6/24/2013. John C. Lipman, MD, FACR, FSIR Atlanta, Georgia. Disclosure. Educational grant: Merit Medical, Boston Scientific

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1 John C. Lipman, MD, FACR, FSIR Atlanta, Georgia Disclosure Educational grant: Merit Medical, Boston Scientific Urban Myths 1. Need bilateral embolization. 2. Contraindicated to treat large fibroids/large uterus. 3. UAE won t work (contraindicated) in adenomyosis. 4. Need calibrated microsphere. 5. Menopause will occur if OAE. 6. Contraindicated to embolize pedunculated fibroids. 7. Patients must be observed overnight. 8. Procedural or post-procedural Abs required. 9. Sexual dysfxn will result from embolization proximal to cv branch. 10. Can t embolize patients c pre-existing hydrosalpinx. 11. Foley catheter required. 12. Contraindicated to embolize intracavitary fibroids. 1

2 Need Bilateral Embolization Based on early reports: -Ravina et al Lancet 1995, 346: uni embo clin failure based on post-op dye studies showing tumor supply from both UAs. -Goodwin et al JVIR 1997, 8: one pt (the only woman who underwent uni embo) demonstrated no response to therapy. -Several case studies supported this but uni embo due to technical failure. Need Bilateral Embolization McLucas et al Br J Rad 2002, 75: pts c uni embo -Broke out anatomic uni embo from technical failures. -4 pts c no UA on one side (3/4 responded, 4 th lost) -8 pts c technical failure: 5 of 8 had 2 nd embo (4/5 responded, 5 th lost). Need Bilateral Embolization Bratby et al CVIR 2008, 31: pts with elective uni embo vs 12 technical failure uni embo. -86% clinical 1yr in elective group -58% for technical failure group Spies et al JVIR 2011, 22(5): elective uni embo vs. bilateral embo controls -Similar clin results & degree of fibroid infarction -Potential benefits: dec ut ischemia dec pain, dec potential ov risk, dec procedure time dec rad dose. 2

3 Pre & 3 mos post Left UAE Pre & 3 mos post Left UAE Pre Left UAE 3

4 UFE: Does size matter? Avoidance of UFE for large fibroids/large ut vol arose from early case reports describing serious complications. Vashisht A et al Lancet 1999, 354:307-8 Pelage et al Radiology 2000, 215: Reported ut fib diameter can be predisposing factor for rare but serious complications. -Recommended UAE not be performed for fib >10cm. Does size matter? con t 1. Katsumori et al AJR 2003, 181: pts c large fibroids from cohort of 152 pts -X f/u 17 mos -No increased risk based on size 2. Smeets et al CVIR 2010, 33: consecutive pts, fib in 3 groups (>10cm and/or ut.vol > 700cm3) -X age 42.5y, X f/u 2y -Vast majority had substantial clinical sx improvement -Rate of AE low, freq of additional treatments necessary no different than unselected pts Does size matter? con t 3. Parthipun et al CVIR 2010, 33: Prospective, single ctr, 121 pts, PVA & TAGM used -Looked at complications -3 tables: relationship of large fib size (>10cm), large ut. vol (>750cm3), and vials of embolic (>4) to complications. 4

5 Parthipun et al Fibroid size >10cm <10cm Complication No complication Total Parthipun et al Fibroid vol >750cm3 <750cm3 Complication No complication Total Parthipun et al Vol of embolic >4 vials <4 vials Complication No complication Total

6 Does Size Matter con t 4. Choi HJ et al JVIR 2013, 24: Retrospective, single ctr, 323 pts -2 grps: 63 pts (longest axis > 10cm or vol > 700cm3 ) & 260 pts control group. -No difference in: -Vol. reduction of dominant fibroid -%volume reduction of uterus -Symptom satisfaction scores (@ 1 & 3mos) -Complication rate Adenomyosis Presence of endometrial islets in subendometrium/myometrium (usu >2.5mm deep to junctional zone) Present in up to 40% hysterectomy specimens 75% asymptomatic Similar sxs to fibroids (pain, bleeding) also dyspareunia. Adenomyosis Pelage et al Radiology 2005, 234: pts: 6( TAGM), 8 (5-7 & 7-9 TAGM), 4 ( PVA), near stasis endpoint -Short-term results encouraging, mid-term disappointing c only 55% show clin 2y. Kim et al AJR 2007, 188: pts, 54 c f/u >3yrs, other 12 lost to f/u. -(22) , (21) & , (11) , complete stasis. -83% c clinical imp at long-term f/u. 6

