After a small catheter is threaded through OBGMANAGEMENT a femoral artery under angiographic imaging and guided into the uterine arteries, polyvinyl alcohol particles or trisacryl gelatin microspheres are released to block the blood vessels that feed the fibroids (or ), causing them to shrink

Ducksoo Kim, MD Director of Cardiovascular and Interventional Radiology Professor of Radiology and Surgery University of Massachusetts Medical Memorial Health Care Worcester, Mass Stephen D. Baer, MD, MPH Instructor of Obstetrics and Gynecology, Harvard Medical School, Staff ObGyn at Brigham and Women’s Hospital, Quincy Medical Center, Caritas Carney Hospital, Caritas St. Elizabeth Medical Center, and Beth Israel Deaconess Medical Center, Boston, Mass

IN THIS ARTICLE CASE-BASED LEARNING ❙ Preoperative Uterine artery embolization imaging: An enormous fibroid for abnormal bleeding and adenomyosis How to treat women with fibroids or adenomyosis, Page 49 the most common myometrial causes of premenopausal ❙ Imaging: abnormal uterine bleeding. Before and after Page 53 Angiography .LISA’S CASE. Pages 49, 58 MRI Ablation fails to ease symptoms Lisa is a 38-year-old mother of 2 who shrink, and her symptoms returned 5 initially reported menometrorrhagia, months after the procedure. DISCHARGE INSTRUCTIONS WALLET INFO-CARD , urinary frequency, pelvic Lisa heard about uterine artery When to call pressure, and increasing abdominal girth. embolization (UAE) through the media your doctor These symptoms worsened over 3 years and now asks about it. Her is

Page 54 before Lisa saw a physician and was 20-week size with an irregular contour. IMAGE: TODD BUCK diagnosed with uterine fibroids. When Magnetic resonance imaging (MRI) offered hysterectomy or endometrial shows a single large fibroid filling the ablation (cryomyolysis), she chose the uterus. Her hematocrit is 22. latter. However, her fibroids failed to Is uterine UAE right for her?

48 OBG MANAGEMENT • July 2005 PREOPERATIVE IMAGING Lisa’s case: Large fibroid Angelina’s case: Adenomyosis

A large fibroid occupies the entire uterus Global uterine enlargement and diffuse (size 20-weeks) adenomyosis, with a junctional zone thickness of 14 mm (arrow) Sagittal fast spin-echo T2 weighted pelvic MRI

.ANGELINA’S CASE. treated using embolization techniques. Menorrhagia and a “boggy” uterus The main advantages of UAE in treat- Angelina, 35, has 2 children and a 10-year ing these diseases:1-8,12,13 history of menorrhagia, dysmenorrhea, • Less invasive than surgery, with sub- and . reveals a stantially less recovery time and lower 10-week size, “boggy” uterus, and MRI morbidity shows global enlargement of the uterus • Usually performed under local anesthe- with a thickened junctional zone, which is sia and intravenous conscious sedation FAST TRACK characteristic of adenomyosis. • No worry about adhesions The ideal patient Her previous physician recommended • Virtually no blood loss or need for hysterectomy after medical therapy failed, transfusion; UAE may be especially is premenopausal, but Angelina is reluctant to undergo surgery. attractive for patients who refuse or can- has symptomatic Is UAE an option? not receive blood products for health or fibroids and/or religious reasons. oth women are very likely to benefit adenomyosis, from UAE, since the ideal candidate has failed therapy, is premenopausal with symptomatic and wants or needs B ❚ Impressive success rates fibroids and/or adenomyosis and has either to avoid surgery failed medical or surgical therapy or wants UAE has demonstrated excellent technical or needs to avoid surgery.1-11 (98% to 100%) and high clinical success This article describes the therapeutic rates (80% to 95%) in the treatment of role of UAE in women with abnormal fibroids.1-8,13 The clinical success rate is uterine bleeding (AUB) due to uterine lower for adenomyosis (56% to 92%), but fibroids and/or adenomyosis—the most UAE often provides sufficient clinical relief frequent myometrial causes of pre- to obviate surgery.9,10,13 menopausal AUB. Although UAE was not initially rec- Other, less frequent myometrial disor- ommended for women desiring future fer- ders (eg, hypervascular pathologies such as tility—because of the 4% risk of prema- intramyometrial and parametrial vascular ture —the pendulum is now malformations or neoplasms) can also be swinging in the other direction. If the risks

