Journal of Mid-life Health

ORIGINAL ARTICLE
Year
: 2022  |  Volume : 13  |  Issue : 2  |  Page : 145--151

Combination of B-mode ultrasound and doppler ultrasound in approaching to uterine intracavitary pathologies among women above 40 years with abnormal uterine bleeding: A multicenter-based study from vietnam


Phuc Nhon Nguyen1, Van Tuan Nguyen2,  
1 Department of High-Risk Pregnancy, Tu Du Hospital, Ho Chi Minh City, Vietnam
2 Department of Obstetric and Gynecology, Hue Medical College, Thua Thien Hue, Vietnam

Correspondence Address:
Phuc Nhon Nguyen
Department of High-Risk Pregnancy, Tu Du Hospital, Ho Chi Minh City
Vietnam

Abstract

Objectives: To determine the role of B-mode ultrasonography combined with Doppler ultrasonography in diagnosing uterine intracavitary pathology in perimenopausal and postmenopausal women with abnormal uterine bleeding (AUB). Patients and Methods: This prospective observational study included 150 women aged >40 years with AUB hospitalized at Hue University Hospital and Hue Central Hospital between 6/2016 and 6/2019. All participants were investigated by B-mode transvaginal ultrasound and Doppler transvaginal ultrasound, and the result of sonography was compared to the histopathological endpoint. Results: The morphological features, structure, margin, border line of the endometrial-mass lesion, intracavitary uterine fluid, and Doppler signal clearly differed between benign and malignant intracavitary pathologies (P < 0.0001). However, echogenicity had a limited value in distinguishing between uterine intracavitary pathologies (P = 0.1). The sensitivity and specificity of the pedicle sign in diagnosing endometrial polyps were 50.0% and 97.6%, respectively; for the circular pattern in subendometrial fibroids were 46.2% and 100.0%, respectively; for the multiple vessel pattern in endometrial cancer were 64.0% and 96.0%, respectively, and for the scattered-vessel pattern in endometrial hyperplasia were 43.96% and 56.43%, respectively. Conclusions: Ultrasound B-mode combined with Doppler as a noninvasive tool was significantly valuable in the diagnostic procedures for uterine intracavitary pathology in perimenopausal and postmenopausal women with AUB. It could also help differentiate malignant diseases from benign endometrial changes.



How to cite this article:
Nguyen PN, Nguyen VT. Combination of B-mode ultrasound and doppler ultrasound in approaching to uterine intracavitary pathologies among women above 40 years with abnormal uterine bleeding: A multicenter-based study from vietnam.J Mid-life Health 2022;13:145-151


How to cite this URL:
Nguyen PN, Nguyen VT. Combination of B-mode ultrasound and doppler ultrasound in approaching to uterine intracavitary pathologies among women above 40 years with abnormal uterine bleeding: A multicenter-based study from vietnam. J Mid-life Health [serial online] 2022 [cited 2022 Dec 10 ];13:145-151
Available from: https://www.jmidlifehealth.org/text.asp?2022/13/2/145/356195


