Clinical outcomes following percutaneous magnetic resonance image guided laser ablation of symptomatic uterine fibroids

J.T. Hindley1, P.A. Law1, M. Hickey2, S.C. Smith3, D.L. Lamping3, W.M.W. Gedroyc4,5 and L. Regan1

1 Department of Obstetrics and Gynaecology, Imperial College School of Medicine, St Mary’s Hospital, London, UK, 2 University of Western Australia, Women and Infants Research Foundation, Department of Obstetrics and Gynaecology, Subiaco WA 6008, Australia, 3 Health Services Research Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK and 4 Department of Interventional Magnetic Resonance Imaging, St Mary’s Hospital, London, UK


    Abstract
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
BACKGROUND: Fibroids are common benign tumours of the uterus. Percutaneous magnetic resonance (MR) image guided laser ablation provides a minimally invasive, day-case alternative to surgery for the treatment of symptomatic fibroids. METHODS: Women with symptomatic fibroids wishing to avoid surgery were treated with laser ablation. MR thermal mapping ensured that maximal safe energy was applied. Fibroid volume was measured at 3 and 12 months, menstrual blood loss was recorded before and after treatment and a menorrhagia outcomes questionnaire (MOQ) was used to assess satisfaction. RESULTS: A total of 66 patients was treated. There was a significant (P < 0.001) reduction in mean fibroid volume of 31%. This was 41% at 1 year follow-up (P < 0.001). Measured menstrual blood loss in eight patients complaining of excessive bleeding was reduced (P = 0.012). The MOQ total outcome score was not as good as that seen in hysterectomy patients (P = 0.02) but the quality of life/satisfaction score was similar (P = 0.06). CONCLUSION: We have used objective and subjective outcome measures to determine the efficacy of MR guided laser ablation for fibroids. Based on this limited study we are encouraged that this procedure may represent a minimally invasive alternative therapy for fibroids.

Key words: fibroid/laser/MRI/outcomes/treatments


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Uterine fibroids are the most common benign tumours of the female genital tract. They are diagnosed in up to 25% of women and have a clinically occult presence in many more (Veasy and Reiter, 1981Go). Fibroids typically present with heavy and/or prolonged menstruation, symptoms due to mass effects such as pain and urinary symptoms, or reproductive dysfunction including infertility, miscarriage, fetal malpresentation and painful degeneration of the fibroid in pregnancy (Stewart, 2001Go).

Magnetic resonance (MR) image guided laser ablation is a new method for the treatment of fibroids. Thermal ablation of fibroids causes cell death and subsequent reduction in fibroid volume (Goldfarb, 1992Go). Previous attempts at laser ablation of fibroids via the laparoscopic approach have encountered problems with pelvic adhesions. These adhesions appear to be secondary to the use of multiple fibroid punctures and thermal damage to the serosal surface (Nisolle et al., 1993Go). Such damage is unsurprising since the only monitoring of the heat application is by a visual change in colour of the fibroid under direct inspection at laparoscopy. This colour change occurs after the serosal surface has already been damaged. The introduction of the lasers percutaneously under MR guidance enables the operator to place them accurately in the target fibroid prior to application of the thermal energy (Law et al., 2000Go). MR imaging allows thermal mapping of the fibroid in real time throughout the treatment using the heat sensitivity of the MR signal and converting the changes in T1 signal, related to temperature, into a colour scale. In this way maximum ablation can be achieved without risk of damage to the serosa or any adjacent structures, which are clearly visualized relative to the area of heating. We have previously shown that this procedure is a safe and acceptable alternative treatment for symptomatic uterine fibroids (Law et al., 1999Go).

