- Email: [email protected]
Limited Efficacy of Uterine Artery Embolization for Cervical Leiomyomas
CLINICAL STUDY
Limited Efficacy of Uterine Artery Embolization for Cervical Leiomyomas Man Deuk Kim, MD, Myungsu Lee, MD, Dae Chul Jung, MD, Sung Il Park, MD, Mu Sook Lee, MD, Jong Yun Won, MD, Do Yun Lee, MD, and Kwang Hun Lee, MD
ABSTRACT Purpose: To explore the effectiveness of uterine artery embolization (UAE) in treating symptomatic fibroids in the uterine cervix. Materials and Methods: Among 537 patients who underwent UAE, 10 who had fibroids located in the cervix were retrospectively analyzed. The mean diameter of the fibroids was 6.0 cm. Seven of the 10 patients presented a total of 10 fibroids in the uterine body or fundus simultaneously. Fibroids of the cervix and fibroids in the body or fundus were compared in terms of the effects of UAE on the treatment thereof and vascularity on angiographic findings. Cervical leiomyomas were classified into three grades based on the vascularity seen on aortography, from grade I, indicating poor vascularity, to grade III, indicating hypervascularity. Necrosis of fibroids was assessed by magnetic resonance imaging 3 months after UAE. Results: Complete necrosis of leiomyomas in the uterine cervix was seen in only two of the 10 patients (20%), whereas all fibroids in the uterine body or fundus were completely infarcted (P ⬍ .05). Partial necrosis (PN) of the fibroid with a thin viable rim was seen in two patients, whereas PN with a thick rim was seen in four and no necrosis was seen in two. Grade I (ie, poor) vascularity was noted in five of nine patients (55.6%) with cervical fibroids larger than 3 cm. Conclusions: Poor vascularity was a frequent finding among cervical leiomyomas, and the outcomes of UAE for cervical leiomyomas were disappointing, indicating a need for caution in selecting and counseling patients for this treatment.
ABBREVIATIONS PN ⫽ partial necrosis, PVA ⫽ polyvinyl alcohol, UAE ⫽ uterine artery embolization
Uterine fibroids, the most common solid tumors of the female genital tract, develop in 20%– 40% of women of childbearing age (1). Ninety-five percent of uterine myomas occur in the uterine corpus, and less than 5% occur in the cervix. The location of a myoma in the cervix increases the difficulty of surgery as a result of a poor operative field, limited access in suturing, and increased blood loss (2,3). Uterine artery embolization (UAE) has become more frequently used in treating symptomatic fibroids, and is gaining acceptance as an alternative to hysterectomy and myomectomy (4 –7). However, reported failure rates of UAE
are 5%–15% (5,7–9). The reasons for failure of this treatment include difficult catheterization, vasospasm, collateral supplies to the fibroids from ovarian arteries, and the combined presence of adenomyosis. As shown in a recent study (10), the cervix always shows perfusion on immediate postembolization magnetic resonance (MR) imaging, which may influence the results of UAE in leiomyomas of the cervix. The aim of the present study was to evaluate the effectiveness of UAE in the treatment of symptomatic fibroids located in the cervix, as compared with those in the body or fundus of the uterus.
From the Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul, Republic of Korea 120-752. Received August 7, 2011; final revision received October 23, 2011; accepted October 26, 2011. Address correspondence to M.D.K.; E-mail: [email protected]
MATERIALS AND METHODS
None of the authors have identified a conflict of interest. © SIR, 2012 J Vasc Interv Radiol 2012; 23:236 –240 DOI: 10.1016/j.jvir.2011.10.020
The institutional review board of Yonsei University College of Medicine approved this study. All 537 patients who underwent UAE for symptomatic fibroids or adenomyosis between 2007 and 2010 were retrospectively analyzed. Among these, a total of 10 patients with fibroids located in the uterine cervix were enrolled and diagnosed by MR imaging.
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A cervical leiomyoma was defined as a fibroid tumor with an epicenter below the internal os of the cervix on T2-weighted sagittal imaging. The maximum diameter of the fibroids was 2.7– 8.1 cm (mean, 6.0 cm). Patients ranged in age from 28 to 50 years (mean, 40.5 y). The mean follow-up period was 3.5 months (range, 3– 4 mo). Seven of the 10 patients had a total of 10 fibroids in the uterine body or fundus, in addition to those in the cervix. Results of UAE in fibroids in the cervix were compared with results of UAE in fibroids in the uterine body or fundus according to angiographic findings and treatment effects.
MR Imaging All patients underwent preoperative MR imaging (1.5-T Signa HD/HDx; GE Healthcare, Waukesha, Wisconsin) of the pelvis and follow-up MR imaging at 3 months after UAE. Axial and sagittal fast spin-echo T2-weighted imaging (repetition time/effective echo time, 4,400/120 ms; 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 MR imaging (repetition time/echo time, 766/9 ms; flip angle 90°; matrix size, 256 ⫻ 160; field of view, 300 mm ⫻ 300 mm; section thickness, 5 mm) was performed 2 minutes after intravenous infusion of 10 mL gadolinium contrast agent (Dotarem; Guerbet, Villapinte, France). Complete necrosis was defined as the absence of contrast enhancement of leiomyoma on T1-weighted imaging. Partial necrosis (PN) was defined as the presence of a nonperfused region in the leiomyoma with perfusion elsewhere. Fibroids with PN were further categorized as having a thick or thin rim based on the presence of peripheral viable regions more or less than 1 cm thick, respectively. A leiomyoma of no necrosis had no detectible necrosis in the fibroid after UAE. The total fibroid volume was calculated from measurements of length, height, and width by using the equation for a prolate ellipse: length ⫻ width ⫻ height ⫻ 0.5233 (11). We determined and described the location of a fibroid with reference to regional uterine anatomy (ie, fundus, body, cervix) as seen on T2-weighted MR images. A leiomyoma of the uterine cervix and body was regarded as a cervical leiomyoma if the epicenter of the fibroid was in the cervix. Cervical myomas were categorized as extracervical (ie, subserosal) or intracervical (ie, within the cervix).
