Acta Radiologica http://acr.sagepub.com/
Ultrasonographic indications for conservative treatment in pregnancy-related uterine arteriovenous malformations Tae Young Lee, See Hyung Kim, Hee Jung Lee, Mi Jeong Kim, Sang Kwon Lee, Young Hwan Kim and Seung Hyun Cho Acta Radiol published online 11 December 2013 DOI: 10.1177/0284185113514222 The online version of this article can be found at: http://acr.sagepub.com/content/early/2013/11/29/0284185113514222
Published by: http://www.sagepublications.com
On behalf of: Nordic Society of Medical Radiology
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>> OnlineFirst Version of Record - Dec 11, 2013 What is This?
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Acta Radiol OnlineFirst, published on December 11, 2013 as doi:10.1177/0284185113514222
Original Article
Ultrasonographic indications for conservative treatment in pregnancy-related uterine arteriovenous malformations
Acta Radiologica 0(0) 1–8 ! The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185113514222 acr.sagepub.com
Tae Young Lee1, See Hyung Kim1, Hee Jung Lee1, Mi Jeong Kim1, Sang Kwon Lee1, Young Hwan Kim1 and Seung Hyun Cho2
Abstract Background: Uterine arteriovenous malformations (AVMs) are known to spontaneously regress. Purpose: To assess the predictive value of ultrasonography for patients requiring conservative treatment for pregnancy related to AVMs. Material and Methods: Our prospective study included 75 patients (conservative management:therapeutic management ¼ 45:30) with vaginal bleeding from pregnancy-related AVM. Clinical and ultrasonography examinations were reviewed, and the following information was gathered: complete blood count, AVM maximal diameter, AVM echogenicity, retained product of conception, number of blood vessels, and spectral Doppler (pulsatility index [PI], resistance index [RI], peak systolic velocity [PSV], time-averaged maximum velocity [TAMXV]). The Doppler criteria by Timmerman (mean PSV >70 cm/s: therapeutic management, mean PSV < 52 cm/s: conservative management) were used for the initial management selection. The association between experimental variables and outcomes was assessed to determine their usefulness for predicting conservative management. Results: Features strongly associated with conservative management and their accuracy were PSV 89.6%, hemoglobin 84.7%, RI 83.1%, TAMXV 79.3%, and PI 78.6%. The overall accuracy for correct outcome classification was 64 (85.3%) of 75 patients. Most patients with conservative management had quicker improvement of symptoms and spontaneous regression at follow-up. Conclusion: Ultrasonography can accurately predict selection of conservative management.
Keywords Arteriovenous malformations (AVMs), uterus, ultrasonography Date received: 10 June 2013; accepted: 4 November 2013
Introduction Uterine arteriovenous malformations (AVMs) can be either congenital or acquired. Congenital AVMs are rare, whereas acquired or traumatic AVMs are being diagnosed at increasing rates (1–5). A prior dilation and curettage (D&C), therapeutic abortion, uterine surgery, and direct uterine trauma are commonly reported causes of AVMs (3,6–8). Endovaginal ultrasonography with color Doppler is usually used for initial identification (‘‘color mosaic’’ pattern) (9–14). To control bleeding, aggressive therapeutic management such as transcatheter embolization of the uterine arteries or
hysterectomy may be required (15–19). However, a few authors have described regression of the AVM with conservative management or spontaneous 1 Keimyung University, Dongsan Hospital, Department of Radiology, Republic of Korea 2 Kyungbook National University Hospital, Department of Radiology, Republic of Korea
Corresponding author: See Hyung Kim, Department of Radiology, Keimyung University Dongsan Hospital, 216 Dalsungro, Jung-gu, Daegu 700-712, Republic of Korea. Email: [email protected]
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resolution (20–22). There are no clear consensus guidelines, and management of symptomatic AVMs is an open question. Few studies have assessed the criteria for and benefits of conservative management, and suggested that suspicious ultrasonographic features are helpful in deciding a course of management (23,24). The purpose of our prospective study was to assess predictive values of ultrasonography for conservative management in AVMs.
Material and Methods Our study protocol was approved by the local ethical committee and the respective institutional review board. Written informed consent was obtained from each patient.
