OB/GYN CONTEMPORARY. Uterine Fibroid Embolization for the Management of Uterine Fibroids. JUNE

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1 Supplement to CONTEMPORARY OB/GYN Translating science into sound clinical practice JUNE Uterine Fibroid Embolization for the Management of Uterine Fibroids Funded by and produced with the assistance of

2 CONTEMPORARY OB/GYN Robert Braun GROUP PUBLISHER Tina Feliciano ACCOUNT MANAGER John C. Marlow, MD CHIEF MEDICAL AND COMPLIANCE OFFICER Joseph Loggia CHIEF EXECUTIVE OFFICER David W. Montgomery VICE PRESIDENT FINANCE, CHIEF FINANCIAL OFFICER AND SECRETARY R. Steve Morris Daniel M. Phillips EXECUTIVE VICE PRESIDENTS Eric I. Lisman EXECUTIVE VICE PRESIDENT CORPORATE DEVELOPMENT Adele D. Hartwick VICE PRESIDENT, TREASURER AND CONTROLLER Francis Heid VICE PRESIDENT PUBLISHING OPERATIONS Rick Treese VICE PRESIDENT AND CHIEF TECHNOLOGY OFFICER Ward D. Hewins VICE PRESIDENT GENERAL COUNSEL Uterine Fibroid Embolization for the Management of Uterine Fibroids Expert Interviews With: DAVID SIEGEL, MD Chief, Division of Vascular and Interventional Radiology Long Island Jewish Medical Center New Hyde Park, New York NEIL SLOANE, MD Private Practice Parkview OB/GYN Philadelphia, Pennsylvania RON CLAUHS, MD Private Practice West Chester, Pennsylvania ROBERT WORTHINGTON- KIRSCH, MD, FSIR Image Guided Surgery Associates, PC Philadelphia, Pennsylvania JOHN C. LIPMAN, MD, FSIR Director, Atlanta Interventional Institute Adjunct Clinical Assistant Professor Department of Obstetrics and Gynecology Morehouse School of Medicine Atlanta, Georgia Since the late 1970s, interventional radiologists have been treating postmyomectomy or postpartum uterine bleeding by embolizing the uterine arteries. In France during the mid 1980s, Jacques Ravina, MD, observed that some of his patients receiving uterine fibroid embolization (UFE) as a preoperative maneuver before myomectomy experienced a resolution of their symptoms and cancelled their surgeries. He subsequently published a brief report in 1995 documenting 16 cases of women who had UFE without further surgery and who experienced durable relief of their symptoms. Later that same year, Bruce McLucas, MD, an American gynecologist from the University of California at Los Angeles (UCLA), met with Dr. Ravina. Soon thereafter, Dr. McLucas and Scott Goodwin, MD, the director of Interventional Radiology at UCLA, initiated the use of UFE as a primary treatment for uterine fibroids. In 1996, UFE became available in the United States. It is estimated that more than 100,000 women have undergone this treatment worldwide. Currently about 15,000 to 18,000 cases are performed each year in the United States. Recently, a group of experts answered a Contemporary OB/GYN interviewer s questions about their experiences with this procedure. The physicians focused on patient selection, pain management, UFE as a treatment option, and strengthening relationships with interventional radiologists. Highlights from those conversations follow. The views and opinions expressed are those of the participants and do not necessarily reflect those of Advanstar Communications Inc, publisher of Contemporary OB/GYN. Advanstar Communications Inc June 2006 All rights reserved ADV-267 Printed in the USA 80094Z

3 Patient Selection for UFE An Interview With David Siegel, MD Interviewer: What preoperative evaluations are necessary to determine if a patient is a candidate for UFE? Dr. Siegel: An evaluation for UFE should begin with a complete medical history, a physical examination, including a recent gynecologic examination with Pap smear, and depending on the clinical indications, appropriate laboratory tests such as a complete blood count and follicle-stimulating hormone (FSH) level. In most patients, especially those with bleeding symptoms, an endometrial biopsy should be done as well. The most important evaluations in the triage of fibroid patients for the various minimally invasive treatments are those obtained from imaging studies, because the size of the fibroid masses and their location relative to the uterine layers are major determinants of UFE candidacy. There is some controversy among clinicians on whether patients being considered for UFE should routinely undergo magnetic resonance imaging (MRI) clearly the best test we have for defining fibroids. Ultrasounds or sonograms are the most common screening tests for fibroids; they are routinely performed in gynecology and radiology offices for evaluating patients who have pelvic pain, bleeding, or a history of fibroids. If a complete pelvic ultrasound examination is performed and the details of the uterus and all the other associated structures are able to be identified and evaluated appropriately, then an MRI may not be necessary, especially in a nonbleeding patient where adenomyosis is not an issue. Having said that, more than 85% of my patients get MRIs because of variability in the quality or documentation of sonography. Interviewer: Which patients are candidates for UFE? Dr. Siegel: It is estimated that about 80% of women who have fibroids with symptoms are candidates for UFE. Patients should be symptomatic with respect to their fibroids. Bulk symptoms include pain or urinary frequency, excessive bleeding, or both. Beyond that, the location and configuration of the fibroids establish the therapeutic options, including UFE. For instance, fibroids sitting on the outside of the serosa but bulging outside of the contour of the uterus are generally acceptable to embolize. If the stalk attaching the fibroid to the uterus is narrow (ie, <50% of the diameter of the entire fibroid), there is a reasonable chance of treatment failure, however. These patients are usually good candidates for laparoscopic myomectomy. Interviewer: Which other patients are not candidates for UFE? Dr. Siegel: Patients with unfavorable fibroid anatomy will not benefit from UFE. The size of the fibroids and whether they are in the uterine cavity are important factors. Large fibroids that sit inside the uterine cavity may be difficult to pass if they detach after embolization, so these patients may be better served with hysteroscopic therapy. The overall size of the uterus is not an absolute contraindication to the procedure. However, when the uterus becomes larger than