Full Text



 Introduction



Abnormal uterine bleeding (AUB) is defined as bleeding from the uterus that differs from the normal menstrual cycle in quantity, duration, regularity, and frequency without relation to pregnancy. The frequency occurs in 70.0% of perimenopausal and postmenopausal women. Among them, uterine intracavitary pathologies (UIPs) are the common causes of uterine bleeding, including endometrial polyps (EP), endometrial hyperplasia (EH), subendometrial fibroids (EF), and endometrial cancer (EC).[1] Investigating the causes of AUB in a comprehensive assessment of perimenopausal and postmenopausal women is a fundamental step in gynecological practice. Currently, there are many tools with different advantages and disadvantages such as imaging modalities (sonography, computed scan, and magnetic resonance imaging) and surgical procedures (blind biopsy and hysteroscopy). Interestingly, transvaginal B-mode ultrasound is an easily accessible and safety which investigates the abnormal structure and morphological features of the uterus. Moreover, there have been many studies showing that Doppler ultrasound is probable to detect vascular proliferation feeding gynecological tumors. The dominant vascular proliferative phenotype helps to differentiate between UIP. Cogendez et al. had shown the value of dopper transvaginal ultrasound in the diagnosis of polyps by pedicle vascular and EF by circle vascular as imagine soft markers. The sensitivity, the positive predictive values (PPV) were 80.0%, 100.0% and 72.0%, 100.0%, respectively.[2] Study of Alcazar et al. suggested that multiple angiogenesis sign was characteristic of EC with sensitivity of 78.8%, specificity of 100.0%, and PPV of 100.0%, while EH is predominantly scattered vascular proliferation.[3] Therefore, we aimed to determine the value of B-mode ultrasound combined with transvaginal Doppler to elucidate this approach method in perimenopausal and postmenopausal women with AUB.

 Patients and Methods



This prospective observational study was conducted according to the ethics committee of our institution and was approved by our institutional review board. All females gave us a written informed consent. This study was done at Hue Central Hospital and Hue University Hospital between June 2016 and June 2019.

The inclusion criteria were as follows: all women above 40 years of age complaining with AUB; the patient underwent uterine B-mode ultrasound combined with Doppler and had histopathological results for comparison.

The exclusion criteria included: bleeding related to pregnancy, hormone replacement therapy, tamoxifen, coagulation disorders, bleeding not originating from the uterine cavity, abnormalities associated with the cervix, iatrogenic bleeding, and lack of information on the study protocol.

Overall, a total of 150 women were recruited and participated in this study.

All patients underwent thorough disease history, general examination, gynecological examination, cervical cytology (Pap. smear), and laboratory investigations (complete blood count, liver function tests, kidney function tests, and a coagulation profile). Transvaginal sonography was performed in all patients using a 5–7.5 MHz endovaginal transducer.

All patients underwent interventional procedures such as endometrial biopsy, hysteroscopy, myomectomy, or hysterectomy. These indications were decided according to the following medical protocol applied at our hospital [Figure 1].{Figure 1}

Features of morphological ultrasound of intracavitary abnormalities

Intracavitary fluid, structure, echogenicity, border, and endometrium-myometrial boundary of the endometrium/lesion were classified according to the International Endometrial Tumor Analysis (IETA) System when evaluated using B-mode ultrasound [Figure 2]. During the evaluation, the practitioner first determined the image of the uterus, occupying 2/3 of the screen to access the clearest image.[4],[5],[6]{Figure 2}

Determination of predominant angiogenosis pattern

According to Doppler flow mapping, four different vascular patterns were defined as description in [Figure 3].{Figure 3}

Multiple-vessel pattern (Pattern A): Multiple vessels were found within the endometrium and in the myometrial–endometrial interface. This pattern is considered a characteristic of EC as it has been demonstrated that important neoangiogenic phenomena occur in EC within the tumor tissue and the surrounding areaPedicle-vessel pattern (Pattern B): A single vessel was identified penetrating the endometrium from the myometrium. This pattern was considered as characteristic of EP as this vessel is thought to correspond to the vascularized polyp's pedicleScattered-vessel pattern (Pattern C): Disseminated vasculature within the endometrium. This pattern is considered characteristic of EH[3]Ring-shaped-vessel pattern (Pattern D): Increased vascularity in the peripheral surrounding of the tumor, common in uterine fibroids.

All morphological and structural features of endometrium, lesion mass, and intracavitary uterine abnormalities were evaluated on B-mode ultrasound following the standards of IETA.

Phenotype of vascular angiogenesis such as single-vessel, scattered-vessel, multiple-vessel, rim-likely vessel (ring-shaped vessel and circle vessel), no vascular flow were determined by sonographer with 5-year experience.

EH, EP, EF, and EC was collected from histopathological result.