Patients In this prospective observation study between January 2009 and November 2011, 85 consecutive patients referred for our tertiary institution with symptomatic uterine AVMs were included for close follow-up. The diagnosis was identified based on ultrasonography performed at our institution. Ten patients had no relevant obstetric or gynecologic history, and we presumed these patients to represent cases of congenital AVMs. The remaining 75 patients had pregnancy-associated uterine AVMs owing to D&C for incomplete abortions, retained products of conception, or therapeutic abortions. Each of these patients had at least one episode of intermittent vaginal bleeding within 1–12 weeks after the procedure. Twenty-seven patients had a history of at least one D&C or therapeutic abortion before the procedure after which vaginal bleeding had occurred. No patient had a history of hypertension, anticoagulation therapy, or immunosuppressive medication. The patients ranged in age from 18 to 40 years (median, 25 years). Initial ultrasonography and clinical examination were performed between the first and third day after the first episode of vaginal bleeding. In patients with follow-up for conservative management, ultrasonography, and clinical examinations, including the presence and degree of vaginal bleeding, complete blood count, and serum beta human chorionic gonadotropin test (b-hCG), were performed at 2, 4, and 8 weeks. A b-hCG positive result suggested the presence of trophoblastic or molar tissues, and continuous rise of b-hCG helped to distinguish uterine AVM from these pregnancy-related gestational tumors.
Assessment of AVM The gynecologists were given the tentative diagnosis of uterine AVMs and a description of all ultrasonographic
findings except for the results of spectral Doppler analysis. During a prospective follow-up with careful observation for each patient for a minimum period of the day after the initial diagnosis, only the patients who were anemic or hemodynamically unstable from persistent excessive vaginal bleeding were referred for therapeutic management such as embolization of the uterine arteries, or hysterectomy. Embolization was performed with polyvinyl alcohol (PVA) particles (Ivalon, Boston Scientific, Mississauga, Canada) and absorbable gelatin sponges (Gelfoam, PharmaciaUpjohn, Kalamazoo, MI, USA). The size of the AVM was not measured on angiography, and therefore could not be correlated with the size on ultrasonography. In the ultrasonography findings and the discussions for clinical situations with referring clinicians, the possibility of careful conservative management and spontaneous disappearance of the lesions was highlighted.
Ultrasonography protocol Endovaginal sonography with grayscale, color, and spectral Doppler imaging was performed using either EV-8CV endovaginal transducer (Sequoia 512, Siemens Healthcare, Erlangen, Germany) or C 103Vendovaginal transducer (IU22, Philips Healthcare, Bothell, WA, USA) in all patients. The examinations were performed and interpreted by the same radiologist (KSH) with experience in gynecologic ultrasonography for at least 10 years according to the following protocol. A transducer was used with an image of 140 . The filter was set on 50 Hz, and the Doppler sample volume was 2 mm. Each examination consisted of a standard grayscale ultrasonography of the uterus in both longitudinal and transverse planes. Color ultrasonography was performed to visualize vascularization of the uterus. Color gain adjustment was calibrated on the corresponding normal myometrium such that no signal was visible outside of the uterus. Transducer pressure was minimized in order to avoid compressing the vasculature. Spectral Doppler in both longitudinal and transverse planes was performed to examine vascular pulse curves. Different morphological criteria were assessed in all patients. The uterus was measured in three dimensions, in addition to the double endometrial thickness. The echogenicity of endometrium and overall appearance of myometrium were assessed. Special attention was paid to the maximal diameter of AVM, the presence of retained products of conception, and number of blood vessels with multidirectional flow on color Doppler. In all patients, spectral analysis of blood flow was performed. Pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV, cm/s), and time-averaged maximum velocity (TAMXV, cm/s) were
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
Lee et al.
3
calculated based on the spectral Doppler curve. These values were not included in the ultrasound report but stored on transparent images. If different measurements had been obtained within the same lesion then the set with the highest PSV and matching TAMXV, PI, and RI were used for statistical analysis.
between conservative and therapeutic managements. With this information, we determined the diagnostic performance of ultrasonography for differentiating conservative and therapeutic managements. All statistical analyses were performed using SAS 9.2 software (SAS Institute, Cary, NC, USA). P values 0.05 were considered statistically significant.
