Dr Guido is Professor of Obstetrics, Gynecology, and Reproductive Sciences and director of the Fibroid Treatment Center, Magee-Womens Hospital, University of Pittsburgh Medical Center.
Dr Stuparich is a fellow in minimally invasive gynecology at Magee-Womens Hospital, University of Pittsburgh.
Uterine fibroids (leiomyoma) are very common among women of reproductive age. The lifetime prevalence is between 70% and 80%, with black women having a higher risk.1 The majority of women who have fibroids are asymptomatic, but some women can experience heavy menstrual bleeding, dysmenorrhea, pelvic pressure, increased urinary frequency, and painful intercourse.
Fibroids are the primary indication for hysterectomy in the United States, accounting for 40% of all hysterectomies performed annually between 1990 and 1997.2 Symptoms associated with uterine fibroids can be quantified using the well-validated Uterine Fibroid Symptom and Quality of Life QoL) questionnaire (UFS-QoL).3 The questionnaire is used to quantify symptom severity as well as measure six domains of health-related QoL. A higher symptom score is indicative of more significant symptoms. The severity of symptoms in women undergoing surgical intervention for fibroids was on average 64.8 (±20) as compared to 15.3 (±14.5) for a control group of women undergoing routine gynecologic care.4
Treatment of fibroids has evolved rapidly over the last decade. The traditional therapy for symptomatic fibroids has been hysterectomy for women who no longer desire to maintain their fertility, and laparotomy and myomectomy for those who want to maintain their uteruses.
With the advent of less-invasive surgical techniques, myomectomy can be performed via hysteroscopy and laparoscopically. The size and location of fibroids are critical in determining which method of myomectomy is appropriate. Laparoscopic approaches have been shown to have reproductive outcomes similar to that for open procedures, with shorter time for recovery.5
Patients desire effective therapy for their symptomatic fibroids with the least amount of intervention and the shortest recovery possible. Uterine artery embolization (UAE) has been used for more than 20 years with good success rates. The technique results in marked reduction of blood flow to the uterus, which in turn produces ischemic necrosis of fibroids, with the normal myometrium maintaining adequate blood flow. The typical patient can return to normal activity within 10 days and this treatment is highly effective for women with bleeding from fibroids. A randomized trial of embolization versus surgical treatment for fibroids demonstrated similar outcomes between the 2 groups at 1 year with regard to their QoL scores.6 Five-year follow-up data from this important trial revealed a higher rate of reintervention for the UAE group with a cost-neutral status at 5 years.6
High-intensity focused ultrasound (HIFU) requires no surgical intervention and can be delivered under magnetic resonance imaging (MRI) guidance. The technique has been approved by the US Food and Drug Administration (FDA). The ultrasound beam is focused on small areas of a fibroid and heats it to a temperature that results in tissue necrosis.
This technique has the appeal of being the least invasive but it does have a variety of limitations. These include clinical situations that prevent the approach from being used, such as bowel loops, or surgical scars that are in the way of the ultrasound beam. Compared to UAE, HIFU has demonstrated a higher rate of reintervention and less improvement in QoL scores.8
Early electrical energy treatment
Initial attempts of treating fibroids with electrical energy included the use of bipolar needles inserted around the fibroid with laparoscopic guidance. Goldfarb was one of the first to report this approach in 1995.9 The technique required multiple insertion of the needles into the fibroid. While it was demonstrated to reduce the size of the fibroid, and therefore demonstrate the feasibility of the approach, excessive serosal adhesion was problematic, and therefore this approach is not viable today.
Photo courtesy of Halt Medical
Concept of radiofrequency
Radiofrequency ablation (RFA) uses monopolar alternating current at frequencies between 350 kHz and 500 kHz to heat tissue to 80° C to 105° C, which results in coagulation necrosis of tissue. RFA has been used successfully to treat a variety of solid abnormalities of the heart, liver, and fibroids.10,11 Unlike with early unsuccessful attempts at bipolar electrical coagulation of fibroids, RFA energy uses volumetric ablation to destroy tissue with a more controlled zone of thermal injury. A significant amount of electrical power is required to ablate tissue and it is not uncommon for ablations to use 100 watts of power. Because of the significant amount of electrical power generated by RFA, 2 large return electrodes are required to dissipate the energy (Figure 1).
