WHAT ARE FIBROIDS?
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UAE SUMMARY | GEORGETOWN UNIV. EXPERIENCE | PUBLISHED GU RESEARCH
LITERATURE REVIEW | PHYSICIAN'S GUIDE for PATIENT PROTOCOL
By James B. Spies M.D.
Associate Professor of Radiology
Georgetown University Hospital
Sept 1, 2001
Uterine artery embolization as a primary therapy for fibroids was reported by Ravina in 1995 (1). In that initial report, 16 patients were treated. Polyvinyl alcohol particles were used as the embolic agent, injected through catheters placed selectively in the uterine arteries. With a mean follow-up of 20 months, symptoms resolved in 11 of 16. 3 patients had partial improvement, and the residual heavy bleeding subsequently controlled with progestins. There were 2 failures, one of which required hysterectomy 6 weeks after the procedure and another requiring myomectomy 6 months after the procedure.
Goodwin at UCLA subsequently reported on the results of this treatment in 11 patients (2). The embolization procedure used by Goodwin was very similar to that of Ravina, although he used a larger size polyvinyl alcohol particle (500-700 micron). They were successful in bilateral embolization in 10 patients and unilateral in one. One patient developed endometritis and pyometrium within 3 weeks of the procedure that required hysterectomy. In the 10 other patients, the dominant symptom was noticeably improved in 8. One patient was lost to follow-up and another had no improvement. The mean decrease in uterine volume was 40% and dominant fibroid volume decreased 60-65% at three-month follow-up.
Ravina's group reported a larger group of patients in February of 1997(3). 88 women underwent attempted embolization. Of these, the procedure was not successfully completed in five and three others were lost to follow-up or required LH-RH analogue for other reasons. This paper reports on the results of the remaining 80 women. 89% (60 of 67 patients) had resolution of their menorrhagia. There were 7 failures. Fibroid volume was reduced by 55% at 2 months and 69% at 6 months. One patient required a hysterectomy for severe ischemic injury.
Bradley and Reidy reported the results of this therapy in 8 patients with large fibroids (4). Menorrhagia was controlled in 4 of 5 patients presenting with that symptom, while bulk related symptoms improved in all patients. These authors reported that most of their patients experienced an intermittent non-purulent vaginal discharge, presumed to be necrotic fibroid tissue debris. One patient did spontaneously pass a substantial portion of a submucosal fibroid 6 weeks after the procedure. In addition, these authors did have one patient, aged 41, who became amenorrheic following the procedure. Serum follicle stimulating hormone was measured at 59.8 IU/L.
A brief report of two patients in Melbourne, Australia details the experience of two patients treated with UFE (5). One patient did not have adequate control of symptoms and underwent supracervical hysterectomy 26 weeks after her embolization procedure. The pathologic specimen revealed aseptic necrosis of two of the fibroids, with hyaline change of the others.
Burn and McCall also have published their results in 14 patients treated at the Chelsea and Westminster Hospital in London (6). No complications were encountered and in follow-up in 6 patients, all were significantly improved. There was a mean fibroid volume reduction of 43%.
Larger Case Series
Worthington-Kirsch reported the results in 53 patients treated with technically successful procedures in 52 (7). Follow-up at three months indicated marked improvement in 88% in menstrual bleeding patterns. For the 31 patients with bulk-related symptoms, 29 (94%) experienced marked improvement. The mean reduction in fibroid volume was 46% in the 32 patients in whom follow-up ultrasound was performed. Complications included extensive infarction requiring in hysterectomy 12 days post-procedure in one patient. Two patients required re-hospitalization for post-embolization syndrome. Another patient developed a self-limited episode of upper gastrointestinal hemorrhage secondary to vomiting.
A large series was recently published by Hutchins and Worthington-Kirsch (8). Three hundred five patients were treated, with follow-up at 3 months, 6 months and 12 months post-therapy. Menorrhagia was controlled in 86% of patients at 3 months, 85% at 6 months, and 92% at 12 months. Pelvic pressure due to the bulk of the fibroids was controlled in 64% of patients at 3 months, 77% at 6 months and 92% at 12 months. The patients reported in this series include those reported previously by Worthington-Kirsch (7). No additional complications were reported other than those mentioned earlier.
The initial results at Georgetown University have been published by Spies et al (9). Of 61 patients reported, all procedures but one were technically successful. Mean clinical follow-up was 8.7 months. Minor complications occurred in five patients during the follow-up period. All were treated without permanent sequelae. One patient (age 49) became amenorrheic post treatment.
