patients into predefined risk groups seems to be limited. However, it is useful in detecting distant metastasis especially in high-grade and non-endometrioid type of tumors. Thus, implementation of PET/CT as a surrogate for surgical staging of endometrial cancer remains enigmatic and is open to further research.

Risk Factors for Lymph Node Metastasis among Lymphovascular Space Invasion-Positive Women with Endometrioid Endometrial Cancer Clinically Confined to the Uterus

Introduction: We aimed to assess risk factors for lymph node (LN) metastasis among lymphovascular space invasion(LVSI)-positive women with pure endometrioid endometrial cancer (EC) clinically confined to the uterus. Methods: Medical records of women who underwent primary surgery for EC between 2007 and 2016 at either of 2 gynecological oncology centers were retrospectively reviewed. Patient data were analyzed with respect to LN involvement, and predictive factors for LN metastasis were investigated. Results: 280 patients with surgically staged endometrioid-type EC with LVSI were identified. LN involvement was detected in 88 patients (31.4%) with a systematic LN dissection. In multivariate analysis, elevated baseline serum CA 125 levels, deep myometrial invasion (MMI), adnexal involvement and positive peritoneal cytology were found to be independent risk factors for LN metastasis. In women without deep MMI and elevated baseline serum CA 125 levels, the rate of LN metastasis was 19%. The presence of solely deep MMI increased this probability up to 29.1%. The rate of LN metastasis was found to be 46.8% for women with both deep MMI and elevated baseline serum CA 125 levels. Conclusion: These findings may be useful in the decision-making process for LVSI-positive women who are unstaged.

EP15.14: Endometrial carcinomas in women with polycystic ovary syndrome: sonohysterographic findings

To describe the sonohysterographic features of endometrial carcinomas in women with polycystic ovary syndrome (PCOS) and to determine the diagnostic role of sonohysterography (SH) in the evaluation of these lesions. SH findings of 52 PCOS patients with histologically confirmed endometrial carcinomas were evaluated. The mean age was 33.5 years (range 22-45 years). Histology included endometrioid type in 51 cases and Grade 1 in 46 cases, and 46 patients was stage IA. 23 Patients had high dose progestin treatment and 29 patients undergo surgery. SH demonstrated the endometrial thickening in 39 cases, endometrial mass in 6 cases, and endometrial thickening with mass in 7 cases. The endometrial thickness ranged from 5.5 to 27 mm (mean 9.6 mm) and the mass size ranged from 2 to 4.3 cm. They appeared as a diffuse polypoid endometrial thickening and a sessile endometrial mass with an inhomogeneous hyperechogenicity, an irregular surface, and obliteration of endometrial cavity. The tumour involved only to the endometrium in 35 cases and there were superficial myometrial invasion in 15 cases, deep myometrial invasion in 2 cases, and cervical invasion in 4 cases. The SH features of endometrial carcinomas associated with PCOS included a diffuse polypoid endometrial thickening and a sessile endometrial mass with an inhomogeneous hyperechogenicity, an irregular surface, obliteration of the cavity, and absent myometrial invasion. SH may provide more diagnostic value in the evaluation of endometrial carcinomas in women with PCOS. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Evaluation of Intraoperative Assessments in the Management of Endometrial Carcinoma: A Retrospective Quality Assurance Review.

Intraoperative assessment (IA) of uteri is often used to help determine whether to perform lymphadenectomy in patients with endometrial carcinoma. We sought to perform a quality assurance review of the practice of IA at our institution. In a 1-yr period, 107 hysterectomies had an IA performed. Grade of neoplasm in preoperative endometrial biopsy, neoplasm size, depth of myometrial invasion at IA, operative management, and final histologic features were recorded. Operative reports were reviewed to assess the surgeon's interpretation of the IA and the effect on surgical management. The sensitivity and specificity for IA of deep myometrial invasion (>50% myometrial thickness) compared with final histology was 76.9% and 91.1%. The positive predictive value was 71.4%, negative predictive value 93.2% and accuracy 88%. Neoplasm size was provided in 47% of cases. In 10% of patients lymphadenectomy was performed despite low-risk features. IA results were included in the operative report in 87% of cases. There were differences in 8.4% of cases between the IA diagnosis and the surgeon's operative report. IA of deep myometrial invasion is reliable at our institution. Several metrics for quality improvement have been identified as a result of this retrospective review. These include but are not limited to more reliable reporting of neoplasm size, documentation, and communication with gynecologic oncologists.

Preoperative tumor texture analysis on MRI predicts high-risk disease and reduced survival in endometrial cancer.