Angiographic Procedure Unilateral right femoral artery access was used in all cases. A 5.0-F RHR catheter (Cook, Bloomington, Indiana) was placed in the internal iliac artery and a coaxial 3-F microcatheter (MicroFerret; Cook) was advanced into the uterine artery. The embolic agent was nonspherical polyvinyl alcohol (PVA) particles (Contour; Boston Scientific, Natick, Massachusetts) mixed with 60 mL of 1:1 saline solution: contrast agent mixture. Eight of 10 patients underwent embolization with 250 –355-m PVA particles followed by 355–500-m particles. In two patients, embolization was
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performed beginning with 150 –250-m PVA particles and progressively increasing the particle size to 250 –355 m and then 355–500 m, up to the endpoint. The tip of the microcatheter was not placed beyond the origin of the cervicovaginal branch or at the proximal transverse segment of the uterine artery when the origin of the cervicovaginal branch was not visualized, as cervical leiomyomas may have feeding arterial supply from the cervicovaginal branch. Embolization was performed until complete cessation of blood flow was achieved in the ascending and transverse segment of the uterine artery for 10 cardiac beats. Cervical leiomyomas larger than 3 cm were classified into three groups based on vascularity as seen on aortography by two interventional radiologists in consensus. Grade I indicated poor and minimal vascularity, with a few small vessels seen in the myoma, without tumor staining. Grade II indicated moderate vascularity, with myoma staining identified, but only in small vessels. Grade III indicated marked vascularity, with myoma staining identified, and showing large, tortuous vessels.
Clinical Follow-Up A symptom severity questionnaire was completed to assess the severity of menstrual bleeding during and between menstrual periods on a scale from 0 (no impact) to 10 (severe impact) at the time of the 3-month follow-up MR imaging study. Also, we questioned patients concerning any changes in urination, vaginal dryness, or the ability to achieve orgasm at 3-month follow-up. We classified the grade of complications of UAE into six categories as previously reported (12,13): grade A complications require no therapy and cause no consequences; grade B complications require nominal therapy or observation and cause no consequences; grade C complications require therapy or unanticipated minor hospitalization (⬍ 48 h); grade D complications require major therapy, unplanned increased level of care, or unanticipated prolonged hospitalization (⬎ 48 h); grade E complications cause permanent adverse sequelae; and grade F complications cause death. Grade A and B complications were defined as minor complications and grade C through F complications as major complications.
Statistical Analysis The Mann–Whitney test and Fisher exact test were used to compare baseline characteristics and the effects of UAE on leiomyomas in different locations. Differences were considered statistically significant at P ⬍ .05.
RESULTS Baseline characteristics and outcomes after UAE are shown in the Table. Cramping pain occurred in all patients after UAE and was managed via an intravenous patient-controlled analgesia pump containing 500 g fentanyl sulfate and 90 mg ketorolac tromethamine. Pain began to subside approximately 8 –10 hours after UAE, and all patients were
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Kim et al 䡲 JVIR
Table. Baseline Characteristics and Outcomes after Uterine Artery Embolization Characteristic/Outcome Size of fibroids (cm) Volume of fibroids (cm3) Necrosis Complete necrosis Partial necrosis Thin rim Thick rim No necrosis Mean VRR at 3 mo (%)
Cervix (n ⴝ 10) 6.0 ⫾ 1.6
Body/Fundus (n ⴝ 10) 5.4 ⫾ 1.8
92.6 ⫾ 54.8
54.8 ⫾ 54.7
2 6 2 4 2 42.8
10 0
0 57.8
P Value .1041* .1051* ⬍.001†
⬎.05*
Note.—Values presented as mean ⫾ SD where appropriate. VRR ⫽ volume reduction rate. * Mann–Whitney test. † Fisher exact test.
Figure 1. Images of leiomyomas in the uterine cervix and body in a 45-year-old woman. (a) Coronal T2-weighted MR imaging shows an 8.1-cm leiomyoma in the uterine cervix (arrows) and two leiomyomas 7.5 cm (arrowheads) and 4.5 cm (not shown) in size in the uterine body. (b) Aortography reveals grade III hypervascularity of two leiomyomas in the uterine body (black arrows and white arrow) and grade I (ie, poor) vascularity of leiomyoma (arrowheads) in the uterine cervix. (c) Gadolinium-enhanced T1-weighted MR image 3 months after embolization reveals complete necrosis of leiomyoma (white arrows) in the uterine body, but partial necrosis with a thin viable rim of leiomyoma (black arrows) in the uterine cervix.
