Original paper
DOI: 10.11152/mu.2013.2066.182.ege
Abstract
Aim: To predict the myometrial invasion with three-dimensional (3D) ultrasonography in a cohort of patients with endo- metrial carcinoma by a previously described technique. Material and methods: The moyometrial infiltration was evaluated by 3D ultrasonography before surgery in 54 patients with endometrial carcinoma. After scanning the whole uterus by ultra- sonography, three perpendicular planes were identified to find the shortest myometrial tumor-free distance to serosa (TDS) by examining the lateral, anterior, posterior, and fundal parts of the myometrium. Myometrial infiltration was also estimated by the subjective impression of the examiner. The reference standards consist of myometrial infiltration and TDS which are measured by an experienced pathologist. Results: Forty-five patients (age range 45-86 years) were included for the final analysis. Myometrial invasion was ˂50% in 36 and ≥50% in 9 cases at histologic sections. The TDS which is measured with 3D ultrasonography was positively correlated with histologically measured TDS (r=0.474, p=0.001). The best cut-off value for ultrasonographically measured TDS was 9 mm with a sensitivity of 89%, specifity of 61%, positive predictive value of 36%, and negative predictive value of 96%. Subjective impression has a sensitivity of 100%, specifity of 88%, positive predictive value of 69%, and negative predictive value of 100%. Cervical involvement was correctly identified in all 6 cases by subjec- tive impression. Conclusion: This validation study confirms the 3D ultrasonography as a valuable tool for the evaluation of myometrial infiltration in patients with endometrial carcinoma.
Keywords: endometrial carcinoma, myometrial infiltration, 3D ultrasonography
The prediction of myometrial infiltration by three-dimensional
ultrasonography in patients with endometrial carcinoma: a validation study from Ege University Hospital.
Mete Ergenoglu
1, Levent Akman
1, Mustafa Cosan Terek
1, Cem Yasar Sanhal
1, Ozgur Yeniel
1, Ozgul Vupa Cilengiroglu
2, Ahmet Aydin Ozsaran
1, Yilmaz Dikmen
1, Osman Zekioglu
31Ege University Medical School, Department of Obstetrics and Gynecology, 2Dokuz Eylul University, Faculty of Sci- ences, Department of Statistics, 3Ege University Medical School, Department of Pathology, Izmir, Turkey
Received 07.11.2015 Accepted 31.01.2016 Med Ultrason
2016, Vol. 18, No 2, 201-206
Corresponding author: Levent Akman, MD
Ege University Medical School
Department of Obstetrics and Gynecology 35100, Bornova, Izmir, Turkey
Phone: +90-232-3901730 E-mail:[email protected]
Introduction
The surgical staging of endometrial carcinoma pa- tients is an essential part of the overall therapy [1]. Pelvic and para-aortic lymphadenectomy is an important part of the complete surgical staging with an inherent compli- cation rate. Retroperitoneal lymphadenectomy may be avoided in low-risk patients. Myometrial infiltration of the tumor is one of the factors that define low-risk pa-
tients along with tumor type and histologic grade [2].
Myometrial infiltration of the tumor can be predicted by magnetic resonance imaging (MRI) and ultrasonography (US) in the preoperative setting. Macroscopic evaluation of the uterus and frozen section analyses are done intra- operatively to predict the myometrial invasion [3]. The accuracy of MRI imaging for the assessment of myome- trial invasion in patients with endometrial carcinoma is reported between 62% to 95% in two studies [4,5].
Transvaginal US is a method to examine the myome- trial invasion and the cervical stromal invasion non-inva- sively, without using contrast agent, in patients with en- dometrial carcinoma. Three-dimensional (3D) US adds a more accurate examination of the uterus with many perpendicular planes [6]. Raine-Fenning et al [7] and Al- cazar et al [8] reported 3D US as less operator dependent than two-dimensional US.
Alcazar et al [8,9] proposed a technique for assess- ing the myometrial invasion in patients with endometrial carcinoma. The aim of the present study was to validate the proposed technique in a cohort of patients with endo- metrial carcinoma.
