Uterine artery embolization (UAE) for diffuse leiomyomatosis of the uterus: Clinical and imaging results

European Journal of Radiology 81 (2012) 2726–2729

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Uterine artery embolization (UAE) for diffuse leiomyomatosis of the uterus: Clinical and imaging results Jieun Koh, Man Deuk Kim ∗ , Dae Chul Jung, Myungsu Lee, Mu Sook Lee, Jong Yun Won, Do Yun Lee, Sung Il Park, Kwang Hun Lee Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea

a r t i c l e

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Article history: Received 25 August 2011 Received in revised form 11 October 2011 Accepted 1 November 2011 Keywords: Leiomyomatosis Uterine artery embolization MRI

a b s t r a c t Purpose: The aim of the current study was to evaluate the efficacy of uterine artery embolization (UAE) in the management of diffuse uterine leiomyomatosis with mid-term follow-up. Materials and methods: All patients who underwent UAE between 2008 and 2010 for symptomatic fibroids were analyzed. Among 360 cases, a total of 7 patients with diffuse uterine leiomyomatosis diagnosed based on MRI were included in this retrospective study. Patient ages ranged from 29 to 38 (mean 32.7) years. The median follow-up period was 16 (range; 6–31) months. The embolic agent was non-spherical polyvinyl alcohol particles. All patients underwent follow-up MRI at 3 months after UAE. Uterine volumes were calculated using MRI. Menorrhagia symptom changes were assessed at mid-term follow-up. Results: There were no technical failures to catheterize the uterine artery and no adverse events requiring therapy after UAE. Contrast-enhanced MRI showed complete necrosis of the leiomyomatous nodules in 5 patients (71%) 3 months after embolization. Two patients (28%) showed mostly leiomyomatous nodules that were necrotized, some of which were still viable. All 7 patients with menorrhagia had improvement of symptoms at the mid-term follow-up. The initial mean uterine volume was 601.30 ± 533.92 cm3 and was decreased to a mean of 278.81 ± 202.70 cm3 at 3 months follow-up, for a mean uterus volume reduction rate of 50.1% (p < 0.05). One patient became pregnant 5 months after UAE treatment. Conclusion: UAE was a highly effective treatment for diffuse uterine leiomyomatosis with mid-term durability and may be a valuable alternative to hysterectomy. © 2011 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Diffuse uterine leiomyomatosis is a rare condition that usually affects younger women between the third and fourth decades of life [1]. In this condition, the uterus is symmetrically enlarged with myometrium replaced by innumerable ill-defined small smooth muscle nodules that cause menorrhagia, infertility, and postpartum hemorrhage [2–4]. Hormonal treatment usually fails to control these symptom as well as anemia and tumor growth continues after the treatment is stopped [5,6]. Hysterectomy has been the only definitive treatment option for diffuse leiomyomatosis since myomectomy for innumerable nodules with unclear margins cannot be easily performed [3,5]. There have been only a few reports investigating the use of uterine artery embolization (UAE) for the treatment of diffuse uterine leiomyomatosis [6,7]. The aim of the current study was to evaluate the efficacy of UAE in the

management of diffuse uterine leiomyomatosis with a mid-term follow-up. 2. Methods and materials 2.1. Patient sample The institutional review board approved for the entire study, and each patient gave written informed consent. All patients who underwent UAE between 2008 and 2010 for symptomatic fibroids were analyzed. Among the 360 cases, a total of 7 patients with diffuse uterine leiomyomatosis diagnosed based on MRI were included in this retrospective study. Patient age ranged from 29 to 38 (mean 32.7) years. The median follow-up period was 16 (range; 6–31) months. 2.2. MRI

∗ Corresponding author. Tel.: +82 2 2228 2355; fax: +82 2 393 3035. E-mail address: [email protected] (M.D. Kim). 0720-048X/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2011.11.010

