The Application Of Transvaginal Rflow Blood Flow Imaging And Three-dimensional Power Doppler Angiography In Endometrial Lesions And Their Correlation Study With VEGF Expression

BackgroundEndometrial lesions are divided into benign and malignant lesions.Endometrial cancer(EC)is a kind of epithelial malignant tumors derived from the endometrium,accounting for 20%to 30%of female reproductive system malignancies.Recent years have witnessed an increase of EC worldwide.There are about 80%of the patients of whom the lesions are confined to the uterus when referred to hospitals,with a 5-year survival of 80%.Nonetheless,the median survival is only 7 to 12 months when metastasis occurs.Therefore,the early diagnosis and accurate assessment of the clinicopathological features of EC are of great importance in clinical decision-making and predicting the prognosis.Transvaginal ultrasonography was recommended by The American College of Obstetricians and Gynecologists as the first choice of screening methods for patients with postmenopausal bleeding(PMB).Conventional transvaginal two-dimensional ultrasound(2D-TVS)is used to measure endometrial thickness(ET)for the initial diagnosis of endometrial lesions.Color-Doppler ultrasound can visualize the blood flow of the lesion,but there lack quantitative methods to evaluate the blood flow.Rflow stereoflow imaging(Rflow)technology on the GE's Voluson E10 color Doppler ultrasound system can display the three-dimensional vascular patterns based on two-dimensional imaging,enhancing the visual imaging effect of the microvessels and their boundaries,and making a clear illustration of blood flows in the lesion.Three-dimensional power doppler angiography(3D-PDA)can detect low-speed blood flow signals,without aliasing effect or angle dependence,able to acquire an omnidirectional view of the blood flows.With the addition of Virtual organ computer-aided analysis(VOCAL),endometrial volume(EV)and blood flow parameters in the lesions can be automatically measured,including vascularization index(VI),blood flow index(bloodflow)Index,FI)and vascularization-blood flow index(VFI).These new techniques can be utilized to differentiate benign and malignant endometrial lesions and assess the staging and grading of EC.The use of Rflow blood flow imaging to classify benign and malignant endometrial lesions has not been reported yet.There are also few studies about transvaginal 3D-PDA in diagnosing endometrial lesions,and the results of the studies using parameters(ET,EV,VI,FI,and VFI)to evaluate endometrial lesions are conflicting.This study was designed to investigate the value of transvaginal ultrasound Rflow flow imaging and 3D-PDA in the diagnosis of endometrial lesions and the prediction of the staging and grading of EC to provide imaging references for diagnosis,treatment selection and prognosis evaluation.ObjectiveTo investigate the value of transvaginal ultrasound Rflow flow imaging and 3D-PDA in the diagnosis of endometrial lesions and the prediction of the staging and grading of EC.MethodsA total of 214 patients with endometrial lesions referred to Yantai Yuhuanhding Hospital from July 2018 to August 2019 were recruited.Conventional 2D-TVS was perfomed to measure the ET,and blood flow was assessed preliminarily by color-Doppler ultrasound.Then EV,VI,FI and VFI of 3D-PDA were calculated using VOCAL.The surgical-pathological classification was deemed as the gold standard to validate the value of TVS,Rflow imaging and 3D-PDA in diagnosing benign and malignant endometrial lesions.The diagnostic efficacy of the parameters(ET,EV,VI,FI,and VFI)in classifying benign and malignant endometrial lesions was evaluated,as well as the role of the five endometrial parameters in the staging and grading of EC.Results1.There were 124 benign endometrial lesions and 90 malignant lesions,with significant differences in age,menopausal age,and endometrial thickness between the two groups(all P<0.001).2.The sensitivity of traditional 2D-TVS,Rflow-TVS and transvaginal 3D-PDA were 74.2%,83.9%,95.2%,and the specificities were 66.7%,77.8%,91.1%,respectively.3.There were significant differences in ET,EV,VI,FI and VFI between the endometrial benign lesion group and the malignant lesion group(P<0.005).ROC curve analysis showed that the sensitivity and specificity of the five parameters were ET(62.9%,80.0%),EV(93.5%,57.8%),VI(67.7%,68.9).%),FI(72.6%,60.0%),VFI(77.4%,62.2%),respectively.The optimal threshold value of EV was 27.265cm3,with a sensitivity of 93.5%.The optimal threshold value of endometrial thickness ET was 1.615cm with a specificity of 80.0%.4.Multivariate logistic regression analysis showed that ET and VFI were independent risk factors of diagnosing endometrial malignant lesions.When other factors remaining unchanged,patients aged above 51 years had a 48.898 times malignant risk of that of under 51 years old.Patients with ET at 1.615 and above had a 4.849 times malignant risk of that of below 1.615.The patients with VFI at 2.6765 and above had a 13.771 times malignant risk of that of 2.6765 or less.5.There were no significant differences in the distribution of 5 endometrial parameters between different stages and grades of endometrial cancer(stages IA and IB,stage ? and stage ?,and grades IA,G1,G2 and G3).Conclusions1.Rflow stereoscopic blood flow imaging mode is more stereoscopic and intuitive than 2D-TVS blood flow display,which is helpful for predicting the diagnosis of benign and malignant lesions.2.Endometrial parameters such as ET,EV,VI,FI and VFI have certain value in the differential diagnosis of benign and malignant qualitative