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The main aim is to compare oncological outcomes and patterns of recurrence of patients with early-stage endometrioid endometrial cancer according to lymphovascular space invasion (LVSI) status. The secondary objective is to determine preoperative predictors of LVSI. We performed a multicenter retrospective cohort study. A total of 3546 women diagnosed with postoperative early-stage (FIGO I-II, 2009) endometrioid endometrial cancer were included. Co-primary endpoints were disease-free survival (DFS), overall survival (OS), and pattern of recurrence. Cox proportional hazard models were used for time-to-event analysis. Univariate and multivariate logistical regression models were employed. Positive LVSI was identified in 528 patients (14.6%) and was an independent prognostic factor for DFS (HR 1.8), OS (HR 2.1) and distant recurrences (HR 2.37). Distant recurrences were more frequent in patients with positive LVSI (78.2% vs. 61.3%, p < 0.01). Deep myometrial invasion (OR 3.04), high-grade tumors (OR 2.54), cervical stroma invasion (OR 2.01), and tumor diameter ≥ 2 cm (OR 2.03) were independent predictors of LVSI. In conclusion, in these patients, LVSI is an independent risk factor for shorter DFS and OS, and distant recurrence, but not for local recurrence. Deep myometrial invasion, cervical stroma invasion, high-grade tumors, and a tumor diameter ≥ 2 cm are independent predictors of LVSI.

Purpose: To predict deep myometrial infiltration (DMI), clinical risk category, histological type, and lymphovascular space invasion (LVSI) in women with endometrial cancer using machine learning classification methods based on clinical and image signatures from T2-weighted MR images. Methods: A training dataset containing 413 patients and an independent testing dataset consisting of 82 cases were employed in this retrospective study. Manual segmentation of the whole tumor volume on sagittal T2-weighted MRI was performed. Clinical and radiomic features were extracted to predict: (i) DMI of endometrial cancer patients, (ii) endometrial cancer clinical high-risk level, (iii) histological subtype of tumor, and (iv) presence of LVSI. A classification model with different automatically selected hyperparameter values was created. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, F1 score, average recall, and average precision were calculated to evaluate different models. Results: Based on the independent external testing dataset, the AUCs for DMI, high-risk endometrial cancer, endometrial histological type, and LVSI classification were 0.79, 0.82, 0.91, and 0.85, respectively. The corresponding 95% confidence intervals (CI) of the AUCs were [0.69, 0.89], [0.75, 0.91], [0.83, 0.97], and [0.77, 0.93], respectively. Conclusion: It is possible to classify endometrial cancer DMI, risk, histology type, and LVSI using different machine learning methods.

Introduction: The clinical role of the molecular endometrial cancer (EC) classification has not been fully explored in patients staged with lymphadenectomy or without adjuvant treatment, conditions that could potentially moderate the prognostic value of the classification. We aimed to evaluate the clinical outcome of the molecular subgroups in patients with high-grade EC staged by lymphadenectomy and those without adjuvant treatment.Methods: DNA-sequencing for the detection of pathogenic POLE-exonuclease domain mutations and immunohistochemistry for mismatch repair (MMR) proteins and p53 expression were performed on 412 high-grade EC from the Danish Gynaecological Cancer Database (2005-2012) to classify them as POLE-ultramutated (POLEmut), MMR-deficient (MMRd), p53-mutant (p53abn), or no specific molecular profile (NSMP). Patients with stage IV or residual disease after surgery were excluded. Kaplan-Meier method, log-rank test and Cox proportional hazard models were used for analysis.Results: Molecular analysis was successful in 367 EC; 251 patients had undergone lymphadenectomy. Five-year recurrence rates in this subgroup of patients was 36.7% for women with p53abn EC, 0.0% for POLEmut EC, 13.4% for MMRd EC and 42.9% for NSMP EC (p < 0.001). Similar results were observed among stage IA-IB patients. Among patients without adjuvant treatment (n = 264), none with POLEmut EC (n = 26) had a recurrence.Conclusion: The molecular EC classification has strong prognostic value, independent of clinicopathological factors, also among high-grade EC patients staged by lymphadenectomy and those without adjuvant treatment. The unfavourable prognosis of early-stage p53abn EC is not due to undetected lymph node metastasis, and the indolent behaviour of POLEmut EC is independent of adjuvant treatment.

Background: We investigated whether there was a difference in prognosis between patients with stage IA endometrial cancer with and without lymphovascular space invasion. Methods: We enrolled patients with stage IA (pT1aN0M0) endometrial cancer admitted to our hospital from 2009 to 2018. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy. We immunopathologically evaluated the presence or absence of lymphovascular space invasion in the tumor tissue using hematoxylin and eosin, Elastica-van Gieson, and podoplanin staining. We analyzed disease-free and overall survival and calculated patients’ survival distribution using the Kaplan–Meier method and log-rank test. The multivariate analysis was performed to determine the prognostic factors. Results: A total of 116 patients were included. The median age of the patients was 57 (range, 30–78) years, and the histological subtype revealed 98 and 18 cases of types 1 and 2, respectively. The median follow-up period was 71.9 (range, 10.8–149) months, and the 3-year disease-free and 3-year overall survival rates were 94% and 99%, respectively. The disease-free and overall survival rates were significantly shorter in type 2 patients than in type 1 patients (type 2 vs. type 1; 77% vs. 97%, P < 0.01, 94% vs. 100%, P = 0.014, respectively). The univariate and multivariate analyses showed that there were no significant differences in disease-free survival between the lymphovascular space invasion-positive and -negative groups among type 1 cases. Conclusion: There was no difference in prognosis between patients with stage IA and type 1 endometrial cancer with and without lymphovascular space invasion.

Background Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients. Methods The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset. Results We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status. Conclusion In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.

Objective: This study assessed the predictive value of the metabolic risk score (MRS) for lymphovascular space invasion (LVSI) in endometrial cancer (EC) patients. Methods: We included 1076 patients who were diagnosed with EC between January 2006 and December 2020 in Peking University People’s Hospital. All patients were randomly divided into the training and validation cohorts in a ratio of 2:1. Data on clinicopathological indicators were collected. Univariable and multivariable logistic regression analysis was used to define candidate factors for LVSI. A backward stepwise selection was then used to select variables for inclusion in a nomogram. The performance of the nomogram was evaluated by discrimination, calibration, and clinical usefulness. Results: Independent predictors of LVSI included differentiation grades (G2: OR = 1.800, 95% CI: 1.050–3.070, p = 0.032) (G3: OR = 3.49, 95% CI: 1.870–6.520, p < 0.001), histology (OR = 2.723, 95% CI: 1.370–5.415, p = 0.004), MI (OR = 4.286, 95% CI: 2.663–6.896, p < 0.001), and MRS (OR = 1.124, 95% CI: 1.067–1.185, p < 0.001) in the training cohort. A nomogram was established to predict a patient’s probability of developing LVSI based on these factors. The ROC curve analysis showed that an MRS-based nomogram significantly improved the efficiency of diagnosing LVSI compared with the nomogram based on clinicopathological factors (p = 0.0376 and p = 0.0386 in the training and validation cohort, respectively). Subsequently, the calibration plot showed a favorable consistency in both groups. Moreover, we conducted a decision curve analysis, showing the great clinical benefit obtained from the application of our nomogram. However, our study faced several limitations. Further external validation and a larger sample size are needed in future studies. Conclusion: MRS-based nomograms are useful for predicting LVSI in patients with EC and may facilitate better clinical decision-making.