7 Adenomyosis Smeets et al CVIR 2012, 35(4): pts c 5 yr f/u (22 adeno & fibs, 18 adeno only) -embo technique: complete stasis -adeno only microspheres -adeno & fibs & sx free, 3 sig sxs, 7 TAH Adenomyosis Popovic et al JVIR 2012, 22(7): Review studies pub women, 15 studies Pure Adeno Adeno & Fibs Short-term (X 9.4mos) Long-term (X 40.6mos) 83% 93% 65% 82% Conclusions A number of urban myths in UAE, science evolving. Can embolize unilaterally when only 1 side supplies fibroid(s). Unilateral UAE due to technical failure should be repeated. Can embolize large fibroids & large fibroid burdens. Can embolize adenomyosis with reasonable long-term success. Consider smaller particles, complete stasis. 7

8 UFE & Fertility: A Comprehensive Review Gary Siskin, MD Professor and Chairman Department of Radiology Albany Medical Center Albany, New York The Situation There are consequences to the growing acceptance of UFE as a treatment option for patients with symptomatic fibroids. A growing number of younger patients are asking questions about UFE and the potential for future childbearing. The answers to these questions can be found in the available data. The Data The Good Patients can become pregnant after UFE (58.6% cumulative pregnancy rate). Author Year N Pregnancies Author Year N Pregnancies Mara Pisco Mara Holub Pron Firouznia Kim Walker Kim Pinto Pabon Dutton McLucas Mohan PP, et al. J Vasc Interv Radiol 2013; In Press 1

9 The Data The Bad UFE has potential complications that may affect fertility. The Data The Bad UFE has potential complications that may affect fertility. Any complication that can result in a hysterectomy will obviously have significant fertility implications (e.g., infection, infarction, etc.) The Data The Bad UFE has potential complications that may affect fertility. Any complication that can result in a hysterectomy will obviously have significant fertility implications (e.g., infection, infarction, etc.) Premature amenorrhea will also have significant effects on fertility. 2

10 The Data The Bad UFE has potential complications that may affect fertility. Any complication that can result in a hysterectomy will obviously have significant fertility implications (e.g., infection, infarction, etc.) Premature amenorrhea will also have significant effects on fertility. Age at UFE N Rate of Permanent Amenorrhea (3 yrs) Rate of Permanent Amenorrhea (6 yrs) < % 0% % 11.2% > % 40.4% Katsumori, et al. Int J Gynaecol Obstet 2008 The Data The Bad UFE has potential complications that may affect fertility. Any complication that can result in a hysterectomy will obviously have significant fertility implications (e.g., infection, infarction, etc.) Premature amenorrhea will also have significant effects on fertility. 15% of women over age 45 have significant elevation in FSH levels after UFE. Spies JB, et al. J Vasc Interv Radiol 2001; 12: The Data The Bad UFE has potential complications that may affect fertility. Any complication that can result in a hysterectomy will obviously have significant fertility implications (e.g., infection, infarction, etc.) Premature amenorrhea will also have significant effects on fertility. 15% of women over age 45 have significant elevation in FSH levels after UFE. FSH level increase after both UFE and hysterectomy; anti-mullerian hormone (AMH) levels decrease after UFE more than expected due to age. Hehenkamp WJ, et al. Hum Reprod 2007; 22:

11 The Data The Bad UFE has potential complications that may affect fertility. Any complication that can result in a hysterectomy will obviously have significant fertility implications (e.g., infection, infarction, etc.) Premature amenorrhea will also have significant effects on fertility. Hysteroscopic abnormalities have been found after UFE that may significantly impair fertility. Yellowish coloration of the endometrium (28%) Intrauterine or cervical adhesions (14%) Communication between the fibroid and the endometrial cavity (10%) Mara M, et al. J Obstet Gynecol Res 2007; 33: The Data The Ugly Problems have been reported in pregnancies after UFE. Pregnancies following UFE have higher rates of preterm delivery and malpresentation when compared to pregnancies after laparoscopic myomectomy. Goldberg J, et al. Curr Opin Obstet Gynecol 2006; 18: The Data The Ugly Problems have been reported in pregnancies after UFE. Review of 12 studies evaluating a total of 312 pregnancies in 242 patients. Miscarriage: 13-60% Preterm Delivery: 0-18% Placental Abnormalities: 0-13% Live Births: % Mohan PP, et al. J Vasc Interv Radiol 2013; In Press 4