endometrial lesions.3.Endometrial parameters such as ET,EV,VI,FI and VFI showed no significant difference in different stages and grades of endometrial cancer.BackgroundTumor growth,infiltration and metastasis are complex processes,which are believed to be mainly dependent on angiogenesis,proposed by Folkman in the 1970s.The formation of tumor blood vessels is based on the vascular network to generate new capillaries around and inside the tumor.There are many growth factors regulating the tumor angiogenesis,and vascular endothelial growth factor(VEGF)is one of the important factors(VEGF).VEGF,also known as vascular permeability factor(VPF),is a protein within the tumor blood vessels that increases vascular permeability and has a strong pro-angiogenic effect.VEGF is also a heparin-binding growth factor,specific to vascular endothelium.VEGF can provide nutrition for the growth,infiltration,and remote metastasis of tumor cells by stimulating the proliferations of the vascular endothelial cells and increasing the permeability of the vessels.Studies found that the expression of VEGF in malignant tumors is significantly higher than that in normal tissues and benign tumors.The expression of VEGF in metastatic tumors is also higher than that in non-metastatic tumors.Therefore,the expression level of VEGF may be an important indicator to distinguish between benign and malignant tumors,and the prognosis of patientsCD31,also known as Platelet endothelial cell adhesion molecule(PECAM-1),is mainly used to identify the presence of endothelial cells and quantitatively evaluate microvessel density(MVD),as an important indicator of angiogenesis.It is closely related to the prognosis of the tumor.Previous studies pertaining to endothelial lesions were mostly the ex-vivo retrospective studies about the expressions of VEGF and measurement of MVD of post-surgical endothelial tissues,unable to evaluate the tumoral vasculature before surgery.Ultrasound is the optical presurgical examination to detect tumoral angiogenesis noninvasively,by measuring resistance index(RI)and pulsatility index(PI)of the blood flow using pulse Doppler ultrasound.Nonetheless,only regional blood flows of the lesions can be assessed through this way,and the assessment of the whole endothelial lesions cannot be done effectively,which is more meaningful for guiding treatment and predicting prognosis.Minimal studies have used in-vivo flow parameters,including VI,FI,VFI or VI of transvaginal 3D power-Doppler ultrasound to evaluate angiogenesis of endothelial cancers,and found good correlations of these parameters between the expressions of VEGF and MVD value.The studies supposed that the blood flow parameters might be utilized as relatively objective indicators for evaluating tumoral angiogenesis.Objective:To investigate the association of the blood flow parameters measured by transvaginal three-dimensional power-Doppler ultrasound and the angiogenesis of endometrial cancer.MethodsThe study was designed as a retrospective study.A total of 214 patients with endometrial lesions referred to Yantai Yuhuanhding Hospital from July 2018 to August 2019 were recruited.Conventional 2D-TVS was perfomed to measure the ET,and blood flow was assessed preliminarily by color-Doppler ultrasound.Then EV,VI,FI and VFI of 3D-PDA were calculated using VOCAL,the same with the methods in Part 1.The expressions of VEGF and CD31 in benign and malignant endometrial lesions,and in lesions with varied clinical and pathological features were analyzed.The correlations of the blood flow parameters(VI,FI,VFI)of transvaginal 3D power-Doppler ultrasound,and VEGF expressions and MVD were also evaluated.Results1.The VEGF-positive rate(22.4%vs 85.5%)and the MVD value(26.94± 10.30 vs 44.94±10.94)in benign and malignant endometrial lesions of were significant different(both P<0.001).2.The differences of VEGF-positive rate(85.0%vs 100%,P<0.001)and MVD value(44.94±11.28 vs 45.00±7.22,P=0.021)between type ? and type ? lesions of endometrial cancer were statistically significant.3.The VEGF-positive rate and MVD value in stage ?A,stage ?B,stage ? and above lesions of endometrioid adenocarcinoma was 82.5%vs 85.7%vs 100.0%,46.74±12.06 vs 42.29±8.26 vs 39.67±13.05,respectively.There demonstrated no significant difference in the positive rate and MVD value between stage ?A and ?B(P=0.443,P=0.311).The difference of VEGF expression and MVD in stage IA,stage IB and stage ? and above were statistically significant(P=0.003,P=0.017).The VEGF-positive rate and MVD value were not significantly different in IAG 1 and IAG2 lesions of endometrioid adenocarcinoma(P=0.709,P=0.37).4.There was no significant correlation between blood flow parameters VI,FI,VFI and VEGF expression and MVD in endometrial cancer.Correlation coefficient of VI and VEGF,MVD(r1=0.168,P=0.359;r2=0.110,P=0.551.r1=-0.121,P=0.510;r2=-0.204,P=0.262);Correlation coefficient of FI and VEGF,MVD(r1=0.159,P=0.384;r2=0.047,P=0.797.rl=-0.207,P=0.255;r2=-0.241,P=0.184).Correlation coefficient of VFI and VEGF,MVD(r1=0.189,P=0.300;r2=0.052,P=0.779;r1=-0.098,P=0.595;r2=-0.215,P=0.238).ConclusionsThe VEGF-positive rates and MVD values were relatively high in malignant endometrial lesions,type ? of endometrial cancer,and stage ? and above lesions of type ? endometrial cancer,indicating that the angiogenesis of endometrial cancer tissues might play a crucial role in the classification of the tumor,and the pelvic metastasis.No significant correlation was found between the blood flow parameters measured by transvaginal 3D ultrasound(VI.FI,and VFI)and VEGF expressions and MVD values.