Materials and methods Study Patients
The Ege University Ethical Committee approval was obtained and written consent was obtained from all pa- tients for the study. Patients with presumed early stage endometrial carcinoma were included in the study, in a single University Hospital. Preoperative work-up of the patients consists of chest X-ray, whole abdominal ultra- sonography, blood biochemical tests, physical and gy- necological examination. The diagnosis of endometrial carcinoma was obtained either by endometrial curettage or hysterescopic endometrial biopsy. The patients with intramural leiomyoma greater than 3 cm and submucous leiomyoma (n=6) were excluded from the study. Surgi- cal treatment and staging was not performed because of cardiac disease (n=1), parametrial involvement with intraabdominal carcinomatosis (n=1) and parametrial in- volvement (n=1) in three patients.
Ultrasonography
All ultrasonographic examinations were performed within two weeks prior surgery with a transvaginal probe (3-9 MHz, E8, GE Healthcare, Milwaukee, WI). All ul- trasonographic examinations were performed by one physician (A.M.E.) with three years of experience in 3D US. Two-dimensional US examination was initially performed to explore the uterus, adnexa and endometrial thickness. The 3D volume box was placed over the endo- metrial and myometrial areas. A total of 4 volumes were obtained and stored on a hard disc for further evaluation [8]. Volume examinations were blinded to histological results. Myometrial infiltration was assessed in the stored volume. Transverse, sagittal, and coronal planes of the uterus were evaluated carefully. Myometrial tumor-free distance to serosa was measured in the lateral walls and fundus in coronal and sagittal planes (fig 1). The subjec- tive shortest tumor-free distance to serosa (TDS) which was found in any area was selected to determine the depth of myometrial infiltration. Myometrial infiltration was also estimated subjectively according to the exam- iner impression of the depth of invasion (≥50% or <50
%) by identifing the point in which the myometrial-endo- metrial interface was not clearly defined. The examiner compared the supposedly tumor-free myometrial wall at that point with the opposite myometrial wall: if a marked asymmetry was identified, deep (≥50%) infiltration was
documented; if myometrial thickness was similar in both myometrial walls, superficial (<50%) infiltration was documented. The involvement of the lower uterine seg- ment of uterus and cervical canal was evaluated subjec- tively by 3D US. The subjective disruption of the lower uterine segment of uterus and cervical canal with irregu- lar appearance of endometrial-myometrial border was determined as subjective cervical involvement of endo- metrial carcinoma.
Control patients
Two control groups of asymptomatic patients were recruited to determine the normal TDS value in normal uteri. The first group included premenopausal patients (n=20) and the second group postmenopausal women (n=20). The postmenopausal period was defined as an absence of menstruation for 1 year in women older than 45 years of age. None of these two groups of patients had uterine or endometrial pathologies including leiomyomas, adenomyosis, congenital anomalies, endometrial polyps, endometrial hyperplasia and endometrial thickness >5 mm in postmenopausal age. None of these patients used oral contraceptives, hormone replacement therapy, or tamox- ifen. Reproducibility studies of TDS measurement were performed previously by Alcazar et al [9].
Surgical staging
Standard surgery included total abdominal hysterec- tomy, bilateral salpingo-oophorectomy, and pelvic wash- ings for cytological examination. Omentectomy was performed in serous papillary and clear cell histological types of endometrial carcinoma. Pelvic and paraaortic lymphadenectomy was performed in grade 3, serous pap- illary and clear cell histological types and outer myome- trial infiltration (≥50%) on frozen section pathological analysis. The pathological data from an individual pa- tient included histological type, histological grade, depth of myometrial infiltration, lymphovascular space in- Fig 1. Three-dimensional ultrasonography images in a case of endometrial cancer in transverse, sagittal and coronal planes.
volvement, TDS, cervical involvement, and lymph node status. The pathological data were used as the reference standard of the study. All surgeries were performed by experienced gynecologic oncologists with dedicated sur- gical and pathological teams in a specialized gynecologic oncology division of University Hospital. Tumor stage was determined according to the International Federa- tion of Gynecology and Obstetrics Criteria [1]. Tumor histologic grade was determined according to the follow- ing three-grade system: grade 1 carcinoma showed solid growth pattern in less than 5% of the tumor; grade 2 car- cinoma showed solid growth pattern in 5%-50% of the tumor; grade 3 carcinoma showed solid growth pattern in more than 50% of the tumor.
Statistical Analysis
The Kolmogorov-Smirnov test was used to assess the normal distribution of continuous data. Continuous data were compared by using one-way analysis of variance when data were normally distributed or by using the Mann- Whitney U test when data were not normally distributed.