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC). Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis. Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the “LVSI index” as “TD×%MMI×tumor grade×cervical stromal involvement.” The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200. Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.

The endoscopic approach for early-stage endometrial cancer (EC) treatment is considered gold standard. Some authors expressed their concern regarding uterine manipulator (UM) as a risk factor for tumor spillage and dissemination allowing peritoneal or lympho-vascular spaces invasion (LVSI). This meta-analysis aimed to evaluate the effect of UM on the presence of LVSI, recurrence rate and presence of atypical or malignant peritoneal cytology in patients with endometrial cancer.We searched electronic databases including PubMed, MEDLINE, Embase, Scopus, EBSCO, Google Scholar, and ClinicalTrials.gov. The pooled results were used to evaluate the association between the use of UM and oncological outcomes. This systematic review was reported according to PRISMA statement 2020. Statistical meta-analysis was performed using Review Manager software.This systematic review included 18 studies (3 prospective studies, 13 retrospective studies, and 2 RCT). The pooled results showed no significant difference (RR: 0.86, 95% CI, 0.69 to 1.08) in the incidence of LVSI between manipulated hysterectomy and total abdominal hysterectomy (TAH) and between UM group and non-UM group in minimally invasive surgery (RR: 1.18, 95% CI, 0.76 to 1.85), no significant difference in the rate of recurrence (RR: 1.11, 95% CI, 0.71 to 1.74), in the incidence of positive peritoneal cytology between manipulated and non-manipulated hysterectomies in minimally invasive surgery (RR: 1.89, 95% CI, 0.74 to 4.83) and before and after the use of uterine manipulator (RR: 1.21, 95% CI, 0.68 to 2.16). We found a positive association between malignant cytology and hysterectomies in which a uterine manipulator had been used in a sub-group analysis where LH/LAVH were compared to TAH. (RR = 2.26, 95% CI, 1.08-4.71. P = 0.03).This meta-analysis supports that the use of uterine manipulator for minimally invasive treatment of endometrial cancer does not increase the rate of recurrence and LVSI. Therefore, the opportunity of any other studies on its use in endometrial cancer women should be questioned.

BACKGROUND Some clinicopathological features play roles in the spread of breast cancer to axillary lymph node (ALN). However, their roles as predictive factors are not well-established. This study was conducted to determine the correlation between the clinicopathological features of breast cancer and the risk of ALN involvement in Indonesian women. METHODS This cross-sectional study was conducted in Margono Soekarjo Hospital using archival data from January 2017 to June 2018. All subjects with breast cancer who had undergone modified radical mastectomies without any evidence of distant metastasis were included. Chi-square and Fisher’s exact tests were performed to assess the relationship between ALN involvement and age, menopausal status, laterality, tumor size, tumor stage, histological type, tumor grade, lymphovascular space invasion (LVSI), skin or nipple infiltration, perineural invasion, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. The odds ratio of each variable was evaluated using ordinal regression analysis. RESULTS Stage 3 breast cancer had the worst status of ALN involvement compared with stage 1 (OR = 3.49; 95% CI = 1.51–8.08) and stage 2 (OR = 3.04; 95% CI = 1.32–6.98). Likewise, positive LVSI also had the worst status of ALN involvement compared with negative LVSI (OR = 8.68; 95% CI = 4.23–17.81). CONCLUSIONS Tumor stage and LVSI could be considered as independent predictive factors of ALN involvement in patients with breast cancer, especially among Indonesian women.

BackgroundDetection of lymphovascular space invasion (LVSI) in early cervical cancer (CC) is challenging. To date, no standard clinical markers or screening tests have been used to detect LVSI preoperatively. Therefore, non-invasive risk stratification tools are highly desirable.ObjectiveTo train and validate a multi-parametric magnetic resonance imaging (mpMRI)-based radiomics model to detect LVSI in patients with CC and investigate its potential as a complementary tool to enhance the efficiency of risk assessment strategies.Materials and MethodsThe model was developed from the tumor volume of interest (VOI) of 125 patients with CC. A total of 1037 radiomics features obtained from conventional magnetic resonance imaging (MRI), including a small field-of-view (sFOV) high-resolution (HR)-T2-weighted MRI (T2WI), apparent diffusion coefficient (ADC), T2WI, fat-suppressed (FS)-T2WI, as well as axial and sagittal contrast-enhanced T1-weighted MRI (T1c). We conducted a radiomics-based characterization of each tumor region using pretreatment image data. Feature selection was performed using the least absolute shrinkage and selection operator method on the training set. The predictive performance was compared with single variates (clinical data and single-layer radiomics signatures) analyzed using a receiver operating characteristic (ROC) curve. Three-fold cross-validation performed 20 times was used to evaluate the accuracy of the trained classifiers and the stability of the selected features. The models were validated by using a validation set.ResultsFeature selection extracted the six most important features (3 from sFOV HR-T2WI, 1 T2WI, 1 FS-T2WI, and 1 T1c) for model construction. The mpMRI-combined radiomics model (area under the curve [AUC]: 0.940) reached a significantly higher performance (better than the clinical parameters [AUC: 0.730]), including any single-layer model using sFOV HR-T2WI (AUC: 0.840), T2WI (AUC: 0.770), FS-T2WI (AUC: 0.710), ADC maps (AUC: 0.650), sagittal, and axial T1c values (AUC: 0.710, 0.680) in the validation set.ConclusionBiomarkers using multi-parametric radiomics features derived from preoperative MR images could predict LVSI in patients with CC.

Objective: Lymph node metastasis (LNM) is the most important factor affecting survival in early-stage cervical cancer (CC). International Federation of Gynecology and Obstetrics revised the staging of CC in 2018 and reported LNM as a staging criterion. We investigated the preoperatively assessable risk factors associated with LNM in surgically treated stage IB1-IIA2 CC patients. Materials and Methods: This was a retrospective cohort study of women who underwent radical hysterectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy for CC stage IB1-IIA2 from 2004 to 2019. All patients included in this study were examined with speculum inspection, parametrial assessment by rectovaginal palpation under general anesthesia, transvaginal ultrasonography, magnetic resonance imaging (MRI), and chest radiography. Clinical staging was done according to the preoperative findings. MRI was used to measure tumor and lymph node dimensions. Results: Out of the 149 women included in the study, 29 (19.4%) had LNM. Univariate analysis revealed that larger tumor size (≥30 mm), lymphovascular space invasion (LVSI) detected with diagnostic biopsy, parametrial involvement, and deep stromal invasion status were significantly different between the group with LNM and the group without LNM. In multivariate analysis, specific preoperative risk factors such as MRI based tumor diameter ≥30 mm and LVSI (+) on the diagnostic biopsy were found to be independent risk factors for LNM in the multivariate analysis. Conclusion: The rate of LNM is high in patients with CC with a tumor size ≥30 mm and preoperative biopsy LVSI status even if they are clinically in early stages. Surgeons can take this into account while deciding between primary surgery and chemoradiotherapy in the treatment of CC. WOS:000908434300015 36412408 Q4