a 20 weeks pregnancy size, or as I like to describe it, the uterus becomes an abdominal rather than a pelvic organ, patients will not respond as well to UFE as would those with smaller uterines. Thus, they are often counseled to consider other options. Most patients with bleeding secondary to adenomyosis may not benefit from UFE in the long term. An article by JP Pelage of France, published in a 2005 issue of Radiology, reported a very high recurrent bleeding rate in cases of symptomatic adenomyosis. Those with chronic pelvic inflammatory disease or active sexually transmitted diseases or other infectious processes also should not be treated with UFE. Because Lupron (leuprolide acetate) can cause spasm in blood vessels, making it more difficult to catheterize the vessels and perform the procedure, patients on this agent should be weaned off the medication at least a month before the UFE procedure. Women with endometriosis and fibroids, both of which cause pain, will not get pain relief with UFE. Also, we must use caution in patients who have allergies to the dyes or contrasts used in UFE. Most of these allergies are minor, and patients can be pretreated with steroids. Rarely, however, the allergies can be life-threatening, and these patients should not be treated with UFE. Interviewer: What should gynecologists be aware of when recommending UFE to a patient? Dr. Siegel: The gynecologist should know the important data about UFE success and failure rates; fertility data; exclusion criteria such as infection, adenomyosis, and pedunculated fibroids; and inclusion criteria in terms of symptoms. There are many patients who have fibroids but do not have symptoms; these patients do not need to be treated. A patient with symptoms should be referred to an interventional radiologist, who in turn will make the evaluation to determine if she is a candidate for the procedure. Interviewer: What should patients be aware of regarding UFE? Dr. Siegel: Patients should be aware that UFE may be an option for them and that interventional radiologists who do this procedure are available for consultation to review their cases and make a recommendation. Patients need to know that UFE is not a surgical procedure and that it has lower risks than available surgical therapies for fibroids. Having said that, patients should also understand that UFE is a real procedure and that they will probably not be able to 3

4 return to work or to resume routine activities for the next 5 to 10 days. As with any procedure that requires an informed consent, they need to know the risks, benefits, and potential complications of UFE. With regard to fertility, there are now enough reports of pregnancy after UFE to present to patients to help them choose the direction of their therapy. Several studies have reported that about a quarter to a third of patients were able to become pregnant after UFE. However, it is not known what percentage of the total number of women in the study were trying to become pregnant. The effects of UFE on the ability to become pregnant and carry a fetus to term and on the development of the fetus have not been determined. Interviewer: What are the expected outcomes for patients treated with UFE? Dr. Siegel: Approximately 90% of patients will have resolution of their heavy bleeding and/or pelvic pain and pressure. Symptom relief is the goal of therapy. By 3 months after UFE, most patients symptoms are better even though an imaging study will not show the fibroids to be completely resolved. Fibroids will continue to shrink beyond this time, and the patient will continue to improve. Of course, the bigger the fibroid, the longer it will take to shrink and for the patient to achieve symptom relief. Interviewer: What should patients expect during the UFE procedure? Dr. Siegel: UFE itself, from puncture to removal of the catheter, takes about 25 or 30 minutes to perform. In general, some form of sedation is used during the procedure. I give my patients the option of a deep twilight sleep or of being awake. Some patients are very nervous and anxious and prefer heavy sedation; others are interested in viewing the procedure and require only little sedation. UFE is essentially painless except for the puncture of the groin, for which a local anesthetic is used. The crampy abdominal pain after UFE comes about as a result of the procedure and is caused by the fibroids being starved for blood and oxygen. Interviewer: What should patients expect during the recovery period? Dr. Siegel: Most patients have some crampy abdominal pain, the duration and severity of which varies dramatically from patient to patient. Some patients will have a little cramping for a few hours after the procedure and maybe one episode the next day and can be managed with ibuprofen. Other patients may have terrible abdominal pain for 5 or 6 days and require daily narcotics. In my experience, most women will have some cramping, which tends to be the worst within 8 to 12 hours after the 4 procedure. For this reason, UFE is generally not done as an outpatient procedure. Rather, most physicians will do it as an overnight stay or a 23-hour admission. Intravenous narcotics are used for pain control for the first 8 to 12 hours after the procedure. Pain will then gradually resolve in the next several days. In the first few days after the procedure, some women may experience postembolization syndrome, ie, generalized malaise with occasional low-grade fever or night sweats. Interviewer: When can patients resume their normal activities or return to work? Dr. Siegel: The vast majority of patients will be back at work in a week to 10 days. There are plenty of patients who are ready to be back to full activity or nearly full activity in about 3 or 4 days, and then there are others who need 2 weeks. Heavy lifting and deep bending are avoided for a few days after the procedure, as is routine after any arterial puncture. Interviewer: What types of adverse events or complications may occur with UFE? Dr. Siegel: Complications that would lead to a hysterectomy after UFE, which is obviously what most patients are trying to avoid, occur in <1% of patients. The most common reason for hysterectomy after UFE is infection. Premature menopause or ovarian failure is very rare in patients younger than 45 