Applied Radiology

Dr. Rougier-Chapman is a Radiology Resident, Ms. Key is a Nurse Practitioner, and Dr. Ryan is an Assistant Professor of Radiology, in the Division of Vascular-Interventional Radiology, Duke University Medical Center, Durham, NC.

Uterine leiomyomas (fibroids) are the most common gynecological tumors in women, occurring in 20% to 25% of women of childbearing age. ¹ They are three times more common in the African-American population than in the white population. Although asymptomatic in the majority of women, fibroids are a common cause of heavy prolonged menstrual bleeding (menorrhagia), intermenstrual bleeding (menometrorrhagia), urinary frequency, stress incontinence, and pelvic pain in approximately 25% of women with fibroids. Although patients may experience these symptoms during their 20s, women usually do not manifest severe symptoms until their late 30s or 40s. Fibroid disease is responsible for the loss of 5 to 10 million person-days, for 900,000 hospital days, and a direct cost of more than $1 billion in the United States annually.

Transcatheter uterine artery embolization (UAE) is a rapidly emerging alternative to conventional medical and surgical therapy in the treatment of symptomatic uterine leiomyomas. The technique of pelvic vessel embolization is well recognized as an effective treatment for acute pelvic hemorrhage, with the first successful uterine artery embolization for this indication reported in 1979. ² Embolization has been used successfully in cases of postpartum hemorrhage, trauma, postsurgical bleeding, ectopic pregnancy, placenta accreta, cervical pregnancy, and vascular malformation. In 1994, Ravina et al ³ described uterine artery embolization as an adjunct to surgery in the treatment of fibroids ³ and a year later described it as a primary therapy. ⁴

Treatment options

Irrespective of what therapeutic method you use, it is justifiable to treat fibroid disease only if it is symptomatic. Before offering UAE to any patient, other less invasive therapeutic options should be explored first. At first, treatment of symptomatic fibroid disease should be attempted with medical therapy. Nonsurgical medical therapy for symptomatic leiomyomas may include the use of nonsteroidal anti-inflammatory agents, the oral contraceptive pill, or progesterone analogs for patients with milder symptoms. Hormonal therapy with gonadotropin-releasing hormone (GnRH) analogs is reserved for patients with more severe intractable symptoms. The GnRH analogs cause involution of fibroids by decreasing estrogen levels but are associated with postmenopausal symptomatology, including hot flashes and demineralization of bone. These medications are limited to use for no longer than 6 months and are primarily used to reduce tumor size and vascularity prior to surgical intervention. On average, a 40% reduction in fibroid volume is observed in the first 3 months of GnRH therapy, ⁵ however, fibroids typically regrow to their original size within several months of discontinuing the medication. ⁶

The established surgical therapy for symptomatic uterine leiomyomas is hysterectomy. Symptomatic fibroids account for nearly a third of all hysterectomies performed in the United States, with estimates of 177,000 to 366,000 hysterectomies performed annually for fibroid disease alone. ⁷ In experienced surgical hands, hysterectomy is a safe operation with a low complication rate. It is, however, a major surgical procedure with an extended recovery period of approximately 6 weeks and with significant postoperative morbidity.

The accepted surgical alternative to hysterectomy is myomectomy. This procedure involves removal of fibroids while preserving both the uterus and the patient's childbearing potential. Myomectomy has a reported 80% success rate in controlling symptoms, but carries an appreciable perioperative and postoperative morbidity. Also, not all patients are candidates for this procedure. The procedure is associated with significant intraoperative bleeding complications, postoperative infections, pain, and a longer hospital stay than that of conventional hysterectomy. ⁸ Because of bleeding complications at the time of operation, approximately 20% of elective myomectomies result in hysterectomy. Furthermore, fibroid recurrence rate of 43% has been reported after myomectomy, ⁹ with 20% to 25% of women eventually requiring an additional surgical procedure for the treatment of fibroids. ⁸

Uterine artery embolization has emerged as a minimally invasive uterine-sparing alternative to surgery and appears to be associated with less morbidity than is conventional surgical modalities. The technique has captured the public imagination, and many interventional radiologists are now being contacted directly by patients who have researched the topic in women's magazines and on the multitude of internet sites dealing with the subject (e.g., www.nuff.org, www.fibroid.org, www.scvir.org, www.radweb.mc.duke.edu/ufe, etc). Early and midterm results are extremely encouraging, and large-scale studies are currently in progress to assess the long-term effectiveness and durability of the technique.