International audience; BACKGROUND: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on overall survival (OS) and recurrence-free survival (RFS) in patients managed for stage I-IIa clear cell carcinoma, mucinous, low-grade serous and low-grade endometrioid ovarian cancer MATERIAL AND METHODS: Retrospective multicentre study of the research group FRANCOGYN between January 2001 and December 2018. All patients managed for stage I-IIa clear cell carcinoma, mucinous /low grade serous and endometrioid ovarian cancer and for whom the presence of histological slides for the review of LVSI was available, were included. Patient’s characteristics with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A cox analysis for OS and RFS analysis were performed in all population. RESULTS: Over the study period, 133 patients were included in the thirteen institutions. Among them, 12 patients had LVSI (9%). LVSI was an independent predictive factor for poorer Overall and recurrence free survivals. LVSI affected OS (p

BackgroundMyometrial invasion has been demonstrated to correlate to clinicopathological characteristics and prognosis in endometrial cancer. However, not all the studies have the consistent results and no meta-analysis has investigated the association of myometrial invasion with lymphovascular space invasion (LVSI), lymph node metastasis (LNM), recurrence, and overall survival (OS). Therefore, a meta-analysis was performed to evaluate the relationship between myometrial invasion and clinicopathological characteristics or overall survival in endometrial cancer.Materials and MethodsA search of Pubmed, Embase, and Web of Science was carried out to collect relevant studies from their inception until June 30, 2021. The quality of each included study was evaluated using Newcastle–Ottawa scale (NOS) scale. Review Manager version 5.4 was employed to conduct the meta-analysis.ResultsA total of 79 articles with 68,870 endometrial cancer patients were eligible including 9 articles for LVSI, 29 articles for LNM, 8 for recurrence, and 37 for OS in this meta-analysis. Myometrial invasion was associated with LVSI (RR 3.07; 95% CI 2.17–4.35; p < 0.00001), lymph node metastasis (LNM) (RR 4.45; 95% CI 3.29–6.01; p < 0.00001), and recurrence (RR 2.06; 95% CI 1.58–2.69; p < 0.00001). Deep myometrial invasion was also significantly related with poor OS via meta-synthesis of HRs in both univariate survival (HR 3.36, 95% CI 2.35–4.79, p < 0.00001) and multivariate survival (HR 2.00, 95% CI 1.59–2.53, p < 0.00001). Funnel plot suggested that there was no significant publication bias in this study.ConclusionDeep myometrial invasion correlated to positive LVSI, positive LNM, cancer recurrence, and poor OS for endometrial cancer patients, indicating that myometrial invasion was a useful evaluation criterion to associate with clinical outcomes and prognosis of endometrial cancer since depth of myometrial invasion can be assessed before surgery. The large scale and comprehensive meta-analysis suggested that we should pay more attention to myometrial invasion in clinical practice, and its underlying mechanism also deserves further investigation.

Background: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) was carried out. Patients with IA to IB2 2018 FIGO stage, who underwent preoperative conization before SLN biopsy were included. Results: Between January 2005 and July 2012, 161 patients from 25 French centers fulfilled the inclusion criteria. Macrometastases, micrometastases and Isolated tumor cells (ITCs) were found in 4 (2.5%), 6 (3.7%) and 5 (3.1%) patients respectively. Compared to negative SLN patients, patients with micrometastatic and macrometastatic SLN were more likely to have lymphovascular space invasion (LVSI) (60% vs. 29.5%, p = 0.04) and deep stromal invasion (DSI) ≥ 10 mm (50% vs. 17.8%, p = 0.04). Among the 93 patients with DSI &lt, 10 mm and absence of LVSI on conization specimens, three patients (3.2%) had ITCs and only one (1.1%) had micrometastases. Conclusions: Patients with DSI &lt, 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection.

Background Lymphovascular space invasion is an independent prognostic factor in early-stage cervical cancer. However, there is a lack of non-invasive methods to detect lymphovascular space invasion. Some researchers found that Tenascin-C and Cyclooxygenase-2 was correlated with lymphovascular space invasion. Radiomics has been studied as an emerging tool for distinguishing tumor pathology stage, evaluating treatment response, and predicting prognosis. This study aimed to establish a machine learning model that combines radiomics based on PET imaging with tenascin-C (TNC) and cyclooxygenase-2 (COX-2) for predicting lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer. Methods One hundred and twelve patients with early-stage cervical squamous cell carcinoma who underwent PET/CT examination were retrospectively analyzed. Four hundred one radiomics features based on PET/CT images were extracted and integrated into radiomics score (Rad-score). Immunohistochemical analysis was performed to evaluate TNC and COX-2 expression. Mann-Whitney U test was used to distinguish differences in the Rad-score, TNC, and COX-2 between LVSI and non-LVSI groups. The correlations of characteristics were tested by Spearman analysis. Machine learning models including radiomics model, protein model and combined model were established by logistic regression algorithm and evaluated by ROC curve. Pairwise comparisons of ROC curves were tested by DeLong test. Results The Rad-score of patients with LVSI was significantly higher than those without. A significant correlation was shown between LVSI and Rad-score (r = 0.631, p r = 0.244, p = 0.024) and COX-2 (r = 0.227, p = 0.036). The radiomics model had the best predictive performance among all models in training and external dataset (AUCs: 0.914, 0.806, respectively, p Conclusion The machine learning model of the combination of PET radiomics with COX-2 and TNC provides a new tool for detecting LVSI in patients with early-stage cervical cancer. In the future, multicentric studies on larger sample of patients will be used to test the model. Trial registration This is a retrospective study and there is no experimental intervention on human participants. The Ethics Committee has confirmed that retrospectively registered is not required.

International audience; BACKGROUND: The aim of this study was to evaluate the impact of Lymphovascular Space Invasion (LVSI) on Overall Survival (OS) and Recurrence-Free Survival (RFS) in patients managed for high-grade serous epithelial ovarian cancer (HGSOC). MATERIALS AND METHODS: Retrospective multicenter study by the FRANCOGYN research group between January 2001 and December 2018. All patients managed for HGSOC and for whom histological slides for the review of LVSI were available, were included. The characteristics of patients with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A Cox analysis for OS and RFS analysis was performed in all populations. RESULTS: Over the study period, 410 patients were included in the thirteen institutions. Among them, 289 patients had LVSI (33.9%). LVSI was an independent predictive factor for poorer Overall and Recurrence-Free Survival. LVSI affected OS (p

