Disclosure · PDF file · 2013-06-266/24/2013 4 UFE: Does size matter? Avoidance of UFE for large fibroids/large ut vol arose from early case reports describing serious complications

6/24/2013

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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.

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Need Bilateral Embolization Based on early reports:

-Ravina et al Lancet 1995, 346: 671-2 uni emboclin failure based on post-op dye studies showing tumor supply from both UAs.

-Goodwin et al JVIR 1997, 8: 517-26 “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: 122-6

-12 pts c uni embo

-Broke out anatomic uni embo from technical failures.

-4 pts c no UA on one side (3/4 responded, 4th lost)

-8 pts c technical failure: 5 of 8 had 2nd embo (4/5 responded, 5th lost).

Need Bilateral Embolization Bratby et al CVIR 2008, 31: 254-9.

-30 pts with elective uni embo vs 12 technical failure uni embo.

-86% clinical response @ 1yr in elective group

-58% for technical failure group

Spies et al JVIR 2011, 22(5): 716-22.

-28 elective uni embo vs. bilateral embo controls

-Similar clin results & degree of fibroid infarction

-Potential benefits: dec ut ischemiadec pain, dec potential ov risk, dec procedure timedec rad dose.

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Pre & 3 mos post Left UAE

Pre & 3 mos post Left UAE

Pre Left UAE

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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: 428-31

-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: 1309-14 -47 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, 33:943-48 -71 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, 33:955-59

-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.

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Parthipun et al Fibroid size >10cm <10cm

Complication 1 5 6

No complication 29 86 115

Total 30 91 121

Parthipun et al Fibroid vol >750cm3 <750cm3

Complication 2 4 6


Total 52 69 121

Parthipun et al Vol of embolic >4 vials <4 vials

Complication 1 4 5


Total 51 28 79

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Does Size Matter con’t 4. Choi HJ et al JVIR 2013, 24:772-8.

-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 sub-

endometrium/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: 98-53.

-18 pts: 6( 500-700 TAGM), 8 (5-7 & 7-9 TAGM), 4 (355-500 PVA), near stasis endpoint

-Short-term results encouraging, mid-term disappointing c only 55% show clin imp @ 2y.

Kim et al AJR 2007, 188: 176-81.

-66 pts, 54 c f/u >3yrs, other 12 lost to f/u.

-(22) 355-500, (21) 250-355 & 355-500, (11) 250-355, complete stasis.

-83% c clinical imp at long-term f/u.

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Adenomyosis Smeets et al CVIR 2012, 35(4): 815-9.

-40 pts c 5 yr f/u (22 adeno & fibs, 18 adeno only)

-embo technique: complete stasis

-adeno only 500-700 microspheres

-adeno & fibs 500-700 & 700-900

-30 sx free, 3 sig sxs, 7 TAH

Adenomyosis Popovic et al JVIR 2012, 22(7): 901-9.

-Review studies pub 1999-2010

-511 women, 15 studies

Pure Adeno Adeno & Fibs

Short-term (X 9.4mos)

83% 93%

Long-term (X 40.6mos)

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.

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UFE & Fertility:

A Comprehensive Review

Gary Siskin, MD

Professor and Chairman

Department of Radiology

Albany Medical Center

Albany, New York

Fertility Preservation & UFE

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 child-

bearing.

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

Mara 2008 58 17

Pisco 2011 74 44

Mara 2012 100 42

Holub 2008 112 28

Pron 2005 555 24

Firouznia 2009 102 15

Author Year N Pregnancies

Kim 2008 87 12

Walker 2008 1200 56

Kim 2005 94 6

Pinto Pabon 2008 100 11

Dutton 2007 649 37

McLucas 2001 400 17

Mohan PP, et al. J Vasc Interv Radiol 2013; In Press

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The Data

The Bad

UFE has potential complications that may affect fertility.


The Data

The Bad


Any complication that can result in a hysterectomy will obviously

have significant fertility implications (e.g., infection, infarction, etc.)


The Data

The Bad




Premature amenorrhea will also have significant effects on fertility.

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Age at UFE N Rate of Permanent Amenorrhea (3 yrs)

Rate of Permanent Amenorrhea (6 yrs)

<40 39 0% 0%

40-44 98 1.4% 11.2%

>44 74 19.7% 40.4%


The Data

The Bad





Katsumori, et al. Int J Gynaecol Obstet 2008


The Data

The Bad





15% of women over age 45 have significant elevation in FSH levels after

UFE.