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of myomectomy are great due to the In some cases, extensive anatomic size or position of fibroids or is the cause of menorrhagia or dysmenor- adenomyosis, the risk-benefit ratio may rhea, often coexisting with fibroids, and shift to UAE to allow preservation of UAE may not be beneficial.11 reproductive capacity.1-8,11 Finally, a subserosal leiomyoma that is Though embolization has been per- sufficiently pedunculated (attachment formed since the early 1970s for acute and point 50% of the diameter) can be at risk chronic bleeding associated with various for detachment from the uterus, a situation medical conditions,14 the first report of that may necessitate surgical intervention.11 UAE did not come until 1995.1 Since then, the procedure has seen rapid growth worldwide, with approximately 50,000 cases performed. About 14,000 cases were ❚ Preop exam and imaging performed in the US last year.2 At the physical examination, the fibroid Although our practice has no fixed size uterus usually is enlarged with an irregular limitation, ideally a uterus less than 20 contour, and adenomyosis usually presents weeks’ gestational size is preferred. as a globally enlarged, “boggy” uterus (typically 6- to 10-weeks’ gestational size). Contraindications • Viable pregnancy MRI is the preferred imaging • Active pelvic infection We prefer MRI since fibroids can be • Presence of an intrauterine device missed with ultrasound due to the limited (though the IUD may be removed field of view. MRI more accurately defines before the procedure) the size, location, and extent of disease. It • Undiagnosed pelvic or also may better differentiate fibroids from • Pelvic malignancies such as ovarian or adenomyosis. endometrial carcinoma MRI clearly depicts uterine zonal • History of pelvic radiation, since UAE anatomy and enables accurate classifica- FAST TRACK may cause ischemic necrosis of the tion of individual masses by their locations: MRI enables uterus and adjacent organs due to pre- submucosal, intramural, or subserosal. existing radiation-induced vasculitis When adenomyosis is present, T2- classification with diffuse vascular narrowing. weighted MRI demonstrates diffuse ade- of masses nomyosis (about 66%) with global as submucosal, Relative contraindications enlargement of the uterus and diffuse • Renal insufficiency, though we have thickening of the junctional zone (at least intramural, used gadolinium, a nonnephrotoxic 12 mm, highly predictive finding) with or subserosal MRI contrast medium, for women homogeneous low signal intensity. Focal with high blood creatinine levels adenomyosis (33%) can be seen as an ill- • History of severe allergic reaction to defined, poorly marginated focal mass iodinated contrast medium, though (adenomyoma) of low signal intensity gadolinium can also be used in these within the .15,16 patients • Coagulopathy Transvaginal ultrasound • Desire to preserve fertility, since it In women with fibroids, ultrasound usual- cannot be assured based on current ly demonstrates an enlarged uterus with data. However, uncomplicated preg- lobulations, contour abnormality, or mass nancies and normal deliveries have effects. been reported after UAE, so this pro- In women with adenomyosis, it usual- cedure may still be preferred for ly demonstrates ill-defined, heterogeneous women who refuse or cannot under- echotexture and small anechoic areas with- go myomectomy.11 in the myometrium of asymmetrically

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enlarged uteri, with indistinct endometrial- ANGIOGRAPHY myometrial borders and subendometrial Before UAE: Hypervascular fibroids 15 halo thickening. Right uterine artery Left uterine artery

Include The patient should have a normal Pap test during the 12 months leading up to UAE,11 and should undergo endometrial biopsy to exclude carcinoma. Laboratory tests should include a complete blood count, blood urea nitro- gen/creatinine, follicle-stimulating hor- Right and left uterine arterial branches supply hypervascular uterine fibroids. mone, human chorionic gonadotropin, and coagulation tests. After UAE: Uterine arteries occluded Right uterine artery Left uterine artery

