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Vascular and Interventional Radiology |
1 From the Departments of Radiology (I.P., P.C., L.P.) and Gynecology and Obstetrics (A.R., J.H., J.B.), and the Intensive Care Unit (M.A.d.l.C.), University Hospital of Getafe, Carretera de Toledo, Km 12,500, 28905 Getafe-Madrid, Spain. Received October 19, 2001; revision requested December 3; final revision received May 7, 2002; accepted June 5. Supported by grants from FIS (Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain) and Cook-Spain. Address correspondence to I.P. (e-mail: pintopabon@mi.madritel.es).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: A prospective clinical trial was performed with patients who were randomly assigned to one of two groups: patients who were offered the option of undergoing either UAE or hysterectomy (group 1) and patients who were not informed of the alternative treatment—that is, UAE (group 2). The primary variables that were considered for evaluation of the effectiveness, efficiency, and safety of the two procedures were, respectively, bleeding cessation, total length of hospital stay, and resulting complications. The lengths of hospital stay in the two study arms were compared on an intent-to-treat basis. Owing to crossover between the treatment arms, however, effectiveness and safety were evaluated on the basis of the actual treatment received.
RESULTS: The clinical success rate for the patients who underwent UAE, which was based on the cessation of bleeding, was 86% (31 of 36 patients). The mean hospital stay for group 1 was 4.14 days shorter than that for group 2 (P < .001). Ten (25%) of the 40 patients who underwent UAE experienced minor complications, in contrast to four (20%) of the 20 who underwent hysterectomy and experienced major complications.
CONCLUSION: Compared with hysterectomy, UAE is safe and effective for treatment of bleeding fibroids, necessitates a shorter hospital stay, and results in fewer major complications.
© RSNA, 2003
Index terms: Arteries, therapeutic embolization, 854.1264, 854.1266, 986.1264, 986.1266 • Leiomyoma, 854.318, 986.7151 • Uterine neoplasms, 854.318, 986.7151 • Uterine neoplasms, therapy, 854.1264, 854.1266, 986.1264, 986.1266
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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In the past 10 years, uterine artery embolization (UAE) has been described as an alternative to hysterectomy for the management of nonacute uterine hemorrhage caused by fibroids (7–29). Although the results of early studies of UAE in most series (12,14,19,22,27,29) have been encouraging, to our knowledge there has been no comparative study of UAE and hysterectomy to determine the effectiveness and safety of embolization. Thus, the purpose of our study was to evaluate the effectiveness of UAE in the management of bleeding in patients with uterine fibroids and to compare UAE with hysterectomy, with a focus on the length of hospital stay and the complications (ie, safety) associated with these two treatments.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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We stratified the randomization by blocks of six patients to yield a ratio of two UAE procedures to each hysterectomy and thus ensure a larger number of patients who underwent the alternative treatment and gain greater experience and insight into the effectiveness and safety of UAE (32). The random patient assignments were generated by computer and kept in sealed, numbered envelopes. The sample size required for the study was calculated while bearing in mind that the mean length of hospital stay for patients who underwent hysterectomy at our hospital in the latter 6 months of 1998 was 8 days (95% CI: 7.6, 9.2). The expected mean length of hospital stay for the patients who underwent embolization was 5 days or shorter (type I error, 5%; type II error, 10%), because the difference in length of hospital stay necessary for the alternative treatment to be deemed efficient had to be at least 3 days. Longer stays would lead to a cost increase. We determined that a minimum of 54 patients (36 embolizations, 18 hysterectomies), with a recruitment period of 2 years, a follow-up period of 2 years, and allowances for a drop-out rate of 10% (33), were needed for the study.
The embolization procedures were always performed by the same two staff members of the vascular and interventional radiology department (I.P., L.P.). The hysterectomy procedures were performed by several staff members of the gynecology department.
At abdominal hysterectomy, which was performed in a total of 20 patients, one or both ovaries were removed in 12 patients. Anatomic pathologic findings were myomata in 14 patients, myomata plus adenomyosis in five patients, and myomata plus endometriosis in one patient.