This is an ongoing observational pilot study to present our outcome data to date. The results are presented from a validated, self reported outcomes questionnaire (Lamping et al., 1998Go) the changes in fibroid volume and variation in measured menstrual blood loss.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Ethical approval for the study was obtained from the St Mary’s Hospital Local Research Ethics Committee. Patients presenting to the general gynaecology outpatient department at St Mary’s Hospital, Paddington, UK with symptomatic uterine fibroids and who would otherwise have been offered either myomectomy or hysterectomy were approached. Those wishing to avoid open surgery were offered MR guided laser ablation of their fibroids. All patients were fully counselled regarding the nature of the treatment and informed consent was obtained. All subjects were specifically advised that the long-term effect of the treatment on their fertility is unknown. All eligible women underwent MR imaging to determine the size and location of their fibroids. T2 weighted, fast spin echo sequences were used in the axial and sagittal planes. Patients in whom the dominant fibroid could not be safely accessed via a percutaneous approach through the anterior abdominal wall were excluded. Negative urinary pregnancy tests were confirmed from all participants on the day of treatment.

Patients complaining of heavy or prolonged menstrual bleeding due to confirmed uterine fibroids were asked to collect all their menstrual blood loss over a complete menstrual cycle prior to the treatment. They were given plastic bags to collect their sanitary protection in and to return it to the clinic with clear instructions to collect as much menstrual effluent as possible. Three months after treatment the patients were asked to repeat this collection procedure. The alkaline haematin method (Hallberg, 1964Go) was used to determine the menstrual blood loss. The blood loss volumes before and after treatment were compared using Wilcoxon signed ranks test using the Statistical Package for the Social Sciences (SPSS) software, version 10.0.

The MR guided laser ablation was performed in an open interventional MR scanner (Signa SPIO 0.5T, General Electrical Medical Systems, Milwaukee, WI, USA). Prior to treatment all patients underwent bladder catheterization. All patients were given a 100 mg Diclofenac sodium suppository (Novartis Pharmaceuticals UK, Camberley, Surrey, UK) and were then placed supine into the open scanner. A flexible transmit–receive imaging coil was placed around the lower abdomen and a sterile field established within the confines of the coil, using disposable self-adhesive drapes (Baxter Healthcare, Chicago, IL, USA). The skin over the abdomen was infiltrated with 10 ml 2% lignocaine. Four MR compatible 18 gauge Turner needles (Cook, Letchworth, Hertfordshire, UK) were placed percutaneously into the largest fibroid under near real-time MR guidance with images updated every 3 s. Bare laser fibres were placed into the needles and an neodymium:yttrium-aluminium-garnet (Nd YAG) laser, wavelength 1068 nm, was used to deliver thermal energy. The length of time that the laser was applied was determined using the real-time thermal map. The loss of T1 signal associated with temperature rise was converted into a colour image that turned from blue to green as the temperature reached 55°C. Irreversible tissue damage is achieved at 55°C and above (Jolesz and Silverman, 1995Go) and this level could be rapidly appreciated using the thermal map. Heat application was continued until a maximal area of green colouration was seen within the region of interest, but stopped if the area of temperature rise threatened to reach outside the desired volume. This ensured that maximum thermal energy was applied to the target without any heating of the uterine surface or extra-uterine structures, thus avoiding the complications associated with laparoscopic laser myolysis. All patients were given pethidine and diazepam i.v. peri-operatively as required and pulse oximetry and blood pressure were monitored throughout.

The fibroid volume was calculated from the images taken immediately prior to the ablation procedure according to Cavalieri’s principal (Gunderson and Jensen, 1987) in which successive T2 weighted sagittal images were viewed across the entire width of the fibroid. The fibroid area on each image was calculated and the sum of the area from each image was multiplied by the sum of the slice thickness and the distance between slices to give the volume in mm3. The fibroid volume was calculated at 3 months and 1 year post-treatment from sagittal T2 MR images taken as part of the follow-up programme. The mean volumes of the treated fibroids prior to treatment and at 3 months, and the mean volumes prior to treatment and at 1 year were compared using the Student’s t-test for paired samples using SPSS version 10.0.

