Involvement In Endometrial Carcinoma Research Articles

Factors Associated with Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy.

Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread (P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread (P = 0.002). Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence.

The Accuracy of MRI in the Local Staging of Endometrial Cancer: An Experience From a Tertiary Care Oncology Institute in Pakistan.

Objective Our objective is to assess the diagnostic accuracy of contrast-enhanced magnetic resonance imaging (MRI) in identifying the depth of myometrial invasion and cervical stromal involvement in endometrial carcinoma (EC) along with nodal status and its correlation with surgical and histopathological (HP) findings. Materials and methods We performed a retrospective study on female patients at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Patients with endometrial carcinoma (CA) were searched from the electronic record system, and a total of 188 patients fulfilling the study criteria were selected. All the patients were evaluated using a 1.5T MRI and underwent a hysterectomy. The outcome of preoperative MRI was correlated withhistopathology results, keeping pathologyas the gold standard. Results A total of 188 patients were included in the study, with a mean age of 56.67 ± 12.47 years. Of the patients, 72 (38.3%)were diagnosed with stage 1a. The second common stage was1b, seen in 43 (22.9%) patients. It was found that the staging of endometrial CA on MRI and HP were significantly correlated for myometrial invasion (stage 1a and 1b), cervical stromal involvement (stage 2b), serosal and adnexal (stage 3a), vaginal(stage 3b), and nodal (stage 3c) involvement as shown by their p-values of <0.01. However, in cases of parametrial invasion (stage 3b), bladderinvolvement, and rectal involvement (stage 4), MRI showed decreased sensitivity as shown by their p-values of 0.833, 0.87, and 0.9, respectively. Conclusion Preoperative MRI can predict local disease and low-risk patients accurately, thereby helping in proper surgical planning and avoiding more extensive surgery such as lymphadenectomy in these patients.

L1CAM Expression in Microcystic, Elongated, and Fragmented (MELF) Glands Predicts Lymph Node Involvement in Endometrial Carcinoma.

Simple SummaryL1CAM overexpression (≥10%) and the microcystic, elongated, and fragmented (MELF) pattern of invasion have previously been assessed as prognostic factors in endometrial carcinoma. We aimed to assess the relationship between L1CAM expression, MELF glands, and lymph node involvement in endometrial carcinoma, as all these factors are related to epithelial-to-mesenchymal transition. We evaluated L1CAM expression in 58 cases of uterine-confined, low-grade endometrioid carcinomas. We found that most cases (65.5%) expressed L1CAM in a limited manner to MELF glands. Cases with L1CAM expression in ≥10% of the MELF component showed a significantly higher tendency to lymph node spread (p < 0.001), even when adjusted for lymphovascular space invasion, depth of myometrial invasion and p53/mismatch repair status. On this account, L1CAM expression in the MELF component may stratify the prognosis and management in patients with uterine-confined, low-grade carcinomas.In endometrial carcinoma, both L1CAM overexpression and microcystic, elongated and fragmented (MELF) patterns of invasion have been related to epithelial-to-mesenchymal transition and metastatic spread. We aimed to assess the association between L1CAM expression, the MELF pattern, and lymph node status in endometrial carcinoma. Consecutive cases of endometrial carcinoma with MELF pattern were immunohistochemically assessed for L1CAM. Inclusion criteria were endometrioid-type, low-grade, stage T1, and known lymph node status. Uni- and multivariate logistic regression were used to assess the association of L1CAM expression with lymph node status. Fifty-eight cases were included. Most cases showed deep myometrial invasion (n = 42, 72.4%) and substantial lymphovascular space invasion (n = 34, 58.6%). All cases were p53-wild-type; 17 (29.3%) were mismatch repair-deficient. Twenty cases (34.5%) had positive nodes. No cases showed L1CAM positivity in ≥10% of the whole tumor. MELF glands expressed L1CAM at least focally in 38 cases (65.5%). L1CAM positivity in ≥10% of the MELF component was found in 24 cases (41.4%) and was the only significant predictor of lymph node involvement in both univariate (p < 0.001) and multivariate analysis (p < 0.001). In conclusion, L1CAM might be involved in the development of the MELF pattern. In uterine-confined, low-grade endometrioid carcinomas, L1CAM overexpression in MELF glands may predict lymph node involvement.