Simple Summary The purpose of modifying a tumor staging system is to incorporate already well-established prognostic factors, allowing one to stratify cases and leading to tailored treatment approaches. Although lymphovascular space invasion (LVSI) has been described as an independent risk-factor of recurrence in early-stage cervical cancer and defined intermediate and high-risk cervical cancer according to the ESGO (European Society of Gynaecological Oncology) guidelines, this factor remains controversial and was not included in the last revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification. The aim of the present study was to determine whether LVSI has an impact on the prognosis of IB1 patients according to 2018 FIGO classification through two French prospective multicentric cohorts. Our results highlighted that LVSI was associated with a significantly decreased 5-year DFS in IB1 2018 FIGO stage compared to negative LVSI. Particular attention should be paid to LVSI status in early-stage cervical cancer for a more precise risk assessment and we suggest that LVSI may be considered in the new 2018 FIGO classification. Abstract Background: The aim of this study was to assess the prognostic impact of Lymphovascular space invasion (LVSI) in IB1 stage of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification for cervical cancer. Methods: A secondary analysis of two French prospective multicentric trials on Sentinel Lymph node biopsy for cervical cancer was performed. Patients with 2009 FIGO IB1 stage who underwent radical surgery between January 2005 and July 2012 from 28 French expert centers were included. The stage was modified retrospectively according to the new 2018 FIGO staging system. Results: According to the 2009 FIGO classification, 246 patients had IB1 disease stage and fulfilled the inclusion criteria. The median follow-up was 48 months (4–127). Twenty patients (8.1%) experienced a recurrence, and the 5-year Disease Free Survival (DFS) was 90.0%. Compared to 2018 IB1 staged patients, new IB2 had significantly decreased 5-year DFS, 78.6% vs. 92.9%, p = 0.006 whereas IIIC patients had similar 5-year DFS (91.7%, p = 0.95). In the subgroup of patients with FIGO 2018 IB1 stage, the presence of LVSI was associated with a significant decrease in DFS (82.5% vs. 95.8%, p = 0.04). Conclusions: LVSI is associated with decreased 5-year DFS in IB1 2018 FIGO stage and LVSI status should be considered in early-stage cervical cancer for a more precise risk assessment.

Introduction: Breast cancer is the commonest cancer among women in India and the leading cause of cancer related deaths. In patients with invasive breast cancer, axillary nodal metastasis remains as the most important predictive factor for recurrence and survival, despite progression made in molecular and genetic characterisation of these cancers. Aim: To know the nodal positivity rate and pathologic predictive factors of nodal positivity in early breast cancer in Indian patients, which may help in predicting the axillary status pre-operatively. Materials and Methods: This study was retrospective review of patients treated in Cancer Institute, Chennai, Tamil Nadu, India between January 2011 to October 2014 for invasive breast cancer which were clinical T1 and T2 and either N0 or N1. Pathologic characteristics of the primary tumour such as size, centricity, histological type, nuclear grade, and Lympho Vascular Invasion (LVSI), Estrogen receptor (ER) and Progesterone Receptor (PR) Status, Human Epidermal growth factor Rector 2 (HER-2)/neu and Ki-67 were analysed and correlated to nodal positivity using univariate and multivariate analysis. Results: In the univariate analysis using chi-square test, Pathological T stage, number of tumours, LVSI, ER and PR status emerged as significant variables. Variables like pT2 (p-0.032), multiple tumours (p-0.007), LVI (p

Wprowadzenie: Celem pracy jest ocena związku między wiekiem chorych na raka endometrium (RE) a występowaniem niekorzystnych, mikroskopowych i klinicznych czynników prognostycznych choroby. Materiał i metody: Analiza retrospektywna materiału klinicznego obejmującego 128 chorych na raka trzonu macicy, leczonych pierwotnie chirurgicznie w krakowskim Oddziale Centrum Onkologii w latach 2012–2014. Głównym źródłem informacji były historie chorób z archiwum COOK. Badanie czasu przeżycia zakończono w maju 2020 r. Stopień zaawansowania procesu nowotworowego oceniano zgodnie z klasyfi - kacją FIGO 2009. Do oceny statystycznej wyników skorzystano z testu Shapiro-Wilka oraz testu Manna-Whitney’a, a na wykresie przedstawiono mediany, kwartyle oraz zakresy wartości poszczególnych zmiennych. Do oceny przeżyć wolnych od wznowy użyto metody Kaplana-Meyera. Wyniki: Średnia wieku chorych wyniosła 63,9 lata, mediana – 65 lat. Rokowanie w całej grupie chorych było bardzo dobre, odsetek 3-letnich przeżyć wolnych od wznowy wyniósł 91,57%, a 5-letnich – 88,3%. Średnia i mediana wieku chorych z negatywnymi czynnikami prognostycznymi była wyższa niż u chorych pozbawionych tych czynników. Wnioski: Można stwierdzić, że najistotniejsze z prognostycznego punktu widzenia jest w RE współwystępowanie różnych czynników populacyjnych, klinicznych i mikroskopowych. Obecnie uważa się, że czynniki molekularne mają kluczowe znaczenie w prognozie chorych na RE, jednak wiek jest ciągle istotnym klinicznie elementem służącym prognozowaniu i planowaniu leczenia chorych na RE. Introduction: The aim of this paper is to assess the relationship between the age of patients with endometrial cancer and the occurrence of unfavorable microscopic and clinical prognostic factors concerning the disease. Materials and methods: A retrospective analysis of clinical material from 128 patients with endometrial cancer, who were initially treated surgically in the Center of Oncology (Cracow Branch) between 2012 and 2014, was carried out. The main source of information was medical records in the COOK archive. A survival time study was completed in May 2020. The stage of the neoplastic process was assessed according to the FIGO 2009 classifi cation system. The results were statistically evaluated using the Shapiro-Wilk test and the Mann-Whitney test, and the graph shows the medians, quartiles and ranges of values or individual variables. The Kaplan-Meyer method was used to assess the relapsefree survival rate. Results: The mean age of the patients was 63.9 years and the median was 65 years. The prognosis in the whole group of patients was very good, the 3-year relapse- free survival rate was 91.57%, and 5-years – 88.3%. The mean and median age of patients with negative prognostic was higher than in patients without these factors. Conclusion: It seems that from a prognostic point of view the most important factor in endometrial cancer is the coexistence of various population, clinical and microscopic factors. It is now considered that it is molecular factors that are of key importance in the prognosis of endometrial cancer patients. However age should be treated still as clinically important element in the prognosis and treatment planning of patients with endometrial cancer.

Histopathological evaluation including subtyping and grading is the current cornerstone for endometrial cancer (EC) classification. This provides clinicians with prognostic information and input for further treatment recommendations. Nonetheless, patients with histologically similar ECs may have very different outcomes, notably in patients with high-grade endometrial carcinomas. For endometrial cancer, four molecular subgroups have undergone extensive studies in recent years: POLE ultramutated (POLEmut), mismatch repair-deficient (MMRd), p53 mutant (p53abn) and those EC lacking any of these alterations, referred to as NSMP (non-specific molecular profile). Several large studies confirm the prognostic relevance of these molecular subgroups. However, this 'histomolecular' approach has so far not been implemented in clinical routine. The ongoing PORTEC4a trial is the first clinical setting in which the added value of integrating molecular parameters in adjuvant treatment decisions will be determined. For diagnostics, the incorporation of the molecular parameters in EC classification will add a level of objectivity which will yield biologically more homogeneous subclasses. Here we illustrate how the management of individual EC patients may be impacted when applying the molecular EC classification. We describe our current approach to the integrated diagnoses of EC with a focus on scenarios with conflicting morphological and molecular findings. We also address several pitfalls accompanying the diagnostic implementation of molecular EC classification and give practical suggestions for diagnostic scenarios.

Background The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer. Methods Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases. Results We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer. Conclusions Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

Background and Objectives To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI. Methods This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome. Results LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047). Conclusion LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma.