All of them were coded in categorical variables.

Statistical analysis

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 20.0 (IBM Corp., Armonk, NY, USA).and P < 0.05 was considered to be statistically significant.

 Results



Regarding the structure of the endometrium/lesion mass, most EFs and malignant lesions had heterogeneous-mixed echogenicity, while other benign pathologies were predominantly homogenous. Most lesions had hyperechogenic echogenicity, however, in fibroids, hypoechoic form was predominant (7/13 cases). Regarding to endometrial-myometrium junction, almost all malignant lesions of cases were irregular, the boundary was not clear, and discontinuous, whereas, the benign lesions had regular margins, and the boundaries were clearly observed. According to the intracavitary lesion, the majority of cases of benign lesions were not identified with fluid (88.0%), different from EC, 56.0% of cases presented with fluid.

In the malignant group, detectable Doppler signals were present in 24/25 (99.0%) cases, more than those in the benign group, 73/125 (58.4%) cases. In the benign group, only 48.4% of cases of EH were detected with Doppler signal, but 81.2% of polyps and 100.0% of EFs had Doppler signal.

In the EC group, multiple vessel pattern occupied to 64.0% of cases. In the cases of polyp, the single-vessel form accounted for 50.0%. In the group of EF group, rim-like vessel accounted for 46.2% of the lesions. However, in the cases of EH, all cases did not have vascular proliferation, however, if there was Doppler signal, most of them had a scattered vessel pattern (44.0%). Most of the dominant vascular phenotypes had low diagnostic sensitivity for intracavitary pathology (<80.0%), but high specificity (over 80.0%), with the exception of scattered-vessel patterns that could be seen in many different pathologies. The rim-likely form was a specific feature of fibroids that was not appeared in others pathologies (Sp: 100.0%, PPV: 100.0%). In 150 cases, there were 25 cases with histopathological endpoint in EC, and Doppler ultrasound identified accurately 21/25 cases. Similarly, regardless of EH, there were 76/91 cases diagnosed by ultrasound compatible with histopathological results, polyps in 13/16 cases and EFs in 12/13 cases [Table 1].{Table 1}

 Discussion



Morphological features of uterine intracavitary pathologies on B-mode ultrasound

[Table 2] showed the echogenic structure of the endometrial lesions in the malignant group accounted for 88.0% was mixed-heterogeneous, compared with 37.6% in the benign group. The main echogenic structure of the benign group was 62.4% homogeneous (P < 0.0001). Similar to the study by Ashour et al., in the malignant group, 100.0% of the echogenic structures were heterogeneous and in the benign group, 51.0% of the cases were homogenous.[7] In a study by Madkour 90.0% of the malignant group had mixed echogenic, whereas, 92.0% of the benign group had homogeneous echogenicity.[8]{Table 2}

Regardless of echogenicity, it was found that the majority of echogenicity in the EC group was hyperechogenic (76.0%) compared with the hypoechogenic form (24.0%), similar to that of Razik et al.[9] In the benign group, 88.2% was hyperechoic, 10.2% were hypoechoic and 1.6% were homogenous with the myometrium. According to Madkour et al. in the group of benign pathologies, regardless of the echogenicity of polyps, hyperechogenicity accounted for 96.9% (31/32) cases, hypoechogenicity only accounted for 3.1% (1/10 cases).[8] Similarly, the echogenic level of polyps was mostly hyperechogenicity, accounting for 91.2% (31/45) cases, and three cases of hypoechogenicity (8.8%) were observed in the study by Talaat et al.[10] In our study, respectively, those cases were 87.5% and 12.5%, respectively, and none of them were homoechogenic. In contrast, in EF, echogenicity accounted for only 5.9% (1/17 cases), hypoechogenicity for 47.1% (8/17 cases) and homoechogenicity for 47.1% (8/17 cases), P < 0.001. According to Cil et al. different from our study, hyperechogenicity accounted for 53.8%, hypogenicity accounted for 46.2%.[11] By Cogendez et al., in the group of EFs, echogenicity accounted for 11.1% (2/18 cases), homoechogenicity accounted for a half of cases (9/18 cases), hypoechogenic form was 38.9% (7/18) cases.[2] Thus, the degree of echogenicity is not a valuable feature to distinguish between benign and malignant pathologies, and is only suggestive of distinguishing between pathologies in the group of benign lesions.[12]