The t test was used to compare the means for two inde- pendent samples. These tests were used for comparing TDS measured by using ultrasonography in the control group according to the site of measurement, and TDS measured by using ultrasonography in study group according to his- tologic depth of invasion. A receiver operating character- istic (ROC) curve was plotted to determine the best cutoff value for TDS for identifying deep myometrial invasion.
The best cutoff value was chosen according to the best sen- sitivity with the lowest false-positive rate. A p value of 0.05 or less was considered to indicate a statistically significant difference. All analyses were performed by using software (SPSS, version 15.0; SPSS, Chicago, Ill).
Results
The mean age of the patients with endometrial carcino- ma was 62.1±10 (45-86) and 89% (n=40) of women were
postmenopausal. Tumor histologic features are shown in Table I. Table II shows median TDS at the level of fundus, anterior and posterior uterine walls, and lateral uterine wall in the control groups. TDS in all uterine walls was longer in premenopausal women than in postmenopausal women.
The Mann-Whitney U test was used to compare TDS measured by 3D ultrasonography and by a pathologist according to myometrial infiltration. Median TDS meas- ured by a pathologist and that measured by using three- dimensional ultrasonography were significantly shorter in those tumors with 50% or more myometrial infiltration than in those with less than 50% infiltration (Table III).
There was a positive correlation between pathologi- cally measured and 3D ultrasonographically-measured TDS (r=0.474, p=0.001); mean and standard deviations of these measurements were found as 9.5, 3.27 and 14.5, 8.27 (mean, standard deviation), respectively. There was a statistically significant difference between 3D ultra- sonographically-measured TDS and histologically meas- ured TDS (p=0.001). Median TDS in the control group Table I. Histologic features of endometrial cancer.
Clinical Features Patients (n, %) Histologic type
Endometrioid 38 (84. 6%)
Serous papillary 4 (8.8 %)
Clear cell 3 (6.6 %)
Histologic grade
G1 18 (40 %)
G2 21 (46.7 %)
G3 6 (13.3 %)
Myometrial infiltration
< 50 % 36 (80%)
≥ 50 % 9 (20%)
Tumor stage
IA 33 (73.4 %)
IB 6 (13.3%)
II 6 (13.3%)
n – number of patients
Table II. Measurement of median tumor-free distance to serosa (TDS) at the level of fundus, anterior and posterior uterine walls, and lateral uterine wall in control groups.
Fundus (mm) Lateral uterine wall (mm) Anterior uterine wall (mm) Posterior uterine wall (mm)
Premenopausal (n=20) 18 (14-24) 17 (11-27) 18 (12-29) 19 (11-30)
Postmenopausal (n=20) 10 (5-13) 11 (8-14) 11 (8-13) 12 (9-16)
P value 0.001 0.002 0.002 0.009
Data are medians, with ranges in parentheses, n – number of patients
Table III. Tumor-free distance measured by 3D ultrasongraphy and histology.
Parameter 3D US-measured TDS (mm) Histologically measured TDS (mm) P value
<50% myometrial infiltration 10 (4.8-19.0) 15 (7.0-40.0) 0.004
≥50% myometrial infiltration 7 (4.0-10.0) 5 (2.0-19.0) 0.000
Data are medians, with ranges in parentheses, TDS: tumor-free distance to serosa
[14 mm (5-30)] was significantly higher than in the study group for tumors infiltrating less than 50% and for those infiltrating more than 50%.
The receiver operating characteristic (ROC) curve determined that a shorter 3D ultrasonographically-meas- ured TDS was a predictor for deep myometrial infiltration.
The best cut-off value for 3D ultrasonographically-meas- ured TDS was 9 mm, which allowed for identification of cases with deep infiltration with 11% false negative and 39% false positive rate. Figure 2 shows a case of deep myometrial infiltration as determined by using 3d US.
Only one case in the postmenopausal control group had a TDS less than 9 mm (5 mm).
(Tables IV). For TD, sensitivity was 89%, specificity 61%, false positive rate 39%, false negative rate 11%.
positive predictive value 36%, and negative predictive value was 96%. For subjective impression, sensitiv- ity was 100.0 %. specificity 88.9 %, positive predictive value 69.0% and negative predictive value 100.0%. With subjective impression, the false positive rate was 11.2%, which was much lower than that of TDS (p<0.001).