Objective: This article shows our experience on sentinel lymph node (SLN) biopsy in early-stage cervical carcinoma since the technique was introduced in our Institution. The main objective is to analyze the detection rate (DR) of metastatic SLNs, identifying prognostic factors for an increased risk of nodal metastases. Our second aim was to compare the accuracy of nodal metastases DR between intraoperative analysis and postoperative ultrastaging. Materials and Methods: Forty-one women with the International Federation of Gynecology and Obstetrics stages IA2-IIA1 who underwent laparoscopic surgical treatment applying the SLN technique, from December 2011 to June 2016, at La Paz University Hospital, were included. The sentinel node was identified using technetium and methylene blue dye or indocyanine green near-infrared fluorescent imaging, analyzed intraoperatively, and compared to deferred ultrastaging. Results: SLN DR was 100%, with a bilaterality rate of 83%. Twelve (26.8%) patients had metastatic nodes, 11 of them (91.7%) detected by SLN technique, of which 9 (81.8%) had only the sentinel node affected. False-negative rate was 2.4% after ultrastaging procedure. Metastatic SLN detection with ultrastaging was 45.5% higher than the intraoperative analysis, 63.6% of which had low tumor burden. The global detection of patients with nodal metastases after SLN technique was 21.9% higher than pelvic lymphadenectomy. Conclusions: Our preliminary results corroborate that SLN biopsy selectively maps metastatic nodes and ultrastaging increases the detection of metastatic SLNs, predominantly due to low tumor burden.

// Jun Li 1, 2 , Shufen Li 3 , Ruifang Chen 1, 2 , Xin Lu 1, 2 1 Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China 2 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China 3 State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Correspondence to: Xin Lu, email: xinludoc@163.com Keywords: ovarian cancer, lymphovascular space invasion, SNAI2, prognosis, survival Received: October 22, 2016 Accepted: November 24, 2016 Published: December 25, 2016 ABSTRACT This study is aimed to conduct a meta-analysis to evaluate the prognostic value of lymphovascular space invasion(LVSI) and to explore the potential association of SNAI1 and SNAI2 with LVSI in ovarian cancer. A systematic literature search in PubMed, ISI Web of Science, and Medline was conducted to identify relevant studies assessing the prognostic value of LVSI in ovarian cancer. The main outcomes analyzed were progression free survival/disease free survival and overall survival. TCGA database was used to explore the potential link of SNAI1 and SNAI2 with LVSI status. A total of 11 eligible studies enrolling 1817 patients were included for the meta-analysis. The overall analysis indicated that LVSI presence was associated with shorter duration of survival in ovarian cancer patients. Multivariate analysis indicated that both advanced stage and SNAI2 expression were associated with increased risk of LVSI presence. Survival analysis indicated that tumors with LVSI presence and high SNAI2 expression were significantly correlated with poorer survival when compared to tumors with both LVSI absence and low SNAI2 expression. In conclusion, LVSI presence was associated with worse clinical outcomes in ovarian cancer. Increased expression of SNAI2 and advanced stage were independent risk factors for LVSI presence. Our findings also emphasizes the potential of SNAI2 in promoting lymphovascular spread of ovarian cancer.

OBJECTIVE This study aims to analyze factors associated with lymphovascular space invasion (LVSI) and evaluate the prognostic significance of LVSI in Chinese endometrioid endometrial cancer (EEC) patients. METHODS Five-hundred eighty-four EEC patients undergoing surgery in our center from 2006 to 2016 were selected for analysis. Univariate analysis and multivariate logistic regression were used to examine relevant factors of LVSI. To evaluate the prognostic role of LVSI, survival analyses were conducted. In survival analyses, both multivariate Cox regression and propensity score matching were used to control the confounders. RESULTS The incidence of LVSI was 12.16% (71/584). Diabetes history (p=0.021), lymph node metastasis (p=0.005), deep myometrial invasion (p

Supplemental Digital Content is available in the text, The metastasis of cervical carcinoma is associated with the lymphovascular spread. The primary objective of the present study was to determine the prognostic value of lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer in Jilin, China. In this retrospective cohort study, patients with early-stage cervical cancer (stage IB-IIA) at the Second Hospital of Jilin University from February 2014 to December 2016 were included in the analysis. All included participants underwent radical hysterectomy with pelvic lymphadenectomy. LVSI was identified by hematoxylin and eosin (H&E) staining. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Kaplan–Meier curves were used to calculate the patient's survival. Survival was compared using the log-rank test, while risk factors for the prognosis were assessed by Cox regression analysis. The incidence of LVSI was positively associated with the depth of stromal invasion (P = .009) and lymph node metastasis (LNM, P

Synopsis: Lymphovascular space invasion is an independent risk factor for disease progression and presence of tumor stalk an independent protective factor. Fertility sparing surgery may be acceptable in cases whose tumors present with stalks and without high risk factors. Objectives: The aim of the present study was to investigate the potential prognostic factors of uterine adenosarcoma. Methods: A total of 49 cases of uterine adenosarcoma were retrospectively reviewed at our institution between April 2006 and October 2018. Results: Median follow-up time was 34 months (range: 1–148). Median age was 47.50 years (19–75). Nineteen (38.9%) patients were uterine cervical adenosarcoma and 30 (61.22%) patients were uterine corpus adenosarcoma. Twenty-nine (59.2%) patients were polypoid with a stalk to the uterine cervix or corpus. Twenty-six (38.8%) patients were stage IA. Fifteen (30.6%) patients showed sarcomatous overgrowth. Six (12.2%) patients displayed lymphovascular space invasion (LVSI). Four (8.16%) patients had heterologous elements. In univariate analysis, Disease-free-survival (DFS) was associated with tumor location, presence of tumor stalk, heterologous elements, LVSI. In multivariate analysis, presence of tumor stalk remained an independently protective factor for recurrence (HR = 0.088, P = 0.005), and LVSI a risk factor for recurrence (HR = 11.953, P = 0.002). Fertility-sparing surgery (FSS) was performed in seven stage IA patients. When patients of stage IA analyzed separately, FSS was not significant with the DFS or OS. Conclusions: Presence of tumor stalk remained an independently protective factor for recurrence. Along with adequate counseling, FSS may be acceptable in cases whose tumors present with stalks and without high risk factors.

Background: The aim of this study was to assess the impact of lymphovascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer (EC). Methods: Patients with EC referred to Imam Khomeini Hospital in Tehran were examined and enrolled over a 10-year period (2004 - 2015). The effect of LVSI on recurrence and overall survival was analyzed using the Kaplan-Meier and log-rank test methods. Results: A total of 160 patients with early stage EC were identified. Out of 160 women with EC, 135 (84.4%) underwent primary surgery. One hundred and twenty-one (76.2%) patients were not found to have LVSI, whereas 38 (23.8%) were found to have LVSI. Of the 38 patients with LVSI, 21 (55.3%) had endometrioid cell type tumor, 10 (26.3%) had serous, one (2.6%) had clear cell and six (15.8%) had adeno-squamous cell type tumor. Conclusion: The presence of LVSI represents a factor strongly associated with high risk of recurrence and poor survival in early stage EC. Patients with lower International Federation of Obstetrics and Gynecology (FIGO) stages may be at increased risk of recurrence and a poor overall survival if the pathological findings confirm the presence of LVSI. Thus, LVSI should be added to the traditional factors used to decide whether patients with early stage EC are at high risk of recurrence and adjuvant therapy planning. World J Oncol. 2016;7(4):70-74 doi: http://dx.doi.org/10.14740/wjon981w