Before UAE, which was performed in a total of 40 patients, an intravenous line and a Foley catheter were placed in all patients. The right common femoral artery was the preferred approach for access in all patients. After a nonselective pelvic angiogram was obtained, by using a 5-F pigtail catheter (Johnson & Johnson, Cordis Europe, Oosteinde, the Netherlands), to identify the uterine arteries, the catheter was exchanged for a 4–5-F Sidewinder catheter (Johnson & Johnson), and bilateral selective uterine artery catheterization was performed with the catheter tips placed within the transverse portions of the uterine arteries. A coaxial microcatheter (Terumo Radiofocus SP; Terumo Europe, Leuven, Belgium) was used in those cases in which the Sidewinder catheter obstructed flow in the uterine arteries. Polyvinyl alcohol particles (Ultradrivalon; Nycomed-Amersham MS, Paris, France) that were 400–600 µm in size were used to embolize the uterine vascular bed. All patients received 1 g of cefazolin intravenously 2 hours before and immediately after the procedure. Conscious sedation was induced with midazolam and fentanyl citrate.
Technical success (as assessed by the two staff members who performed the embolization) was considered to have been achieved when the uterine artery was selectively catheterized and the injected polyvinyl alcohol particles mixed with contrast agent (iohexol, Omnigraf 300; Juste, Madrid, Spain) had occluded the uterine vascular bed and led to markedly reduced flow in the uterine artery.
The technical success rate with bilateral UAE in our study was 88%: 35 of 40 patients. Unilateral embolization was performed in five (12%) patients: in one patient because of the absence of one of the uterine arteries, in two patients because of spasm, and in two patients because of the extremely small size of one of the uterine arteries. A microcatheter had to be employed in 18 (45%) of the 40 patients who underwent UAE. The mean polyvinyl alcohol dose received was 257 mg ± 117 (SD) (range, 15–600 mg). The mean time to perform the procedure was 87.8 minutes ± 30 (range, 60–180 minutes); the mean time to perform fluoroscopy was 30 minutes ± 13 (range, 10–73 minutes).
Effectiveness, Efficiency, and Safety
Bleeding was the primary effectiveness variable considered. The patients completed a standard questionnaire, on which they provided the following information: the number of days of menstruation and/or bleeding between menses (continuous variable) and the number of tampons and/or sanitary napkins used after the embolization—specifically, was this number reduced two thirds, reduced one third, unchanged, or increased? The only verification of clinical success, as assessed by another staff member (P.C.), who was in charge of quality control in the study, was the oral communication from the patients.
The secondary effectiveness variable considered was dominant fibroid volume, as determined with magnetic resonance (MR) imaging in all except the first 11 patients, in whom vaginal ultrasonography (US) was used. The uterine fibroid volume was calculated by using the formula for a prolate ellipse: length x width x depth x 0.5233.
The primary efficiency variable was total length of hospital stay after the intervention, which was calculated from the day of the procedure to the day of the patient’s discharge from the hospital and included readmissions (in days). The secondary efficiency variables considered included frequency of readmissions and number of emergency department visits.
The primary safety variable was complications that ensued as a result of each procedure. Secondary safety variables included time that elapsed before patients could resume routine daily activities (in days after the intervention) and level of patient satisfaction with each procedure, as assessed by means of a patient questionnaire. The patients were asked whether they would undergo the same treatment again, and the possible answers were yes, no, and maybe.
Clinical follow-up examinations were performed 10 days, 3 and 6 months, and 1 and 2 years after the procedures. The patients underwent MR imaging evaluation and blood testing 3 months, 6 months, and 1 and 2 years after the treatments.
All data regarding effectiveness, efficiency, and safety were collected by one author of this study (P.C.). Another radiologist, who was not directly involved in this study and was in charge of the MR imaging examinations, determined the fibroid volume changes.
Definitions
To our knowledge, the literature contains neither consistent criteria to evaluate UAE results nor uniform definitions of the different variables. We therefore established the following definitions: Full recovery was defined as the cessation of menorrhagia and metrorrhagia when both were present or the cessation of either when only one was present. Partial recovery (or improvement) was defined as a reduction in menorrhagia, metrorrhagia, or both (in number of days). No improvement was defined as the continuation of symptoms. Worsening was defined as the augmentation of symptoms. Amenorrhea was defined as the absence of menses for more than 6 months after UAE.