able to be discharged the next day and completely recovered after 1–2 weeks. Fibroids in the uterine cervix and fibroids in the uterine body or fundus did not differ significantly in mean diameters or volumes before UAE. With regard to treatment effects, complete necrosis of leiomyomas located in the uterine cervix was seen in only two of 10 patients (20%), whereas all fibroids in the uterine body or fundus were completely infarcted on follow-up MR imaging at 3 months (P ⬍ .05). Two patients showed fibroids with PN with a thin rim, four showed fibroids with PN with a thick rim (Fig 1), and two showed no necrosis of the fibroid. Five of six patients with PN with a thick rim or no necrosis after UAE had menorrhagia, but none of the patients showed symptom improvement. Three of four patients with complete necrosis or PN with a thin rim had menorrhagia, and all these patients reported considerable symptom improvement, with the average score of menorrhagia reduced from 8.3 to 1.7. A single major complication was found in one patient (10%) with a 7-cm cervical fibroid who experienced vaginal expulsion after UAE, but MR
imaging revealed a thick peripheral viable portion of the fibroid, which could not be removed in the outpatient clinic because of bleeding risk. This patient underwent hysteroscopic resection under general anesthesia. The mean volume of fibroids in the cervix and in the body or fundus decreased nonsignificantly, by 42.8% (from 92.6 cm3 ⫾ 54.8 to 46.9 cm3 ⫾ 31.4) and 57.8% (from 54.8 cm3 ⫾ 54.7 to 30.8 cm3 ⫾ 41.4) at 3 months, respectively. In terms of the vascularity of cervical leiomyomas, grade I (ie, poor) vascularity was noted in five of nine patients (55.6%), grade II vascularity in two patients, and grade III vascularity in two patients. One patient who underwent MR-guided focused ultrasound (US) for cervical leiomyoma 15 months earlier exhibited grade I vascularity on angiography (Fig 2). The follow-up MR images after UAE showed no evidence of the fibroid remaining. Eight patients had fibroids at intracervical locations, and two patients had them at extracervical locations. One of two extracervical-type fibroids showed complete necrosis, and the other showed no necrosis. A 50-year-old patient with a fibroid with PN with a thick rim developed amenorrhea after UAE. No patient had
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Figure 2. A 41-year old woman with leiomyomas in the uterine cervix underwent MR-guided focused US for cervical myoma 15 months before imaging. (a) Sagittal T2-weighted MR image reveals a 6.8-cm cervical leiomyoma. (b) Aortography reveals grade I (poor) vascularity (arrowheads) in a leiomyoma. Both uterine arteries (arrows) are visualized. Embolization was performed beginning with 150 –250-m PVA particles, with the particle sizes progressively increased to 250 –355 m and then 355–500 m, up to the endpoint. (c) Follow-up MR image confirms disappearance of the cervical leiomyoma and shows a remaining linear scar (arrow) after embolization.
urinary incontinence or vaginal dryness, or lost the ability to achieve orgasm, after UAE.
DISCUSSION Cervical leiomyomas comprise fewer than 5% of all uterine leiomyomas. They may be categorized as those that occur at a subserosal location (ie, extracervical type) and those that occur within the cervix (ie, intracervical type). Myomectomy for cervical leiomyoma is empirically difficult and may be specifically complicated by a deep intracervical location or a large myoma size, which increases the risk for blood loss during surgery (14,15). When performing myomectomy for a cervical myoma, care must be taken to avoid injuries to neighboring pelvic structures such as the bladder, rectum, and ureters. Although UAE is increasingly presented to women as an alternative to hysterectomy for symptomatic fibroids (3,4), reported treatment failure rates remain at 5%–15% (5,7). This may largely reflect the presence of collateral vasculature, which includes the ovarian collateral vessels. Our results with the use of UAE for cervical leiomyomas were disappointing, with only 20% of patients showing complete necrosis. Even if the achievement of PN with thin rim enhancement in two patients is regarded as a success, our success rate would still only be 40%. Pollard and Goldberg (16) suggested that cervical myomas should be considered a contraindication to UAE because of significant risk for vaginal expulsion of the fibroid, requiring hysterectomy. However, vaginal expulsion of a fibroid is generally manageable without serious complications, and should be regarded as a treatment response, not a complication (17). The problem, as we observed with one patient, is that, in expulsion of a cervical myoma without complete necro-