Improved methods for preoperative risk stratification in endometrial cancer are highly requested by gynecologists. Texture analysis is a method for quantification of heterogeneity in images, increasingly reported as a promising diagnostic tool in various cancer types, but largely unexplored in endometrial cancer. To explore whether tumor texture parameters from preoperative MRI are related to known prognostic features (deep myometrial invasion, cervical stroma invasion, lymph node metastases, and high-risk histological subtype) and to outcome in endometrial cancer patients. Prospective cohort study. In all, 180 patients with endometrial carcinoma were included from April 2009 to November 2013 and studied until January 2017. Preoperative pelvic MRI including contrast-enhanced T1 -weighted (T1 c), T2 -weighted, and diffusion-weighted imaging at 1.5T. Tumor regions of interest (ROIs) were manually drawn on the slice displaying the largest cross-sectional tumor area, using the proprietary research software TexRAD for analysis. With a filtration-histogram technique, the texture parameters standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis were calculated. Associations between texture parameters and histological features were assessed by uni- and multivariable logistic regression, including models adjusting for preoperative biopsy status and conventional MRI findings. Multivariable Cox regression analysis was used for survival analysis. High tumor entropy in apparent diffusion coefficient (ADC) maps independently predicted deep myometrial invasion (odds ratio [OR] 3.2, P lt 0.001), and high MPP in T1 c images independently predicted high-risk histological subtype (OR 1.01, P = 0.004). High kurtosis in T1 c images predicted reduced recurrence- and progression-free survival (hazard ratio [HR] 1.5, P lt 0.001) after adjusting for MRI-measured tumor volume and histological risk at biopsy. MRI-derived tumor texture parameters independently predicted deep myometrial invasion, high-risk histological subtype, and reduced survival in endometrial carcinomas, and thus, represent promising imaging biomarkers providing a more refined preoperative risk assessment that may ultimately enable better tailored treatment strategies in endometrial cancer. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1637-1647.

Preoperative prediction of deep myometrial invasion and tumor grade for stage I endometrioid adenocarcinoma: a simple method of measurement on DWI.

To explore the utility of the tumor area ratio (TAR) for predicting deep myometrial invasion and tumor grade in stage I endometrioid adenocarcinoma (EEA). We retrospectively evaluated 86 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I EEA. All patients underwent unenhanced contrast MRI and diffusion-weighted imaging (DWI) procedures. The volume and maximum area of the tumor and uterus were obtained, and the tumor volume ratio (TVR) and TAR were calculated. The Kruskal-Wallis test and Mann-Whitney U test were used to compare the differences in indexes (TVR and TAR) between the different tumor grades and between superficial and deep myometrial invasion. The TVR and TAR values for deep myometrial invasion and high-grade EEA tumors were significantly higher than the values for superficial myometrial invasion and low-grade tumors (all p = 0.000). According to the receiver-operating characteristic (ROC) curve, the area under the curve (AUC) was significantly higher for TAR than for TVR for tumors with deep myometrial invasion (0.936 vs. 0.844, p = 0.045). However, no significant differences in the AUCs for TVR and TAR were observed between high- and low-grade tumors (0.865 vs. 0.863, p = 0.956). A TAR ≥ 34.6% predicted deep myometrial invasion in EEA with a sensitivity, specificity, and accuracy of 85.0%, 84.8%, and 86.0%, respectively. A TAR ≥ 38.9% predicted high-grade tumors with a sensitivity, specificity, and accuracy of 83.3%, 81.1%, and 82.6%, respectively. TAR is useful for predicting deep myometrial invasion and high-grade stage I EEA KEY POINTS: • TAR is useful for predicting risk factors for EEA. • TAR is easy to obtain and has high accuracy. • TAR has excellent interobserver repeatability agreement (ICC range 95.1-99.6%).

Endometrial cancer off-line staging using two-dimensional transvaginal ultrasound and three-dimensional volume contrast imaging: Intermethod agreement, interrater reliability and diagnostic accuracy

ObjectivesThe aim is to estimate agreement between two-dimensional transvaginal ultrasound (2D-TVS) and three-dimensional volume contrast imaging (3D-VCI) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) of endometrial cancer and to compare the two methods regarding inter-rater reliability and diagnostic accuracy. MethodsFifteen ultrasound experts assessed off-line de-identified 3D-VCI volumes and 2D-TVU video clips from 58 patients with biopsy-confirmed endometrial cancer regarding the presence of deep (≥50%) MI and CSI. Video clips and 3D volumes were assessed independently. Interrater reliability was measured using kappa statistics. Histological diagnosis after hysterectomy served as gold standard. Accuracy measurements were correlated to rater experience using Spearman's rank correlation coefficient (ρ). ResultsAgreement between 2D-TVU and 3D-VCI for diagnosing MI was median 76% (range 64–93%) and for CSI median 88% (range 79–97%). Interrater reliability was better for 2D-TVU than for 3D-VCI (Fleiss' kappa 0.41 vs. 0.31 for MI and 0.55 vs. 0.45 for CSI). Median accuracy for diagnosing deep MI was 76% (range 59–84%) with 2D-TVU and 69% (range 52–83%) for 3D-VCI; the corresponding figures for CSI were 88% (range 81–93%) and 86% (range 72–95%). Accuracy was significantly correlated to how many cases the raters assessed annually. ConclusionsOff-line assessment of MI and CSI in women with endometrial cancer using 3D-VCI has lower interrater reliability and lower accuracy than 2D-TVU video clip assessment. Since accuracy was correlated to the number of cases assessed annually it is advised to centralize these examinations to high-volume centres.