Cervical involvement was correctly identified in all of six (100%) cases by subjective sonographic impres- sion.
Discussions
Myometrial infiltration is one of the most important factors determining lymph node metastasis and adjuvant radiotherapy in patients with endometrial carcinoma. The reliable estimation of myometrial infiltration before sur- gery by a non-invasive methods is surely very helpful for the planning of surgical procedure and informing the patient about the extent of surgical procedure [10]. The lymphadenectomy procedure also has an inherent mor- bidity including lymphocele formation, vascular injury, and thrombosis [11]. Intraoperative gross evaluation of the uterus has a sensitivity of 67%-77% with a false neg- ative rate for detection of deep myometrial invasion of about 23%-33% [3,12-14]. MRI has a sensitivity of 80%
to 91% for preoperative evaluation of myometrial infil- tration by endometrium carcinoma [4,15-17]. Also, add- ing diffusion weighted imaging sequence to the standard MRI, increases the detection of deep myometrial inva- sion of endometrial cancer [18]. However, MRI has a high cost and is not available in all institutions.
3D US provides multiplanar imaging of uterus in real-time including coronal planes. Alcazar et al [8] dem- onstrated that this technique is much less operator de- pendent than two-dimensional US. The sagittal plane of uterus can be assessed by two-dimensional US but it is almost impossible to gain knowledge regarding the coro- nal plane of the uterus which is easily visualized by 3D US.
Alcazar et al [9] were able to predict the deep myo- metrial infiltration in all cases of endometrial cancer by uterine virtual navigation. Their data indicated that with a 9.0 mm cut-off, TDS can accurately identify all cases of deep infiltration without any false-negative patients.
They also showed that with subjective impression, the false-positive rate is 17.4%. In the present study, with subjective impression, the false positive rate was 11.2%
which is much lower than that of TDS (p<0.001).
In line with the original study, we validated that the best cut-off value for 3D ultrasonographically-measured TDS was 9 mm for identifying myometrial infiltration of 50% or more [9]. Moreover in our study subjective impression had a better diagnostic performance than 3D ultrasonography in determining the deep myometrial in- filtration.
However, false positive cases have less clinical im- portance from the perspective of oncological surgery. It is more important to leave the positive lymph nodes un- Fig 2. Three-dimensional ultarsonography image shows meas-
urement of tumor-free distance to serosa (TDS) in case with deep myometrial infiltration. The shortest TDS was 5.28 mm. (D: di- ameter)
Table IV. Diagnostic performance of tumor-free distance to se- rosa (TDS) as measured by 3D ultrasonography and the subjec- tive impression of the examiner by ultrasonography.
Parameter Myometrial infiltration Total
≥ 50 % < 50 % TDS
≤ 9.0 mm 8 14 22
> 9.0 mm 1 22 23
Subjective impression
≥ 50% 9 4 13
< 50 % 0 32 32
Total 9 36 45
TDS: Tumor-free distance
attended in cases with deep myometrial invasion. In line with the study of Alcazer et al [9] the low false negative rate rather than false positive rate and higher sensitivity of both subjective impression and TDS, 3D US is a good alternative to MRI.
TDS is important for predicting recurrence in endo- metrial cancer. Lindauer et al [19] determined whether a tumor-free distance from the uterine serosa is more pre- dictive of patient outcome than the depth of endometrial cancer invasion into the myometrium. In a multivariate model, tumor-free distance from the uterine serosa was shown to correlate with surgicopathologic variables, re- currence risk, and survival.
Karlson et al [20] first suggested the use of the tumor/
uterine anteroposterior diameter ratio, a result of >0.5 indicating high risk of deep myometrial invasion, with a sensitivity of 79% and a specifity of 100%. Mascilini et al [21] compared the diagnostic accuracy of subjective US assessment with that of objective measurement techniques in women with endometrial cancer. They found that the sensitivity (72%) and specifity (76%) of tumor/uterine an- teroposterior diameter is not significantly different from those of subjective evaluation (sensitivity 77%, specifity 81%). They proposed the distance from outer cervical os to lower margin of tumor for predicting cervical invasion;
however, it had only non-significantly higher sensitivity than subjective evaluation (73% vs 54%).