years, but occurs in probably 10% or 12% of patients who are older than 47 years. Obviously, the closer a woman is to reaching menopause, the more likely the UFE procedure will push her over into that state. Many of my patients who have bleeding symptoms would welcome menopause, although this is never the goal of the procedure. The most common vascular complication with UFE is a groin hematoma, which is usually self-limited and resolves spontaneously. Bleeding complications from the groin puncture and complications from the angiographic portion of the procedure may also occur, and rarely, arterial damage or perforation of the treated vessels. Some patients may also experience urinary retention after UFE, which is addressed with a Foley catheter. A persistent vaginal discharge that is clear, yellow, nonfoul smelling, and lasts for more than 3 months is a minor complication that may occur in some patients. Dilatation and curettage is curative for nearly all of these cases. Interviewer: What studies are being conducted to evaluate patient selection for UFE? Dr. Siegel: There are many ongoing studies at institutions all over the United States examining various aspects of UFE. I think the best study currently being conducted to answer many questions relating to UFE is the FIBROID

5 Registry established by the Society of Interventional Radiology. Twenty-five high-volume core sites and 50 to 60 other participating sites enrolled more than 3300 patients. The FIBROID Registry should give us valuable data regarding the types of patients who did well with UFE and those who did not. Such information can obviously be used to guide future patient selection. Offering UFE as a Treatment Option and Strengthening Relationships With Interventional Radiologists Interviews With Neil Sloane, MD, and Ron Clauhs, MD Interviewer: Although UFE has been performed safely and effectively in the United States for more than a decade, hysterectomy still appears to be the recommended treatment for uterine fibroids, with 40% of hysterectomies performed due to fibroids. Why has the acceptance of UFE in the gynecologic community been so slow? Dr. Sloane: There are several reasons for the slow acceptance of UFE. First, over the past 50 years, the general community has been accustomed to having its gynecologic needs met by women s specialists, who have developed close relationships with their patients over the years. Second, by the time a woman decides to consult her physician about her symptoms, usually pain and bleeding, she may want a definitive procedure that will cure those symptoms. Third, UFE is a relatively new procedure; therefore, patients are slow to accept it as mainstream. Dr. Clauhs: UFE is still considered a new procedure by many gynecologists, who may be reluctant to recommend it. Also, gynecologists may be resistant to referring a patient elsewhere for a condition that they themselves are capable of treating. Interviewer: What are the obstacles for including UFE as an option for uterine fibroids in a private gynecology practice? Dr. Sloane: It s a time and education factor. Gynecologists must first learn all about a procedure they are about to recommend. They must take time out of their busy schedules to consult with an interventional radiologist to learn the ins and outs of UFE. They should also visit patients who have had UFE soon after their procedures to view firsthand a patient s condition during the recuperative period. Dr. Clauhs: The biggest obstacle is that gynecologists are faced with sending patients with a medical problem that they themselves can handle on to another physician. 5 Interviewer: How can gynecologists overcome these obstacles and offer UFE as a treatment option for their patients? Dr. Sloane: Overcoming the obstacles I mentioned above is a matter of education. It is essential that the gynecologist include consultation with an interventional radiologist so that patients obtain the necessary information about UFE. Although time consuming, the patient should return to her gynecologist and integrate what she learned from the interventional radiologist into her decision-making process. The gynecologist should then be able to answer any final questions that she has concerning the procedure. Dr. Clauhs: You need to show the gynecologist that this new emerging technology is better for the patient. It offers a higher level of patient satisfaction, fewer complications, and lower morbidity and mortality compared with other surgical treatments for fibroids. Interviewer: What advice would you give colleagues regarding the addition of UFE in their treatment armamentarium for uterine fibroids? Dr. Sloane: My advice is to consider the fact that in a modern-day practice, gynecologists must inform patients of all options available to them for treating fibroids. An example I can give is breast care. Although we gynecologists are usually not in the position to treat most breast cancers, we still examine a patient s breasts and take charge of her finding the proper physician to treat her. Dr. Clauhs: Gynecologists have to look long and hard at the outcomes of UFE and at the level of patient satisfaction, which is extremely high in my practice. I ve been fortunate to find an interventional radiologist (Dr. Worthington- Kirsch) who is very competent in performing UFE, and I can comfortably inform my patients of that fact. I also inform them of the length of the procedure, recovery experience of my other patients, and the level of satisfaction that they can expect. It sounds very good to patients when you can offer a procedure that is relatively minimally invasive and has a high degree of satisfaction and success. Interviewer: What are the necessary steps for gynecologists to successfully include UFE as a treatment option? Dr. Sloane: The first step involves investigating which interventional radiologists in the area are performing the procedure, and then meeting with these physicians to determine their personal philosophies on the procedure and their thoughts on which patients are and which are not candidates for UFE. Gynecologists must remember that any referral out of their practice is a direct reflection on themselves and should therefore select an interventional radiologist who they feel is compatible with their own style of practice.

