Applied Radiology

Uterine leiomyomata or fibroids are the most common tumors of the female genital tract. One in every three women over the age of 35 has uterine fibroids.1 They are found commonly in women in their 30s and 40s and are more frequently seen in African-American women.1 Their etiology is unknown and they consist of bundles of smooth muscle surrounded by a pseudocapsule of uterine tissue. Their growth appears to be under estrogenic control. These tumors of reproductive-age women may grow during pregnancy and with use of oral contraceptives. They undergo degeneration and involute with menopause. They have a role in infertility and can cause problems in each step of the "pregnancy pathway" from conception to delivery.

Fibroids are classified by location. Submucosal fibroids project into the endometrial cavity, intramural fibroids are located in the myometrium, and subserosal fibroids protrude away from the external surface of the uterus. The subserosal and submucosal fibroids may be sessile or pedunculated. Occasionally, a myoma may detach from the uterus and parasitize a new blood supply.

Less than 25% of patients with fibroids are symptomatic.2 The most common symptom is abnormal uterine bleeding (menorrhagia). The bleeding usually starts as a prolonged menses, which can lead to anemia. Fibroids typically do not bleed between periods, but can if they are quite large. Fibroids can also cause symptoms due to their size and mass effect. This can lead to pressure symptoms, abdominal/pelvic fullness or pain, and increased girth. The patient may notice increased urinary frequency from pressure effects on the bladder causing her to wake up each night to urinate. Pain in the back, flank, or thigh may be caused from pressure on the nerves of the pelvis. If sufficiently large, fibroids can compress the ureters leading to hydronephrosis or on the bowel and cause constipation.

Treatment of fibroids

Management of fibroids may be conservative, medical, surgical, or interventional. No treatment is required for asymptomatic fibroids, which are usually followed by ultrasound to document growth.

A number of drugs are used in the medical management of fibroids. Non-steroidal anti-inflammatory medicines, oral contraceptive pills, and gonadotropin-releasing hormone ana-logs (Lupron, TAP Pharmaceuticals Inc., Deerfield, IL) are all part of the medical regimen. Lupron is effective in shrinking fibroids, however, there are common side effects (most notably, hot flashes) and the beneficial treatment effects are reversed following cessation of therapy. Patients can be treated with Lupron typically for 3 months and not more than 6 to 9 months.3 The most common usage in the past was initiation of treatment several months before an anticipated surgical procedure. Often, this would shrink the myomas prior to elective surgery to allow a less invasive or safer surgical approach. While medical management offers relief to some and allows others time to enter menopause, often more definitive therapy is needed.

The surgical treatment of fibroids consists of two main procedures:

hysterectomy and myomectomy. Hysterectomy may be performed laparoscopically, vaginally, or by the traditional open abdominal route. Approximately 30% of the 600,000 hysterectomies performed each year in the United States are for fibroids. It is the single largest indication for hysterectomy in this country. Traditionally, asymptomatic women with uteri >12 week gestational size who did not desire future fertility were often treated with hysterectomy. Due to the im-proved imaging of the adnexa and the low incidence of leiomyosarcoma, performing a hysterectomy based on size criterion alone is no longer warranted and is outweighed by the morbidity and mortality risk of hysterectomy. Myomectomy was developed to preserve the uterus and allow a woman to maintain her fertility. It can be performed hysteroscopically, laparoscopically, or by open abdominal approaches. Both procedures often require general anesthesia and hospitalization. Myomectomy is a local therapy with a relatively high recurrence rate. Roughly one in every three women who undergo myomectomy will have a recurrence and require an additional procedure in the future.4,5 In the past, that was either repeat myomectomy or hysterectomy, but now those patients can undergo uterine artery embolization (UAE). Hysterectomy is obviously a definitive treatment, although it is at the price of a woman losing her uterus. These procedures can have a significant morbidity (adhesions, blood loss, thromboembolic disease, infection) and possible loss of fertility.