12 The Explanation Confounding Factors Advanced Age The probability of achieving pregnancy in one menstrual cycle begins to decline in the early 30s and has a much more rapid decline after the mid 30s. Faddy MJ, et al. Hum Reprod 1002; 7: The Explanation Confounding Factors Advanced Age The probability of achieving pregnancy in one menstrual cycle begins to decline in the early 30s and has a much more rapid decline after the mid 30s. The preterm delivery and spontaneous abortion rates increase with age. Astolfi P, et al. Hum Reprod 1999; 14: The Explanation Confounding Factors Fibroids Women with fibroids are less likely to become pregnant compared with controls; fibroids are present in 5-10% of infertile patients and may be the sole cause of infertility in 1-2.4%. Guo XC, et a. Obstet Gynecol Clin N Am 2012; 39:

13 The Explanation Confounding Factors Fibroids Women with fibroids are less likely to become pregnant compared with controls; fibroids are present in 5-10% of infertile patients and may be the sole cause of infertility in 1-2.4%. The risk of infertility is greater in patients with submucosal or intramural fibroids that distort the endometrial cavity. Pritts EA, et al. Fertil Steril 2009; 91: The Explanation Confounding Factors Fibroids Women with fibroids are less likely to become pregnant compared with controls; fibroids are present in 5-10% of infertile patients and may be the sole cause of infertility in 1-2.4%. The risk of infertility is greater in patients with submucosal or intramural fibroids that distort the endometrial cavity. Women with fibroids have an increased risk of spontaneous abortion; 20.4% for intramural tumors and 46.7% for submucosal tumors. Klatsky PC, et al. Am J Obstet Gynecol 2008; 198: The Explanation Confounding Factors Fibroids Guo XC, et a. Obstet Gynecol Clin N Am 2012; 39:

14 The Explanation What does this mean? We cannot be certain if the pregnancy-related complications seen after UFE are caused by the procedure OR are an expected risk in any fibroid patient in this age group. The Explanation What does this mean? We cannot be certain if the pregnancy-related complications seen after UFE are caused by the procedure OR are an expected risk in any fibroid patient in this age group. There is a cumulative miscarriage rate of 28% after UFE, but this is similar to the rates in patients with untreated fibroids. There is a cumulative preterm delivery rate of 7.3% after UFE, but this is similar to that seen in the general population. There is a cumulative pregnancy rate of 58.6% after UFE, but this is similar to the age-adjusted pregnancy rates in the general population. Mohan PP, et al. J Vasc Interv Radiol 2013; In Press The Explanation What does this mean? We can t ignore the reported complications seen in association with post-ufe pregnancies BUT a definitive link between these complications and UFE has not yet been established. 7

15 The Recommendations Patients need to know the following Many successful pregnancies have been reported after UFE and the vast majority of these pregnancies are carried to term. The Recommendations Patients need to know the following Some of the known complications of UFE (e.g., premature amenorrhea, infection, etc.) can impair future fertility. Issues with pregnancy have been reported after UFE, but the frequency may not be any different than that seen in similarly aged women with fibroids who are not treated with UFE. The Recommendations Myomectomy should probably be the first procedure considered in a patient with fibroids and a desire for future fertility. 8

16 The Recommendations Myomectomy should probably be the first procedure considered in a patient with fibroids and a desire for future fertility. Pregnancy rates of 50-60% have been reported after laparoscopic and open myomectomy. Myomectomy for intramural fibroids is beneficial for infertile patients. Myomectomy for submucosal fibroids is associated with higher pregnancy rates than doing nothing. Guo XC, et a. Obstet Gynecol Clin N Am 2012; 39: The Recommendations Myomectomy should probably be the first procedure considered in a patient with fibroids and a desire for future fertility. There is no similar data reporting that UFE can help improve the chances of a successful pregnancy in women with fibroids. The Recommendations Myomectomy should probably be the first procedure considered in a patient with fibroids and a desire for future fertility. There is only one prospective randomized trial comparing fertility outcomes in UFE and myomectomy. 121 patients with an intramural fibroid >4 cm in diameter were evaluated (58 UFE patients and 63 myomectomy patients); 118 patients had at least 1 year follow-up (mean follow up of 24.9 months). 66 patients tried to conceive (40 after myomectomy and 26 after UFE). There were 50 pregnancies in 45 patients (33 after myomectomy and 17 after UFE). Mara M, et al. Cardiovasc Interven Radiol 2008; 31:73 9