Statistical analysis The Kolmogorov-Smirnov test was used to determine whether values were normally distributed. The statistical differences in ultrasonography and clinical features between conservative and therapeutic managements were tested by Student’s t-test, the Fisher exact test, and the Mann-Whitney U test. Guidelines by Timmerman et al. (22,23) and hemodynamic status assessed by the clinician are applied to initial selection of management. A mean PSV of 70 cm/s was associated with likelihood of further therapeutic management, whereas conservative management patients had a mean PSV of 52 cm/s (no problems). A stepwise logistic regression model was used to determine the best predictors of differential diagnosis
Results Univariate analysis Forty-five of the 75 patients were included in the conservative management group, and 30 patients in the therapeutic management group. Ultrasonography features were analyzed in these patients. The average period between the D&C or therapeutic abortion and the first ultrasonography examination was 3.8 weeks, with a minimum of 2 days and a maximum of 12 weeks. The different clinical and ultrasonography features observed in patients with conservative or therapeutic management are summarized in Table 1. Patient age and platelet count were not significantly different
Table 1. Clinical and ultrasonography features by management type. Variable Age (years) D&C or therapeutic abortion Hx First episode Over first episode Complete blood count Hemoglobin (g/dl) Platelet (103/uL) AVM maximal diameter (mm) AVM echogenicity Hypoechoic Iso to hyperechoic Retained product of conception Number of blood vessel Single Multiple Doppler findings Pulsatility index (PI) Resistance index (RI) Peak systolic velocity (PSV, cm/s) Time-averaged maximum velocity (TAMXV, cm/s)
Conservative management (n ¼ 45)
Therapeutic management (n ¼ 30)
28.2 12.8
30.2 11.2
n ¼ 30 n ¼ 15
n ¼ 18 n ¼ 12
11.2 1.7 252.00 13.1 2.7 1.2
9.40 2.2 235.00 14.5 3.0 1.3
n ¼ 18 n ¼ 27 n ¼ 15
n ¼ 18 n ¼ 12 n ¼ 20
n ¼ 32 n ¼ 13
n ¼ 18 n ¼ 12
0.43 0.06 (0.27–0.52) 0.40 0.09 (0.30–0.55) 35.8 13.2 (18–68) 34.2 8.8 (19–52)
0.53 0.08 0.28 0.05 76.2 14.2 51.8 11.0
P value 0.295 0.105
0.015 0.300 0.209 0.03
0.03 0.03
(0.43–0.60) (0.22–0.42) (53–103) (41–91)
0.02 0.01 0.005 0.02
Values are mean standard deviation, and values in parentheses are ranges rounded to nearest whole number.
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between the groups. Fifteen (33.3%) of 45 patients in the conservative management group had more than one prior D&C or therapeutic abortion, which was not significantly different to the 12 (40.0%) of 30 patients in therapeutic management. The previous history of D&C or therapeutic abortion did not differ significantly between conservative and therapeutic management. The mean hemoglobin of patients with conservative management was significantly higher (11.2 1.71, mean standard deviation) than of those with therapeutic management (9.40 2.2, P
Ultrasonographic indications for conservative treatment in pregnancy-related uterine arteriovenous malformations Tae Young Lee, See Hyung Kim, Hee Jung Lee, Mi Jeong Kim, Sang Kwon Lee, Young Hwan Kim and Seung Hyun Cho Acta Radiol published online 11 December 2013 DOI: 10.1177/0284185113514222 The online version of this article can be found at: http://acr.sagepub.com/content/early/2013/11/29/0284185113514222
Published by: http://www.sagepublications.com
On behalf of: Nordic Society of Medical Radiology
Additional services and information for Acta Radiologica can be found at: Email Alerts: http://acr.sagepub.com/cgi/alerts Subscriptions: http://acr.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Dec 11, 2013 What is This?
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
Acta Radiol OnlineFirst, published on December 11, 2013 as doi:10.1177/0284185113514222
Original Article
Ultrasonographic indications for conservative treatment in pregnancy-related uterine arteriovenous malformations
Acta Radiologica 0(0) 1–8 ! The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185113514222 acr.sagepub.com
Tae Young Lee1, See Hyung Kim1, Hee Jung Lee1, Mi Jeong Kim1, Sang Kwon Lee1, Young Hwan Kim1 and Seung Hyun Cho2
Abstract Background: Uterine arteriovenous malformations (AVMs) are known to spontaneously regress. Purpose: To assess the predictive value of ultrasonography for patients requiring conservative treatment for pregnancy related to AVMs. Material and Methods: Our prospective study included 75 patients (conservative management:therapeutic management ¼ 45:30) with vaginal bleeding from pregnancy-related AVM. Clinical and ultrasonography examinations were reviewed, and the following information was gathered: complete blood count, AVM maximal diameter, AVM echogenicity, retained product of conception, number of blood vessels, and spectral Doppler (pulsatility index [PI], resistance index [RI], peak systolic velocity [PSV], time-averaged maximum velocity [TAMXV]). The Doppler criteria by Timmerman (mean PSV >70 cm/s: therapeutic management, mean PSV < 52 cm/s: conservative management) were used for the initial management selection. The association between experimental variables and outcomes was assessed to determine their usefulness for predicting conservative management. Results: Features strongly associated with conservative management and their accuracy were PSV 89.6%, hemoglobin 84.7%, RI 83.1%, TAMXV 79.3%, and PI 78.6%. The overall accuracy for correct outcome classification was 64 (85.3%) of 75 patients. Most patients with conservative management had quicker improvement of symptoms and spontaneous regression at follow-up. Conclusion: Ultrasonography can accurately predict selection of conservative management.