According to the present study, 20/25 cases of EC with irregular borders were unidentified, making up to 80.0% of cases, whereas, in EH, 97.8% of cases were still clearly observed in the endometrium-myometrial boundary of the uterus and 100.0% of cases of polyp and fibroid were detected clearly with P < 0.0001. The myometrial-endometrial boundary in EC was not identified in 5/6 cases (83.3%), and was intact in 1/6 cases (16.7%). In contrast, clear borderline EH in 32/32 cases (100.0%), was also described by Razik et al.[9]

Regardless of endometrial-myometrial junction, in the benign group, the large majority was regular, accounted for 94.4% of case, irregular junction only accounted for 5.6% of case. In contrast, in the malignant group, there were 24 irregular cases out of 25 (96.0%) (P < 0.0001). According to Ashour et al. borderline in the benign group were regular accounting for 94.4% of cases, and irregular accounted for 5.6%. In contrast, for endometrial margins in the malignant group, regular margins accounted for 25.0%, irregular margins accounted for 75.0%.[7] This can be explained by the invasive tendency of malignant lesions, thus, the endometrium-myometrial boundary is lost, resulting in the border of the endometrium/lesion border becoming irregular.

In our study, there were 14/25 cases in EC, accounting for 56.0%, including hypoechogenic and mixed echogenic fluid, in contrast, in benign diseases, only 11.8% of cases were present (P < 0.0001). Of the 9/91 cases of EH, 3/16 cases of polyps, 2/13 cases of EFs and 1/5 cases in other groups had fluid, most of which were negative and hypoechogenic. In the study of Talaat et al., there were 3/45 cases of polyps with fluid.[10] In the study by Razik et al., 83.3% of EC cases had intracavitary uterine fluid and 100.0% of other diseases were absent of fluid through ultrasound (P < 0.001).[9] Thus, the presence of fluid in cavitary uterine in perimenopausal and postmenopausal women with AUB could be found in benign disease but it is also a suggestive sign of EC, especially, in women with postmenopausal bleeding,[12],[13] In benign pathology, the presence of fluid can help in the differential diagnosis of EP from fibroids.[14]

Presence of Doppler signal in uterine intracavitary pathologies

[Figure 4] shows that most of the malignancy group had a Doppler signal (96.0%), in the contrast, in the benign group, this was detected only 58.4%. This feature is consistent with the vascular proliferative properties of malignancies. In a study by Alcazar et al., signs of vascular proliferation were found in of 32/33 cases of EC, and only 1/33 cases had no Doppler signal.[3] Similarly, in a recent study by author Li and Li, 66.7% of EC cases had Doppler signal, whereas, only 11.1% of cases were detected with Doppler sign in the benign group. Therefore, the presence of Doppler signal in endometrial lesions is strongly associated with the risk of malignancy, odds ratios: 16.0, 95% confidence interval: 1.3–192.8,[15],[16] However, we also found that in the benign group, Doppler signal was present in 13/16 cases of polyps (81.2%) and 13/13 cases of EFs (100.0%).{Figure 4}

Distribution characteristics and diagnostic value of dominant vascular phenotypes

Diagnostic value of endometrial cancer by signs of multiple angiogenesis

In the present study, the predominant pattern in EC was multiple vessel: 16/25 cases (64.0%), and a scattered-vessel pattern accounted for 32.0%, similar to result of El Kady et al. in Egypt.[17] In a study by Madkour signs of multiple angiogenesis were found in 7/10 cancer cases, remaining 1 case of disseminated vascular proliferation and 2 cases of no Doppler signal.[8] The LR (+) index was 16.0, showing signs of multiple vascular proliferations that were valuable for diagnosing EC in our study [Table 3].{Table 3}