The patient-reported outcomes were measured using the Menorrhagia Outcomes Questionnaire (MOQ) (Lamping et al., 1998Go). The 26 item MOQ includes questions about symptoms (two items), post-operative complications (three items), quality of life (seven items), and satisfaction with treatment (five items). Questions are scored to create two main summary scales: (i) the total outcome scale (17 items) provides an estimate of the woman’s overall outcome, including clinical outcomes, quality of life and her satisfaction with her outcome; (ii) the quality of life/satisfaction scale (12 items) includes items on fatigue, irritability, depression, general health, improvement in symptoms, limitations in daily activities, sexual functioning, body image, speed of recovery, satisfaction with information about the operation and with the results of surgery and willingness to recommend the operation to a friend with a similar problem. For all scores, high values indicate poorer outcomes. The MOQ also includes non-scored questions about sociodemographic characteristics and treatment (eight items) and a question asking for the woman’s global evaluation of symptoms in the 4 weeks before surgery (one item). The MOQ was administered by postal survey at least 3 months after surgery. Standard techniques to ensure a high response rate, including personalized letters, standardized instructions and follow-up reminder letters, were used. For questionnaires not returned within 3 weeks, a first reminder letter was sent out, including the initial letter, another copy of the questionnaire and a stamped return envelope. If the questionnaire had not been returned within 2 weeks of the first reminder, a second reminder with only a letter from the researcher was sent out. The initial patients were treated before the MOQ was available and results for the earliest patients are therefore not available. The MOQ continues to be sent out to patients as they reach the 3 month follow-up. The authors do not believe that there is a selection bias in the MOQ follow-up since the MOQ and volume measurements were made on consecutive patients. The MOQ was scored using the SPSS PC+ software to calculate the mean total outcome score and quality of life/satisfaction score. These were compared with historical controls from the validation studies. The controls were women undergoing hysterectomy for symptomatic uterine fibroids. Comparison of the means was performed with Student’s t-test using SPSS version 10.0.


    Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In total, 66 patients were eligible for MR guided laser ablation of their symptomatic uterine fibroids and underwent treatment, 47 of these patients had 3 month follow-up MRI scans and the volumes of the treated fibroids were compared. The mean volume reduction was 31% (range 21% increase to 76% decrease). The mean volume of the treated fibroid prior to treatment was 617 521 mm3 (618 cc) (SD 422 522) and the mean volume following treatment 460 432 mm3 (460 cc) (SD 380 677). The mean reduction was 157 088 mm3 (157 cc) [SD 195 157, 95% confidence intervals (CI) 98 456–215 720]. This reduction in fibroid volume is highly statistically significant (P < 0.001).

A total of 24 patients were followed up with MRI scans 1 year post-ablation. The mean volume reduction was 41% (+13% to –78%). The mean fibroid volume was reduced from 476 140 mm3 (476 cc) (SD 312 082) to 275 545 mm3 (275 cc) (SD 210 960), a mean shrinkage of 200 595 mm3 (201 cc) (SD 216 738, 95% CI 109 075–292 116). Once again this is a statistically significant change (P < 0.001).

The MOQ was sent to 37 patients and after the collection techniques outlined above 35 replies were received. The total outcome score and quality of life/satisfaction score are shown in Table IGo. The scores are shown compared with scores from an historical group of patients undergoing hysterectomy for symptomatic fibroids. The MOQ shows a significantly higher, and therefore worse, total outcome score for MR guided laser ablation compared with hysterectomy (P = 0.02) but fails to show a significant difference for quality of life/satisfaction score (P = 0.06).


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Table I. Menorrhagia outcomes questionnaire (MOQ) results. Overall score and satisfaction sub-score for laser ablation compared with historical hysterectomy controls
 
The responses to single questions taken from the MOQ can be reviewed without reference to the MOQ scoring system (Table IIGo). These responses show that 80% of those treated would recommend MR guided laser ablation to a friend if she had a similar problem, that 69% of women feel that their symptoms have improved since the treatment and that 69% state that they feel better than prior to MR guided laser ablation.