The utility of measuring the apparent diffusion coefficient for peritumoral zone in assessing infiltration depth of endometrial cancer

BackgroundThe invasion depth of endometrial cancer is one of the most important prognosis factors. The aim of the current study was to investigate the diagnostic value of the apparent diffusion coefficient (ADC) of the peritumoral zone for assessing the infiltration depth of endometrial cancer.MethodsAn institutional review board approved this prospective study, and all study participants provided informed consent. A total of 58 patients (mean age 54 ± 8.3 years, range 34–69 years) with endometrial cancer were prospectively enrolled. Two radiologists assessed all preoperative magnetic resonance images with T1, T2, and diffusion-weighted imaging, and determined the location of the deepest invasion of the tumor. The peritumoral zone was defined as a 5-mm-thick zone surrounding and adjacent to the cancerous endometrium. The mean ADC (ADCm) values of the tumor and the peritumoral zone were measured. Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristic curve (Az) were calculated for visual inspection, and an ADC cutoff value for the peri-endometrial zone was determined for predicting the myometrial invasion depth.ResultsThe ADCm values of tumors and peritumoral zones were 0.83 × 10− 3 mm2/sec and 1.06 × 10− 3 mm2/sec, respectively. There was no significant difference between the ADCm values of the tumors in the superficial and deep myometrial invasion groups (P > 0.05). However, the ADCm value at the peritumoral zone in the deep myometrial invasion group (1.23 × 10− 3 mm2/sec) significantly differed from that in the superficial myometrial invasion group (0.99 × 10− 3 mm2/sec) (p = 0.005). In assessments of deep myometrial invasion, the sensitivity, specificity, negative predictive value, and positive predictive value were 0.58, 0.93, 0.84, and 0.77, respectively, for the ADCm cutoff value of the peritumoral zone, and 0.71, 0.80, 0.87, and 0.60. respectively, for visual inspection. The accuracy of myometrial invasion depth assessment using the ADCm cutoff value and visual inspection were 83 and 78%, respectively. The Az for both was 0.76.ConclusionADCm at the peritumoral zone can predict deep myometrial invasion of endometrial cancer. This value can therefore enhance confidence in preoperative endometrial cancer evaluation, and when tailoring surgical approaches.

Multidisciplinary Approach in Large-sized Submucosal Myoma: Hysteroscopic Myomectomy after Uterine Artery Embolization

To evaluate the safety and effectiveness of hysteroscopic myomectomy after uterine artery embolization (UAE) for the treatment of large-sized submucosal myomas with deep intramural invasion that are difficult to treat with 1-step hysteroscopy. A retrospective cohort study (Canadian Task Force classification II-2). An academic university hospital. Eight premenopausal patients with symptomatic submucosal myomas with intramural invasion. All of the patients after bilateral UAE underwent subsequent hysteroscopic operation 3 to 15 months after UAE. A total of 8 patients who had a large-sized submucosal myoma with deep myometrial invasion were included. The average volume of the submucosal myomas was 87.7±39.9 cm3 as confirmed by magnetic resonance imaging, and the average patient age was 37.6 years. The mean volume reduction of the submucosal myomas was 83.3±16.4% after UAE, and no immediate complications were observed. One-step hysteroscopic myomectomy after UAE was successfully performed in all patients. Leiomyomas with hyaline degeneration were pathologically confirmed. All women showed improved symptoms, and there was no evidence of recurrence 1 year later. One patient conceived naturally and delivered a full-term baby. In premenopausal women with large-sized symptomatic submucosal myomas with deep myometrial invasion, hysteroscopic myomectomy after UAE is very effective and safe.

Uterine Carcinosarcoma with Alpha-Fetoprotein-Producing Hepatoid Component: A Case Report and Literature Review

A 67-year-old woman presented with postmenopausal vaginal bleeding. Full body imaging demonstrated an intrauterine mass with deep myometrial invasion but no nodal or other metastatic disease. Uterine curettage was performed. Histologically, the tumor was an endometrioid adenocarcinoma with sarcomatous element and a hepatoid component, the latter was immunohistochemically positive for alpha-fetoprotein, HepPar-1, and arginase-1. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Serum alpha-fetoprotein level decreased from 31896 ug/l preoperatively to 2063 ug/l postoperatively. Eight weeks later, a rise in serum alpha-fetoprotein was detected, and a biopsy-proven vaginal recurrence was diagnosed. Palliative chemotherapy led to tumor shrinkage and a concurrent decrease in the serum alpha-fetoprotein level. A rise in serum alpha-fetoprotein, refractory to second-line chemotherapy, was accompanied by subsequent development of ureteric obstruction, ascites, and radiological evidence of peritoneal metastases. This is an unusual case of uterine carcinosarcoma with an alpha-fetoprotein-producing hepatoid adenocarcinoma component. Serum alpha-fetoprotein level corresponds to disease recurrence and progression.