It is important to ensure that meticulous preprocedural work-up is performed in all cases. In our practice, before we consider a patient for UAE, she must be seen by a gynecologist, imaging must be obtained (ultrasound or magnetic resonance imaging), and a Pap smear must be up to date. When all of this information is made available to us, we then have a preprocedural consultation with the patient, during which the severity of the patient's symptoms are assessed, and alternative forms of therapy are discussed. The UAE procedure is discussed in detail, including postprocedural expectations, results reported in the literature, and the possible complications associated with the technique. We specifically discuss issues of fertility and premature ovarian failure, and we explore the patient's wishes for future pregnancy. Coexisting conditions, such as acute pelvic infection or endometrial cancer, must be excluded, as these are contraindications to UAE.

Embolization procedure

Informed consent is obtained when the patient presents for the procedure. The embolization procedure is performed in the interventional radiology suite, and a combination of local anaesthetic and intravenous conscious sedation is used for patient comfort. Patients receive prophylactic antibiotics (cefazolin), and then cannulation of the right or left common femoral artery is performed. We use a unilateral approach; however, some groups use bilateral common femoral artery cannulation, citing easier cannulation of the uterine artery from a contralateral approach, shorter procedure times, and decreased pelvic radiation dose. ¹⁰

Before embolization, an arteriogram is performed to examine the blood supply to the uterus (figure 1). The usual blood supply of leiomyomas is through branches of the arcuate arteries, arising from the uterine artery by way of the anterior branch of the internal iliac artery. ¹¹ In order to prevent nontarget embolization to other branches of the anterior branch of the internal iliac artery, it is necessary to advance the catheter into the distal descending portion or the horizontal portion of the uterine artery. We find that the uterine arteries are easily selected using a 4F hydrophilic catheter, or Roberts Uterine Curve catheter (Cook, Inc., Bloomington, IN), following a selective angiogram of the internal iliac artery with contralateral anterior oblique imaging (figure 2). Occasionally we use a microcatheter to cannulate the uterine artery if the artery is small or if vasospasm is encountered. With the catheter in its proposed final position for embolization, a selective angiogram should be performed to detect ovarian branches or cervicovaginal branches of the uterine artery, which should be avoided during embolization (figure 3). It is not uncommon for fibroids to get additional blood supply from other pelvic vessels. ¹²

We perform embolization with 355 to 500 µm polyvinyl alcohol particles (Ivalon, Cook, Inc.) or 500 to 700 Embosphere Microspheres (Biosphere Medical, Rockland, MA) until near-complete stasis of flow within the branches of the uterine artery is achieved. Some investigators use larger particles, citing increased pain with smaller particles, although we have not experienced this. The embolic particles are mixed with iodinated contrast to facilitate visualization during embolization. The catheter is then replaced into the ipsilateral uterine artery and embolization is similarly performed. Bilateral UAE should be performed in all patients, as unilateral embolization is associated with treatment failure. After the embolization is completed, an arteriogram is performed to confirm absence of flow to the fibroids (figure 4).

Upon completion of the procedure, patients are transferred to a 24-hour observation bed. Most patients experience mild to moderate pelvic pain starting 4 to 6 hours postprocedure and lasting up to 18 hours. We put patients on a self-administered analgesic pump during this period to ensure adequate pain-relief. Moderate pain may persist for several days, but does not appear to be related to size, location, or number of fibroids present. ¹³ Pain control is best maintained with a combination of opiates and nonsteroidal anti-inflammatory agents. In addition to pain, a "postembolization" syndrome is not uncommon; this syndrome includes nausea, vomiting, fever, and leukocytosis. Most symptoms substantially improve after 24 hours, allowing for discharge from the hospital on the first postprocedural day. During the immediate postprocedural period, we ask patients to immediately report to us any high fevers, increasing pain, or purulent vaginal discharge. After discharge from the hospital, women usually experience intermittent pain and cramping over a 3- to 5-day period, with 90% of women back to normal activities within 10 days of the embolization procedure. ¹⁴ We see all patients at a follow-up appointment at 10 to 14 days, and follow-up imaging is currently performed at 3, 6, and 12 months.