Menstrual bleeding was improved in 89%, with 81% of patients moderately to markedly improved. Pelvic pain and pressure was improved in 96% of patients, with moderate to marked improvement in 79%. At initial imaging follow-up (mean 4.4 months post-procedure), median uterine volume decreased 34% and the median dominant fibroid volume decreased 50 %. Imaging at one-year (mean 12.3 months) post-procedure showed continued reduction with a median uterine volume reduction of 48% and median dominant fibroid volume decrease of 78%.
Goodwin has reported mid-term results on his initial group of 60 patients (10). With a mean of 16.3 months follow-up, 81% had continued control of symptoms. Mean reduction of uterine volume was 42.8%. Dominant fibroid volume decreased 48.8%. Seven patients have undergone hysterectomy in the follow-up, one for a complication (mentioned above) and six in patients who did not improve after embolization. One patient became amenorrheic after treatment and four patients expelled significant portions of their fibroids in the follow-up period.
Siskin at Albany Medical College (11) used an outpatient management protocol in 49 patients. In addition to showing the potential feasibility of an all oral pain management protocol, his patient series showed a similar outcome with 88.5% of patients at three months follow-up reporting improvement of symptoms. Dominant uterine volume reduction was 47.5%.
Pelage has most recently reported on the results of 80 consecutive patients treated for menorrhagia caused by fibroids at the Hotel Lariboisiere in Paris (12). This group of patients had a minimum of 2 years follow-up. Menorrhagia was controlled in 90% of patients. Hysterectomy was required in one patient for infection while portions of fibroids were expelled in four patients in the first month post-procedure. Four patients experienced permanent amenorrhea after the procedure. Three full term pregnancies were reported among this group.
Brunneau, also from Paris, has published the results on 58 patients with a mean duration of follow-up of 12 months (13). As in the other series, a high percentage of patients had improved bleeding ((90% at 3 months, and 93% at 12 months. These authors reported similar reductions in uterine volume, with reduction of the dominant fibroid of 51% at 12 months. While there were not hysterectomies required for complications, there was one patient sho suffered an external iliac artery dissection.
McLucas et al from Los Angeles reported on the results in 167 patients with a mean of 6 months follow-up (14). At 6 months after treatment, menorrhagia was improved in 82% of patients with 52% mean reduction in dominant fibroid. These fibroid passage in 5% of patients and a hysterectomy was required in one for infection.
From Anderson's group, there was a recent report of 62 patients with 96% of patients noting improved menstrual bleeding and70% improved bulk symptoms (15). These authors report 2 episodes of fibroid expulsion and one case of endometritis in follow-up.
The Georgetown group has recently reported on results, including subsequent gynecologic interventions in 200 patients (including the 61 noted above) (16). This patient group had a mean follow-up of 21 months, with a range of 12 to 37 months. Menorrhagia was improved in 87 % at 3 months and 90% at 12 months. Similarly, bulk symptoms were improved in 93% at 3 months and 91% of patients at 12 months. During the course of follow-up, subsequent gynecologic interventions or re-hospitalizations occurred in 21 patients (10.5%). Of these, approximately half were for failure to improve or recurrence of fibroids, while the others were for acute gynecologic problems, such as fibroid tissue passage, endometritis or recurrent heavy bleeding. It is interesting to note that the cause for recurrent bleeding was often a polyp or hyperplasia, rather than recurrent fibroids.
An evidence table (Table 1 [PDF file]) has been appended to this review which focuses on the results of treatment in the larger series (those with 40 or more patients, excluding duplicate reports).
Early in the experience with UAE, two papers report a total of 4 cases of fibroid expulsion as a consequence of UFE. One of these patients had the fibroid removed during a simple pelvic examination and had no sequelae (17). The other three patients had clinical evidence of infection that responded to oral antibiotics (18). Fibroid passage is now recognized to occur in 2 to 5% of patients after uterine embolization.
The causes of failure of UAE have not yet been completely explored, but two case reports shed some light on potential causes. Nikolic and Spies (19) have reported a case of ovarian artery supply to the uterus and fibroids, which prevented successful infarction of the fibroids. Another patient, reported by Smith (20), failed to respond to embolization as a result of coincident adenomyosis. These are single cases, but they point to areas that would benefit from further research.