Cyclooxygenase-2 (COX-2) is associated with carcinogenesis and tumor progression. The current study analyzed the effect of COX-2 expression in patients with invasive squamous cervical cancer. Tissue samples from 123 cervical cancer patients were collected for a retrospective analysis using immunohistochemistry (IHC) with an antibody against COX-2. The clinical and survival data of the patients were analyzed. Positive staining for COX-2 (defined as an immunoreactivity score of ≥4) was detected in 28 patients (23%), with significantly higher percentages of staining in tumor cells compared with peritumoral stroma cells (P

Background Circulating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive “liquid biopsy” biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients. The aim of our study was to evaluate the possible role of cfDNA and its integrity index as a complementary tool for endometrial cancer (EC) management. Methods Alu-quantitative real-time PCR (qPCR) analysis wasprformed on 60 serum samples from preoperative EC patients randomly recruited. Both cfDNA content and DNA integrity index were measured by qPCR-Alu115 (representing total cfDNA) and qPCR-Alu247 (corresponding to high molecular weight DNA) and correlated with clinicopathologic characteristics. Lymphovascular space invasion (LVSI) was detected by hematoxylin and eosin staining. In case of doubt, LVSI status was further evaluate by immunohistochemistry using anti-CD31 and anti-CD34 antibodies. Results Total cfDNA content significantly increases in high grade EC. A significant decrease of DNA integrity index was detected in the subset of hypertensive and obese high grade EC. Serum DNA integrity was higher in samples with LVSI. The ordinal regression analysis predicted a significant correlation between decreased integrity index values and hypertension specifically in tumors presenting LVSI. Conclusions Our study supports the utility of serum DNA integrity index as a noninvasive molecular biomarker in EC. We show that a correlation analysis between cfDNA quantitative and qualitative content and clinicopathologic features, such as blood pressure level, body mass index (BMI) and LVSI status, could represent a potential predictive signature to help stratification approaches in EC. Electronic supplementary material The online version of this article (doi:10.1186/s13046-018-0688-4) contains supplementary material, which is available to authorized users.

Object: To assess the effects of lymphovascular space invasion (LVSI) on cancer recurrence and survival in patients with primary epithelial ovarian cancer. Methods: A retrospective study was conducted of patients with stage I-IV primary epithelial ovarian cancer who underwent cytoreductive surgery. LVSI is defined as the presence of tumor cells within an endothelium-lined space, and the patients' pathologic slides were reevaluated by gynecological pathologists. Survival analysis was performed to compare risk factors. Results: A total of 492 patients were included in the analysis. The incidence of LVSI was 58.5% in our cohort (288 cases), and it was significantly associated with advanced stage, high-grade serous histology, high grade, and lymph node metastasis (P

WOS: 000423954800008 PubMed ID: 28890428 Objective: To investigate the association of microcystic, elongated, and fragmented (MELF) pattern of invasion with prognostic factors in endometrioid endometrial adenocarcinoma (EEA). Material and Methods: Stained tissue sections from 83 cases of EEA operated by the same gynecologic oncologist were reviewed to identify cases showing MELF-type invasion in this retrospective study. The association of MELF pattern with age, tumor grade, depth of myometrial invasion, and presence of lymphovascular space invasion (LVSI) was analyzed. Results: FIGO grade 2 and grade 1 tumors were evident in 53.0% and 38.6% of patients, respectively. Depth of myometrial invasion was = 50%) myometrial invasion (78.3% vs. 21.7%, p

Objective: Local surgical pathological factors that determine lymphovascular space invasion (LVSI) and LVSI impact on lymph node spread of tumor were investigated in Endometrial Cancer(EC). Material and Method: A total of 355 patients,systematic lymphadenectomy staging surgery performed between January 1993 and December 2012,diagnosed with stage 1A-IVB EC were included.Pathological data was obtained from the final pathology report.Staging was made according to FIGO 2009 criteria.Patients who had diagnosis of uterine sarcoma, tumors with component of sarcoma and patients with two primary tumors were excluded.LVSI was described as tumor cells or cell clusters that attached to vessel wall on hematoxylin and eosin(H&E)stain. Results: The average age of patients was 59 years and tumor size was 43.4mm.279 patients had tumor with endometrioid type and 120 of them had grade 3 tumor.LVSI was detected in 147(41.4%) patients.20 of patients didn’t have myometrial invasion while the tumor spread through serosa was detected on 11 patients.Cervical invasion was detected in 78 patients and there was also stromal invasion in 68 of them.Tumor spread out lymph nodes in 77 (21.7%) patients.Lymphatic invasion was at para-aortic region in 49 (13.8%) patients and in pelvic region in 64 patients (18%).Grade, depth of myometrial invasion,involvement of uterine serosa,cervical invasion and tumor size increased the existence of LVSI.However tumor type and age had no relation with LVSI.LVSI has been defining the tumor spread to lymph nodes.Lymph node metastasis was found in 38.8% of the patients who had LVSI compared to 9.6% of those without LVSI.When both regions (para-aortic and pelvic) were evaluated separately,LVSI was significant in terms of tumor metastasis. Conclusion: LVSI was observed in 40% of patients who were staged with diagnosis of EC and the spread of lymph node was present in 40% of these patients.It is clear that this parameter will play an important role in determining adjuvant therapy and surgery type.

International audience; Objective: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on nomogram-based predictions of lymph node (LN) metastasis in endometrial cancer. Methods: The data from 485 patients with presumed stage I or II endometrial cancer who underwent hysterectomy and lymphadenectomy were analyzed. Calibration curves were designed and compared for three different subgroups: LVSI-positive tumors (n = 113), LVSI-negative tumors (n = 213) and LVSI-undetermined tumors (n = 159). Results: In the entire population, the nomogram showed good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.80 and was well calibrated. In the subgroup analyses, in LVSI-positive, LVSI-negative and LVSI-undetermined patients, the nomogram was not well calibrated (p of the U index of 0.028, 0.087 and 0.011, respectively) with underestimation in LVSI-positive patients and overestimation in LVSI-negative and LVSI-undetermined patients of LN metastasis. In the univariate analysis and after adjusting for the LN metastasis probability provided by the nomogram, LVSI-positive tumors were associated with an increased risk for LN metastasis compared with LVSI-negative tumors (RR = 7.29 [3.87-13.7] and 5.04 [2.30-11.08], respectively). In contrast, the univariate analysis and after adjusting for the LN metastasis probability provided by the nomogram showed that LVSI-undetermined tumors were not associated with an increased risk for LN metastasis compared with LVSI-negative tumors (RR = 0.73 [0.32-1.69] and 1.26 [0.47-3.37], respectively). Conclusions: Our results suggested that LVSI should be considered to be an independent risk factor for LN metastasis. In this multicenter study, the risk for LN metastasis is similar when the LVSI is negative or is not detailed in the pathological report.