6 Finally, once an appropriate interventional radiologist who has performed a large number of procedures successfully has been found, various education materials describing UFE and its benefits and risks should be obtained from this physician. The materials need be only an introduction to UFE, as the referral to the interventional radiologist will complete the education process. Dr. Clauhs: First, gynecologists need to be aware of UFE and second, they need to understand how the procedure is performed, its benefits and risks, recovery period, and quality of outcomes expected for a particular patient. When this information is presented to physicians, it will be difficult for them not to appreciate the patient benefits. The biggest challenge for the gynecologist is, How do I take this procedure out of my own hands, put it into someone else s hands, and feel good about it? Interviewer: What is the role of the interventional radiologist in UFE? Dr. Sloane: The interventional radiologist should spend the necessary time to learn the procedure well. As with most procedures, practice makes perfect. He or she needs to determine who is a good candidate for the procedure and must involve the gynecologist in all facets of the procedure. Should there be setbacks or complications, the gynecologist must be notified immediately and encouraged to be involved in the postprocedure care. Finally, the interventional radiologist should strongly encourage the patient to return to the referring gynecologist after the immediate postprocedure care. No one wants to lose a patient. selective in the patients he or she will treat, and careful with patient care and follow-up, then he or she will win over the gynecologist. Dr. Clauhs: Gynecologists and interventional radiologists have to communicate and talk with each other. I want to make sure that whoever is doing UFE on my patients is very competent at doing it and has performed many of them. My patients come back very satisfied with the procedure and they re comfortable with my practice, knowing that I am making wise recommendations to them. Interviewer: What is the best way to communicate patient history and evaluation to the interventional radiologist? Dr. Sloane: Communication between the two specialists is essential. The gynecologist must communicate and forward to the interventional radiologist all available office notes and procedures performed on the patient prior to the referral appointment. After consultation with the interventional radiologist, a prompt telephone call and follow-up letter should be made to the gynecologist, including any reservations the patient may have had concerning the procedure. Next, the patient should return to the gynecologist s office to compare the information received from the interventional radiologist with any other treatment options the gynecologist had suggested. The patient should be allowed to make her own decision without any persuasion. If she chooses UFE, a letter needs to be sent to the interventional radiologist, and the gynecologist should facilitate the procedure. Dr. Clauhs: When beginning my association with Dr. Worthington-Kirsch, we talked about the type of patient work-up that would be most beneficial to him in helping to determine whether a patient was a good candidate for UFE. After completing the agreed-upon work-up, I then refer the patient to him. He sees her, reviews my work-up and makes a decision at that time as to whether she is or is not a candidate for UFE. If she is a candidate, he does the procedure, then typically visits her immediately postprocedure and sees her at least once, possibly twice, thereafter, following up with a pelvic ultrasound at about 3 months to confirm that the procedure worked correctly. At that point, the patient is sent back to me; I usually see her once and then do a follow-up later. I feel comfortable that I m involved in the patient s care every step along the way. The only thing that I m not physically doing is the UFE procedure itself. Interviewer: How can gynecologists strengthen their relationships with interventional radiologists? Dr. Sloane: Gynecologists can strengthen the relationship with an interventional radiologist by carefully choosing one who has the same goals and philosophies as they do. If the interventional radiologist is dedicated to the procedure, 6 Dr. Clauhs: There are several different approaches. If a gynecologist has a very close working relationship with the interventional radiologist, information about the patient can be conveyed via the work-up that is provided physical examination, endometrial biopsy results, and MRI scan essentially the same as that for a myomectomy or hysterectomy, with the exception of the MRI. On the other hand, if the gynecologist doesn t know the interventional radiologist, a letter of introduction would be proper, outlining the patient s information and history, the physical findings, and the laboratory results. Interviewer: What is the best way to communicate patient follow-ups with the interventional radiologist? Dr. Sloane: After the UFE procedure is performed, the interventional radiologist should make a prompt telephone call to the gynecologist describing how the procedure went and what the follow-up care will entail. Gynecologists should be familiar with the ins and outs of the postprocedure care and must encourage the patient to feel free to call their offices or the office of the interventional radiologist if there are any problems. Interventional radiologists should be very receptive to giving patients good follow-up care.