sis, the stalk of the fibroid cannot be easily resected in view of the possibility of uncontrolled bleeding. The uterus is anatomically composed of three parts: the fundus, body, and cervix. In a study by Scheurig-Muenkler et al (10), only the cervix was usually perfused at all time points on postinterventional MR imaging. This phenomenon may explain the high frequency of treatment failure of UAE for cervical leiomyomas. The authors suggested that placement of the microcatheter tip beyond the cervicovaginal branch of the uterine artery may explain this phenomenon (10). However, this suggestion is not entirely satisfying: first, the cervicovaginal branch is visible in only 53% of cases (18); and second, we were able to embolize the uterine arteries including the transverse segment of the uterine artery. Thus, treatment of UAE for cervical myomas may fail not because of microcatheter tip location, but rather because the uterine cervix has a fine arterial supply, with or without the targeted vessels, through collateral vessels that cannot be detected on angiography and that we usually do not embolize. The size of the cervicovaginal and ovarian branches are known to be smaller than 500 m, whereas the size of the perifibroid plexus arteries range from 500 to 1,000 m (19). These differences in artery size provide the rationale for fibroid-targeted embolization with calibrated embolization materials 500 –700 m or larger, so as to preserve cervicovaginal or uteroovarian branches. However, if the cervicovaginal branch is a main feeding vessel to the cervical fibroid, materials 355–500 m in diameter or larger cannot reach the perifibroid plexus for embolization, which results in treatment failure. The anterior branches of the internal iliac artery include the inferior gluteal, obturator, internal pudendal, vesical, middle hemorrhoidal, and genital (ie, uterine and vaginal) arteries. Cervical and vaginal branches of the uterine arteries supply the cervix and upper vagina, but there is considerable
240 䡲 Limited Efficacy of UAE for Cervical Leiomyomas
anatomic variation and anastomoses in the uterine cervix with vaginal and middle hemorrhoidal arteries, which might explain another cause of frequent failure of UAE. After repeated failure of UAE for cervical leiomyomas, we acknowledge here that we altered our UAE protocol for the last two patients enrolled in the present study. We began the procedure by using 150 –250-m PVA particles and progressively increased the particle size to 250 –355 m and then to 355–500 m until the endpoint, which is similar to that for the treatment of adenomyosis (20). In one of the two patients, we succeeded; however, the other showed PN with thick rim enhancement. Even though we did not succeed completely in both cases, our results may indicate the need for more aggressive embolization in cervical leiomyomas than for those of the uterine body or fundus, perhaps by using a procedure similar to those used for adenomyosis. However, it cannot be recommended without further study on its effectiveness and safety. The cervicovaginal branch is believed to supply the cervicovaginal plexus, which consists of nerves surrounding and innervating the cervix and upper vagina. Lai et al (21) described a case in which embolization of the cervicovaginal branches may have caused injury to the uterovaginal plexus, the vascular supply to the cervix, or both, leading to potential sexual dysfunction. In contrast, the majority of embolization treatments involving the cervicovaginal branch have nonadverse outcomes. Although most leiomyomas display a defined arterial supply with hypervascularity on angiography, the cervical leiomyomas in the present study frequently showed no defined arterial supply and poor to minimal vascularity, making them difficult to treat with use of medium-sized PVA particles. Interestingly, fibroids of the cervix and fibroids of the body or fundus of the uterus did not differ significantly in the rate of volume reduction achieved with the use of UAE. Even the cervical leiomyomas that showed PN with a thick rim of enhancement were reduced in volume to approximately the same extent as those of the body or fundus. However, long-term follow-up is needed to establish the duration of the treatment effect. Pelage et al (22) suggest that regrowth of noninfarcted fibroid tissue may ultimately result in symptom recurrence. The present study may lack the statistical power to test this possibility in view of the small number of patients enrolled; hence, further studies are needed. In conclusion, poor vascularity was a frequent finding among cervical leiomyomas, and the results of UAE were disappointing, indicating a need for caution in selecting and counseling patients for this treatment. Further study with larger groups of patients is justified to determine whether UAE for cervical leiomyomas necessitates a more aggressive approach with the use of procedures similar to those used for adenomyosis.
Kim et al 䡲 JVIR
REFERENCES 1. Buttram VC Jr, Reiter RC. Uterine leiomyomata: etiology, symptomatology, and management. Fertil Steril 1981; 36:433– 445. 2. Sinha R, Sundaram M, Lakhotia S, Hegde A. Cervical myomectomy with uterine artery ligation at its origin. J Minim Invas Gynecol 2009; 16:604 – 608. 3. Takeuchi H, Kitade M, Kikuchi I, et al. A new enucleation method for cervical myoma via laparoscopy. J Minim Invas Gynecol 2006; 13:334 – 336. 4. Goodwin SC, McLucas B, Lee M, et al. Uterine artery embolization for the treatment of uterine leiomyomata midterm results. J Vasc Interv Radiol 1999; 10:1159 –1165. 5. Walker WJ, Pelage JP. Uterine artery embolisation for symptomatic fibroids: clinical results in 400 women with imaging follow up. Br J Obstet Gynaecol 2002; 109:1262–1272. 6. Spies JB, Cooper JM, Worthington-Kirsch R, Lipman JC, Mills BB, Benenati JF. Outcome of uterine embolization and hysterectomy for leiomyomas: results of a multicenter study. Am J Obstet Gynecol 2004; 191:22–31. 7. Pron G, Bennett J, Common A, Wall J, Asch M, Sniderman K. The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids. Fertil Steril 2003; 79:120 –127. 8. Nikolic B, Spies JB, Abbara S, Goodwin SC. Ovarian artery supply of uterine fibroids as a cause of treatment failure after uterine artery embolization: a case report. J Vasc Interv Radiol 1999; 10:1167–1170. 