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Ultrasonographic 3D Evaluation in The Diagnosis of Bladder Endometriosis: A Prospective Comparative Diagnostic Accuracy Study
Ultrasonographic 3D Evaluation in The Diagnosis of Bladder Endometriosis: A Prospective Comparative Diagnostic Accuracy Study
aDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI),
University of Genova, Genova, Italy; bAcademic Unit of Obstetrics and Gynecology, IRRCS Ospedale Policlinico
San Martino, Genova, Italy; cPiazza della Vittoria 14 SRL, Genova, Italy; dUnit of Obstetrics and Gynecology, IRRCS
Ospedale Policlinico San Martino, Genova, Italy; eUnit of Obstetrics and Gynecology, Gaslini Institute, Genova, Italy
c d
Fig. 1. Ultrasonographic acquisition of BE nodule of the posterior wall of the bladder base sagittal plane (a), ax-
ial plane (b), coronal plane (c), and 3D reconstruction (d). * Endometriotic nodule. BE, bladder endometriosis.
ine wall. During each ultrasonographic exam, the following Statistical Analysis
parameters were evaluated: presence of BE, largest diameter and Accuracy, sensitivity, specificity, positive predictive value, neg-
volume of BE, distance between the endometriotic nodule, and ative predictive value, positive likelihood ratio, and negative likeli-
the closest ureteral meatus. hood ratio were evaluated for TVS with and without 3D acquisi-
The location of the ureteral meatus for estimating its distance tions. Efficacy parameters were calculated with 95% confidence
from the nodule was identified by visualization streaming of urine intervals (CIs). The accuracy of diagnostic procedures in the diag-
from the ureteric orifice by color Doppler, as previously described nosis of BE was compared by using McNemar’s test with the Yates
[14]. The size of the nodule was measured in 3 orthogonal planes. continuity correction. The limits of agreement between the mea-
The volumes of BE nodules were calculated using the ellipsoid for- surements were calculated as mean difference ±2 standard devia-
mula (volume = 0.523 × length × depth × width). During 3D ren- tions (SDs) of the difference. The Kolmogorov-Smirnov normal-
dering, multiple acquisitions were made in the sagittal and coronal ity test was employed to assess the normality of distribution of
planes. Tomographic ultrasound imaging (TUI) was used for eval- continuous variables. A post-power calculation was performed to
uating the infiltration of the bladder muscular layer. The volume calculate the statistical power of the study in evaluating the preva-
of the nodule was assessed using the virtual organ computer-aided lence of disease and the ultrasound accuracy based on the previous
analysis (VOCAL; online suppl. Fig. 1), as reported in our previous data reported in the literature. The data were analyzed by SPSS
experience [16]. Two specific quality enhancement tools (GE software version 24.0 (SPSS Science, Chicago, IL, USA). p values
Healthcare Ultrasound, Milwaukee, WI, USA) were applied dur- <0.05 were considered statistically significant.
ing 3D acquisitions in surface mode: the advanced Speckle Reduc-
tion Imaging, which improves the visibility of nodules by high-
definition contrast resolution and the CrossXBeamCRITM, allow-
ing a high enhancement of tissue and border differentiation. Results
In TVS, BE lesions appear as a filling defect of the posterior
wall, with a variable protrusion into the lumen, with an iso/hy- Figure 2 shows the flow of participants in the study.
poechoic aspect sometimes visible with small transonic formations During the study period, 523 patients referred to our in-
that usually are not vascularized. In the 3D, BE lesions can be vi-
stitution with clinical suspicion of DE; 194 (37.1%) pa-
sualized as intraluminal spiculated nodules, with a retracting line
all around the nodule (Fig. 1). Patients underwent surgery within tients underwent surgical approach; among these latter,
8 weeks from the ultrasonographic exams. Imaging findings were BE was found in 34 patients (17.5%; 95% CI: 12.8–23.5%)
compared to surgical and histopathological results. from the surgery and confirmed with histopathologic
130.209.6.61 - 8/13/2021 2:14:22 PM
Within 1 week
Another operator
performed ultrasound
with 3D acquisition
Within 8 weeks
BE was confirmed at
Fig. 2. Flow of participants of the study. surgery in
34 patients
DE, deep endometriosis; BE, bladder endo-
metriosis.
analysis, detecting the infiltration of the bladder muscular 29/34) of the cases, respectively; the McNemar test dem-
layer by endometriotic tissue. After performing a post hoc onstrated that the 2 techniques have similar diagnostic
power calculation based on the previous studies [17–20], performance (p = 0.125). After performing a post hoc
the sample size of the study was judged appropriately for power calculation based on a previous meta-analysis [10],
the prevalence observed (power 98.1% and alpha 0.05). the sample size of the study was judged appropriately for
The mean (±SD) largest diameter of BE was 20.2 (±9.1) the diagnostic accuracy estimated (power 100% and alpha
mm. Eighteen nodules (52.9%) were located in the blad- 0.05). Table 2 reports the diagnostic parameters of both
der base, 8 (23.5%) were in the bladder dome, 3 (8.8%) techniques, and Figure 3 shows their ROC curves.