7 Those who perform UFEs but then are not immediately available to patients to address any problems are not ideal choices for good working relationships. Dr. Clauhs: In terms of communication from the interventional radiologist to the gynecologist, I recommend a letter from the referral consultation, outlining the assessment of the gynecologist s work-up, appropriateness of UFE, and its plans and timing. After the procedure, I expect a letter explaining what was done and how well the patient did, and later, another letter stating that the patient was seen after the procedure, whether it was successful, and the recommended postprocedure care. Interviewer: There s a perception that UFE shifts income from the gynecologist to the interventional radiologist. Can you provide some insight on why this is not necessarily the case? Dr. Sloane: A shift in income from the gynecologist to the interventional radiologist need not be the case. In my practice, there s probably a greater shift in the other direction. Not all patients seen by the interventional radiologist are good candidates for UFE. If the patient has any significant adenomyosis, she will be sent back to the gynecologist for probable hysterectomy. If her gynecologist does not perform surgery, the interventional radiologist could refer her to another gynecologist with whom he or she has a working relationship. In addition, in our practice, an MRI is always obtained before the UFE is performed. Very often other pathology is noted on the MRI that needs to be treated by the gynecologist or by a combination procedure with both the interventional radiologist and gynecologist. with this type of referral all the time when their patients develop liver or heart disease; they get referred to a specialist and then return to the general practitioner for continued normal care. UFE: An Overview An Interview With Robert Worthington-Kirsch, MD Interviewer: How many women suffer from uterine fibroids? Dr. Worthington-Kirsch: Fibroids run in families. It is estimated that about 30% of reproductive-age women in the United States have fibroids. The incidence is considerably higher in African American women and lower in Asians. About half of the patients who have fibroids will experience symptoms, which include abnormal bleeding; pressure symptoms, in which the enlarged uterus pushes against adjacent structures; and subfertility or repeated miscarriages. Interviewer: How many women seek treatment for uterine fibroids? Dr. Worthington-Kirsch: One of the problems with uterine fibroids is that they often cause only gradual changes. Thus, many women do not realize that they have developed abnormally heavy bleeding or that their bleeding has changed over time. Probably only half of the women with symptomatic fibroids actively seek treatment. As more minimally invasive therapies are offered and women become aware of them, more patients will seek treatment. Dr. Clauhs: In my part of the country, gynecologists are struggling with income-related issues. On one side, they re being pressured by managed care organizations paying reduced fees on the other side, by overhead costs and medical malpractice insurance. In general, every penny in a practice counts; therefore, when a patient is referred out of the practice, there s loss of potential income. Having said that, gynecologists need to offer appropriate technology to their patients. Health care is now being marketed directly to patients, and patients today are very smart and savvy. Word of new treatment gets around quickly, and soon a gynecologist may be labeled old fashioned because he or she doesn t believe in new technology. In referring my patients for UFE, I m not relinquishing the patient to someone else and losing her. I participate in the referral and see the patient postprocedure. As a result, she feels good about my participation in the procedure and returns to me knowing that I presented her with a wise option. The situation is similar to sending a patient with breast cancer to an oncologist. General practitioners deal 7 Interviewer: How does UFE compare with some of the surgical treatments for uterine fibroids? Dr. Worthington-Kirsch: Myomectomy is the standard of care for fibroid treatment in women who want to preserve fertility. Compared with myomectomy, UFE is superior in terms of durability and relieving bleeding symptoms and some types of pain. However, it is not quite as effective as myomectomy for relief of pressure symptoms, at least initially: It takes a bit longer to see improvement because volume reduction after UFE is a gradual process, rather than immediate as it is after myomectomy. One drawback of myomectomy is that although the larger fibroids are removed, small seed fibroids are left behind and can continue to grow. The recurrence rate of fibroid symptoms after myomectomy is 10% per year, cumulative. Therefore, 3 years after the procedure, about a third of patients will experience symptoms again, and by 10 years, most patients who have not yet entered menopause will have at least some of their symptoms return. There are no comparable 10-year data for recurrence of symptoms after UFE.

