CME/CE

FEBRUARY 2008

New Developments in Uterine Fibroid Ablation

Francis L. Hutchins, Jr, MD

Recent years have witnessed an explosion in new ablative techniques for uterine fibroids, all aimed at minimizing operative exposure, sedation, complications, and recovery time. This article looks at the latest information on the newest of these "cutting-edge" approaches.

Continuing Medical Education

GOAL To review current ablation techniques for treating uterine fibroids in women, including history and comparisons. OBJECTIVES To examine ablation techniques for uterine fibroids, including cryotherapy, image-guided, and radiofrequency procedures. To look at the history of fibroid myolysis and ablation. To compare ablation techniques and discuss the requisite training, skills, and equipment. ACCREDITATION This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Albert Einstein College of Medicine and Quadrant HealthCom Inc. Albert Einstein College of Medicine is accredited by the ACCME to provide continuing medical education for physicians. This activity has been peer reviewed and approved by Brian Cohen, MD, professor of clinical ObGyn, Albert Einstein College of Medicine. Review date: January 2008. It is designed for -ObGyns, primary care physicians, and nurse practitioners. Albert Einstein College of Medicine designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Participants who answer 70% or more of the questions correctly will obtain credit. To earn credit, see the instructions on page 53 and mail your answers according to the instructions on page 54. CONFLICT OF INTEREST STATEMENT The "Conflict of Interest Disclosure Policy" of Albert Einstein College of Medicine requires that authors participating in any CME activity disclose to the audience any relationship(s) with a pharmaceutical or equipment company. Any author whose disclosed relationships prove to create a conflict of interest, with regard to their contribution to the activity, will not be permitted to present. The Albert Einstein College of Medicine also requires that faculty participating in any CME activity disclose to the audience when discussing any unlabeled or investigational use of any commercial product, or device, not yet approved for use in the United States. Dr Hutchins discusses experimental use of intrauterine ultrasound-guided procedures. Dr Hutchins reports no conflict of interest. Dr Cohen reports no conflict of interest.

Uterine leiomyomata are the most common benign tumors of the uterine smooth muscle, occurring in 25% to 44% of premenopausal women older than 30 years of age.1 Most women with fibroids are asymptomatic, but menorrhagia is the most common symptom (30%) in those who are symptomatic.2 Fibroid-associated menorrhagia is generally due to submucosal or possibly large intramural tumors distorting the uterine cavity.

Infertility has long been recognized as a complication of fibroids, and may be caused by faulty implantation—again due to distortion of the cavity. However, debate persists as to whether myomas that are completely intramural can interfere with fertility.3

Symptomatic fibroids not only take a toll on the quality of life of women, they also represent an economic burden both in lost productivity and substantial health costs. In a report from an employer claims database of 1.2 million beneficiaries (1999 to 2003), women with leiomyomata were 3 times more likely than controls to have disability claims (relative risk [RR] 3.1, 95% CI 2.7-3.6).4 The average annual excess cost for each patient with leiomyomata, when adjusted for confounders, was $4,624, and the average annual work loss cost was $771. Total costs for patients with leiomyomata were 2.6 times greater than for controls. In terms of social consequences, fibroids primarily affect women who must delay childbearing to complete education or attain an adequate income level. Underscoring the significance of the societal impact of this disorder, bills have been introduced both in the US House of Representatives (HR 2157) and Senate (S. 1833) to increase funding for fibroid research.

The definitive treatment for fibroids traditionally has been hysterectomy. However, patients are increasingly choosing less invasive approaches that have fewer complications. Still, approximately 200,000 hysterectomies are performed annually in the United States to treat fibroids.5 Both surgical and medical approaches have been developed to either reduce the morbidity associated with hysterectomy or to avoid hysterectomy altogether. With the advent of minimally invasive procedures, ablative treatment of fibroids is steadily gaining popularity as techniques and devices are continually refined.

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MYOLYSIS

Early myolysis used the neodymium:yttrium aluminum garnet (Nd:YAG) laser, followed by bipolar electroenergy. The energy probe was repeatedly introduced into the fibroid, necrosing the myoma, denaturing protein, and destroying the tumor's vascularity. The original goal of fibroid ablation was destruction of the entire tumor without sacrificing healthy tissue or adjacent organs.6 The technique could be limited to disruption of the blood supply to individual tumors by circumscribing them with areas of coagulation.