Factors Associated to Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy

Factors Associated to Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy

Supraclavicular lymph node involvement in endometrial carcinoma, rare site of metastasis: A case report

Supraclavicular lymph node involvement in endometrial carcinoma, rare site of metastasis: A case report

Different Risk Stratification Models for Prediction of Lymph Node Involvement in Endometrial Carcinoma

Different Risk Stratification Models for Prediction of Lymph Node Involvement in Endometrial Carcinoma

FAM98A promotes cancer progression in endometrial carcinoma.

To investigate the expression status of FAM98A and its potential involvement in endometrial carcinoma, the relative expression of FAM98A in clinical endometrial carcinoma tissues was analyzed by immunohistochemistry and real-time polymerase chain reaction. Endogenous FAM98A protein was determined by Western blotting. The overall survival was calculated by the Kaplan-Meier's analysis. Cell growth/viability/proliferation was evaluated by cell counting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay, and clonogenic assay, respectively. Cell apoptosis was determined by the Annexin V/7-AAD double-staining methods followed by flow cytometry analysis. The regulatory effect of miR-142-3p on FAM98A was interrogated by luciferase reporter assay. Aberrant overexpression of FAM98A was found in endometrial carcinoma both in vitro and in vivo. Furthermore, high level of FMA98A was associated with poor prognosis. FAM98A deficiency in Ishikawa and RL95-2 cells significantly inhibited cell growth, cell viability, and cell proliferation. In addition, FAM98A-knockdown stimulated remarkable cell apoptosis, which might be mediated by down-regulation of BCL2 and up-regulation of BAX. Mechanistically, it was demonstrated that miR-142-3p directly targeted FAM98A, and modulated its expression. In conclusion, we unraveled the oncogenic properties of FAM98A in endometrial carcinoma and highlighted the miR-142-3p-FAM98A signaling in this disease.

Diagnostic Value of Pelvic MRI for Assessment of the Depth of Myometrial Invasion and Cervical Involvement in Endometrial Cancer: Comparison of New Versus Old FIGO Staging

BackgroundEndometrial carcinoma is a highly prevalent gynecologic malignancy. The International Federation of Gynecology and Obstetrics (FIGO) staging system underwent significant revision on 2009. Key changes in the FIGO staging system include simplification of stage I endometrial cancer and removal of cervical mucosal invasion as a separate stage. MRI is a noninvasive diagnostic method for preoperative staging of endometrial cancer.ObjectivesThe main purpose of this study was to investigate the diagnostic efficacy of pelvic MRI in determining the depth of myometrial invasion and cervical involvement in endometrial carcinoma. The other aim was to compare the accuracy of pelvic MRI using the old and new FIGO staging systems in endometrial carcinoma.Patients and MethodsBetween November 2010 and January 2012, 54 patients underwent primary surgical staging in our department due to endometrial adenocarcinoma. Pre-operative pelvic MRI was performed and MRI staging was done according to old and new FIGO staging, separately. The sensitivity, specificity, positive and negative predictive values as well as the accuracy of MRI for deep myometrial invasion and cervical infiltration were calculated. MRI accuracy was also compared for old and new FIGO staging. Pathological staging was the standard of reference.ResultsThe mean age was 53.31 (SD = 11.52) and the most common histological subtype was the endometrioid type of endometrial adenocarcinoma (90.8%). In the evaluation of deep tumoral invasion of the myometrium (> 50%), sensitivity, specificity, diagnostic accuracy and positive and negative predictive values of MRI were 82.35%, 94.59%, 90.74%, 87.5% and 92.1%, respectively. For cervical stromal involvement, these values were 54.54%, 100%, 90.74%, 100% and 89.58%, respectively. In case of cervical mucosal involvement (in old FIGO staging), the positive predictive value was only 50% and the accuracy decreased to 74.07%. Agreement between MRI and the final histology using the old and new FIGO classification was appropriate with Kappa = 0.62 and 0.72, respectively (P < 0.001).ConclusionUsing 2009 FIGO classification increases the accuracy of pelvic MR imaging for preoperative staging of patients with early stages of endometrial cancer.