8 Hysterectomy is the only procedure that cures uterine fibroids in every patient; however, there are legitimate reasons why women may want to avoid it. Some women may suffer surgical complications or hormonal disturbances. Others may want to avoid a lengthy postprocedure recovery period. versus 20+ days with surgery. In addition, risk of significant or severe complications after UFE is half that of hysterectomy or myomectomy. Interviewer: What are the potential complications of UFE? The newest therapy available for treating uterine fibroids is ExAblate, or magnetic resonance-guided focused ultrasound therapy. It can be applied only to fibroids of specific size and location and to uteri of certain sizes. It is currently expensive and lengthy and can treat only a small number of fibroids. Recent data from Europe and Japan show that about 60% to 70% of patients have improvement with ExAblate, and the procedure is associated with very high rates of symptom recurrence and complication. Interviewer: How is UFE performed? Dr. Worthington-Kirsch: UFE is performed as any other angiogram. After prepping the skin and administering local anesthesia, a needle is placed into the femoral artery and then switched for a diagnostic catheter. Fluoroscopy is used to guide the catheter into the uterine artery where tiny round particles (ie, embolic material) are injected directly into the main uterine artery segment; individual fibroids are not injected. There are a variety of embolic materials used for this procedure; Embosphere Microspheres is the most common one used in the United States. Blood flow carries the particles into the uterus, where they permanently lodge in the small vessels around the fibroids to block the flow of blood and oxygen to these fibroids. The fibroids choke, shrink, and die, and the body converts them into scar tissue. This process is called hyaline degeneration, and is similar to what occurs naturally after menopause. Fibroids need estrogen as much as oxygen to live; after menopause, they stop receiving any estrogen and turn into scar tissue. Since the entire uterus is embolized, every fibroid, including seed fibroids, is infarcted. Clinical studies have shown that UFE does not affect the rest of the uterus because there is sufficient collateral blood flow to maintain a healthy myometrium. There are women who have had successful pregnancies after UFE, and most women continue to have menstrual periods on a normal schedule after the procedure. That said, the advisability of UFE in women who desire future fertility currently remains unresolved. Interviewer: What are the advantages of UFE? Dr. Worthington-Kirsch: Patients are typically discharged a day after having the procedure. Recovery time with UFE is more rapid than with surgery. Typically, patients are back to full activity levels in 10 to 14 days after UFE versus 35 to 40 days with surgery, and miss about 5 to 8 days of work 8 Dr. Worthington-Kirsch: The most significant complication with UFE is infection, which fortunately is relatively uncommon. About 5% of patients will slough a fibroid. Complications associated with the arteriography itself are about 1 in 1000 to 1 in 500. Interviewer: Are there limitations to UFE? Dr. Worthington-Kirsch: Yes. As fibroids get larger and the uterus increases in size, the degree to which the uterus will return to normal after UFE decreases. Some very respected interventional radiologists will not perform UFE on a uterus greater than 20 weeks in size. I find that if patients clearly understand that their uteri will remain fairly large after embolization, but that they should get relief of at least some of the pressure symptoms and of their bleeding, they will be happy with those outcomes as a means of avoiding major abdominal surgery. Interviewer: What long-term data are available to support UFE? Dr. Worthington-Kirsch: In addition to several case series with about 1000 patients followed for 5 years and a few recent prospective, randomized trials in Europe, there exists a registry sponsored by the Cardiovascular and Interventional Radiology Research and Education Foundation of the Society of Interventional Radiology that is following a large group of women treated with UFE for fibroids. The Fibroid Registry for Outcomes Data (FIBROID) is the largest study ever done to investigate any treatment for fibroids. I am one of the physicians who designed the study and am on its steering committee. Interviewer: What is the purpose of the FIBROID Registry? Dr. Worthington-Kirsch: There have been four previous attempts at conducting randomized controlled trials to examine UFE for uterine fibroids in the United States; however, patients were unwilling to be randomized between UFE and a major surgical procedure. The FIBROID Registry was therefore initiated to obtain rapid and reliable data on UFE. We are looking at a large number of patients treated with UFE. We are examining the different technical methods used and analyzing patient outcomes to determine which patient types do better, which do worse, what the true complication rate is, and what the long-term effects are. Unfortunately, there will not be enough data to determine the effects of UFE on fertility.