Spies JB, et al. J Vasc Interv Radiol 2001; 12:437-

442


The Data

The Bad





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; 22:1996-

2005.

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The Data

The Bad





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; 33:316-

324


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;

18:402-406


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: 40-100%


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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; 7:1342-1346


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; 14:2891-2894


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; 39:521-

533

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The Explanation

Confounding Factors

Fibroids




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; 91:1215-1223


The Explanation

Confounding Factors

Fibroids




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; 198:357-

366


The Explanation

Confounding Factors

Fibroids


533

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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


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.



The Explanation


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.

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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.

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The Recommendations



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.


533


The Recommendations



fertility.

There is no similar data reporting that UFE can help improve the

chances of a successful pregnancy in women with fibroids.


The Recommendations



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

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The Recommendations



fertility.



The Recommendations



fertility.

Myomectomy has superior reproductive outcomes compared to

UFE in the first 2 years after treatment.



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

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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.

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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

• > 100.5 oF – 102 oF 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 oF + 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.

• Read more: Pelvic Inflammatory Disease (PID;

Salpingitis, Endometritis) -Gynecology articles -

http://www.health.am/gyneco/more/pelvic_inflam

matory_disease_pid_salpingitis_endometritis/#ix

zz2C9CWb4e6

*Walker and Pelage BJOG 2002; 109:1262

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Post embolization late fever

• Endometritis

• Pyometra

• Myometritis

• TOA

• UTI

• Post- embo syndrome

Pre UFE Post UFE day 12

with fever 102oF

IV antibiotics

Post-embo pain and fever

Pre embo 5 days post embo with pain & 104o F

Serosal surface

Endometrial surface

AJR 2005 184:555

Partial infarction

Pre UAE Post 2 weeks

Complaints of malaise and low grade fever

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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

Endometrium

Myometrium

submucosal/

transmural fibroid

sloughing

bulk expulsion

Afebrile Febrile

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HUP expulsion study

• 37/759 patients: 12 nulliparous; 25 parous

• Time to expulsion: ~ 3 months

• Average fibroid size ~ 8.3 cm. (1.6 -15 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

• 20 @ 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

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Frequency of expulsion/months

after UAE

JVIR 2011; 22:1586

Expulsion: Bulk

Endometrium

Myometrium

Cause of expulsion: Infection with endometrial contact due to

reflux of bacteria thru cervix

submucosal/

transmural

fibroid

Bulk expulsion

Pre UAE 2 months post

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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

*

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Expulsion: Sloughing

Endometrium

Myometrium

cause of expulsion: Infection with endometrial contact due to

reflux of bacteria thru cervix

submucosal/

transmural

fibroid

Sloughing expulsion

sag T2 pre-UAE 6 months post-UAE

3 months post-UAE 15 months post-UAE

How sick is the patient?

How concerned/conservative is

the your surgeon?

How resolved/prepared is the

patient?

Hysterectomy risk ~1%

(recommend/urge surgery)

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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.

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UFE Practice Building: A Fifteen Year Experience

Northwestern IR UFE History

Began UFE practice in 1996

Slow growth of UFE volume 1996-1999

25-40 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….

2

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?

3

Targeted marketing for Uterine Fibroid Patients

Targeted marketing for Uterine Fibroid Patients

Target market: African-American women age 35-45

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

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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 patient-targeted 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

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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

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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 (1998-2000) : Educating Gynecologists

Strategy B (2001-present): Direct Consumer Marketing

Chi-Square test

Results

Gynecology referrals

1998---20/24(83%)

2001---14/160(9%)

Self Referral (Media/Family)

1998---4/24(17%)

2001---142/160(89%)

Chi-Square test p<0.001

7

Results

Gynecology referrals decreased numerically and as an overall percentage

Self-referral increased numerically and as an overall percentage

Percentage referrals from Gynecology

0

10

20

30

40

50

60

70

80

90

1 2 3 4

Year

perc

en

t

Series1

NMH ANNUAL UFE VOLUMES

0

20

40

60

80

100

120

140

160

180

1 2 3 4

year

tota

l

Series1

Linear (Series1)

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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?

9

Northwestern UFE Program

Established in 1996 Two dedicated IRs, full-time nurse, medical

assistant, administrative assistant Annual volume ranges between 280-320 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

10

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

11

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

Documents

Disclosure · PDF file · 2013-06-266/24/2013 4 UFE: Does size matter? Avoidance of UFE for large fibroids/large ut vol arose from early case reports describing serious complications