Endometrial carcinoma: MR staging and causes of error

This study was undertaken to prospectively determine the diagnostic capabilities of magnetic resonance (MR) imaging in detecting myometrial and cervical invasion and lymph node involvement in endometrial carcinoma and to identify the causes of errors in staging endometrial carcinoma. Twenty consecutive patients with a histological diagnosis of endometrial carcinoma underwent preoperative MR imaging. MR findings were compared with surgical staging, considered as the standard of reference. In assessing myometrial invasion, MR imaging showed 70% accuracy, 80% sensitivity, 40% specificity, 80% positive predictive value (PPV), and 40% negative predictive value (NPV). In detecting cervical invasion, MR imaging had 95% accuracy, 100% sensitivity, 94.4% specificity, 66.7% PPV, and 100% NPV. In evaluating lymph node involvement, MR imaging showed 100% accuracy, sensitivity, specificity, PPV and NPV. Errors in evaluating myometrial invasion were caused by polypoid tumour, adenomyosis and leiomyomas, whereas those in evaluating cervical invasion were caused by dilatation and curettage. MR imaging is a reliable technique for preoperative evaluation of endometrial carcinoma. Its main limitation is differentiating between stage IA and IB carcinomas, which is not highly important for surgical planning. Cooperation between the gynaecologist and radiologist is mandatory to avoid staging errors.

Significant Variation in the Assessment of Cervical Involvement in Endometrial Carcinoma: An Interobserver Variation Study

Significant Variation in the Assessment of Cervical Involvement in Endometrial Carcinoma: An Interobserver Variation Study

Creating a risk model to determine paraaortic lymph node involvement in endometrial carcinoma

To define a high-risk group for paraaortic (PA) lymph node metastasis among endometrial carcinoma patients. Materials and methods: Prognostic factors determining PA lymph node metastasis were defined. Using these factors in different combinations, 14 risk groups were formed. A patient with at least one of these factors was considered as high-risk for PA lymph node metastasis. Results: This study included 152 patients. Of these patients, 18 had tumors in the PA region. Lymphovascular space invasion (LVSI) and pelvic lymph node metastasis were independent prognostic factors for PA lymph node involvement. In the risk modeling system, pelvic lymph node metastasis was an important factor in predicting PA lymph node status, and in groups where this factor was included for risk modeling, PA lymph node involvement was significantly increased in high-risk patients. Best results were obtained with the risk group model (group 10) involving cell type, LVSI, serosal spread, adnexal metastasis, and pelvic lymph node as prognostic factors. In this group sensitivity was 94%, specificity was 53.7%, and negative and positive predictive values were 98.6% and 21.5%, respectively. According to this model, 52% of all patients were in the high-risk group. Conclusion: Group 10 seemed to include the guiding properties for a decision on paraaortic lymphadenectomy and it was possible to reduce unnecessary paraaortic lymphadenectomies by 50%.