9 Interviewer: What have been the findings thus far? Dr. Worthington-Kirsch: About 3300 patients have been enrolled in the entire registry. Currently, at 2 to 3 years follow-up, there are between 1300 and 1500 patients who continue to provide additional data annually through self-reporting questionnaires. The remainder of patients either did not qualify for longer follow-up or were lost due to inevitable attrition. Data analyzed thus far from the FIBROID Registry have been published in the gynecologic literature and are reasonably well known in the interventional radiology community. Based on 30-day and 1-year data, close to 90% of patients responded to UFE during this time. Most patients, particularly older ones, experience durable responses to the treatment. Recurrence of symptoms and repeat procedures occur in about 10% of patients by 3 years, and we predict that about 20% of patients will have another procedure after UFE by 5 years. These rates are the same as or better than the rates seen with myomectomy. Interviewer: What are the limitations of the FIBROID Registry? Interviewer: What type of pain management is used for UFE? Dr. Lipman: We have a specific pain protocol in place at our institution and have skilled nurses who implement this protocol. We also have a 1:1 patient:nurse ratio at our center, which is unique and allows for continual surveillance and immediate attention to any potential pain issues. There are a number of medications we can use before, during, and after the UFE procedure. Of the last 250 UFE procedures performed at our center, only six patients have needed to stay overnight, and none beyond overnight. Those who stayed overnight were placed on a Dilaudid (hydromorphone hydrochloride) patient-controlled analgesia pump and were discharged the following morning. Two of the 250 patients required 2-day readmissions for pain control. A few days prior to the procedure, the patient takes Colace (docusate sodium), because constipation is common due to the narcotic medication administered during both the procedure and recovery. Activia yogurt from Dannon is a new product that is a natural way to keep patients regular in the postprocedural period. Dr. Worthington-Kirsch: The limitations are the same as those of any other registry. There is no comparison group, and so it does not constitute a controlled prospective trial. We do worry about attrition; patients drop out for a variety of reasons over which we have no control. However, overall, the study is well designed, and the answers it provides are very valuable. Pain Management for UFE An Interview With John C. Lipman, MD Interviewer: What can patients expect in terms of pain during and after UFE? Dr. Lipman: Despite the myriad anecdotes and misinformation, pain after UFE is typically easily tolerated, particularly after the first 24 hours. Most patients describe the pain as heavy, menstrual-like, crampy discomfort. This pain begins after the procedure and improves each day over the next several, with the average recovery in 4 to 5 days after UFE. The most important aspects of UFE pain management are that the patient has a thorough understanding of what to expect, and that there is a pain management regimen in place beginning prior to the onset of the pain (ie, preprocedure). More severe pain can be felt in the following three scenarios: 1) Too small an embolic is used (<500 microns); 2) Overembolization by an inexperienced operator; 3) Insufficient or nonexistent pain regimen protocol. Before entering the angiography suite, the patient will receive an intravenous line with Zofran (ondansetron hydrochloride) injection 4 mg and Toradol (ketorolac tromethamine injection) 30 mg, as well as a 1-time dose of Ativan (lorazepam) 2 mg, either sublingually or intravenously. She also wears a low-dose scopolamine patch. As we prep the patient, we begin administering fentanyl, Versed (midazolam HCl injection), and Dilaudid, all three of which are continued during the procedure for an average total dose of 75 µg, 3 mg, and 1 mg, respectively. Often, 12.5 mg of Phenergan (promethazine hydrochloride) is given intravenously during the procedure and in the immediate postrecovery period, as well. When the patient is discharged, she goes home on an oral regimen of naproxen (550 mg po bid x 7 days) and Colace (100 mg po qd x 5 days). Lortab (hydrocodone bitartrate and acetaminophen) is prescribed prn and is usually needed only for 24 to 48 hours postprocedure. Occasionally, Phenergan suppositories are needed for nausea or to promote sleep on the first postprocedural night. 9 Interviewer: What is the recovery time after UFE? Dr. Lipman: I tell my patients to take 1 week off from work or from routine activities. The average recovery time is 4 days. Almost every patient who is not back to baseline in 4 to 5 days is constipated, and this condition is a major factor in their discomfort at that time.

10 Interviewer: Are there guidelines for the type of pain management that works best for different patient types or different fibroid types? Dr. Lipman: The same protocol is followed for every patient, regardless of fibroid size or location. When we tried to predict which types of patients would have more pain, we couldn t. Having said that, in general, when fibroids are very large (>10 cm), patients will tend to have more postprocedural issues, and this can mean more pain. Interviewer: How satisfied are your patients with pain management for UFE? Dr. Lipman: Extremely satisfied. Patients will come in saying that they heard the UFE procedure was painful, and they are very pleased that it was not as bad as they thought it might be. Interviewer: Have there been any studies conducted evaluating pain and pain management for UFE? Dr. Lipman: There have been several UFE pain studies performed. Worthington-Kirsch and Koller looked at the time course of pain after UFE. They showed that after the procedure, the pain tends to increase over the first 2 postprocedural hours, plateaus for several hours, and then declines. It is the length of the plateau that determines if the patient will need to be admitted overnight. As stated earlier, 98% of our patients are discharged the day of the UFE procedure. Another study of note was one by Roth that looked at whether the severity of postprocedural symptoms had an effect on clinical outcome. No predictors were found for those patients who had increased pain after UFE, and the degree of their pain had no impact on clinical outcome. The Ontario Uterine Fibroid Embolization Trial published in the Journal of Vascular and Interventional Radiology in 2003 reported on 555 women who had undergone UFE in a number of different centers in Canada by interventional radiologists of varied clinical skill and experience. Patients had a planned overnight admission with an average length of stay of 1.3 days. Recovery time was also longer (13 days). The readmission rate due to pain control issues was 3%. Postprocedural pain varied considerably and most likely