Alcazar et al compared the diagnostic performance of six different approaches (impression of examiner, Karls- son’s criteria, endometrial thickness, tumor/uterine 3D volume ratio, TDS and von Holsbeke’s subjective model) for assessing myometrial infiltration using transvaginal/
transrectal US in endometrial carcinoma [22,23]. The study showed that the subjective impression seems to be the best approach for assessing myometrial infiltra- tion in grade 1 or 2 endometrioid carcinoma and the use of mathematical models and other objective 2D and 3D measurement techniques do not improve diagnostic per- formance. Also, their metaanalysis showed that objective measurement techniques were not superior to subjective assessment [24].
The results on the use of US to assess cervical inva- sion are generally very good for subjective assessment, with sensitivities ranging from 77 to 93% and specifities ranging from 85 to 99% [25-27]. Subjective evaluation takes more features into account in addition to size and proportion, including regularity of the endometrial-my- ometrial border and vascular pattern. In large exophytic tumors, the tumor proportion will be great but the endo- metrial-myometrial border will be regular and the focal vessel pattern will indicate that it is a large polypoid le- sion bulging into the cavity and stretching the surround-
ing myometrium, rather than infiltrating [28]. In the pre- sent study, cervical involvement was correctly identified in all cases by subjective sonographic impression.
The limitation of the study was relatively few patient numbers. Further prospective studies with a larger popu- lation are required in order to determine a more accurate cut-off value for identifying myometrial infiltration of 50% or more in endometrial cancer.
In conclusion, tumors may infiltrate any region of the myometrium and 3D US allows the assessment of the uterus in all planes. In this present study, a subjective im- pression with 3D US determined deep myometrial infil- tration in all cases. In line with the original study the best cut-off value for 3D ultrasonographically-measured TDS is 9 mm for identifying myometrial infiltration of 50% or more. However, more studies are required to prove the practicability of 3D US to the assessment of the depth of myometrial infiltration by endometrial cancer.
Conflict of interest: none
References
1. Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet 2009; 105: 109.
2. Aalders JG, Thomas G. Endometrial cancer: revisiting the importance of pelvic and paraaortic lymph nodes. Gynecol Oncol 2007; 104: 222-231.
3. Traen K, Hølund B, Mogensen O. Accuracy of preoperative tumor grade and intraoperative gross examination of myo- metrial invasion in patients with endometrial cancer. Acta Obstet Gynecol Scand 2007; 86: 739-741.
4. Rockall AG, Menoni R, Sohaib SA, et al. Evaluation of en- dometrial carcinoma on magnetic resonance imaging. Int J Gynecol Cancer 2007; 17: 188-196.
5. Torricelli P, Ferraress S, Fiocchi F, et al. 3-T MRI in the preoperative evaluation of depth of myometrial infiltartion in endometrial cancer. AJR Am J Roentgenol 2008; 190:
489-495.
6. Benacerraf BR, Shipp TD, Bromley B. Impoving the effi- ciency of gynecologic sonography with 3-dimensional vol- umes: a pilot study. J Ultrasound Med 2006; 25: 165-171.
7. Raine-Fenning NJ, Campbell BK, Clewes JS, Kendall NR, Johnson IR. The reliability of virtual organ computer- aided analysis (VOCAL) for the semiquantification of ovarian, endometrial and subendometrial perfusion. Ultrasound Ob- stet Gynecol 2003; 22: 633-639.
8. Alcázar JL, Merce LT, Manero MG, Bau S, Lopez-Garcia G. Endometrial volume and vascularity measurements by transvaginal 3-dimensional ultrasonography and power Doppler angiography in stimulated and tumoral endome- tria: an interobserver reproducibility study. J Ultrasound Med 2005; 24: 1091-1098.
9. Alcázar JL, Galvan R, Albela S, et al. Assessing myome- trial infiltration by endometrial cancer: Uterine virtual navi-
gation with three dimensional US. Radiology 2009; 250:
776-783.
10. Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer: a Gynecologic Oncology Group study. Cancer 1987; 60: 2035–2040.
11. Christensen JW, Dueholm M, Hansen ES, Marinovskij E, Lun- dorf E, Ortoft G. Assessment of myometrial invasion in endo- metrial cancer using three-dimensionalultrasound and magnetic resonance imaging. Acta Obstet Gynecol Scand 2016; 95: 55-64 12. Fischerova D, Frühauf F, Zikan M, et al. Factors affecting
sonographic preoperative local staging of endometrial can- cer. Ultrasound Obstet Gynecol 2014; 43: 575-585.