❚ Technique UAE begins with insertion of a small catheter (4-5 French) through a femoral artery in conjunction with percutaneous angiography. The catheter is guided into the uterine arteries—left first, then right— and contrast medium is injected into each artery to confirm the position of the Both uterine arteries successfully occluded, including their branches. catheter and the presence of fibroids or adenomyosis, which appear as hypervascu- lar lesions in angiograms (see above, right). ❚ Patient care UAE usually requires 1 to 2 hours. Conscious sedation, NSAIDs, FAST TRACK and antibiotics Embolic agents Intravenous conscious sedation in conjunc- The patient Polyvinyl alcohol (PVA) particles or tris- tion with nonsteroidal anti-inflammatory should have acryl gelatin microspheres, usually 500 to drugs (NSAIDs) usually provides sufficient a normal Pap test 700 and/or 700 to 900 microns in size, are pain relief. released through the catheter into the uter- In addition, intravenous broad-spec- (in the past year) ine arteries. These agents block the blood trum antibiotics are used as prophylaxis and should undergo vessels that feed the fibroids and/or adeno- for infection linked to the embolization endometrial biopsy myosis, causing them to shrink. The agents itself and to subsequent ischemia of the to rule out are biocompatible and have been approved fibroids and uterus. by the US Food and Drug Administration. Other, less frequently used embolic Managing postop pain syndrome agents include gelatin sponge particles More than 90% of women experience (which are temporary) and coils (which postembolization syndrome, which are permanent). Coils are generally used includes moderate to severe abdominal for conditions such as arteriovenous mal- pain/cramping and nausea and vomiting in formations or fistulae, which have large the first several hours following the proce- feeding vessels (iliac or enlarged uterine or dure. As a result, they may require hospital- ovarian vessels). This fluoroscopy-guided ization (less than 24 hours) for pain man- procedure usually is performed under agement. In our experience, few women local anesthesia and conscious sedation or, stay in the hospital more than 1 day. less often, epidural anesthesia. A patient-controlled analgesia pump

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WALLET INFO- CARD infections, expulsion of infarcted fibroids, FREE Comprehensive chronic , chronic vaginal dis- Home care after uterine artery embolization discharge instructions When to call your doctor charge, and cessation or irregularity of are available at menses, all of which have been observed www.obgmanagement.com Patient’s name: after UAE.11 Doctor’s name: Transvaginal ultrasound is usually per- Doctor’s phone: formed 3 to 6 months and 1 year after UAE to determine whether existing Recovery from uterine artery embolization fibroids have been infarcted and begun to is usually uneventful. However, if you experience any of the following, contact decrease in volume. It also reveals any your health care provider without delay. uterine or adnexal complications. • Uncontrolled pain In addition, this imaging provides a • Unusually heavy bleeding new baseline measurement of fibroid vol- ume, against which any subsequent • Foul-smelling increase in size (which may indicate • Temperature >100.6 degrees (by mouth) regrowth of fibroids or undiagnosed • Uncontrolled vomiting leiomyosarcoma) can be compared.11 • Intractable constipation • Bleeding or infection at the puncture site • Rash, hives, or other unusual drug reaction. ❚ • or....unanswered questions. Key findings of outcome studies Photocopy and laminate for your patients Two large series reported significant improvement in AUB in 77% to 90% of and NSAIDs are used in women with fibroid cases, and bulk-related symptoms abdominal/pelvic cramping and pain were controlled in 86% to 91%.6-8 In these (more than 90% of cases) if epidural studies, average uterine volumes decreased anesthesia is not used for pain. by 35% and 58% at 3 and 12 months, FAST TRACK Low-grade fever and leukocytosis are not respectively, with dominant fibroid shrink- Abnormal bleeding uncommon after embolization, and are age of 42%. Several large series also report- usually treated with acetaminophen. Other ed high patient satisfaction (91% to 93%) improves symptoms are anorexia and fatigue, but and significant improvement in quality-of- in 77% to 90% they gradually subside within 3 to 4 days. life measures.4,6-8 of fibroid cases, After discharge Side effects and complications and bulk-related Oral NSAIDs and narcotics are often need- Although UAE is considered very safe, it symptoms resolve ed for several days. Many women resume carries some risks. Spies et al17 reported on in 86% to 91% light activities in a few days, and most complications in 400 consecutive patients return to normal activities within 1 week.11 undergoing UAE for fibroids at their insti- Give her comprehensive discharge tution: instructions on taking medications, what • 1.25% serious complication rate to expect, and when to contact a doctor. • 5% overall periprocedural morbidity Follow-up visit in 1 to 4 weeks. We sched- rate ule an outpatient visit 1 to 4 weeks after • no deaths and no major permanent the procedure. At this visit, we confirm injuries healing of the puncture sites, screen for In addition, 1 patient required hysterec- unusual symptoms or potential problems, tomy as a result of a complication, and 1 and repeat follow-up instructions.11 patient had an undiagnosed leiomyosarco- We then follow the patient periodical- ma, which was discovered during an elec- ly (3, 6, and 12 months) to monitor her for tive myomectomy 31 months after UAE. symptoms and complications such as late Goldberg et al18 reported another case