All patients underwent preprocedural MRI (1.5-T Signa HD/HDx; GE Healthcare, Waukesha, WI, USA) of the pelvis and

J. Koh et al. / European Journal of Radiology 81 (2012) 2726–2729

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Table 1 Symptom outcomes after uterine artery embolization (n = 7). Factor evaluated

Before procedure

Mid-term follow-up

Difference in scoresa

p

Mean bleeding score (n = 7) Mean pain score (n = 3) Bulk-related symptoms (n = 4) Improved No change

10 10

3.4 1

6.6 9

<0.05b <0.01b

a b c

<0.05c

4 0

Score before procedure minus score at mid-term follow-up. Wilcoxon signed-rank test. McNemar’s test.

follow-up MRI 3 months after UAE. Axial and sagittal fast spin echo T2-weighted imaging (TR/effective TE, 4400/120; matrix size, 384 × 224; field of view, 300 mm × 300 mm; section thickness, 5 mm) and contrast-enhanced sagittal T1-weighted imaging were performed in all cases. Enhanced MRI (TR/TE, 766/9; flip angle 90◦ ; matrix size, 256 × 160; field of view, 300 mm × 300 mm; section thickness, 5 mm) was performed 2 min after intravenous administration of 10 mL gadolinium (Dotarem, Guerbet) by hand. Necrosis was defined as the absence of contrast enhancement on T1-weighted imaging. Total volume of the uterus and predominant fibroids were determined by measuring the length, height, and width of the uterus and calculating the volume with the following equation for a prolate ellipse: length × width × height × 0.5233 [8]. 2.3. Angiographic procedure A unilateral right femoral artery access was used in all cases. A 5.0-F RHR catheter (Cook, Bloomington, IN, USA) was placed in the internal iliac artery and a coaxial 3-F microcatheter (MicroFerret; Cook) was advanced into the uterine artery. Embolization was performed with the catheter tip beyond the origin of the cervicovaginal branch. Non-spherical polyvinyl (PVA) alcohol particles (Contour; Boston Scientific, Natick, MA, USA) were used as the embolic agent and mixed with 60 mL 1:1 saline solution/contrast agent mixture. All patients underwent embolization with 250–355␮m PVA particles followed by 355–500-␮m particles. Embolization was performed until complete cessation of blood flow was achieved in the ascending uterine artery for 10 cardiac beats. 2.4. Clinical follow-up Short-term follow-up consisted of an outpatient visit and MRI 3 months after UAE. Mid-term follow-up began with a telephone call to each patient to recommend a follow-up visit to an outpatient clinic, where a questionnaire interview was conducted. Women who lived far from the clinic underwent a telephone interview only. Symptom status in terms of menorrhagia was scored on a scale of 0–10, with 0 representing no symptoms and 10 indicating baseline initial symptoms. Symptom changes were assessed at the mid-term follow-up. Changes in symptom scores of menorrhagia and dysmenorrhea, which were determined by subtracting the mid-term follow-up score from the baseline score, were analyzed. For bulk related symptoms, we evaluated whether initial symptoms were present at the mid-term follow up and asked if the patient still had symptoms or experienced a resolution of the symptoms. 2.5. Statistical analysis A nonparametric method was used to determine all statistical analyses. A Wilcoxon signed-rank test was used for continuous variables and McNemar’s tests were used for categorical variables. Student’s t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom score and uterine volume. The McNemar’s test was used to evaluate changes in bulk related