Keywords Arteriovenous malformations (AVMs), uterus, ultrasonography Date received: 10 June 2013; accepted: 4 November 2013
Introduction Uterine arteriovenous malformations (AVMs) can be either congenital or acquired. Congenital AVMs are rare, whereas acquired or traumatic AVMs are being diagnosed at increasing rates (1–5). A prior dilation and curettage (D&C), therapeutic abortion, uterine surgery, and direct uterine trauma are commonly reported causes of AVMs (3,6–8). Endovaginal ultrasonography with color Doppler is usually used for initial identification (‘‘color mosaic’’ pattern) (9–14). To control bleeding, aggressive therapeutic management such as transcatheter embolization of the uterine arteries or
hysterectomy may be required (15–19). However, a few authors have described regression of the AVM with conservative management or spontaneous 1 Keimyung University, Dongsan Hospital, Department of Radiology, Republic of Korea 2 Kyungbook National University Hospital, Department of Radiology, Republic of Korea
Corresponding author: See Hyung Kim, Department of Radiology, Keimyung University Dongsan Hospital, 216 Dalsungro, Jung-gu, Daegu 700-712, Republic of Korea. Email: [email protected]
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
2
Acta Radiologica 0(0)
resolution (20–22). There are no clear consensus guidelines, and management of symptomatic AVMs is an open question. Few studies have assessed the criteria for and benefits of conservative management, and suggested that suspicious ultrasonographic features are helpful in deciding a course of management (23,24). The purpose of our prospective study was to assess predictive values of ultrasonography for conservative management in AVMs.
Material and Methods Our study protocol was approved by the local ethical committee and the respective institutional review board. Written informed consent was obtained from each patient.
Patients In this prospective observation study between January 2009 and November 2011, 85 consecutive patients referred for our tertiary institution with symptomatic uterine AVMs were included for close follow-up. The diagnosis was identified based on ultrasonography performed at our institution. Ten patients had no relevant obstetric or gynecologic history, and we presumed these patients to represent cases of congenital AVMs. The remaining 75 patients had pregnancy-associated uterine AVMs owing to D&C for incomplete abortions, retained products of conception, or therapeutic abortions. Each of these patients had at least one episode of intermittent vaginal bleeding within 1–12 weeks after the procedure. Twenty-seven patients had a history of at least one D&C or therapeutic abortion before the procedure after which vaginal bleeding had occurred. No patient had a history of hypertension, anticoagulation therapy, or immunosuppressive medication. The patients ranged in age from 18 to 40 years (median, 25 years). Initial ultrasonography and clinical examination were performed between the first and third day after the first episode of vaginal bleeding. In patients with follow-up for conservative management, ultrasonography, and clinical examinations, including the presence and degree of vaginal bleeding, complete blood count, and serum beta human chorionic gonadotropin test (b-hCG), were performed at 2, 4, and 8 weeks. A b-hCG positive result suggested the presence of trophoblastic or molar tissues, and continuous rise of b-hCG helped to distinguish uterine AVM from these pregnancy-related gestational tumors.
Assessment of AVM The gynecologists were given the tentative diagnosis of uterine AVMs and a description of all ultrasonographic
findings except for the results of spectral Doppler analysis. During a prospective follow-up with careful observation for each patient for a minimum period of the day after the initial diagnosis, only the patients who were anemic or hemodynamically unstable from persistent excessive vaginal bleeding were referred for therapeutic management such as embolization of the uterine arteries, or hysterectomy. Embolization was performed with polyvinyl alcohol (PVA) particles (Ivalon, Boston Scientific, Mississauga, Canada) and absorbable gelatin sponges (Gelfoam, PharmaciaUpjohn, Kalamazoo, MI, USA). The size of the AVM was not measured on angiography, and therefore could not be correlated with the size on ultrasonography. In the ultrasonography findings and the discussions for clinical situations with referring clinicians, the possibility of careful conservative management and spontaneous disappearance of the lesions was highlighted.