Indications for myolysis varied, but it was preferred for large fibroids that caused bulk (pressure) symptoms. Myolysis was initially advocated over laparoscopic myomectomy, especially when multiple intramural tumors were present and future fertility was not at issue. Advantages included small incisions, significant shrinkage of the treated fibroids, substantial symptom reduction, and performance with only basic operative laparoscopy skills. Disadvantages included increased risk of adhesion formation, unintended myometrial damage, and ineffectiveness for menorrhagia.

Despite 6-month postoperative reports of 50% reduction in fibroids using myolysis, several authors reported rupture of the pregnant uterus postprocedure,7-9 especially prior to 2000.7 The procedure was tedious, requiring as many as 50 probe insertions to treat a single fibroid. With advances in operative laparoscopy and the introduction of uterine artery embolization (UAE), myolysis has largely been abandoned.

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ABLATION TECHNIQUES

Cryoablation

Cryoablation is a technique for destroying the fibroid tissue by inserting probes cooled using liquid nitrogen or differential gas exchange under laparoscopic guidance. The cryoprobe reduces the temperature of the surrounding 3.5 to 5 cm of tissue to less than -90°C, creating an elliptical "ice ball" that causes sclerohyaline degeneration. The temperature at the outer edge of the ice ball is 0°C, which is not destructive to tissue.7,10 Therefore, visualizing the ice ball with (for example) ultrasonography allows the surgeon to predict the limits of the ablation.

The impact of cryoablation on fertility is unclear, and the method is still experimental. In one study of 20 women, laparoscopic cryoablation was used to treat symptomatic uterine fibroids 4 to 8 cm in diameter. Nineteen of the patients had complete resolution of their complaints (abnormal uterine bleeding, pelvic pain/pressure, urinary frequency). Myoma volume 6 months after cryoablation was reduced by approximately 55%, with a corresponding reduction in symptoms.7,11 These data suggest that cryoablation may offer a safe, minimally invasive option for treating myomas,12 but it has not yet been approved by the FDA.

Magnetic Resonance-Guided Ablation

Magnetic resonance imaging can be used to guide lasers percutaneously through the anterior abdominal wall and target fibroid tissue.13 Such imaging permits thermal mapping of the tumor in real time as the ablation proceeds. Therefore, maximum ablation can be achieved with minimal risk of damage to the serosa or adjacent structures. One of the aims of magnetic resonance-guided (MRg) ablation is preservation of uterine function.14 Bare nd:yag laser fibers are introduced through needles that have been inserted through the anterior abdominal wall and into the target fibroid under local anesthesia. This is a variation of the original myolysis technique, and is subject to the same shortcomings and outcomes.

The FDA recently approved a technique that combines MRg ablation with focused ultrasonography (MRgFUS) to treat fibroids. Safety and efficacy was established in a multicenter study in which 55 subjects were entered and 26 were available for complete reporting.15 Although requiring no incisions and no anesthesia, the procedure is tedious for the patient (median treatment time of 1 hour, 45 minutes plus median scanner time of 3 hours), and the amount P of tissue ablated is limited to 50% of total volume. Subjects experienced minimal discomfort during and after the procedure. In a study to evaluate long-term symptom relief, a 24-month follow-up was conducted for 359 women treated with MRgFUS. As measured by a symptom severity score, improvement continued over time, and correlated with the extent of fibroid ablation.16

In a series of 50 women with symptomatic fibroids, 27 subjects were given 3 months of pretreatment therapy with gonadotropin-releasing hormone agonists followed by outpatient MRgFUS to maximize the volume of treatable fibroid. The remaining 23 controls received MRgFUS alone. The volume of ablation in the women who received pretreatment was significantly greater than that in the control group: 0.06 cm3 versus 0.03 cm3 (P<.05) per Joule of energy applied.17

Contraindications for MRgFUS include organ position, abdominal scars, presence of a pacemaker, or desire to maintain reproductive function. Treatments are expensive ($10 000 to $20 000+), and insurance coverage is limited. However, the procedure has an excellent safety profile compared with hysterectomy.15

Laparoscopic Radiofrequency Ablation

Radiofrequency (RF) ablation has been used widely in laparoscopic gynecology and urogynecology, and has been applied to the treatment of fibroid tumors. Several types of RF ablation have been developed, and with imaging guidance—it is a promising tool in the management of symptomatic leiomyomata.