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with delayed diagnosis of leiomyosarcoma years of age following UAE. In our series of 705 • 15% to 20% for perimenopausal patients, 1 had an undiagnosed leiomyosar- women 45 and older coma, which presented as a pelvic mass 15 Worsening of uterine bleeding is rare months after UAE. She subsequently under- after UAE, but can occur. Kerlan et al21 went hysterectomy. reported massive uterine bleeding 1 month after UAE in a woman who underwent the When to suspect leiomyosarcoma procedure for menorrhagia. When she was Unlike hysterectomy or myomectomy, no treated with emergent hysterectomy, a tissue is obtained in UAE for pathologic bleeding ulceration of the diagnosis to exclude leiomyosarcoma, overlying the necrotic fibroid was found. which is found in approximately 0.1% to Other complications include spotting, 0.4% of women with fibroids and is diffi- hot flashes, fever, vaginal discharge, mood cult to differentiate from a benign leiomy- swings, pain at the puncture site, and oma using clinical tests or imaging.17,18 dysuria.6-8,17 Suspect leiomyosarcoma if the fibroids continue to grow even after technically Our UAE experience successful embolization. The New England Fibroid Center began offering fibroid embolization in 1997. Infection is rare, but can be lethal Since then, we have performed 705 proce- A small number of patients have experi- dures at 5 hospitals in the Greater Boston enced infection, which usually is controlled region, with a technical success rate of with antibiotics. In a series of 414 UAE 99%. Technical failure occurred in 1% of procedures in 410 fibroid patients, Rajan patients; these women had very difficult et al19 reported: vascular anatomy involving uterine arter- • 1.2% rate of intrauterine infection ies, or ovarian arteries formed the domi- requiring intravenous antibiotic thera- nant blood supply to the fibroids. py and/or surgery Clinical success or improvement was seen • no significant difference seen with var- in 80% of women with bulk-related symp- FAST TRACK ious embolic agents, quantity of toms and 94.3% with bleeding symptoms. Of 400 consecutive embolic particles, use of preprocedure Clinical failure occurred in 5.7% of women antibiotics, or size or location of the (1.6% required repeat UAE and 1.4% hys- fibroid patients: dominant fibroid. terectomies due to persistent symptoms). ❙ 1.25% serious However, at least 2 deaths have been Complications occurred in 4% of cases complications reported due to infection since UAE for (2% rate of premature ovarian failure, ❙ fibroids was introduced in the mid-1990s: 1.5% rate of transvaginal passage of 5% periprocedural 1 fatal sepsis in a woman who underwent infarcted fibroids, and 0.5% rate of groin morbidity UAE for fibroids and 1 other sepsis fatali- hematoma). There were no major compli- ❙ 0 deaths or major 17,20 ty. The first case was caused by necrosis cations requiring transfusion or emergent permanent injuries of the vaginal wall and uterine . At surgeries such as hysterectomy. autopsy, microspheres were found not only in arteries in the leiomyomata and myometrium, but also in the parametria and vagina, causing ischemic necrosis. ❚ Fertility after UAE .LISA’S CASE. or worsened AUB “Cure” and pregnancy In some cases, amenorrhea can follow Lisa successfully underwent UAE, and UAE for fibroids due to ovarian emboliza- had no symptoms after the procedure. tion and subsequent ovarian failure.6-8,17 The uterine fibroids resolved almost The literature indicates a rate of: completely in 1 year. • 1% to 2% in patients less than 45 Three years after the procedure, she