17 The Recommendations Myomectomy should probably be the first procedure considered in a patient with fibroids and a desire for future fertility. Mara M, et al. Cardiovasc Interven Radiol 2008; 31:73 The Recommendations Myomectomy should probably be the first procedure considered in a patient with fibroids and a desire for future fertility. Myomectomy has superior reproductive outcomes compared to UFE in the first 2 years after treatment. Mara M, et al. Cardiovasc Interven Radiol 2008; 31:73 The Recommendations UFE can be considered for a patient who is not a candidate for myomectomy or does not wish to undergo that procedure. Large number or large size of fibroids History of previous surgery Comorbidities which increase operative risk 10

18 Conclusions Patients with symptomatic fibroids who require treatment and desire future fertility should consider myomectomy before UFE. UFE is a potential treatment option for these patients if they are not candidates for myomectomy or do not wish to undergo that procedure. The most important thing that we can do for these patients is to make sure that they are informed about the risks and benefits of all of their options. 11

19 UFE complications and their management Richard Shlansky-Goldberg MD Associate Professor of Radiology, Surgery and Obstetrics/Gynecology Complications from UFE, management: PES/Infection* Fibroid expulsion* Angiographic* Hysterectomy Ovarian failure Skin ulceration Vaginal ulceration Ureteral stricture Sarcoma Adhesions Pyosalpinx PE Death early days to weeks late weeks to months standard stuff Post UAE with fever week 1-2 > o F 102 o F with +/-pain > *4 days post UAE Consider antibiotics- amoxycillin/clavulanic acid 850 mg bid or levofloxacin 500 mg qd and metronidazole 500 mg bid > 102 o F + constitution symptoms Seen in IR clinic or ED MRI UA, CBC, Gyn Consider admission for IV antibiotics: Cefoxitin, 2 g intravenously every 6 hours, or cefotetan, 2 g every 12 hours, plus doxycycline, 100 mg intravenously or orally every 12 hours. *Walker and Pelage BJOG 2002; 109:1262 1

20 Post embolization late fever Endometritis Pyometra Myometritis TOA UTI Post- embo syndrome Pre UFE Post UFE day 12 with fever 102 o F IV antibiotics Post-embo pain and fever Endometrial surface Serosal surface AJR :555 Pre embo 5 days post embo with pain & 104 o F Partial infarction Pre UAE Post 2 weeks Complaints of malaise and low grade fever 2

21 Partial infarction Patient was stable, with intermittent fevers and malaise 3 weeks post, normal wbc, decided to have hysterectomy Fibroid expulsion Submucosal/ transmural fibroids Asymptomatic to cramps ± low grade fever Bulk versus sloughing Weeks to years post UAE in 5% of pts Infection from bacterial reflux through the cervix Myometrium Endometrium sloughing bulk expulsion submucosal/ transmural fibroid Afebrile Febrile 3

22 HUP expulsion study 37/759 patients: 12 nulliparous; 25 parous Time to expulsion: ~ 3 months Average fibroid size ~ 8.3 cm. ( cm) 35 had clinical symptoms 4 sloughing fibroids complaining primarily of a discharge 31 had bulk expulsion with cramps +/- fever JVIR 2011; 22:1586 Outcomes home or office (54%), 10 transvaginal myos, 3 hysteroscopies 4 emergent hysterectomies (infection) All bulk expellers 3 nulliparous (3/12),1 parous(1/25) 25% vs 4% p= 0.09 Fisher s exact 2 late hysterectomies due to discharge/sloughing (elective)- 1.3, 2 yrs 4

23 Frequency of expulsion/months after UAE JVIR 2011; 22:1586 Expulsion: Bulk Myometrium Endometrium submucosal/ transmural fibroid Cause of expulsion: Infection with endometrial contact due to reflux of bacteria thru cervix Bulk expulsion Pre UAE 2 months post 5

24 Fibroid expulsion Post-TVM Bulk expulsion over several weeks managed with antibiotics Saggital MR post gad, initial 6 weeks Multiparous women with persistent 102 fever on antibiotics * Sag T2 Pre Post with fever and *pus 6

25 Expulsion: Sloughing Myometrium Endometrium submucosal/ transmural fibroid cause of expulsion: Infection with endometrial contact due to reflux of bacteria thru cervix Sloughing expulsion sag T2 pre-uae 6 months post-uae 3 months post-uae 15 months post-uae Hysterectomy risk ~1% (recommend/urge surgery) How sick is the patient? How concerned/conservative is the your surgeon? How resolved/prepared is the patient? 7

26 UAE complications: Conclusions Infections and expulsion are the most likely complications that need to be managed by IR. Expulsion is relatively infrequent with a range of symptoms. Generally expulsion is well tolerated but may need other procedures. Parous patients with expulsion seem to do better than nulliparous patients. 8