In an evaluation of the feasibility and efficacy of laparoscopic RF ablation of uterine fibroids under general anesthesia,18 a pilot study was conducted in 18 women with symptomatic, intramural fibroids. The median reductions in tumor volumes were 41.5%, 59%, and 77% at 1-, 3-, and 6-month follow-up, respectively. Significant improvements in the symptoms and quality-of-life scores were observed at 3 and 6 months' follow-up.

The disposable RF needle electrode used in the procedure consisted of a series of seven extendible prongs that bracketed the target tissue. The depth of needle penetration was determined by preoperative ultrasonography. These results suggest that RF ablation may be a safe, well tolerated, and effective alternative to conventional surgery for symptomatic fibroids in select patients.

Percutaneous image-guided RF ablation using ultrasonography or computed tomography has been studied to treat symptomatic fibroids larger than 5 cm. It was performed under sedation after the patient underwent UAE to minimize embolization failures.19 Exclusion criteria were a desire to maintain reproductive function, bladder or bowel loop in the path of the RF applicator, and tumors with less than 25% contrast enhancement. Mean volume reduction at 6 months was 56.5%, and there were no subsequent surgical interventions. The technique requires only one small skin incision and moderate sedation. It is difficult to assess the efficacy of RF ablation without prior UAE, and a larger study of image-guided percutaneous RF ablation as a primary treatment is needed.

Intrauterine ultrasound-guided (IUUS) RF ablation comprises a somewhat different technique, and has been studied in women prior to hysterectomy for symptomatic uterine fibroids.20 Preoperative transvaginal ultrasonographic examination confirmed the location of the leiomyomata. Before hysterectomy, with the abdomen open, a novel 7-mm intrauterine probe with a channel for IUUS RF delivery was introduced into the uterine cavity. The active electrode delivered RF energy (30 W) into the myoma. Thermocouples were placed on the uterine serosa overlying the treated area to assess temperature change in real time. The hysterectomy was completed after the procedure. The extirpated uteri were grossly assessed for serosal burns, and then sectioned in the plane of the RF needle. The dimensions of the individual thermal ablations were assessed, and triphenyltetrazolium chloride (TTC) viability staining confirmed the absence of serosal burns. The procedure was successfully completed in all patients, averaging one or two leiomyomata per patient. The image from the intrauterine probe was considered adequate for the procedure. The needle penetrated the leiomyomata, myometrium, or pseudocapsule in all cases. The serosal surface temperature was always less than 45°C. Pathologic analysis showed no serosal thermal damage.

A prospective, nonrandomized study assessed the capability of the IUUS RF device to diagnose and measure fibroids against a transvaginal ultrasonographically guided device.21 The operative system provides an entirely transcervical approach, obviating the need for incisions and general sedation. The imaging mechanism is incorporated into the surgical probe, thereby providing real-time imaging data. The IUUS imaging was more accurate than the transvaginal imaging based on concordance correlation coefficients of 0.151 versus 1.141, respectively. Imaging is an important variable in ablative modalities, as it defines the boundaries of the tumor, serosa, and adjacent tissues.

It appears that IUUS RF ablation of fibroid tumors enables visualization of lesion dimensions that closely corresponds to pathology lesion measurements, providing a visual context for safe and effective RF treatment. This procedure is still experimental. It is expected to take 20 to 30 minutes, and may be used to treat intramural and submucosal fibroids of <6 cm on an out-patient or office basis, under local or light sedation.

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CONCLUSION

Ablative techniques of fibroids are generally safe and minimally invasive, but—in contrast to UAE or hysterectomy—are used to treat individual tumors as opposed to global management. However, this need not be a disadvantage if the targeted myomas are specifically known to cause symptoms. In such cases, particularly with submucosal and some intramural tumors, ablative techniques may offer the least invasive and equally effective approach compared with UAE and hysterectomy.

Ablative methods are part of a continuum from laparotomy to increasingly less invasive treatment alternatives, offering fewer adverse events, reduced morbidity, lower cost, and faster recovery. Given this progress, women with symptomatic fibroids are no longer condemned to hysterectomy and/or infertility. Nonetheless, ablative procedures are generally not recommended in women who wish to maintain fertility, and this issue remains unresolved. In the meantime, as more ablative procedures become clinically available, they should be limited to women who do not desire future fertility or who are carefully counseled if they do.

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Francis L. Hutchins, Jr, MD, is Adjunct Professor of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA.

References

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DISCLAIMER

The opinions expressed herein are those of the author and do not necessarily represent the views of the sponsor or the publisher. Please review complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings and adverse effects before administering pharmacologic therapy to patients.

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