Significant Variation in the Assessment of Cervical Involvement in Endometrial Carcinoma

The histologic assessment of cervical involvement in endometrial carcinoma may be problematic for a number of reasons, but an accurate evaluation of this is important for correct staging, dictating the need for adjuvant therapy, and prognostication. In this study, we assessed interobserver variation in the evaluation of cervical involvement in hysterectomy specimens of endometrial carcinoma among 6 specialist gynecologic pathologists. Seventy-six cases of endometrial carcinoma enriched for cases exhibiting some perceived issue in the assessment of cervical involvement were used. In all the cases, a single slide of the primary tumor in the uterine corpus and a single slide of the cervix were circulated among the 6 participants who filled in a proforma. On the basis of the responses, the tumors were staged according to the 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system (I, IIA, IIB) and the 2009 FIGO staging system (I, II). Using the 1988 FIGO staging system, the unweighted and weighted κ values between individual observers ranged from 0.3115 to 0.6139 (average 0.4675) and from 0.3492 to 0.6533 (average 0.5065), respectively. The κ values between observers for the 2009 FIGO staging system ranged from 0.3481 to 0.6862 (average 0.4908). Although enriched for problematic cases, our study shows that there is at most a fair-to-good agreement among specialist gynecologic pathologists in the assessment of cervical involvement in endometrial carcinoma. Problematic factors include determination of the junction between the lower uterine segment and upper endocervix, the distinction between "floaters" and true cervical glandular involvement, the distinction between cervical glandular involvement and stromal involvement, and the distinction between cervical glandular involvement and reactive non-neoplastic lesions of the endocervical glands. There is a need for specialist pathology groups dealing with gynecologic cancers to develop and disseminate recommendations regarding the assessment of cervical involvement in endometrial carcinoma.

The Levels of the Endocannabinoid Receptor CB2 and Its Ligand 2-Arachidonoylglycerol Are Elevated in Endometrial Carcinoma

The endocannabinoid system plays protective roles against the growth and the spreading of several types of carcinomas. Because estrogens regulate this system both in physiological states and cancer, in this paper we evaluated its involvement in endometrial carcinoma, a well-known estrogen-dependent tumor. To test whether the endocannabinoid system is expressed in endometrial cancer, tissue samples were collected both from 18 patients undergoing surgical treatment for endometrial adenocarcinoma and 16 healthy age-matched controls, and treated for Western blot and immunohistochemical analysis. Moreover, tissues were dounce homogenized and submitted to endocannabinoid measurement by liquid chromatography-mass spectrometry. To evaluate the physiological role of the endocannabinoid system, a human endometrial cancer cell-line (AN3CA) was used and transiently transfected with a plasmid containing the cDNA for the endocannabinoid receptor CB(2). Cells were incubated for 48 h with an agonist (JWH133) (10 mum) or antagonist (SR144528) (1 mum) of CB(2) 24 h after transfection, and cell proliferation was measured by the 3-[4,5-dimethyltiazol-2yl]-2,5 diphenyltetrazolium bromide formazan assay. In human endometrial carcinoma biopsies the expression of CB(2) receptor and the levels of its ligand, 2-arachidonoylglycerol increased, whereas monoacylglycerol lipase, an enzyme responsible for 2-arachidonoylglycerol degradation, was down-regulated. Immunohistochemical analysis revealed that CB(2) was overexpressed only in malignant endometrial cells. CB(2)-overexpressing AN3CA cells showed a significant reduction in cell vitality compared with parental AN3CA cells: incubation with the selective CB(2) antagonist SR144128 restored the viability of CB(2)-overexpressing cells to that of untransfected cells. In conclusion, the endocannabinoid system seems to play an important role in human endometrial carcinoma, and modulation of CB(2) activity/expression may account for a tumor-suppressive effect.