Objective: The purpose of this study was to assess survival and recurrence site and rate in patients with histological high grade endometrial cancer (grade 3 endometrioid and non endometrioid carcinoma) treated with staging surgery, which included pelvic lymphadenectomy without para aortic lymph node dissection. We have also looked at other histological factors within this group in relationship to survival. Methods: A total of 120 patients diagnosed with high grade endometrial cancer between August 2002 and December 2008 were included in the study. All of them underwent total abdominal (TAH) or laparoscopic assisted vaginal hysterectomy (LAVH) with bilateral salpingo oophorectomy (BSO), with pelvic lymphadenectomy, with or without omentectomy. Results: Pelvic lymph node positivity was noted in 37 patients (31%). The mean follow up was 47 months. Forty-four patients (37%) developed recurrence with a mean time to relapse of 20 months. The majority of the recurrences (77%) occurred in both the para aortic area and at distant sites. Among 44 patients with recurrence, 37 (84%) were lymphovascular invasion (LVSI) positive at primary histology as compared to 41 (54%) patients without recurrence with LVSI (p

Objective The aim of this study was to build a model to predict the risk of lymphovascular space invasion (LVSI) in women with endometrial cancer (EC). Methods From December 2010 to June 2013, 211 patients with EC undergoing surgery at Shanghai First Maternity and Infant Hospital were enrolled in this retrospective study. Those patients were divided into a positive LVSI group and a negative LVSI group. The clinical and pathological characteristics were compared between the two groups; logistic regression was used to explore risk factors associated with LVSI occurrence. The threshold values of significant factors were calculated to build a risk model and predict LVSI. Results There were 190 patients who were negative for LVSI and 21 patients were positive for LVSI out of 211 patients with EC. It was found that tumor grade, depth of myometrial invasion, number of pelvic lymph nodes, and International Federation of Gynecology and Obstetrics (FIGO) stage (p0.05) were not associated with LVSI. Receiver operating characteristic (ROC) curves revealed that the threshold values of the following factors were correlated with positive LVSI: 28.1 U/mL of CA19-9, 21.2 U/mL of CA125, 2.58 mg/dL of fibrinogen (Fn), 1.84 U/mL of carcinoembryonic antigen (CEA) and (6.35×109)/L of white blood cell (WBC). Logistic regression analysis indicated that CA125 ≥21.2 (p=0.032) and Fn ≥2.58 mg/dL (p=0.014) were significantly associated with LVSI. Conclusion Positive LVSI could be predicted by CA125 ≥21.2 U/mL and Fn ≥2.58 mg/dL in women with EC. It could help gynecologists better adapt surgical staging and adjuvant therapies.

The objective of this study was to evaluate the clinicopathological characteristics, treatment and prognosis of advanced endometrial cancer (EC). Patients who underwent surgery for advanced EC between January 1995 and December 2012 were retrospectively reviewed. Patients with missing data, concurrent cancers or uterine sarcomas and those who did not undergo surgery were excluded. The effects of clinicopathological factors on progression-free survival (PFS) and overall survival (OS) were analyzed. A total of 104 patients were included. Most presented with endometrioid histology (74%) and stage-III disease (87.5%), and 76.9% underwent optimal cytoreduction. A multivariate analysis confirmed that lymphovascular space invasion (LVSI) is an independent poor prognostic factor for PFS [odds ratio (OR): 21.37, p = 0.005] and OS [OR: 8.09, p = 0.044]. Suboptimal cytoreduction is another independent poor prognostic factor for PFS [OR: 5.68, p < 0.001]. Our study demonstrated that LVSI and optimal cytoreduction are the most significant factors affecting the survival of advanced EC patients. © 2015 Taylor & Francis Group, LLC.

While the prognostic significance of lymphovascular space invasion (LVSI) is well established in endometrial and cervical cancer, its role in ovarian cancer is not fully understood. First, a training cohort was conducted to explore whether the presence and quantity of LVSI within the ovarian tumor correlated with nodal metastasis and survival (n = 127). Next, the results of the training cohort were applied to a different study population (validation cohort, n = 93). In both cohorts, histopathology slides of epithelial ovarian cancer cases that underwent primary cytoreductive surgery including pelvic and/or aortic lymphadenectomy were examined. In a post hoc analysis, the significance of LVSI was evaluated in apparent stage I cases (n = 53). In the training cohort, the majority of patients had advanced-stage disease (82.7%). LVSI was observed in 79.5% of cases, and nodal metastasis was the strongest variable associated with the presence of LVSI (odds ratio [OR]: 7.99, 95% confidence interval [CI]: 1.98-32.1, P = 0.003) in multivariate analysis. The presence of LVSI correlated with a worsened progression-free survival on multivariate analysis (hazard ratio [HR]: 2.06, 95% CI: 1.01-4.24, P = 0.048). The significance of the presence of LVSI was reproduced in the validation cohort (majority, early stage 61.3%). In apparent stage I cases, the presence of LVSI was associated with a high negative predictive value for nodal metastasis (100%, likelihood ratio, P = 0.034) and with worsened progression-free survival (HR: 5.16, 95% CI: 1.00-26.6, P = 0.028). The presence of LVSI is an independent predictive indicator of nodal metastasis and is associated with worse clinical outcome of patients with epithelial ovarian cancer.

OBJECTIVE : The aim of this study was to determine the lymph node status in a large cohort of women with endometrial cancer from the public health system who were referred to an oncology reference center in Brazil to identify candidates for the omission of lymphadenectomy based on clinicopathological parameters. METHODS : We retrospectively analyzed a cohort of 310 women with endometrial cancer (255 endometrioid, 40 serous, and 15 clear cell tumors) treated between 2009 and 2014. We evaluated the histological type, grade (low vs. high), tumor size (cm), depth of myometrial invasion (≤50%, >50%) and lymphovascular space invasion to determine which factors were correlated with the presence of lymph node metastasis. RESULTS : The factors related to lymph node involvement were tumor size (p=0.03), myometrial invasion (p

PubMed: 26225684 Background: The aim of this study was to investigate the predictive value of white blood cells (WBC), the neutrophil to lymphocyte ratio (NLR), platelet indices including mean platelet volume (MPV), platelet distribution width (PDW), platelet crit (PCT) and platelet to lymphocyte ratio (PLR) in discrimination between benign and malign endometrial lesions, and early and advanced stage endometrial adenocarcinomas. Materials and Methods: Data for 105 patients undergoing total abdominal or vaginal hysterectomy for benign uterine diseases and 114 patients surgically staged for endometrium adenocarcinoma at Ondokuz Mayis University, Department of Gynecology and Obstetrics, between 2008 and 2014, were collected. Parameters were preoperative and postoperative complete blood counts in the week prior to surgery with differentials including WBC, platelet count, platelet indices (MPV, PCT, PDW), NLR and PLR. Pathologic evaluations for both benign and malign endometrium lesions, grade of endometrium adenocarcinoma, tumor stage, presence of lymphovascular space invasion (LVI) were retrospectively analyzed. Results: Regarding definitive factors in discriminating patients with endometrium cancer from those with benign diseases, MPV was significantly increased in the malign group whereas there was a significant decrease in the PDW value compared to the benign group. The best cut-off value in differentiation of the benign and malign groups, malign cases were found to increase over the value of 7.54 for MPV, and under 37.8 for PDW. When definitive factors in discrimination of early stage endometrium cancer from advanced stage disease and LVI in the malign group were evaluated according to the ROC analysis, no significant relation was detected between blood parameters and the stage and the LVI of the disease. Conclusions: MPV and PDW may have predictive value in the discrimination of benign and malign endometrium diseases. Nevertheless, since there have been few reports on this topic, further large-scale prospective studies are necessary.