Valuable diagnosis of pedicle vessel pattern

[Table 4] shows that in the polyp group, the predominant pattern was pedicle vascular in 8/16 (50.0%) cases, scattered vessels in 3/16 cases (18.8%) and multiple vessel in 1/16 (5.9%) cases. In the study of Amreena et al. the vascular peduncle sign was found in 13/16 cases, accounting for 76.5% and this author found that the polyp size was related to the pedunculated vascular sign, the more common vascular peduncle sign with the larger size of polyp, the average size of polyps in this study was 17.77 mm with P = 0.044.[18] This assessment differs from that of Medina et al. who found no relationship between polyp size and pedunculated vessel sign.[19] The LR (+) index of 22.32 showed the value of the pedicle vessel sign to diagnose polyps in our study [Table 3].{Table 4}

Valuable diagnosis of rim-likely vessel pattern

In our study, the predominant vascular pattern of EF was rim-likely vascularity in 6/13 cases (46.2%), followed by scattered-vessel in 4/13 cases (30.8%), multiple vessel occupied 2/13 cases (15.4%) and pedicle vessel pattern in 1/13 cases (7.7%). According to Cogendez et al., among fibroids, 72.2% had signs of rim-likely vascularity, and there were 27.8% had multiple angiogenesis and there was no case with single vascular pattern.[2] Thus, in EF, circular flow may be present or absent, but if the circular vessel pattern was present, the diagnostic value for the fibroid was 100.0%, so this was an extremely specified phenotype for fibroid [Table 3].

Diagnostic value of endometrial hyperplasia by signs of disseminated vascular proliferation

According to our study, in EH group, 47/91 cases were diagnosed without vascular proliferation, accounting for 51.6%, 40/91 cases with scattered vascular proliferation accounting for 44.0%, 2/91 cases with multiple vessel patterns, and 2/91 cases had pedicle vessel pattern. According to Cogendez et al., signs of disseminated vascular proliferation were found in 72.7% of EH cases, however, this sign was also observed in 66.7% cases of endometrial atrophy cases.[2] The signs of disseminated vascular proliferation were common but uncommon in EH, it could be seen in other UIP. The diagnostic value of scattered vascular sign in EH was low, with the sensitivity, specificity, PPV, negative predictive value, and accuracy of 43.96%, 56.43, 68.97%, 34.51%, and 54.0%, respectively, and the positive likelihood index LR (+) was 1.0 [Table 3].

 Conclusions



The morphological, structural, border, endometrial- myometrium junction, fluid, and Doppler signal are clearly different among uterine pathologies, between benign and malignant groups, whereas, the level of echogenicity was less useful. Using Doppler ultrasound, we found a difference in the proportion of dominant vessel patterns among UIP.

Author's contributions

Phuc Nhon Nguyen was reponsible for data analysis, contributed to writing and editing the manuscript. Van Tuan Nguyen supervised the study. Both authors read and approved the final manuscript.

Acknowledgment

We thank the patients, who agreed to allow us to participate in our research and to publish their clinical data. The authors are also grateful to all teachers and colleagues working at the Department of Gynecology, the Department of Image Diagnostic, and the Department of Histopathology at Hue Central Hospital and at Hue University Hospital. We are thankful directly to PhD. M.D Van Duc Vo, Ph. D. M.D Thao Nguyen Nguyen Tran, M.D. Ngoc Ty Nguyen Thi, M.D. Diem Thu Nguyen Thi, M.D. Phuong Minh Nguyen Thi, M.D. Thanh Thuy Tran Thi. All of them attributed to provide us the pictures, take care for patient and shared their precious experiences related to manage this clinical course with us.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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