symptoms. Differences were considered statistically significant at p < 0.05. 3. Results Symptom outcomes are summarized in Table 1. There were no technical failures to catheterize the uterine artery and no adverse events requiring therapy after UAE. Contrast-enhanced MRI showed complete necrosis of the leiomyomatous nodules in 5 patients (71%) 3 months after embolization. Two patients (29%) showed that the majority of the leiomyomatous nodules were necrotized, but some were still viable. In one of these two patients, one of the uterine arteries was absent and was replaced by an ovarian artery and embolization of the ovarian artery with PVA particles was performed. All 7 patients with menorrhagia had improvements in symptoms at the mid-term follow-up, with changes in the mean scores from the initial score to the mid-term follow-up of −6.6 (p < 0.05). Three of the 7 patients (42%) had initial symptoms of dysmenorrhea and all showed improvement. A −9 change in the mean score from initial to mid-term follow-up was observed (p < 0.01). Four of the 7 patients initially had bulk-related symptoms; after UAE all patients showed resolution of symptoms (p < 0.05). The mean initial uterine volume was 601.30 ± 533.92 cm3 (median 371.70; range 285.0–1786.7), which was decreased at 3 months follow-up to a mean of 278.81 ± 202.70 cm3 (median 199.0; range 103.0–708.6). The mean volume reduction rate of the uterus was 50.1% (p < 0.05). One patient underwent pretreatment with gonadotropin-releasing hormone (GnRH) agonist (3.75 mg leuprolide acetate, administered subcutaneously once a month) 3 times before UAE to reduce uterine volume (Fig. 1). The uterine volume was reduced from 1787 cm3 before GnRH to 1288 cm3 after GnRH (27.9% volume reduction) treatment. The uterine volume was subsequently reduced to 709 cm3 (45.0%) 3 months after UAE. One patient became pregnant 5 months after UAE. At the mid-term follow-up, she was successfully maintaining her pregnancy without complications. 4. Discussion Diffuse leiomyomatosis of the uterus is a rare condition in which innumerable, poorly defined, and confluent nodules produce symmetrical enlargement of the uterus. Hysterectomy remains the treatment of choice because the diffuse nature of the lesions make it difficult to perform a complete myomectomy. Leiomyomatosis can be distinguished from leiomyoma due to the uniform symmetrical involvement of the entire border between the nodules, whereas cases of multiple leiomyoma tend to have asymmetrical involvement of the uterus and sharp circumscription of the individual lesions [9]. Similar to uterine leiomyoma, patients with leiomyomatosis present with menorrhagia, dysmenorrhea, abdominal pain, infertility, and pelvic pressure. Several studies have focused a conservative management that can preserve the uterus [3,4]. In a study by Fedele et al., 1 patient out of 3 with diffuse leiomyomatosis was managed with a GnRH analogue that resulted in hysterectomy

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J. Koh et al. / European Journal of Radiology 81 (2012) 2726–2729

Fig. 1. A 29-year-old woman with diffuse uterine leiomyomatosis. (a) Sagittal T2-weighted MRI shows an enlarged uterus with innumerable smooth muscle nodules and confluent nodules (arrows) replacing the normal myometrium with a measured 1787 cm3 volume before embolization. After administration of GnRH agonists before UAE, the uterine volume was reduced to 1288 cm3 (not shown). (b) Three months after UAE, sagittal T2-weighted MRI reveals a marked volume reduction of the uterus to 709 cm3 . (c) Gadolinium-enhanced T1-weighted MRI shows an absence of contrast enhancement within the nodules, indicating complete necrosis of the leiomyomatous nodules (arrows).

at the 34th gestational week as a result of profuse vaginal bleeding. A second patient was treated with a GnRH agonist followed by hysteroscopic resection resulting in a repeated myomectomy 3 years later. The third patient underwent an extreme myomectomy [3]. In Yen et al., 5 cases of successful hysteroscopic resection of submucosally located leiomyomas were described while leaving other intramural myomas in place for early-stage diffuse uterine leiomyomatosis [4]. The uterus was successfully preserved and normal menstruation was restored in all patients. Three patients who wished to conceive had successful conceptions. Although this is an incomplete and temporary treatment, uterine synechiae is still a major concern after extensive hysteroscopic operation for patients who desire future pregnancy. UAE is currently used with increasing frequency to treat symptomatic fibroids and is gaining acceptance as an alternative to hysterectomy and myomectomy [10–13]. However, there have only been a few studies regarding the use of UAE in the treatment of diffuse uterine leiomyomatosis with