OBJECTIVE To investigate the rate, predictors of lymph node metastasis (LNM) and pattern of recurrence in clinically early stage endometrial cancer (EC) with positive lymphovascular space invasion (LVSI). METHODS Women with clinically early stage EC and positive LVSI 2005 to 2012 were identified. Kaplan-Meier curves and logistic regression models were used. RESULTS One hundred forty-eight women were identified. Of them, 25.7% had LNM (21.7% pelvic LNM, 18.5% para-aortic LNM). Among patients with LNM who had both pelvic and para-aortic lymphadenectomy, isolated pelvic, para-aortic and both LNM were noted in 51.4%, 17.1%, and 31.4% respectively. Age and depth of myometrial invasion were significant predictors of LNM in LVSI positive EC. Node positive patients had high recurrence rate (47% vs. 11.8%, p

Background: Minimally invasive surgery has become a standard treatment for endometrial cancer and offers significant benefits over abdominal approaches. There are discrepant data regarding lymphovascular space invasion (LVSI) and positive peritoneal cytology with the use of a uterine manipulator, with previous small-scale studies demonstrating an increased incidence of these prognostically important events. We sought to determine if there was a higher incidence of LVSI in patients who underwent robot-assisted surgery for endometrial cancer. Methods: We performed a single-institution review of medical records for patients who underwent open abdominal or robot-assisted hysterectomy for endometrial cancer over a 24-month period. The following data were abstracted: age, tumor grade and stage, size, depth of invasion, LVSI, and peritoneal cytology. For patients with LVSI, slides were reviewed by 2 pathologists for confirmation of LVSI. Results: Of 104 patients identified, LVSI was reported in 39 (37.5%) and positive peritoneal cytology in 6 (4.8%). Rates of peritoneal cytology were not significantly different between the 2 groups (odds ratio, 0.55; 95% confidence interval, 0.10–3.17; P = .50). LVSI was reported in significantly fewer robot-assisted hysterectomies than open procedures (odds ratio, 0.39; 95% confidence interval, 0.17–0.92; P = .03). In subgroup analyses restricted to early-stage disease (stage ≤ II), there was no significant difference in LVSI between open and robot-assisted hysterectomies (odds ratio, 0.64; 95% confidence interval, 0.22–1.85; P = .43). Conclusion: In this retrospective study, we found that use of a uterine manipulator in robot-assisted surgery did not increase the incidence of LVSI.

International audience; Background: The 2010 guidelines of the French National Cancer Institute (INCa) classify patients with endometrial cancer into three risk groups for lymph node invasion and recurrence on the basis of MRI and histological analysis of an endometrial specimen obtained preoperatively. The classification guides therapeutic choices, which may include pelvic and/or para-aortic lymphadenectomy. The purpose of this study was to evaluate the diagnostic performance of preoperative assessment to help identify intermediate- or high-risk patients requiring lymphadenectomy. Methods: The study included all patients who underwent surgery for endometrial cancer between January 2010 and December 2013 at either Rennes University Hospital or Vannes Regional Hospital. The criteria for eligibility included a preoperative assessment with MRI and histological examination of an endometrial sample. A histological comparison was made between the preoperative and surgical specimens. Results: Among the 91 patients who underwent a full preoperative assessment, the diagnosis of intermediate-or high-risk endometrial cancer was established by MRI and histology with a sensitivity of 70 %, specificity of 82 %, positive predictive value (PPV) of 87 %, negative predictive value (NPV) of 61 %, positive likelihood ratio (LR+) of 3.8 and negative likelihood ratio (LR-) of 0.3. The risk group was underestimated in 32 % of patients and overestimated in 7 % of patients. MRI underestimated endometrial cancer stage in 20 % of cases, while endometrial sampling underestimated the histological type in 4 % of cases and the grade in 9 % of cases. Conclusion: The preoperative assessment overestimated or underestimated the risk of recurrence in nearly 40 % of cases, with errors in lesion type, grade or stage. Erroneous preoperative risk assessment leads to suboptimal initial surgical management of patients with endometrial cancer.

Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P= 4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (>= 4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.

Background The application value of T(2)mapping in evaluating cervical cancer (CC) features remains unclear. Purpose To investigate the role of T(2)values in evaluating CC classification, grade, and lymphovascular space invasion (LVSI) in comparison to apparent diffusion coefficient (ADC), and to compare synthetic T-2-weighted (T2W) images calculated from T(2)values to conventional T2W images for CC staging. Study Type Retrospective. Population Sixty-three patients with histopathologically confirmed CC. Field Strength/Sequence 3T, conventional T2W turbo spin-echo, diffusion-weighted echo-planar, and accelerated T(2)mapping sequence. Assessment T(2)and ADC values between different pathological features of CC were compared. The diagnostic accuracies of conventional and synthetic T2W images in staging were also compared. Statistical Tests Parameters were compared using an independentt-test, Wilcoxon signed-rank test, and the chi-square test. Receiver operating characteristic analysis was performed. Results The T(2)values varied significantly between well/moderately differentiated and poorly differentiated tumors ([92.8 +/- 9.5 msec] vs. [83.8 +/- 9.5 msec],P < 0.05) and between LVSI-positive and LVSI-negative CC ([82.2 +/- 8.2 msec] vs. [93.9 +/- 9.1 msec],P < 0.05). The ADC values showed a significant difference for grade ([0.76 +/- 0.10 x 10(-3)mm(2)/s] vs. [0.65 +/- 0.11 x 10(-3)mm(2)/s],P < 0.05) and no difference for LVSI status ([0.71 +/- 0.11x 10(-3)mm(2)/s] vs. [0.73 +/- 0.12x 10(-3)mm(2)/s],P= 0.472). There was no significant difference in T(2)and ADC values between squamous cell carcinoma and adenocarcinoma (P= 0.378 andP= 0.661, respectively). In MRI staging, the conventional and synthetic T2W images resulted in a similar accuracy (71% vs. 68%,P= 0.698). Data Conclusion The accelerated T(2)mapping sequence may facilitate grading and staging of CC by providing quantitative T(2)maps and synthetic T2W images in one acquisition. T(2)values may be superior to ADC in predicting LVSI. Level of Evidence 2 Technical Efficacy Stage 2

Although endometrial carcinoma (EC) is generally considered to have a good prognosis, over 20% of women with EC die of their disease, with a projected increase in both incidence and mortality over the next few decades. The aim of accurate prognostication is to ensure that patients receive optimal treatment and are neither overtreated nor undertreated, thereby improving patient outcomes overall. Patients with EC can be categorized into prognostic risk groups based on clinicopathologic findings. Other than tumor type and grade, groupings and recommended management algorithms may take into account age, body mass index, stage, and presence of lymphovascular space invasion. The molecular classification of EC that has emerged from the Cancer Genome Atlas (TCGA) study provides additional, potentially superior, prognostic information to traditional histologic typing and grading. This classifier does not, however, replace clinicopathologic risk assessment based on parameters other than histotype and grade. It is envisaged that molecular and clinicopathologic prognostic grouping systems will work better together than either alone. Thus, while tumor typing and grading may be superseded by a classification based on underlying genomic abnormalities, accurate assessment of other pathologic parameters will continue to be key to patient management. These include those factors related to staging, such as depth of myometrial invasion, cervical, vaginal, serosal surface, adnexal and parametrial invasion, and those independent of stage such as lymphovascular space invasion. Other prognostic parameters will also be discussed. These recommendations were developed from the International Society of Gynecological Pathologists Endometrial Carcinoma project.