9. Ambekar A, Vogelzang RL. Aberrant uterine artery as a cause of uterine artery embolization treatment failure. Int J Gynaecol Obstet 2001; 74: 59 – 60. 10. Scheurig-Muenkler C, Wagner M, Franiel T, Hamm B, Kroencke TJ. Effect of uterine artery embolization on uterine and leiomyoma perfusion: evidence of transient myometrial ischemia on magnetic resonance imaging. J Vasc Interv Radiol 2010; 21:1347–1353. 11. Orsini LF, Salardi S, Pilu G, Bovicelli L, Cacciari E. Pelvic organs in premenarcheal girls: real-time ultrasonography. Radiology 1984; 153: 113–116. 12. Spies JB, Spector A, Roth AR, Baker CM, Mauro L, Murphy-Skrynarz K. Complications after uterine artery embolization for leiomyomas. Obstet Gynecol 2002; 100:873– 880. 13. Goodwin SC, Bonilla SM, Sacks D, et al. Reporting standards for uterine artery embolization for the treatment of uterine leiomyomata. J Vasc Interv Radiol 2001; 12:1011–1020. 14. Takeda A, Koyama K, Imoto S, Mori M, Sakai K, Nakamura H. Temporary endovascular balloon occlusion of the bilateral internal iliac arteries for control of hemorrhage during laparoscopic-assisted myomectomy in a nulligravida with a large cervical myoma. Fertil Steril 2009; 91:935e5– e9. 15. Chang WC, Chen SY, Huang SC, Chang DY, Chou LY, Sheu BC. Strategy of cervical myomectomy under laparoscopy. Fertil Steril 2010; 94:2710 –2715. 16. Pollard RR, Goldberg JM. Prolapsed cervical myoma after uterine artery embolization. A case report. J Reprod Med 2001; 46:499 –500. 17. Park HR, Kim MD, Kim NK, et al. Uterine restoration after repeated sloughing of fibroids or vaginal expulsion following uterine artery embolization. Eur Radiol 2005; 15:1850 –1854. 18. Pelage JP, Le Dref O, Soyer P, et al. Arterial anatomy of the female genital tract: variations and relevance to transcatheter embolization of the uterus. AJR Am J Roentgenol 1999; 172:989 –994. 19. Lampmann LE, Smeets AJ, Lohle PN. Uterine fibroids: targeted embolization, an update on technique. Abdom Imaging 2004; 29:128 –131. 20. Kim MD, Kim YM, Kim HC, et al. Uterine artery embolization for symptomatic adenomyosis: a new technical development of the 1-2-3 protocol and predictive factors of MR imaging affecting outcomes. J Vasc Interv Radiol 2011; 22:497–502. 21. Lai AC, Goodwin SC, Bonilla SM, et al. Sexual dysfunction after uterine artery embolization. J Vasc Interv Radiol 2000; 11:755–758. 22. Pelage JP, Guaou Guaou N, Jha RC, Ascher SM, Spies JB. Uterine fibroid tumors: long-term MR imaging outcome after embolization. Radiology. 2004; 230:803– 809.
Limited Efficacy of Uterine Artery Embolization for Cervical Leiomyomas Man Deuk Kim, MD, Myungsu Lee, MD, Dae Chul Jung, MD, Sung Il Park, MD, Mu Sook Lee, MD, Jong Yun Won, MD, Do Yun Lee, MD, and Kwang Hun Lee, MD
ABSTRACT Purpose: To explore the effectiveness of uterine artery embolization (UAE) in treating symptomatic fibroids in the uterine cervix. Materials and Methods: Among 537 patients who underwent UAE, 10 who had fibroids located in the cervix were retrospectively analyzed. The mean diameter of the fibroids was 6.0 cm. Seven of the 10 patients presented a total of 10 fibroids in the uterine body or fundus simultaneously. Fibroids of the cervix and fibroids in the body or fundus were compared in terms of the effects of UAE on the treatment thereof and vascularity on angiographic findings. Cervical leiomyomas were classified into three grades based on the vascularity seen on aortography, from grade I, indicating poor vascularity, to grade III, indicating hypervascularity. Necrosis of fibroids was assessed by magnetic resonance imaging 3 months after UAE. Results: Complete necrosis of leiomyomas in the uterine cervix was seen in only two of the 10 patients (20%), whereas all fibroids in the uterine body or fundus were completely infarcted (P ⬍ .05). Partial necrosis (PN) of the fibroid with a thin viable rim was seen in two patients, whereas PN with a thick rim was seen in four and no necrosis was seen in two. Grade I (ie, poor) vascularity was noted in five of nine patients (55.6%) with cervical fibroids larger than 3 cm. Conclusions: Poor vascularity was a frequent finding among cervical leiomyomas, and the outcomes of UAE for cervical leiomyomas were disappointing, indicating a need for caution in selecting and counseling patients for this treatment.
ABBREVIATIONS PN ⫽ partial necrosis, PVA ⫽ polyvinyl alcohol, UAE ⫽ uterine artery embolization
Uterine fibroids, the most common solid tumors of the female genital tract, develop in 20%– 40% of women of childbearing age (1). Ninety-five percent of uterine myomas occur in the uterine corpus, and less than 5% occur in the cervix. The location of a myoma in the cervix increases the difficulty of surgery as a result of a poor operative field, limited access in suturing, and increased blood loss (2,3). Uterine artery embolization (UAE) has become more frequently used in treating symptomatic fibroids, and is gaining acceptance as an alternative to hysterectomy and myomectomy (4 –7). However, reported failure rates of UAE
are 5%–15% (5,7–9). The reasons for failure of this treatment include difficult catheterization, vasospasm, collateral supplies to the fibroids from ovarian arteries, and the combined presence of adenomyosis. As shown in a recent study (10), the cervix always shows perfusion on immediate postembolization magnetic resonance (MR) imaging, which may influence the results of UAE in leiomyomas of the cervix. The aim of the present study was to evaluate the effectiveness of UAE in the treatment of symptomatic fibroids located in the cervix, as compared with those in the body or fundus of the uterus.