Minor complications were those that led to no consequences for the patient and necessitated no or only nominal treatment: arterial spasm, postpuncture hematoma, and surgical wound hematoma. Moderate complications were those that necessitated non–life-threatening additional treatment and had no sequelae for patients: postembolization syndrome and urinary infection. Major complications were death or complications that, in themselves or as a result of the additional treatment required, represented a threat to the patient’s life or a source of permanent sequelae: deep venous thrombosis, transfusion, and/or intraabdominal abscess.
Care before and after Random Assignment of Patients
The diagnostic evaluation of patients before and after they were randomly assigned to treatment groups included blood testing (ie, complete blood count, prothrombin time, and partial thromboplastin time) and vaginal US and/or pelvic MR imaging to evaluate the type, size, and number of fibroids. MR imaging was performed by using a 1.5-T system (Magnetom Vision; Siemens Medical Systems, Erlangen, Germany) and a circular polarized body coil. Transverse and sagittal pelvic MR imaging examinations were performed. T1- and T2-weighted MR images were obtained before and after contrast agent (gadoteridol, ProHance; Bracco International, Amsterdam, the Netherlands) administration. Prerandomization endometrial cytologic results were normal in all patients.
The analgesic regimen for the first 30 patients involved the use of PCA (personal control of analgesia) pumps to intravenously deliver morphine during the first 24 hours after the procedure. For the remaining patients, 30 mg of intravenously administered ketorolac was alternated with 2 g of intravenously administered paracetamol every 6 hours until discharge.
The patients who underwent UAE were discharged 24 hours after the procedure if they had no fever and had not requested pain relief medication in addition to that already prescribed. The patients who underwent hysterectomy were discharged when they fulfilled the criteria used by our gynecology department: normal body temperature, tolerance to oral food intake, and resumed bowel movement.
The home medication regimen for the patients who underwent UAE is outlined in Figure 1. Patients were instructed to take their temperature daily for 1 week and to contact our team by telephone at the first sign of any symptoms of concern.
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Statistical Analysis
Data are presented as mean values ± SDs for the quantitative variables and as frequencies for the qualitative variables. For an unbiased assessment of efficiency, comparisons between groups were based on the intent-to-treat principle: Patient data were analyzed according to the treatment group to which the patients were assigned. To evaluate safety and compare the complications, we analyzed patient data on the basis of the actual treatment received.
The Wilcoxon rank-sum test was performed to analyze the quantitative data, and the Fisher exact test was performed to analyze the qualitative data. All tests of significance were two sided, and a P value of <.05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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After 6 months of follow-up, the overall clinical success rate for the 36 patients who underwent UAE, which was based on the cessation of bleeding, was 86% (31 of 36 patients). Twenty (56%) of 36 patients had a full recovery; five (14%), a partial recovery; and six (17%), amenorrhea. Four of the 31 patients who experienced clinical improvement had undergone unilateral embolization only. The clinical failure rate was 14% (five of 36 patients) and included three (8%) patients who experienced no improvement and two (6%) whose bleeding worsened. Only one of these five patients had undergone unilateral embolization. The mean dominant fibroid volume decreased in 46% (95% CI: 27%, 66%) at 6 months of follow-up. The mean uterine fibroid volume was 84.42 cm3 (range, 1.8–408.0 cm3) before embolization and 45.46 cm3 (range, 0.53–408.0 cm3) after embolization.
We performed intent-to-treat analysis to evaluate efficiency. The 38 patients in group 1 spent a mean of 1.71 days ± 1.59 in the hospital, as compared with the mean of 5.85 days ± 2.52 that the patients in group 2 (n = 19) spent in the hospital—a difference of 4.14 days (95% CI: 3.06, 5.22) (P < .001).
Treatment received analysis revealed that 13 (32%) of the 40 patients who underwent UAE, as compared with four (20%) of the 20 who underwent hysterectomy, made emergency department visits (P = .4). The reasons for the emergency department visits are listed in Table 2.