Uterine artery embolization

Pelvic embolization is a well-recognized therapeutic intervention that has been performed for many years.6,7 It is most commonly performed in postpartum hemorrhage with essentially 100% success.6,7 Uterine artery embolization (UAE) for symptomatic uterine fibroids is a newer application based on principles of pelvic embolization and tumor embolization in other organ systems. It is a global therapy that is designed to treat all of the uterine fibroids. The tumors are rendered ischemic, with resultant necrosis, sclerosis, and subsequent shrinkage.

UAE was first reported by Ravina et al8 in 1995. Goodwin and coworkers9 published the results of the first U.S. trial in 1997. Since then, an estimated 4000 UAE procedures have been performed in the United States and more than 6000 worldwide.7 Of the more than 4100 U.S. cases reported, there were no reported deaths, and only 25 patients (0.6%) had complications that resulted in additional surgery within 30 days of the procedure. There is a very high patient satisfaction rate (>90%) with the procedure.10 Hutchins et al11 have published their results in 305 patients with up to 2-year follow-up. Both menorrhagia and bulk symptoms were controlled in 92% of patients at 1 year postprocedure with "no major complications." From this and a number of initial trials, the clinical success rate (symptomatic improvement following UAE such that no further treatment is needed) is 85% to 90%.7-18 There is some variability in the volume (3 dimensions ¥ 0.52) reductions following UAE. This is particularly true when extrapolating ultrasound data from different operators. In general, uterine volume can be expected to decrease an average of 30% to 40% at 3 months and 50% to 60% 1 year postprocedure. Approximately 10% to 15% of patients will not find enough symptom relief from UAE and many of these will need surgical therapy. However after the UAE, the risk of morbidity of this subsequent surgery may be decreased or a less invasive surgical approach may now be possible for these patients.

UAE technique

Typically, the UAE procedure is performed from a right femoral approach, although some institutions prefer a bilateral femoral approach with criss-crossing catheters. The uterine artery is a branch of the anterior division of the internal iliac artery. It has a characteristic "L" or "U" shape (figure 1) and can be divided into descending, horizontal, and ascending segments with numerous spiral intramural branches (figure 2A).

Polyvinyl alcohol (PVA) particles are the embolic agent used most frequently; they are made by several different manufacturers and come in a wide array of sizes. The most common PVA sizes used for UAE are 355 to 500 micron and 500 to 710 micron, although some use the 150 to 300 micron size.14 Gelfoam (Upjohn, Kalamazoo, MI) has been used by some investigators, particularly in Japan. A third embolic agent (Embosphere Biosphere Medical, Marlborough, MA) is undergoing clinical trials. Embolization is performed in each uterine artery with either a 4F or 5F catheter or a coaxial system with a microcatheter to near or complete stasis (figure 2). Some interventionalists cap off their particulate embolization with a Gelfoam plug in the main uterine arterial trunk. While Gelfoam is a temporary agent, this combination may cause complete thrombosis of the main uterine artery and not allow preservation of the normal myometrial perfusion. At our institution, we embolize with PVA alone and embolize to near stasis. The main trunk is preserved and may be responsible for maintaining myometrial perfusion. In addition, we embolize beyond the cervicovaginal branches (figure 3), as embolization of these non-target branches may interfere with some patients' sexual response.

Following the procedure, almost all patients experience pain to some degree. Fever and nausea may also occur, although this "postembolization syndrome" is usually less severe than that seen following hepatic chemoembolization. The pain typically begins soon after the procedure and has plateaued in most by 6 hours. Some patients have a longer initial pain response but almost all patients report that the pain has improved significantly by the morning after the embolization. The pain typically improves each day over the next several days, yet can persist in some patients for up to 2 weeks postprocedure. Most procedures are performed under conscious sedation, although some centers use routine epidural or intrathecal administration of analgesic agents. This latter approach necessitates an overnight stay in the hospital, but almost all patients, regardless of pain control regimen, leave by the first day after UAE. Readmission to the hospital for postprocedural pain is rare.