Treatment of fibroids with RFA requires very accurate localization or targeting of the placement of the RFA device. Currently a variety of approaches are available for localization of the RFA device, including laparoscopic ultrasound guidance (Acessa; Halt Medical), transcervical-intrauterine ultrasound guidance (Gynesonics), and transvaginal ultrasound guidance.
The Acessa system is the only FDA-approved approach for RFA ablation of fibroids in the United States. Laparoscopic-guided RFA of fibroids was performed by Lee using an off-label application of the Rita medical RFA system (AngioDynamics, Inc) which was FDA-approved for treatment of liver tumors.12 Early studies demonstrated that the technique would safely volumetrically treat the fibroids and reduce symptoms, but the RFA needle was difficult to introduce into the fibroids. A RFA needle specifically designed for fibroids now has made the technique a viable option for treatment of fibroids. The system includes a generator, grounding pads, supporting cables and the handpiece, which is used to insert the RFA device into the fibroid and deploy 7 needle electrodes (Figure 2). The needle and electrodes serve both to distribute the electrical energy and to measure the temperature of the tissue.
Localization of a fibroid and placement of the RFA needle is all directed by a laparoscopic ultrasound probe. The surgeon is required to incorporate visual images from laparoscopy and ultrasound simultaneously to correctly place the RFA device into the fibroid and deploy the needle electrodes. This approach allows for treatment of submucosal, intramural and subserosal fibroids. The device is designed to treat fibroids up to 7 cm with a single deployment. Larger fibroids can be treated in multiple deployments with overlapping treatment zones.
Photo courtesy of Halt Medical
Clinical results with the Acessa system have been favorable. Thirty-one women aged 28 to 51 underwent RFA treatment for fibroids, with 1-year follow up. Primary outcome measures were patient safety, frequency of adverse events, repeat intervention rate due to fibroid symptoms, symptom severity, and results from the Uterine Fibroid Symptoms and Quality of Life Questionnaire.13 A median of 2 fibroids were treated in each subject. At 12 months the subjects’ mean symptom severity scores improved by 82% (70.9%–93.1%), and mean health-related QoL scores statistically improved from a baseline value of 60.15 to 97.8 at 12 months. Mean uterine volume decreased from 194.4 cm3 at baseline to 113.2 cm3 at 12 months, a statistically significant difference. There were no procedure-related repeat hospitalizations or repeat treatments.
A prospective, dual-center, longitudinal, open-label single-arm study conducted in Mexico and Guatemala followed the outcome of 206 consecutive subjects.14 This study demonstrated outcomes similar to those from earlier studies, with significant improvement in symptoms, QoL scores, and an average reduction in uterus size of 26% in 12 months. There were 5 device-related adverse events in treatment of 206 subjects including an abdominal wall hematoma, pelvic abscess, superficial laceration of the sigmoid colon serosa from the ultrasound probe, a mild superficial uterine serosal burn, lower abdominal pain, and vaginal bleeding. The subjects did well, with the majority returning to work 4 to 5 days after the procedure.14
The FDA approved the Acessa procedure following the outcome of the pivotal trial that has now followed the outcome of 135 women treated at 36 months post-procedure.15 The study enrolled subjects with a uterus size <14 weeks’ gestation, fibroids without adenomyosis determined by MRI, and a very precise definition of bleeding determined to be ≥160 mL and ≤500 mL per cycle. The majority of subjects treated (98%) were discharged the same day as the procedure. The statistically significant improvement in QoL scores and reduction of symptoms seen at 3 months were demonstrated to be stable over a period of 36 months. The surgical intervention rate for the entire cohort was 10.4% with 11 subjects undergoing hysterectomy, 1 undergoing a UAE, and 2 who underwent hysteroscopic resection of a fibroid.15
A randomized, prospective, single-center, longitudinal study compared RFA with the Acessa procedure to laparoscopic myomectomy (LM).16 In the study, 51 women were randomized equally to the 2 interventions. The surgeons were blinded to the procedure until after laparoscopic mapping of the uterus for fibroids. Mean hospitalization time for RFA treatment was 10.0 hours with a mean blood loss of 16 mL, as compared to 30 hours and 51 mL for LM. There was no statistical difference in operative time between the 2 procedures. The RFA subjects had 98% of mapped fibroids treated as compared to 80% of mapped fibroids removed at the time of LM.