Ultrasonography protocol Endovaginal sonography with grayscale, color, and spectral Doppler imaging was performed using either EV-8CV endovaginal transducer (Sequoia 512, Siemens Healthcare, Erlangen, Germany) or C 103Vendovaginal transducer (IU22, Philips Healthcare, Bothell, WA, USA) in all patients. The examinations were performed and interpreted by the same radiologist (KSH) with experience in gynecologic ultrasonography for at least 10 years according to the following protocol. A transducer was used with an image of 140 . The filter was set on 50 Hz, and the Doppler sample volume was 2 mm. Each examination consisted of a standard grayscale ultrasonography of the uterus in both longitudinal and transverse planes. Color ultrasonography was performed to visualize vascularization of the uterus. Color gain adjustment was calibrated on the corresponding normal myometrium such that no signal was visible outside of the uterus. Transducer pressure was minimized in order to avoid compressing the vasculature. Spectral Doppler in both longitudinal and transverse planes was performed to examine vascular pulse curves. Different morphological criteria were assessed in all patients. The uterus was measured in three dimensions, in addition to the double endometrial thickness. The echogenicity of endometrium and overall appearance of myometrium were assessed. Special attention was paid to the maximal diameter of AVM, the presence of retained products of conception, and number of blood vessels with multidirectional flow on color Doppler. In all patients, spectral analysis of blood flow was performed. Pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV, cm/s), and time-averaged maximum velocity (TAMXV, cm/s) were
Downloaded from acr.sagepub.com at Abant Izzet Baysal University on May 18, 2014
Lee et al.
3
calculated based on the spectral Doppler curve. These values were not included in the ultrasound report but stored on transparent images. If different measurements had been obtained within the same lesion then the set with the highest PSV and matching TAMXV, PI, and RI were used for statistical analysis.
between conservative and therapeutic managements. With this information, we determined the diagnostic performance of ultrasonography for differentiating conservative and therapeutic managements. All statistical analyses were performed using SAS 9.2 software (SAS Institute, Cary, NC, USA). P values 0.05 were considered statistically significant.
Statistical analysis The Kolmogorov-Smirnov test was used to determine whether values were normally distributed. The statistical differences in ultrasonography and clinical features between conservative and therapeutic managements were tested by Student’s t-test, the Fisher exact test, and the Mann-Whitney U test. Guidelines by Timmerman et al. (22,23) and hemodynamic status assessed by the clinician are applied to initial selection of management. A mean PSV of 70 cm/s was associated with likelihood of further therapeutic management, whereas conservative management patients had a mean PSV of 52 cm/s (no problems). A stepwise logistic regression model was used to determine the best predictors of differential diagnosis
Results Univariate analysis Forty-five of the 75 patients were included in the conservative management group, and 30 patients in the therapeutic management group. Ultrasonography features were analyzed in these patients. The average period between the D&C or therapeutic abortion and the first ultrasonography examination was 3.8 weeks, with a minimum of 2 days and a maximum of 12 weeks. The different clinical and ultrasonography features observed in patients with conservative or therapeutic management are summarized in Table 1. Patient age and platelet count were not significantly different
Table 1. Clinical and ultrasonography features by management type. Variable Age (years) D&C or therapeutic abortion Hx First episode Over first episode Complete blood count Hemoglobin (g/dl) Platelet (103/uL) AVM maximal diameter (mm) AVM echogenicity Hypoechoic Iso to hyperechoic Retained product of conception Number of blood vessel Single Multiple Doppler findings Pulsatility index (PI) Resistance index (RI) Peak systolic velocity (PSV, cm/s) Time-averaged maximum velocity (TAMXV, cm/s)
Conservative management (n ¼ 45)
Therapeutic management (n ¼ 30)
28.2 12.8
30.2 11.2
n ¼ 30 n ¼ 15
n ¼ 18 n ¼ 12
11.2 1.7 252.00 13.1 2.7 1.2
9.40 2.2 235.00 14.5 3.0 1.3
n ¼ 18 n ¼ 27 n ¼ 15
n ¼ 18 n ¼ 12 n ¼ 20
n ¼ 32 n ¼ 13
n ¼ 18 n ¼ 12
0.43 0.06 (0.27–0.52) 0.40 0.09 (0.30–0.55) 35.8 13.2 (18–68) 34.2 8.8 (19–52)
0.53 0.08 0.28 0.05 76.2 14.2 51.8 11.0
P value 0.295 0.105
0.015 0.300 0.209 0.03
0.03 0.03
(0.43–0.60) (0.22–0.42) (53–103) (41–91)
0.02 0.01 0.005 0.02
Values are mean standard deviation, and values in parentheses are ranges rounded to nearest whole number.
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between the groups. Fifteen (33.3%) of 45 patients in the conservative management group had more than one prior D&C or therapeutic abortion, which was not significantly different to the 12 (40.0%) of 30 patients in therapeutic management. The previous history of D&C or therapeutic abortion did not differ significantly between conservative and therapeutic management. The mean hemoglobin of patients with conservative management was significantly higher (11.2 1.71, mean standard deviation) than of those with therapeutic management (9.40 2.2, P