Follow-up imaging

Imaging follow-up can be performed with ultrasound or magnetic resonance imaging (MRI). We prefer MRI, since it is less operator-dependent, allowing more accurate measurements of both the uterus and the dominant fibroids (figures 4 and 5). In addition, the ovaries are sometimes difficult to image in an enlarged myomatous uterus with ultrasound and are evaluated more easily with MRI. We have detected adnexal masses on MRI that were not seen by pelvic ultrasound and we will not embolize patients who have had a pelvic ultrasound that did not demonstrate the ovaries. MRI also demonstrates the dominant fibroid's position within the uterus, which will often help to determine which type of treatment approach (e.g., interventional versus surgical, hysteroscopic versus laparoscopic) is needed. MRI is also helpful in the follow-up evaluation to detect any residual areas of enhancement that might lead to a treatment failure. Finally, we prefer MRI because it is more accurate in the detection of adenomyosis. The junctional zone is depicted on MRI very nicely and therefore the diagnosis of adenomyosis is much easier to make on MRI than it is with ultrasound.

Patients with adenomyosis can still be candidates for UAE, although the success rate appears to be less (and may account for a significant portion of the clinical failures). UAE is still a reasonable approach despite the lower success rate, as the current alternative for adenomyosis is often hysterectomy.

Complications

Complications of UAE appear to be rare. The two most important are amenorrhea and fibroid slough. One of the most significant unanswered questions about UAE is what effect it has on ovarian function. There is a small incidence of both temporary (several cycles) and permanent amenorrhea following embolization. The mechanism is believed to be embolic from uterine-ovarian collateral vessels (figures 2 and 6). All reported cases in the literature have been in women over 40 years of age, and most over 45. The embolization may have hastened or initiated menopause in a perimenopausal patient whose ovaries depended on the uterine contribution of flow. Ongoing studies are examining follicle-stimulating hormone levels in patients before and after embolization to improve our understanding in this area. Some patients resumed having periods following several months of amenorrhea. The incidence of permanent amenorrhea is believed to be low (~2%), but further study of ovarian physiology is needed.7,19 It has been reported that hysterectomy can also compromise ovarian function with resulting earlier menopause than age-matched controls.20 It is clear that patients desiring future fertility must be counseled thoroughly on the risks of amenorrhea versus the risks of any surgical alternative. Patients have conceived and delivered normally following em-bolization, however the actual pregnancy rate is unknown.19 We currently do not perform UAE on patients desiring to become pregnant unless the alternative is hysterectomy or complex myomectomy.

Fibroid slough is a phenomenon that can occur spontaneously in fibroid patients and is also seen in patients that have undergone UAE. The fibroids are typically submucosal, but can be intramural as well. Usually, this material is expelled without incident, although it can get "stuck" in the cervix or become secondarily infected (or both). Patients describe a rather typical "wave-like" pattern of pain (similar to labor pain) prior to the subsequent passage of the material. Patients need to be in close contact with their interventional radiologist during this period as antibiotics (oral or IV), and even hospital admission (for hysteroscopy and dilation and curettage to remove this material) may be required. A few patients (out of thousands) have needed elective hysterectomy for acute septic uterine necrosis.7,16,17

Radiation dose to the ovaries and skin entrance is also a concern, even in patients that are not interested in future fertility. Nikolic et al21 estimated the absorbed ovarian dose during UAE, which was higher than comparable fluoroscopic procedures, but much less than the dose seen in radiotherapy for patients with Hodgkin's disease.

Conclusion

Uterine artery embolization is an exciting, innovative application of tumor embolization for the treatment of symptomatic uterine fibroids. While there are many unanswered questions, the early data is very promising. Patients report a high satisfaction with the procedure.We await the results of long-term studies to assess the durability of the procedure and the effects on fertility. AR

References

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