mid-term follow-up. Kido et al. successfully demonstrated 1 case of diffuse uterine leiomyomatosis treated with UAE that resulted in controlled symptoms and reduced uterine volume with no major complications at a 10-month follow-up after the failure of hormonal treatment for 5 years [6]. Scheurig et al. reported that 5 out of 6 patients who had undergone UAE showed a marked and sustained improvement in clinical symptoms that was not associated with a higher periprocedural complication rate at a 16-month followup, although 1 patient exhibited a negligible leiomyoma infarction and rapidly increased uterine volume that finally resulted in a hysterectomy [7]. The mean age of patients enrolled in the Scheurig et al. study was 37 years while that of our study was 32.7 years; both were significantly younger than the other study sample. Kido et al. used gelatin sponge particles as embolic agents while Scheurig et al. used 500–700-␮m and 700–900-␮m tris-acryl gelatin microspheres in most patients and used PVA microspheres in 1 patient. Non-spherical PVA particles were employed in our study;

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indicating that PVA particles were effective in this study as well. Specifically, embolization was performed beginning with 250–355␮m PVA particles followed by 355–500-␮m particles in our study with the hope that the small PVA particles would result in better UAE treatment outcomes for the numerous small leiomyomatous nodules. In our study, there were no failures of treatment by UAE and all 7 patients showed symptom improvement at the mid-term follow-up, supporting the effectiveness of UAE for diffuse leiomyomatosis treatment. In two patients with incomplete infarction of leiomyomatous nodules, the majority of the nodules were infarcted but 10–20% of numerous nodules were viable. These viable nodules did not affect the result at 6 months and 19 months follow-up, respectively, but long-term follow-ups are needed. In our study, 1 patient who underwent GnRH treatment before UAE reached a uterine size of about 24 weeks. Several reports in the literature have suggested an increased complication rate when UAE was used to treat either large fibroids or uteri with large volumes [14–17]. Spies et al. reported results from 200 women, having excluded women with uteri greater than 24 weeks in size [18]. Since treatment with GnRH agonists tends to make the uterine arteries smaller and more spastic, GnRH can cause treatment failure due to decreased particle delivery to the distal uterine vasculature [17]. However, after waiting for 6 weeks from the last GnRH injection before UAE in our study, embolization was successfully completed with a satisfactory volume reduction of the uterus. Other treatment options are endometrial ablations with laser, thermal balloon, or roller ball to control the menorrhagia. However, these ablation techniques have some limitations because of the significant amenorrhea rate between 25 and 40%, given that leiomyomatosis frequently affects younger women [19–22]. Previous reports have suggested an association between diffuse leiomyomatosis and infertility or subfertility [23,24]. Frequently, the endometrium overlying the submucous myomas is inflamed and may interfere with implantation as well as distortion of the endometrial vasculature. In our study, 1 patient who had suffered from infertility for 2 years became pregnant 5 months after UAE and was maintaining the pregnancy without complications at an 8-month follow-up. Nodules located in the submucosa have a tendency to be spontaneously expelled after UAE treatment, which may be helpful for facilitating implantation. There were no adverse events after UAE even though all of the myometrium was replaced by leiomyomas; however, the normal myometrium expanded and was clear after UAE as infarction of the leiomyomatous nodules led to an impressive remodeling of the uterus. One limitation of the present study was the relatively small number of patients, and as such further studies are needed. In conclusion, UAE was a highly effective treatment for diffuse uterine leiomyomatosis with mid-term durability and may be a valuable alternative to hysterectomy. Given that hysterectomy is known as the only definite treatment for diffuse leiomyomatosis, we believe any patient with symptomatic leiomyomatosis who wishes to preserve the uteri will be a candidate for UAE.

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