reflected varied operator experience and lack of a uniform pain regimen. The last study I want to mention is one by Rasuli reporting on 139 consecutive UFE patients who underwent a hypogastric nerve block prior to UFE. All patients were discharged on the day of the procedure. This group had a set postprocedural pain regimen of long-acting morphine tablets for baseline pain and short-acting morphine tablets and naproxen rectal suppositories for breakthrough pain. Interviewer: How would you describe the level of pain with UFE compared with that of myomectomy or hysterectomy? Dr. Lipman: Universally, patients who have had both myomectomy and UFE report that the pain after myomectomy was much greater than that after UFE. Intuitively, it is not difficult to understand why this is so. Studies have demonstrated a lower pain control requirement for patients recovering from UFE than for those recovering from myomectomy or hysterectomy. Interviewer: What are the similarities and/or differences in pain management for UFE, myomectomy, and hysterectomy? Dr. Lipman: Types of pain medications, such as narcotics, given after all three procedures are the same. It is not difficult to understand why the level of pain is much higher after the two surgical procedures than after UFE, which is nonsurgical. After an open surgical procedure like myomectomy or hysterectomy, there is a 2- to 3-day hospitalization and a 6- to 8-week recovery period at home. An open surgical procedure obviously requires much more pain medication in the postprocedural period than UFE does. Interviewer: What contributes to your success in UFE? Dr. Lipman: Two important factors contribute to success in our facility. First, I spend a great deal of time with each patient. Every patient has been seen in the office for a 45 minute consult, and candidates for UFE leave with a thorough understanding of what to expect after UFE. Second, we have a great team of nurses and technologists who have as deep regard for patient care as I do. In our center, the same corps of nurses who perform the preadmission testing help medicate patients during the procedure. They also participate in postprocedural recovery. They all have participated in the care of hundreds of UFE patients and are very knowledgeable about all aspects of the procedure. I work very closely with a large number of gynecologists who know that they can entrust me with the care of their patients. Every patient has my cell phone number, so she can call day or night with any question or concern about her care. Many patients are surprised by this, but they do not abuse the privilege. 10

11 Suggested Reading ACOG Committee Opinion. Uterine artery embolization. Obstet Gynecol. 2004;103: Bachmann G. Expanding treatment options for women with symptomatic uterine leiomyomas: timely medical breakthroughs. Fertil Steril. 2006;85:46-7; discussion Goodwin SC. Uterine artery embolization: a legitimate option for the treatment of uterine fibroids. Fertil Steril. 2006;85:48. Goodwin SC, Bradley LD, Lipman JC, et al; UAE versus Myomectomy Study Group. Uterine artery embolization versus myomectomy: a multicenter comparative study. Fertil Steril. 2006;85: Huang JYJ. Valenti D, Tulandi T. Treatment of uterine fibroids for the interest of patients not specialists. Fertil Steril. 2006;85:50. Lipman JC, Smith SJ, Spies JB, et al. IV. Uterine fibroid embolization: follow-up. Tech Vasc Interv Radiol. 2002; 5: Mara M, Fucikova Z, Maskova J, Kuzel D, Haakova L. Uterine fibroid embolization versus myomectomy in women wishing to preserve fertility: Preliminary results of a randomized controlled trial. Eur J Obstet Gynecol Reprod Biol Nov 14; [Epub ahead of print]. Pelage JP, Jacob D, Fazel A, et al. Midterm results of uterine artery embolization for symptomatic adenomyosis: initial experience. Radiology. 2005;234: Pron G. New uterine-preserving therapies raise questions about interdisciplinary management and the role of surgery for symptomatic fibroids. Fertil Steril. 2006;85:44-45; discussion Pron G, Bennett J, Common A, et al; Ontario UFE Collaborative Group. Technical results and effects of operator experience on uterine artery embolization for fibroids: the Ontario Uterine Fibroid Embolization Trial. J Vasc Interv Radiol. 2003;14: Roth AR, Spies JB, Walsh SM, Wood BJ, Gomez-Jorge J, Levy EB. Pain after uterine artery embolization for leiomyomata: can its severity be predicted and does severity predict outcome? J Vasc Interv Radiol. 2000;11: Spies JB, Bruno J, Czeyda-Pommersheim F, Magee ST, Ascher SA, Jha RC. Long-term outcome of uterine artery embolization of leiomyomata. Obstet Gynecol. 2005; 106: Spies JB, Cooper JM, Worthington-Kirsch R, Lipman JC, Mills BB, Benenati JF. Outcome of uterine artery embolization and hysterectomy for leiomyomas: results of a multicenter study. Am J Obstet Gynecol. 2004;191: Spies JB, Myers ER, Worthington-Kirsch R, Mulgund J, Goodwin S, Mauro M; FIBROID Registry Investigators. The FIBROID Registry: symptom and quality-of-life status 1 year after therapy. Obstet Gynecol. 2005;106: Worthington-Kirsch R, Spies JB, Myers ER, et al; FIBROID Investigators. The Fibroid Registry for outcomes data (FIBROID) for uterine embolization: short-term outcomes. Obstet Gynecol. 2005;106: Erratum in: Obstet Gynecol. 2005;106:869. Worthington-Kirsch RL, Koller NE. Time course of pain after uterine artery embolization for fibroid disease. Medscape Womens Health. 2002;7:4. Activia is a trademark of Compagnie Gervais Danone. Ativan and Phenergan are registered trademarks of American Home Products Corporation. Colace is a registered trademark of Roberts Laboratories Inc. Dilaudid and Lupron are registered trademarks of Abbott Laboratories. Embosphere is a registered trademark of Biosphere Medical Inc. ExAblate is a registered trademark of Insightec Image Guided Treatment Ltd. Lortab is a registered trademark of UCB Phip Inc. Toradol is a registered trademark of Syntex (U.S.A.) Inc. Versed is a trademark of Hoffman-LaRoche Inc. Zofran is a registered trademark of Glaxo Group Limited. 11

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