From the Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul, Republic of Korea 120-752. Received August 7, 2011; final revision received October 23, 2011; accepted October 26, 2011. Address correspondence to M.D.K.; E-mail: [email protected]
MATERIALS AND METHODS
None of the authors have identified a conflict of interest. © SIR, 2012 J Vasc Interv Radiol 2012; 23:236 –240 DOI: 10.1016/j.jvir.2011.10.020
The institutional review board of Yonsei University College of Medicine approved this study. All 537 patients who underwent UAE for symptomatic fibroids or adenomyosis between 2007 and 2010 were retrospectively analyzed. Among these, a total of 10 patients with fibroids located in the uterine cervix were enrolled and diagnosed by MR imaging.
Volume 23 䡲 Number 2 䡲 February 䡲 2012
A cervical leiomyoma was defined as a fibroid tumor with an epicenter below the internal os of the cervix on T2-weighted sagittal imaging. The maximum diameter of the fibroids was 2.7– 8.1 cm (mean, 6.0 cm). Patients ranged in age from 28 to 50 years (mean, 40.5 y). The mean follow-up period was 3.5 months (range, 3– 4 mo). Seven of the 10 patients had a total of 10 fibroids in the uterine body or fundus, in addition to those in the cervix. Results of UAE in fibroids in the cervix were compared with results of UAE in fibroids in the uterine body or fundus according to angiographic findings and treatment effects.
MR Imaging All patients underwent preoperative MR imaging (1.5-T Signa HD/HDx; GE Healthcare, Waukesha, Wisconsin) of the pelvis and follow-up MR imaging at 3 months after UAE. Axial and sagittal fast spin-echo T2-weighted imaging (repetition time/effective echo time, 4,400/120 ms; 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 MR imaging (repetition time/echo time, 766/9 ms; flip angle 90°; matrix size, 256 ⫻ 160; field of view, 300 mm ⫻ 300 mm; section thickness, 5 mm) was performed 2 minutes after intravenous infusion of 10 mL gadolinium contrast agent (Dotarem; Guerbet, Villapinte, France). Complete necrosis was defined as the absence of contrast enhancement of leiomyoma on T1-weighted imaging. Partial necrosis (PN) was defined as the presence of a nonperfused region in the leiomyoma with perfusion elsewhere. Fibroids with PN were further categorized as having a thick or thin rim based on the presence of peripheral viable regions more or less than 1 cm thick, respectively. A leiomyoma of no necrosis had no detectible necrosis in the fibroid after UAE. The total fibroid volume was calculated from measurements of length, height, and width by using the equation for a prolate ellipse: length ⫻ width ⫻ height ⫻ 0.5233 (11). We determined and described the location of a fibroid with reference to regional uterine anatomy (ie, fundus, body, cervix) as seen on T2-weighted MR images. A leiomyoma of the uterine cervix and body was regarded as a cervical leiomyoma if the epicenter of the fibroid was in the cervix. Cervical myomas were categorized as extracervical (ie, subserosal) or intracervical (ie, within the cervix).
Angiographic Procedure Unilateral right femoral artery access was used in all cases. A 5.0-F RHR catheter (Cook, Bloomington, Indiana) was placed in the internal iliac artery and a coaxial 3-F microcatheter (MicroFerret; Cook) was advanced into the uterine artery. The embolic agent was nonspherical polyvinyl alcohol (PVA) particles (Contour; Boston Scientific, Natick, Massachusetts) mixed with 60 mL of 1:1 saline solution: contrast agent mixture. Eight of 10 patients underwent embolization with 250 –355-m PVA particles followed by 355–500-m particles. In two patients, embolization was
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performed beginning with 150 –250-m PVA particles and progressively increasing the particle size to 250 –355 m and then 355–500 m, up to the endpoint. The tip of the microcatheter was not placed beyond the origin of the cervicovaginal branch or at the proximal transverse segment of the uterine artery when the origin of the cervicovaginal branch was not visualized, as cervical leiomyomas may have feeding arterial supply from the cervicovaginal branch. Embolization was performed until complete cessation of blood flow was achieved in the ascending and transverse segment of the uterine artery for 10 cardiac beats. Cervical leiomyomas larger than 3 cm were classified into three groups based on vascularity as seen on aortography by two interventional radiologists in consensus. Grade I indicated poor and minimal vascularity, with a few small vessels seen in the myoma, without tumor staining. Grade II indicated moderate vascularity, with myoma staining identified, but only in small vessels. Grade III indicated marked vascularity, with myoma staining identified, and showing large, tortuous vessels.
Clinical Follow-Up A symptom severity questionnaire was completed to assess the severity of menstrual bleeding during and between menstrual periods on a scale from 0 (no impact) to 10 (severe impact) at the time of the 3-month follow-up MR imaging study. Also, we questioned patients concerning any changes in urination, vaginal dryness, or the ability to achieve orgasm at 3-month follow-up. We classified the grade of complications of UAE into six categories as previously reported (12,13): grade A complications require no therapy and cause no consequences; grade B complications require nominal therapy or observation and cause no consequences; grade C complications require therapy or unanticipated minor hospitalization (⬍ 48 h); grade D complications require major therapy, unplanned increased level of care, or unanticipated prolonged hospitalization (⬎ 48 h); grade E complications cause permanent adverse sequelae; and grade F complications cause death. Grade A and B complications were defined as minor complications and grade C through F complications as major complications.