Evaluation of the accuracy of intra-operative gross examination for the surgical management of endometrial cancer

Objective The aim of this study was to explore the clinical value of intra-operative gross examination for the surgical management of endometrial carcinoma. Study design A retrospective study was conducted in 424 women who underwent surgical treatment for endometrial carcinoma between January 2002 and December 2006. The results of myometrial invasion and cervical infiltration as assessed by intra-operative gross examination were compared with the final microscopic histopathological results in 401 patients. The accuracy, sensitivity, and specificity were calculated. Chi-squared or Fisher’s exact tests were used for the comparison of categorical variables. Results Intra-operative gross examination correctly identified the depth of microscopic myometrial invasion in 90.3% of patients. The sensitivity in detecting myometrial invasion was 80.6% and the specificity was 92.4%. With regard to cervical involvement, gross examination had an overall accuracy of 84.3%. The sensitivity in detecting cervical involvement was 32.6% and the specificity was 99.0%. Usually, cervical involvement cannot be correctly identified by intra-operative gross examination in patients with diffuse foci. Conclusion The data suggest that intra-operative gross examination is a simple and good method of predicting myometrial invasion, but it may not be the ideal way to assess cervical involvement in endometrial carcinoma.

Lower uterine segment involvement as a predictor for lymph node spread in endometrial carcinoma

Objectives. Several predictive factors for lymph node spread in endometrial cancer have been identified including tumor grade, depth of invasion, lymphatic or vascular-space invasion, and histologic subtype. Lower uterine segment involvement may also be predictive of lymph node spread. The objective of this study was to investigate the relationship between lower uterine segment involvement in endometrial carcinoma and lymph node spread. Methods. This was an IRB approved retrospective study. Data were collected for all patients diagnosed with endometrial cancer from June 1999 to December 2004. The primary end point was the presence of nodal involvement. Subset analysis was performed by histologic subtype. Univariate and multivariate nominal logistic regression was performed. Categorical variables were compared using Chi-square and Fischer’s Exact Test. Results. Two-hundred and ninety-nine subjects were eligible for review. One-hundred seventy four (58%) had lower uterine segment involvement. Forty-four (25%) of those with lower uterine segment involvement had positive nodes compared to 10 (8%) of those without ( p = 0.0001). On univariate analysis, lower uterine segment involvement, lymphovascular-space invasion, and deep invasion predicted nodal disease. On multivariate analysis, lower uterine segment remained predictive of nodal spread for the endometrioid subset. For high-risk histologies, only lymphovascular-space invasion and deep myometrial invasion were predictive of nodal spread. Conclusions. Lower uterine segment involvement in endometrial carcinoma is an important predictor of lymph node involvement for patients with endometrioid histologies. Tumor within the lower uterine segment may be an important factor to consider in intraoperative decision making regarding staging.

Assessment of cervical involvement in endometrial carcinoma by hysteroscopy and directed biopsy

The objective of this study was to assess the diagnostic validity of hysteroscopy and directed biopsy for assessing cervical involvement in endometrial carcinoma. We conducted a study of 240 hysteroscopies and 44 cervical biopsies performed on 240 patients with endometrial carcinoma between 2000 and 2005. Hysteroscopy results suggested cervical involvement in 55 cases, of which only 31 were confirmed (a subtotal hysterectomy was performed in two cases, and the resection margins were examined for tumor invasion). In the 31 patients with confirmed cervical involvement, 19 of the hysteroscopy-directed biopsies were positive, 3 were negative, and 3 provided insufficient material. Six patients did not undergo biopsy. In the 24 patients with hysteroscopy false positive, 10 directed biopsies were positive and 9 were negative. Five patients did not undergo biopsy. Hysteroscopy suggested an absence of cervical involvement in 185 patients. Diagnosis was confirmed in 177 cases, and there were eight false negatives. In our case, office hysteroscopy proved to be a valid means of ruling out cervical involvement in endometrial carcinoma. However, it was not a valid means of detecting tumor involvement, even when combined with directed biopsy.