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FOLLOW-UP MRI Lisa’s case: Large fibroid Angelina’s case: Adenomyosis 1 year after embolization 3 months after embolization

Uterus appears normal in size and shape. Almost Normal junctional zone and uterus. Imaging at 1 complete resolution of the fibroid with a small year showed no essential change from 3 months, residual avascular area in the myometrium, with no evidence of recurrence. seen as a small, round, dark spot in the fundus.

became pregnant and delivered a age of 40 who wanted to preserve fertility healthy, full-term infant. became pregnant and successfully deliv- ered full-term infants. Although UAE is generally not performed In general, the risks of , pre- in women who wish to preserve their fer- mature ovarian failure/menopause, radia- tility, it is sometimes used in fibroid tion exposure, and hysterectomy following FAST TRACK patients when myomectomy is contraindi- UAE are small and compare favorably Successful cated because of the size and/or number of with those associated with myomectomy. fibroids.11,22,23 Only a few small series and Fertility rates are similar to those for pregnancies case reports describe successful pregnan- women undergoing myomectomy.24 have followed UAE, cies following UAE. Nevertheless, well-controlled studies but so have higher For example, in a study involving 400 and additional data are needed before women, McLucas et al22 reported 17 preg- UAE can be confidently recommended as a rates of cesarean, nancies in 14 women among 149 patients first-line approach for preserving fertility.11 miscarriage, who stated a desire for fertility after UAE. and preterm birth Of these, 5 spontaneous abortions were observed, and 10 women had normal term ❚ deliveries. No perfusion or other problems Treating adenomyosis were reported during pregnancy or labor. .ANGELINA’S CASE. Goldberg and colleagues23 analyzed 50 Adenomyosis resolves published cases of post-UAE pregnancies During Angelina’s UAE procedure, and found higher rates of cesarean delivery, angiographies showed enlarged right preterm birth, malpresentation, small-for- and left uterine arteries with numerous gestational-age infants, spontaneous abor- prominent intrauterine branches supplying tion, and postpartum hemorrhage than in the enlarged uterus. After UAE with PVA the general population, though the reasons microspheres, post-embolization were unclear. angiograms showed occlusion of the right In our experience at the New England and left uterine arteries and their branches. Fibroid Center, 5 of 12 patients below the Her symptoms resolved completely