Statistical Analysis The Mann–Whitney test and Fisher exact test were used to compare baseline characteristics and the effects of UAE on leiomyomas in different locations. Differences were considered statistically significant at P ⬍ .05.
RESULTS Baseline characteristics and outcomes after UAE are shown in the Table. Cramping pain occurred in all patients after UAE and was managed via an intravenous patient-controlled analgesia pump containing 500 g fentanyl sulfate and 90 mg ketorolac tromethamine. Pain began to subside approximately 8 –10 hours after UAE, and all patients were
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Table. Baseline Characteristics and Outcomes after Uterine Artery Embolization Characteristic/Outcome Size of fibroids (cm) Volume of fibroids (cm3) Necrosis Complete necrosis Partial necrosis Thin rim Thick rim No necrosis Mean VRR at 3 mo (%)
Cervix (n ⴝ 10) 6.0 ⫾ 1.6
Body/Fundus (n ⴝ 10) 5.4 ⫾ 1.8
92.6 ⫾ 54.8
54.8 ⫾ 54.7
2 6 2 4 2 42.8
10 0
0 57.8
P Value .1041* .1051* ⬍.001†
⬎.05*
Note.—Values presented as mean ⫾ SD where appropriate. VRR ⫽ volume reduction rate. * Mann–Whitney test. † Fisher exact test.
Figure 1. Images of leiomyomas in the uterine cervix and body in a 45-year-old woman. (a) Coronal T2-weighted MR imaging shows an 8.1-cm leiomyoma in the uterine cervix (arrows) and two leiomyomas 7.5 cm (arrowheads) and 4.5 cm (not shown) in size in the uterine body. (b) Aortography reveals grade III hypervascularity of two leiomyomas in the uterine body (black arrows and white arrow) and grade I (ie, poor) vascularity of leiomyoma (arrowheads) in the uterine cervix. (c) Gadolinium-enhanced T1-weighted MR image 3 months after embolization reveals complete necrosis of leiomyoma (white arrows) in the uterine body, but partial necrosis with a thin viable rim of leiomyoma (black arrows) in the uterine cervix.
able to be discharged the next day and completely recovered after 1–2 weeks. Fibroids in the uterine cervix and fibroids in the uterine body or fundus did not differ significantly in mean diameters or volumes before UAE. With regard to treatment effects, complete necrosis of leiomyomas located in the uterine cervix was seen in only two of 10 patients (20%), whereas all fibroids in the uterine body or fundus were completely infarcted on follow-up MR imaging at 3 months (P ⬍ .05). Two patients showed fibroids with PN with a thin rim, four showed fibroids with PN with a thick rim (Fig 1), and two showed no necrosis of the fibroid. Five of six patients with PN with a thick rim or no necrosis after UAE had menorrhagia, but none of the patients showed symptom improvement. Three of four patients with complete necrosis or PN with a thin rim had menorrhagia, and all these patients reported considerable symptom improvement, with the average score of menorrhagia reduced from 8.3 to 1.7. A single major complication was found in one patient (10%) with a 7-cm cervical fibroid who experienced vaginal expulsion after UAE, but MR
imaging revealed a thick peripheral viable portion of the fibroid, which could not be removed in the outpatient clinic because of bleeding risk. This patient underwent hysteroscopic resection under general anesthesia. The mean volume of fibroids in the cervix and in the body or fundus decreased nonsignificantly, by 42.8% (from 92.6 cm3 ⫾ 54.8 to 46.9 cm3 ⫾ 31.4) and 57.8% (from 54.8 cm3 ⫾ 54.7 to 30.8 cm3 ⫾ 41.4) at 3 months, respectively. In terms of the vascularity of cervical leiomyomas, grade I (ie, poor) vascularity was noted in five of nine patients (55.6%), grade II vascularity in two patients, and grade III vascularity in two patients. One patient who underwent MR-guided focused ultrasound (US) for cervical leiomyoma 15 months earlier exhibited grade I vascularity on angiography (Fig 2). The follow-up MR images after UAE showed no evidence of the fibroid remaining. Eight patients had fibroids at intracervical locations, and two patients had them at extracervical locations. One of two extracervical-type fibroids showed complete necrosis, and the other showed no necrosis. A 50-year-old patient with a fibroid with PN with a thick rim developed amenorrhea after UAE. No patient had
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Figure 2. A 41-year old woman with leiomyomas in the uterine cervix underwent MR-guided focused US for cervical myoma 15 months before imaging. (a) Sagittal T2-weighted MR image reveals a 6.8-cm cervical leiomyoma. (b) Aortography reveals grade I (poor) vascularity (arrowheads) in a leiomyoma. Both uterine arteries (arrows) are visualized. Embolization was performed beginning with 150 –250-m PVA particles, with the particle sizes progressively increased to 250 –355 m and then 355–500 m, up to the endpoint. (c) Follow-up MR image confirms disappearance of the cervical leiomyoma and shows a remaining linear scar (arrow) after embolization.
urinary incontinence or vaginal dryness, or lost the ability to achieve orgasm, after UAE.