There was a recent report from England of a death that occurred after UFE (21). The patient developed a uterine infection 7 to 10 days post-embolization and presented to the emergency room with septicemia. Despite antibiotic therapy, emergency hysterectomy and supportive care, she developed multi-system organ failure and died 15 days later. This is the onlycase report of a death published in the literature thus far. There has been another death reported at the 1999 SMIT meeting (22). There have been two additional anectdotal reports of fatal complications, one from sepsis and another from pulmonary embolus (23). To date, approximately 20,000 women have been treated world-wide.
Spies has published results of a study of health-related quality of life before and after uterine embolization (24). Fifty consecutive women were enrolled in the study and completed the baseline assessment. Health-related quality of life scores improved in all instances at follow-up. Mean change scores were statistically significant for all domains between baseline and month 3 (p<0.01) and between baseline and month 6 (p<0.05), except backache (p=0.12). The study authors concluded that patients undergoing UFE report significant improvements in health-related quality of life and fibroid-specific symptoms.
In a related subject, Nikolic and Spies (25) reported on the radiation dose associated with UAE. In 20 patients, the mean estimated ovarian dose was 22.34 cGy and the mean skin dose was 162.32 cGy. This is an order of magnitude (10 to 30 times) larger than typical diagnostic radiographic studies, but is 10 to 30 times less than radiotherapy for Hodgkin's Disease of the pelvis. Studies on Hodgkin's patients have not shown any increase in infertility or genetic defects and thus an effect from UAE is extremely unlikely. Further, in follow-up studies, the group at Georgetown demonstrated that the large majority (93%) of the radiation dose was during fluoroscopy . By combining pulsed fluoroscopy, dose reduction methods and bilateral femoral access for simultaneous embolization of both uterine arteries, the dose was reduced by 60% with a mean absorbed ovarian dose of 9.8 cGY (26).
In each of the major published series, there have been cases of amenorrhea that have occurred after embolization. In most reports this has occurred in between 2 and 7% of patients (8, 10, 12, 14, 27, 28). However, Chrisman et al noted a much higher rate of amennorhea, including 43% of patients over the age of 45 and 15% of all patients treated (29). The group at Georgetown University also reported on the initial results of a study of ovarian function before and after uterine embolization (28). Basal FSH levels were obtained in 61 patients before and after embolization. Although the study is not complete, no patient under the age 45 had any permanent change in FSH after embolization. Four of 25 (15%) of patients over the age of 45 did have change in FSH from less than 20 to over 20 IU/L. None of these four had cessation of menses, although 2 developed symptoms suggesting the entry into peri-menopause.
Scientific Abstract Presentations
A number of investigators have presented results of their experience, but these findings have not yet been published. Because it details the use of gelfoam, one of these is reviewed below.
At the Society of Cardiovascular and Interventional Radiology Meeting in San Francisco, CA in March of 1998, Katz presented the preliminary results of a randomized comparison of polyvinyl alcohol particles with gelfoam pledgets (30). Although the study size was small (n=17), the initial symptomatic control was similar both groups, raising the possibility that temporary occlusive agents may be effective in treating fibroids. Amenorrhea occurred in two of the patients in this study, both treated with polyvinyl alcohol particles. These patients were aged 52 and 47.
The results from the published series and those presented at scientific meetings are similar. It appears from this initial experience that this treatment controls both menorrhagia and symptoms caused by the bulk of these fibroids in 85 to 90% of patients. Patients have tolerated the procedure well and patient satisfaction is high. While severe ischemic injury to the uterus has been feared, it appears that this occurs in only 1 to 2 % of patients. Late infection of the endometrium or myometrium may be the most common serious complication and the report of a death post-treatment from sepsis related to uterine infection is a reminder of the potential for catastrophic outcome after any medical intervention. Other reported complications have included spontaneous passage of fibroid tissue and amenorrhea, which has also been reported by several investigators. This is more likely in peri-menopausal women with the incidence probably 5% or less. The true incidence of all these complications requires the completion and publication of larger studies.
Pregnancies have been reported in a number of patients, but the pregnancy rate is not known. The large majority of patients treated to date do not wish additional children. Further, the number of patients seeking pregnancy is not known and there are currently no reports of pregnancy rates in the literature. It is likely that a registry or large multi-center study will be needed to answer this question.
The accumulating reported experience with the procedure suggests that it is effective and generally safe in the short term and midterm results suggest that it is a durable alternative to surgical therapy for this very common medical condition.
WHAT ARE FIBROIDS?
PATIENT'S GUIDE | FIBROID REGISTRY | FINDING A PHYSICIAN
PHYSICIAN'S RESOURCE | ADENOMYOSIS | MEET OUR STAFF