Prediction of cervical involvement in endometrial cancer by hysteroscopy

This study evaluated the ability of hysteroscopy to preoperatively predict cervical involvement in endometrial cancer. The records of 110 surgically staged consecutive endometrial cancer patients treated at our institution from 1997 to 2003 were retrospectively analyzed. Data on demographics, preoperative staging procedures, surgical pathology reports, and adjuvant treatments were retrieved. Fourteen (12.7%) patients had cervical involvement (stage II) according to the surgical pathology report, of whom nine (8.1%) had stage IIA and five (4.6%) had stage IIB. Clinical evaluation by speculoscopy and palpation had failed to reveal any indication of cervical involvement. Preoperative diagnostic hysteroscopy procedures were included. None of the hysteroscopy procedures revealed any suspicious lesion in the cervical canal. Hysteroscopy and clinical examination fail to adequately predict cervical involvement in endometrial carcinoma. Fractional D&C appears to be the best method until a more effective alternative becomes available.

Preoperative Staging of Endometrial Carcinoma by MRI

Background: In patients with endometrial carcinoma, preoperative evaluation of exact staging has important prognostic and therapeutic implications. The incidence of pelvic and aortic lymph node involvement in endometrial carcinoma depends on grade of tumor differentiation and depth of myometrial invasion. Material and method: To evaluate whether MRI provides a preoperative assessment for staging of endometrial carcinoma, MRI was undertaken in 28 patients, a few weeks before operation. Myometrial invasion was devided in three categories, and involvement of cervix, adnexa, and pelvic cavity were classified. Results: The results of MR imaging were compared with these of pathology. The preoperative MRI staging of endometrial carcinoma was correct in 22 out of 28 patients. In the evaluation of myometrial invasion, the MR imaging underestimated in 4 cases and overestimated in 1 case. Conclusion: In patients with endometrial carcinoma, MR imaging is very useful in the assessment of the depth of myometrial invasion, stromal invasion of cevix, lymphatic & pelvic metastases and extent of the lesion.

Histologic study of patterns of cervical involvement in FIGO stage II endometrial carcinoma.

The pathology of cervical involvement in endometrial carcinoma has not been fully defined previously. We reviewed the histopathology of 66 hysterectomies of women with stage II endometrial carcinoma. Cervical spread was categorized as macroscopic or microscopic; stage IIA or IIB; direct spread, surface or lymphvascular metastasis; and size, number, and location. The cervical tumor was macroscopically identified in 15 (23%) women and microscopically identified in 51 (77%). Twenty-one patients (32%) were stage IIA and 45 (68%) stage IIB. The method of spread was direct spread in 28 patients, surface metastases in 27, lymphovascular in 3, both direct spread and surface metastases in 7 and both direct spread and lymphovascular in 1. The cervical tumor had a mean horizontal dimension of 3 mm and a median of 2 mm. There were multiple sites of cervical tumor in 31 (47%) patients and single in 35 (53%). The sites of spread, including cases with multiple sites, were the endocervix in 60 women (90%), transformation zone in 24 (37%), and ectocervix in 3 (5%). Most patients had minimal microscopic cervical tumor. Small examples of direct spread may be an artifact of definition depending on the histology of the isthmian-endocervical junction and many surface metastases appear to follow dilatation and curettage. In 7 of 66, 11%, however, the cervical tumor was greater than 5 mm depth of invasion and/or the result of lymphvascular metastasis. Survival studies are required to compare minimal stage II endometrial carcinoma patients and those with larger and/or lymphvascular derived cervical tumor. Patients with minimal stage II and stage I patients should also be compared.

The use of endocervical curetage in the preoperative assessment of cervical involvement in endometrial carcinoma: A comparison between fractional curetage and office endocervical curetage

International Journal of Gynecology & ObstetricsVolume 70, Issue S1 p. A71-A71 Uterine cancer The use of endocervical curetage in the preoperative assessment of cervical involvement in endometrial carcinoma: A comparison between fractional curetage and office endocervical curetage J. Toral, J. ToralSearch for more papers by this author J. Toral, J. ToralSearch for more papers by this author First published: 09 December 2003 https://doi.org/10.1016/S0020-7292(00)82715-0AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume70, IssueS12000Pages A71-A71 RelatedInformation