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Intraprocedural safety analysis revealed that 10 (25%) of the 40 patients who underwent UAE, as compared with four (20%) of the 20 who underwent hysterectomy, had complications (P = .8) (Table 3). Within the 30 days following the procedures, complications were recorded for 29 (72%) of the 40 patients who underwent UAE and for nine (45%) of the 20 patients who underwent hysterectomy (P = .05) (Table 4).
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After 6 months of follow-up, the patients were asked whether they would undergo the same treatment again. Of 36 patients who underwent UAE, 28 (78%) answered yes; five (14%), no; and three (8%), maybe. Of 17 patients who underwent hysterectomy, 15 (88%) answered yes and two (12%) answered no.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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It is difficult to compare our results with those of other researchers to evaluate the effectiveness of embolization because of the lack of uniformity in defining the different degrees of improvement. Depending on the series, 37% (12) to 90% (29) of patients have reportedly experienced a full recovery, and 86% (23) to 96% (12) have reportedly had overall improvements, including full, pronounced, moderate, or slight improvement and amenorrhea, as variously described in the literature. Our results are within the ranges reported. The same is true with regard to the reduction in dominant fibroid volume, the reported measurements of which have been highly variable, between 20% and 100%, depending on the time of the follow-up examination after embolization (8,11,26,29).
In our study, the results regarding hospital stay, emergency department visits, and readmissions for the patients who underwent hysterectomy did not differ substantially from the data reported in the literature (41–43).
One purpose of our study was to compare the length of hospital stay between the two treatments. The results of this comparison demonstrated that the hospital stay for the patients who underwent UAE was shorter than that for the patients who underwent hysterectomy. Therefore, one could propose that UAE, as compared with hysterectomy, has proven to be an efficient treatment of abnormal bleeding in patients with uterine fibroids in our health care system.
On the other hand, we want to emphasize that although the patients who underwent UAE made more emergency department visits than did those who underwent hysterectomy, the latter group tended to do so for major complications, whereas the UAE group visited the emergency department because of postembolization syndrome or pelvic pain. Pelvic pain in patients who have undergone UAE has been described in 83.7% or more cases (8,9,11,14,19,22,26,27,29), but, to our knowledge, the seriousness of this complication has been discussed specifically in only one series, in which 4% of patients went to the emergency department and 8% were readmitted because of pain (14). In addition, the differences between the two treatment groups (with regard to emergency department visits) might have been attributable in part to the strict instructions that the patients who underwent UAE were given: to report to the emergency department at the first sign of any symptom.
We believe that another interesting fact regarding our study is that although the amount of time needed before the patients who underwent hysterectomy could resume ordinary daily activities was shorter than that reported in the literature (48), the period before resuming normal activities for the patients who underwent UAE was substantially shorter than that for the patients who underwent hysterectomy. The degree of patient satisfaction in the two groups was very similar.
An important result of our study is that we did not have to perform any postembolization hysterectomy procedures owing to the types of complications described in the literature—namely, pyometra and endometrial necrosis (9), hematometra (19), persistent pain (12,27), ureteral compression (19), infection (19,47), or acute septic uterine necrosis (29). Two cases of hysterectomy with bowel resection performed owing to necrosis of a subserous fibroid (11,47) and one death due to sepsis (15) also have been reported in the literature.
With regard to safety, the percentage of patients with complications was higher in the UAE group; however, the patients who underwent hysterectomy had more major complications than did those who underwent UAE.
In light of the findings just described, one can conclude that UAE is safe and thus should be offered as an alternative treatment to patients whose only other therapeutic option is hysterectomy. Assessment of the long-term outcomes of embolization is warranted, however, and, to that end, the patients who participated in this clinical trial will continue to be followed up for 2 years.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, I.P.; study concepts, I.P., P.C., J.H., M.A.d.l.C., J.B.; study design, all authors; literature research, I.P., P.C.; clinical studies, I.P.; data acquisition, P.C.; data analysis/interpretation, all authors; statistical analysis, M.A.d.l.C.; manuscript preparation and definition of intellectual content, I.P., P.C.; manuscript editing and revision/review, I.P.; manuscript final version approval, all authors.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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This article has been cited by other articles:
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