Transcervical, intrauterine ultrasound-guided RFA (the Sonata system, Gynesonics) is an alternative method for targeting fibroids with RFA energy. The key element of the technology is the Sonata system treatment device (Figure 3), which incorporates a small reusable curvilinear ultrasound probe and a single-use, disposable, articulating RF handpiece combined into a single-treatment device. The device is inserted through the cervix into the uterine cavity where the articulated ultrasound tip allows for localization of the fibroids. The surgeon must be skilled at ultrasound and trained to recognize uterine landmarks and fibroids viewed from inside the uterus, as compared to the more familiar transvaginal probe orientation. Once the probe is inserted into the uterine cavity, the locations of the fibroids are mapped. Treatment requires articulation of the distal end of the ultrasound probe to allow for direct deployment of the needle into the fibroid.
Photo courtesy of Gynesonics
The device is equipped with a graphical overlay to simulate ablation zones and ensure that the ablation zone remains safely within the uterus. The trocar tip is then deployed as are the electrodes. The ultrasound probe is rotated to assess the location of the ablation and ensure safety. Ablation is initiated by foot control, and treatment times are automatically calculated and treatment discontinued by the generator. The distance from the ablation zone to the uterine serosa is between 6 mm and 9.5 mm.17 This safety margin permits partial ablation of some fibroids that are close to the serosal surface.
The FAST-EU trial was a multicenter, prospective, single-arm trial of 50 women suffering from menorrhagia related to uterine fibroids.18 The trial was conducted in the United Kingdom, the Netherlands, and Mexico. Women with up to 5 fibroids, the largest fibroid being ≤ 5 cm, who were suffering from menorrhagia were enrolled and treated. The primary outcome of the study was the percentage change in perfused fibroid volume at 3 months. The study also assessed at 6 months and 12 months the subject safety, reduction in menstrual flow, and change in symptom severity score of the Uterine Fibroid Symptom-QoL questionnaire. The study demonstrated significant reductions in both perfused (67.4%) and total fibroid volume (66.6%) at 12 months. Statistically significant reductions in menstrual blood loss and symptom scores also were reported.
The majority of the procedures were done under conscious sedation alone or regional anesthesia, with 30% being conducted under general anesthesia. Four subjects (8%) required surgical reintervention. One woman underwent a hysterectomy for persistent anovulatory bleeding, 2 required hysteroscopic resection of a fibroid from the cavity, and 1 underwent endometrial ablation.
A trial of transcervical, intrauterine ultrasound-guided RFA for uterine fibroids is currently under way and the treatment phase should be completed by the end of 2016.
Management of fibroids is rapidly evolving. Patients are seeking less-invasive methods of managing symptoms associated with what is almost always a benign gynecologic condition. RFA is a viable option for treatment. One such device is FDA-approved, with others possibly available in the near future.
The benefits of RFA include the relatively short operative time, quick return to function, and the ability for a woman to retain her uterus. The current technology allows localization of a fibroid with ultrasound guidance. Clinicians who want to perform RFA need to receive specific training on the technique to acquire sufficient comfort with the localization process.
There is much to be learned regarding the RFA technique, such as the long-term success rates with the procedure, how to identify the appropriate surgical candidates, and impact of the treatment on subsequent fertility and pregnancy outcomes. RFA is an exciting new method of managing fibroids.
Dr Guido reports performing contracted research for Gynesonics and Halt Medical. Dr Stuparich has no conflicts of interest to report in respect to the content of this article.
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