13. Eriksson LS, Lindqvist PG, Flöter Rådestad A, et al. Trans- vaginal ultrasound assessment of myometrial and cervical stromal invasion in women with endometrial cancer: inter- observer reproducibility among ultrasound experts and gy- necologists. Ultrasound Obstet Gynecol 2015; 45: 476-482.
14. Berretta R, Merisio C, Piantelli G, et al. Preoperative trans- vaginal ultrasonography and intraoperative gross examina- tion for assessing myometrial invasion by endometrial can- cer. J Ultrasound Med 2008; 27: 349–355.
15. Antonsen SL, Jensen LN, Loft A, et al. MRI, PET/CT and ultrasound in the preoperative staging of endometrial can- cer - a multicenter prospective comparative study. Gynecol Oncol 2013; 128: 300-308.
16. Park JY, Kim EN, Kim DY, et al. Comparison of the valid- ity of magnetic resonance imaging and positron emission tomography/ computed tomography in the preoperative evaluation of patients with uterine corpus cancer. Gynecol Oncol 2008; 108: 486–492.
17. Andreano A, Rechichi G, Rebora P, Sironi S, Valsecchi MG, Galimberti S. MR diffusion imaging for preoperative staging of myometrial invasion in patients with endometrial cancer: a systematic review and meta-analysis. Eur Radiol 2014; 24: 1327-1338.
18. Das SK, Niu XK, Wang JL, et al. Usefulness of DWI in preoperative assessment of deep myometrial invasion in pa- tients with endometrial carcinoma: a systematic review and meta-analysis. Cancer Imaging 2014; 14: 32.
19. Lindauer J, Fowler JM, Manolitsas TP, et al. Is there a prognostic difference between depth of myometrial inva-
sion and the tumor-free distance form the uterine serosa in endometrial cancer? Gynecol Oncol 2003; 91: 547-551.
20. Karlsson B, Norstrom A, Granberg S, Wikland M. The use of endovaginal ultrasound to diagnose invasion of endoem- trial carcinoma Ultrasound Obstet Gynecol 1992; 2: 35-39.
21. Mascilini F, Testa AC, Van Holsbeke C, Ameye L, Timmer- man D, Epstein E. Evaluating myometrial and cervical in- vasion in women with endometrial cancer: comparing sub- jective assessment with objective measurement techniques Ultrasound Obstet Gynecol 2013; 42: 353-358.
22. Van Holsbeke C, Ameye L, Testa AC, et al. Development and external validation of new ultrasound-based math- ematical models for preoperative prediction of high-risk endometrial cancer. Ultrasound Obstet Gynecol 2014; 43:
586-595.
23. Alcazar JL, Pineda L, Martinez-Astorquiza Corral T, et al.
Transvaginal/transrectal ultrasound for assessing myome- trial invasion in endometrial cancer: a comparison of six different approaches. J Gynecol Oncol 2015; 26: 201-207.
24. Alcázar JL, Orozco R, Martinez-Astorquiza Corral T, et al. Transvaginal ultrasound for preoperative assessment of myometrial invasion in patients with endometrial cancer:
a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015; 46: 405-413.
25. Akbayır O, Corbacioglu A, Numanoglu C, et al. Preopera- tive assessment of myometral and cervical invasion in en- dometrial carcinoma by transvaginal ultrasound Gynecol Oncol 2011; 122: 600-603.
26. Savelli L, Ceccarini M, Ludovisi M, et al. Preoperative lo- cal staging of endoemtrial cancer: transvaginal sonography vs. magnetic resonance imaging. Ultrasound Obstet Gy- necol 2008; 31: 560-566.
27. Sawicki W, Spiewankiewicz B, Stelmachow J, Cendrowski K. The value of ultrasonography in preoperative assess- ment of selected prognostic factors in endometrial cancer.
Eur J Gynaecol Oncol 2003; 24: 293-298.
28. Leone FP, Timmerman D, Bourne T, et al. Terms, defini- tions and measurements to describe the sonographic fea- tures of the endometrium and intrauterine lesions: a con- sensus opinion from the International Endometrial Tumor Analysis (IETA) group. Ultrasound Obstet Gynecol 2010;
35: 103-112.