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following the procedure. One year later, a uterine artery embolisation to treat large uterine fibroids. Br J Obstet Gynaecol. 1998;105:235–240. follow-up MRI showed normal uterine 4. Worthington-Kirsch RL, Popky GL, Huchins FL Jr. size and shape, with complete resolution Uterine artery embolization for the management of leiomyomas: quality-of-life assessment and clinical of adenomyosis. response. Radiology. 1998;208:625–629. 5. Goodwin SC, Vedantham S, et al. Preliminary experi- ence with uterine artery embolization for uterine Several small series have reported success- fibroids. J Vasc Interv Radiol. 1997;8:517–526. ful treatment of women with symptomatic 6. Walker WJ, Pelage JP. Uterine artery embolisation for adenomyosis. For example, of 23 women symptomatic fibroids: clinical results in 400 women with imaging follow-up. BJOG. 2002;11:1262–1272. who underwent UAE for this indication, 7. Pron G, Bennett J, Common A, et al. The Ontario Chen and colleagues9 reported: Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine • Complete resolution of dysmenorrhea artery embolization for fibroids. Fertil Steril. in 19 women and significant improve- 2003;79:120–127. 8. Spies JB, Ascher SA, Roth AR, et al. Uterine artery ment in 2. Two other patients had embolization for leiomyomata. Obstet Gynecol. recurrent symptoms. 2001;98:29–34. • A substantial decrease in uterine 9. Chen C, et al. Uterine arterial embolization in the treat- ment of adenomyosis. Zhonghua Fu Chan Ke Za Zhi. volume in most of the women. 2002; 37:77–79. • An immediate decrease in intrauterine 10. Pelage JP, Jacob D, et al. Midterm results of uterine artery embolization for symptomatic adenomyosis: blood flow detected by color Doppler initial experience. Radiology. 2005;234: 948–953. ultrasonography. 11. Andrews RT, Spies JB, Sacks D, et al. Patient care and 10 uterine artery embolization for leiomyomata. J Vasc In a prospective study involving 18 Interv Radiol. 2004;15:115–120. women with symptomatic adenomyosis: 12. Broder MS, et al. Uterine Artery Embolization: A Systematic Review of the Literature and Proposal for • 94% had diminished menorrhagia 6 Research. Santa Monica, Calif: Rand; 1999. Publication months after UAE, and 94% had a slight MR-1158. decrease (mean: 15%) in uterine volume. 13. Siskin GP, Tublin ME, Stainken BF, et al. Uterine artery embolization for the treatment of adenomyosis: clini- • After 1 year, 73% of women had cal response and evaluation with MR imaging. AJR diminished menorrhagia, and 53% Am J Roentgenol. 2001;177:297–302. 14. Rosch J, Dotter CT, Brown MJ. Selective arterial had complete resolution. embolization. A new method for control of acute gas- • After 2 years, 56% of women had trointestinal bleeding. Radiology. 1979;102:303–306. 15. Outwater EK, Siegelman ES, Van Deerlin V. complete resolution of menorrhagia, Adenomyosis: current concepts and imaging consider- FAST TRACK 44% required additional treatment due ations. AJR Am J Roentgenol. 1998;170:437–441. UAE advantages: to failure or recurrence, and 28% 16. Byun JY, Kim SE, Choi BG, Ko GY, Jung SE, Choi KH. Diffuse and focal adenomyosis: MR imaging findings. underwent hysterectomy. Radiographics. 1999;19:S161–S170. less invasive, In our limited experience with adeno- 17. Spies JB, Spector A, Roth AR, et al. Complications local anesthesia after uterine artery embolization for leiomyomas. myosis at the New England Fibroid Center, Obstet Gynecol. 2002;100:873–880. plus conscious we saw no significant difference in techni- 18. Goldberg J, Burd I, et al. Leiomyosarcoma in a pre- menopausal patient following uterine artery emboliza- sedation, virtually cal success rates (100%) after UAE, com- tion. Am J Obstet Gynecol. 2004;191:1733–1735. pared with fibroid patients. However, 19. Rajan DK, Beecroft JR, Clark TW, et al. Risk of intrauter- no blood loss, there was a relatively high recurrence rate ine infectious complications after uterine artery embolization. J Vasc Interv Radiol. 2004;15:1415–1421. no adhesions (2 of 6 patients) of presenting symptoms 20. Vashisht A, Studd J, Carey A, Burn P. Fatal septicemia (menorrhagia or dysmenorrhea), and 2 after fibroid embolisation [letter]. Lancet. 1999;354:307–308. patients later underwent hysterectomy. 21. Kerlan K Jr, Coffey JO, Milkman MS, et al. Massive Well-controlled studies are needed vaginal hemorrhage after uterine fibroid embolization. before UAE can confidently be recom- J Vasc Interv Radiol. 2003;14:1465–1467. 22. McLucas B, Goodwin S, Adler L, Rappaport A, Reed R, mended for symptomatic adenomyosis. ■ Perrella R. Pregnancy following uterine fibroid embolization. Int J Gynaecol Obstet. 2001;74:1–7.

REFERENCES 23. Goldberg J, Pereira L, Berghella V. Pregnancy after uterine artery embolization. Obstet Gynecol. 1. Ravina JH, Herbreteau D, Ciraru-Vigneron N, et al. 2002;100:869–872. Arterial embolisation to treat uterine myomata. 24. Goldberg J, Pereira L, Berghella V, et al. Pregnancy Lancet. 1995;346:671–672. outcomes after treatment for fibromyomata: uterine 2. Worthington-Kirsch RL, Siskin GP. Uterine artery artery embolization versus laparoscopic myomecto- embolization for symptomatic myomata. J Intensive my. Am J Obstet Gynecol. 2004;191:18–21. Care Med. 2004;19:13–21. The authors report no financial relationships relevant to this 3. Bradley EA, Reidy JF, Forman RG, et al. Transcatheter article.

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