Results

Since 1995, more than 25,000 women worldwide (more than 15,000 in the United States) have undergone selective UAE for symptomatic fibroid disease; and early and mid-term results are promising. Results in 661 patients have been published in peer-reviewed literature, and 7 studies of >40 patients have been published.

Results from the reported studies indicate that UAE is effective in improving symptoms in the majority of patients; 81% to 94% report significant improvement in their menorrhagia. Bulk-symptoms, including pain, pressure, bloating, and urinary frequency, are improved in 64% to 96% of patients. Compared with the standard uterine-sparing procedure (myomectomy), UAE has similar effectiveness. Most of the data published to date refer to UAE with polyvinyl alcohol particles. Comparable results have been recently reported using the new synthetic microsphere particle of a trisacryl polymer matrix embedded with gelatin (Embosphere Microspheres, Biosphere Medical). We have had similar successful personal experience with this agent.

As with any invasive procedure, transcatheter uterine artery embolization is not completely without complications. Short-term complications are related primarily to arterial access, and include thromboembolic phenomena, groin hematomas, and local infection at the arterial puncture site. Long-term complications are uncommon, with the need for postembolization hysterectomy indicated in <1% of cases, usually due to infective sequelae. ¹⁵ Goodwin ¹⁶ reported a single case of postprocedure endometritis requiring hysterectomy, while Walker et al ¹⁷ reported 2 cases of postprocedure infection leading to hysterectomy. In 1999, a fatal case of Escherichia coli septic anemia was reported after UAE. The origin of infection was an infarcted fibroid. ¹⁸ Transvaginal expulsion of fibroids has also been reported following UAE. The estimated mortality rate of UAE is 2 per 10,000 cases. Hysterectomy has an estimated mortality rate of 11 per 10,000 cases.

At this time, it remains undetermined what effect embolization of the uterine arteries has on long-term ovarian function and the ability of women to carry a pregnancy to term. Successful pregnancies have been achieved after bilateral UAE for postpartum hemorrhage, placenta accreta, and trauma, and for symptomatic fibroid disease. ¹³ Studies report a 2% to 3.7% incidence of permanent amenorrhea after embolization, mainly due to nontarget embolization to the ovaries. ¹⁹ The incidence rises to approximately 15% in patients age 45 years and older, presumably due to decreased ovarian reserve as patients approach meno-pause. For this reason, when we are assessing patients for suitability for UAE, if the patient is young or future fertility is an important issue, we consider myomectomy as the first line of treatment. If myomectomy is not appropriate, or if the patient is completely resistant to surgery, only then will we proceed with UAE. It has been shown that performing UAE with gelfoam (a nonpermanent embolic agent) is effective in treating symptomatic fibroid disease with reduced incidence of ovarian dysfunction. ²⁰

Conclusion

Uterine artery embolization represents an exciting, promising, and minimally invasive new option for patients with symptomatic fibroid disease. ²¹ The data reported thus far indicates that success rates are comparable to the standard uterine-sparing surgical therapy. A shorter postprocedural recovery period and lower morbidity and mortality rates are associated with UAE compared with the surgical option. Considerable ongoing research is aimed at long-term follow-up of patients who undergo UAE. ^7,21-22 The Society of Cardiovascular and Interventional Radiology (SCVIR) has an ambitious and comprehensive research strategy for the validation of UAE for treatment of symptomatic uterine fibroids. A national registry has been established and will be coordinated by the Duke Clinical Research Institute. In addition, comparative studies among UAE, hysterectomy, and myomectomy are currently under consideration. The SCVIR has proposed to the American College of Obstetricians and Gynecologists that a joint practice bulletin be issued to assist patients and health-care participants to make informed decisions regarding treatment of symptomatic fibroids.

As a result of the research being currently performed, one certainty remains for the future treatment of this disease: our patients will ultimately benefit, and that, of course, should remain the goal for all involved in the treatment of symptomatic fibroid disease. AR