27 UFE Practice Building: A Fifteen Year Experience Northwestern IR UFE History Began UFE practice in 1996 Slow growth of UFE volume annually Principally based on Northwestern gyne referrals Many talks given to hospital and local gynecologists Northwestern IR UFE History Many internal discussions about how to achieve UFE growth: Patient-centric vs. Gynecologist-centric (Spies) NMH Ad campaign. 1

28 NMH Ad campaign Volume of patient calls quadrupled UFE volume doubled year-over year Answered the question for our practice definitively Does Ford Refer Customers to General Motors? 2

29 Targeted marketing for Uterine Fibroid Patients Targeted marketing for Uterine Fibroid Patients Target market: African-American women age Local weekly magazine 8 weeks worth of ads Tracked outcome Targeted UFE marketing: Results 90 calls 35 clinic visits 17 UFEs 27% increase in volume over three months Cost: $8000 Professional revenue (includes MR): $58,000 Rate of return: 625% Conclusion: Patient-oriented advertising has an immediate positive effect on a UFE practice 3

30 Phase 2 Radio advertising Radio ad targeted at A-A women using a local station whose principal demographic is Black women 5 days/ week for 12 weeks (2-3 spots/day) Cost $40,000 Phase 2 Radio advertising Results 361 calls resulting in: 58 evaluative pelvic MRIs 53 clinic visits with E&M billing 32 UFE procedures 32 follow-up MRIs 11 new patient referrals to gyne Conclusion UFE is an ideal model for patienttargeted marketing of new medical procedures Most patients know their diagnosis Common disease UFE readily managed by IRs Very positive for IR and DR IO and UFE practice docs now in top 10 of referring MDs for imaging studies 4

31 Northwestern UFE Program 2 MDs 3 full-time staff 1 APN 1 secretarial staff 1 medical assistant Currently performing 350 UFEs per year 65% are self-referred The Impact of Direct Consumer Marketing on a Uterine Fibroid Embolization(UFE) Program Chrisman HB, Omary RO,Nemcek A, et al Northwestern University Medical School Background IR: Historic reliance on referrals from competitors. Recognition that gynecology referrals at NMH were decreasing Belief that a strategy based on competitor referrals is flawed 5

32 Purpose Test hypothesis that direct consumer marketing minimizes need for gynecologist s referrals Materials and Methods Prospective UFE database (1998) including origin of referral Strategy A ( ) : Educating Gynecologists Strategy B (2001-present): Direct Consumer Marketing Chi-Square test Results Gynecology referrals /24(83%) /160(9%) Self Referral (Media/Family) /24(17%) /160(89%) Chi-Square test p<

33 total percent Results Gynecology referrals decreased numerically and as an overall percentage Self-referral increased numerically and as an overall percentage Percentage referrals from Gynecology Series Year NMH ANNUAL UFE VOLUMES Series1 Linear (Series1) year 7

34 Conclusions Direct consumer marketing is a successful alternative strategy Sole reliance on gynecological referrals may not allow for a successful, sustainable UFE program Fibroids: To Compete or not to compete Questions How many IRs get the majority of referrals from gynecology? Do you ask the patient if UFE was given as an option? How many IRs get majority of referrals from primary care or other specialties? How many IRs have shared clinic? Shared marketing? Shared economics? 8

35 Northwestern UFE Program Established in 1996 Two dedicated IRs, full-time nurse, medical assistant, administrative assistant Annual volume ranges between UFEs Program volume and growth related to direct consumer marketing Good relationship with gynecology, but limited referral Top referring gynecologist works at free women s clinic What they really think about IR What do we mean by Competition Limited resources, survival of species (Darwin) Market Share and Profitability (economics) In health care, the role of competition is good in a broad sense to help control cost, but in specific disease states not good for the patient Patients have limited ability to understand product and limited ability to try product Unfortunately many physicians are still driven by their own compensation and patients left vulnerable I believe that many gynecologists are unwilling to consider UFE as a true option for their patients 9

36 Competition All successful UFE programs are competing Attempts to initiate UFE program without effective competitive model is doomed to fail. Successful competitive model leads to successful collaboration e.g. NW Vein center Collaborate with Competitors Shared marketing Promote women's health care and fibroid therapy Cross-promotion Acknowledge options Shared expertise Referrals Expense sharing Clinic space, staff Integrated Service Model Shared economics! The simplest model--a true integrated service model will allow for the removal of any economic incentives and align economics 10

37 Life Cycle of a Successful UFE Program Competition Collaboration with Competitors Integrated Service Model Successful for the patient Question is not whether competition is the right approach but when can you begin considering collaboration and integration 11