were in the bladder trigone, and 5 (14.7%) in the extra- Both exams similarly estimated the largest diameter of
abdominal bladder. At least another concomitant DE BE (mean difference ± SD, 95% CI: −3.12 ± 4.5 mm; −6.7
nodule was found in 27 patients (79.4%) and a concomi- to 2.3 mm; −2.98 ± 3.9 mm; −5.8 to 2.1 mm; and p = 0.652)
tant endometrioma in 7 patients (20.5%). Evidence of fo- and the distance between the endometriotic nodule and
cal/diffuse adenomyosis was detected in 12 patients the closest ureteral meatus (−8.62 ± 7.2 mm; −11.6 to −2.9
(35.3%); among these, 6 women had BE located in the mm; −7.44 ± 6.5 mm; −9.2 to −1.1 mm; and p = 0.341)
bladder dome, 4 in the bladder base, and 1 in the bladder (Fig. 4). The ureteral meatus was bilaterally identified by
trigone; in 4 cases, BE was considered an extension of dis- both techniques in 30 of 32 (93.8%) women.
ease for the anterior uterine adenomyotic wall. The other However, TVS with 3D reconstructions was more
demographic characteristics of the study population are precise in estimating the volume of BE (5.44 ± 4.1 cm3;
reported in Table 1. −1.3 to 8.1 cm3; 3.11 ± 2.8 cm3; −1.5 to 5.3 cm3; and p =
Both the exams were able to detect the endometriotic 0.031). In one case (2.9%), TVS without and with 3D re-
bladder nodule in 82.4% (n = 28/34) and 85.3% (n = constructions detected the infiltration of the intramural
130.209.6.61 - 8/13/2021 2:14:22 PM
True positive, n 28 29
True negative, n 147 144
False negative, n 6 5
False positive, n 13 16
Sensitivity1 82.2% (63.1–93.9%) 85.3% (67.3–96.0%)
Specificity1 91.9% (83.2–97.0%) 90.0% (84.3–94.2%)
Positive likelihood ratio2 10.1 (4.6–22.2) 8.5 (5.3–13.9)
Negative likelihood ratio2 0.2 (0.09–0.4) 0.2 (0.07–0.4)
PPV1 79.3% (63.6–89.4%) 64.4% (52.7–74.7%)
NPV1 93.6% (86.0–96.8%) 96.6% (92.8–98.5%)
BE, bladder endometriosis; PPV, positive predictive value; NPV, negative predictive
value; CI, confidence interval. 1 Values presented as percentages and 95% CI. 2 Values
presented as ratio and 95% CI.
high clinical suspicion of BE after ultrasonographic nega- 114/194; 58.8%); moreover, there was no negligible prev-
tive findings. Furthermore, different from our study, the alence of urinary symptoms; this may justify the presence
authors preoperatively compared TVS results with those of multiple nodules of DE, including BE, in this popula-
obtained by cystoscopy, in particular for estimating the tion. Indeed, the extensive experience of the gynecolo-
distance between the ureteral meatus and the endome- gists performing ultrasonographic scans, respectively,
triosis lesion. When a nodule of BE is diagnosed by ultra- may have influenced the accuracy of TVS with and with-
sound, cystoscopy may be considered for assessing the out 3D modality in assessing the presence and character-
grade of infiltration and ureteral meatus involvement. istics of BE.
However, as previously reported [30], nodules that par-
tially affect the muscular layer tend to have normal cysto-
scopic findings, thereby minimizing the need for this Conclusion
technique.
Our study has some limitations. First, a second expert This diagnostic accuracy study confirmed that trans-
sonographer performed real-time 3D acquisitions. As vaginal ultrasound has an elevated accuracy for diagnos-
done in a previous study done by our research group [12], ing BE. The addition of 3D reconstructions does not im-
evaluating off-line 3D reconstructions would have avoid- prove the performance of TVS in diagnosing the presence
ed the bias related to the influence of 2D scan, which was and characteristics of BE. However, the volume of BE may
necessary for acquiring 3D images. However, the current be more precisely assessed by 3D ultrasound.
study aimed to investigate if 3D reconstructions improve
the performance of TVS in assessing the presence and
characteristics of BE. Overall, in our clinical practice, we Acknowledgements
deem that 3D modality should be complementary to 2D
scan and should be dynamically done during convection- This preliminary analysis will be presented as a virtual poster
in the ISUOG 30th World Congress on Ultrasound in Obstetrics
al TVS. Additionally, although a post-power calculation and Gynecology.
was performed to calculate the statistical power (based on
results of previous studies) for evaluating the prevalence
of BE and the ultrasound accuracy, we did investigate the Statement of Ethics
optimal sample size a priori. In our study, the prevalence
of BE was approximately 17%; this prevalence may have All the procedures performed in studies involving human par-
been influenced by the selected study population due to ticipants were in accordance with the ethical standards of the in-
the position of the institution as the referral center spe- stitutional and/or national research committee and with the 1964
Helsinki declaration and its later amendments or comparable eth-
cialized in the diagnosis and treatment of severe endome- ical standards. The local Ethics Committee approved the study
triosis; the majority of patients underwent surgery suf- protocol (CE Liguria N 10074/2019). Women participating in the
fered from pain persistent to the medical treatment (n = study provided written informed consent.
130.209.6.61 - 8/13/2021 2:14:22 PM
The authors have no conflicts of interest to declare. F.B.: protocol/project development and writing/editing. C.S.:
data collection or management. S.F.: writing/editing the manu-
script.
Funding Sources
References
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