DISCUSSION Cervical leiomyomas comprise fewer than 5% of all uterine leiomyomas. They may be categorized as those that occur at a subserosal location (ie, extracervical type) and those that occur within the cervix (ie, intracervical type). Myomectomy for cervical leiomyoma is empirically difficult and may be specifically complicated by a deep intracervical location or a large myoma size, which increases the risk for blood loss during surgery (14,15). When performing myomectomy for a cervical myoma, care must be taken to avoid injuries to neighboring pelvic structures such as the bladder, rectum, and ureters. Although UAE is increasingly presented to women as an alternative to hysterectomy for symptomatic fibroids (3,4), reported treatment failure rates remain at 5%–15% (5,7). This may largely reflect the presence of collateral vasculature, which includes the ovarian collateral vessels. Our results with the use of UAE for cervical leiomyomas were disappointing, with only 20% of patients showing complete necrosis. Even if the achievement of PN with thin rim enhancement in two patients is regarded as a success, our success rate would still only be 40%. Pollard and Goldberg (16) suggested that cervical myomas should be considered a contraindication to UAE because of significant risk for vaginal expulsion of the fibroid, requiring hysterectomy. However, vaginal expulsion of a fibroid is generally manageable without serious complications, and should be regarded as a treatment response, not a complication (17). The problem, as we observed with one patient, is that, in expulsion of a cervical myoma without complete necro-
sis, the stalk of the fibroid cannot be easily resected in view of the possibility of uncontrolled bleeding. The uterus is anatomically composed of three parts: the fundus, body, and cervix. In a study by Scheurig-Muenkler et al (10), only the cervix was usually perfused at all time points on postinterventional MR imaging. This phenomenon may explain the high frequency of treatment failure of UAE for cervical leiomyomas. The authors suggested that placement of the microcatheter tip beyond the cervicovaginal branch of the uterine artery may explain this phenomenon (10). However, this suggestion is not entirely satisfying: first, the cervicovaginal branch is visible in only 53% of cases (18); and second, we were able to embolize the uterine arteries including the transverse segment of the uterine artery. Thus, treatment of UAE for cervical myomas may fail not because of microcatheter tip location, but rather because the uterine cervix has a fine arterial supply, with or without the targeted vessels, through collateral vessels that cannot be detected on angiography and that we usually do not embolize. The size of the cervicovaginal and ovarian branches are known to be smaller than 500 m, whereas the size of the perifibroid plexus arteries range from 500 to 1,000 m (19). These differences in artery size provide the rationale for fibroid-targeted embolization with calibrated embolization materials 500 –700 m or larger, so as to preserve cervicovaginal or uteroovarian branches. However, if the cervicovaginal branch is a main feeding vessel to the cervical fibroid, materials 355–500 m in diameter or larger cannot reach the perifibroid plexus for embolization, which results in treatment failure. The anterior branches of the internal iliac artery include the inferior gluteal, obturator, internal pudendal, vesical, middle hemorrhoidal, and genital (ie, uterine and vaginal) arteries. Cervical and vaginal branches of the uterine arteries supply the cervix and upper vagina, but there is considerable
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anatomic variation and anastomoses in the uterine cervix with vaginal and middle hemorrhoidal arteries, which might explain another cause of frequent failure of UAE. After repeated failure of UAE for cervical leiomyomas, we acknowledge here that we altered our UAE protocol for the last two patients enrolled in the present study. We began the procedure by using 150 –250-m PVA particles and progressively increased the particle size to 250 –355 m and then to 355–500 m until the endpoint, which is similar to that for the treatment of adenomyosis (20). In one of the two patients, we succeeded; however, the other showed PN with thick rim enhancement. Even though we did not succeed completely in both cases, our results may indicate the need for more aggressive embolization in cervical leiomyomas than for those of the uterine body or fundus, perhaps by using a procedure similar to those used for adenomyosis. However, it cannot be recommended without further study on its effectiveness and safety. The cervicovaginal branch is believed to supply the cervicovaginal plexus, which consists of nerves surrounding and innervating the cervix and upper vagina. Lai et al (21) described a case in which embolization of the cervicovaginal branches may have caused injury to the uterovaginal plexus, the vascular supply to the cervix, or both, leading to potential sexual dysfunction. In contrast, the majority of embolization treatments involving the cervicovaginal branch have nonadverse outcomes. Although most leiomyomas display a defined arterial supply with hypervascularity on angiography, the cervical leiomyomas in the present study frequently showed no defined arterial supply and poor to minimal vascularity, making them difficult to treat with use of medium-sized PVA particles. Interestingly, fibroids of the cervix and fibroids of the body or fundus of the uterus did not differ significantly in the rate of volume reduction achieved with the use of UAE. Even the cervical leiomyomas that showed PN with a thick rim of enhancement were reduced in volume to approximately the same extent as those of the body or fundus. However, long-term follow-up is needed to establish the duration of the treatment effect. Pelage et al (22) suggest that regrowth of noninfarcted fibroid tissue may ultimately result in symptom recurrence. The present study may lack the statistical power to test this possibility in view of the small number of patients enrolled; hence, further studies are needed. In conclusion, poor vascularity was a frequent finding among cervical leiomyomas, and the results of UAE were disappointing, indicating a need for caution in selecting and counseling patients for this treatment. Further study with larger groups of patients is justified to determine whether UAE for cervical leiomyomas necessitates a more aggressive approach with the use of procedures similar to those used for adenomyosis.
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