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Table II. Responses to individual questions on menorrhagia outcomes questionnaire (MOQ)
 
The mean menstrual blood loss, as measured using the alkaline haematin method, before treatment was 121.2 ml (range 42.7–205.5 ml) Figure 1Go. Three months post-treatment the measured blood loss fell for all patients. The mean loss following MR guided laser ablation of the fibroids was 81.2 ml (range 26.8–157.4 ml). Despite the small sample size a significant reduction in measured menstrual blood loss was shown following MR guided laser ablation (P = 0.012). The graph demonstrates that the efficacy of MR guided laser ablation of uterine fibroids in the treatment of excessive menstrual blood loss appears to be greater in women with higher initial measured losses.



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Figure 1. Change in measured menstrual blood volume before (1) and 3 months after (2) MR guided laser ablation of fibroids.

 
No patients required readmission to hospital; one woman chose to remain in hospital overnight since she lived alone. All women were sent home with simple analgesia and none required additional analgesia. Three women required antibiotic therapy for urinary tract infections and two women sustained minor skin burns, neither of which required additional therapy.


    Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The subjective and objective data obtained from this study suggest that MR guided laser ablation is a promising minimally invasive alternative for the treatment of symptomatic uterine fibroids.

The main treatment for uterine fibroids remains abdominal hysterectomy and is a curative procedure with high satisfaction rates (Carlson et al., 1994aGo) and, indeed, fibroids remain the most common indication for hysterectomy in the USA (Agency for Healthcare Research and Quality, 2001Go). Traditionally, myomectomy was the uterine-sparing alternative for the treatment of fibroids, but it is a major operation with morbidity and recovery times comparable with abdominal hysterectomy (Iverson et al., 1996Go).

There appears to be a move to develop less invasive treatments for fibroids with the advent of several new techniques. Laparoscopic myomectomy and trans-cervical resection of fibroids are now widely offered to suitable patients. Uterine artery embolization is an increasingly popular and effective alternative to traditional treatments.

Medical treatments for fibroids are largely symptomatic, and include non steroidal anti-inflammatory agents and antifibrinolytics. The exceptions to this are GnRH agonists which reduce fibroid volume and menstrual blood loss (Carlson et al., 1994bGo). Unfortunately, prolonged use is associated with menopausal symptoms and loss of bone density (Lumsden et al., 1994Go) and GnRH agonists are mainly used prior to surgery to reduce fibroid volume and peri-operative blood loss (Crosignani et al., 1996Go).

The volume measures carried out in this study show a significant and persistent reduction in volume of the treated fibroid in most cases. It appears that the significant reduction achieved at 3 months is maintained and may be further reduced at 12 months in the majority of patients. It is possible that the improved result at 12 months is a statistical anomaly due to those with disappointing early results being lost to follow-up or seeking other treatments. Review of the 3 and 12 month volumes for the patients who have had both measurements, suggests that the continued volume reduction is a genuine observation (Table IIIGo). There are some patients (six of 20) who had a substantial increase in volume between the 3 and 12 month imaging studies, which could represent regrowth of residual viable fibroid tissue. Additional long-term observation will be needed to determine whether this apparent increase continues.


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Table III. The volumes of the treated fibroids prior to treatment and at 3 months and at 12 months post-treatment
 
Excessive menstrual loss is the most common complaint amongst women with fibroids presenting to gynaecologists (Veasy and Reiter, 1981Go) and therefore we felt that it was important to measure the effect that MR guided laser ablation had on this parameter. Only a small number of women agreed to collect their menstrual effluent but a statistically significant reduction in measured menstrual loss was seen. It is interesting to note that there was a wide variation in the measured menstrual blood loss in a group of women who all complained of excessive menstrual bleeding; indeed two of the women did not meet the accepted cut-off for menorrhagia of 80 ml per cycle, but all still saw significant reductions in blood loss. It appears that the effect of MR guided laser ablation is greatest in the women with the highest volume loss (Figure 1Go).

The most important measure of the success of any procedure is the effect that the procedure has on the lives of the patients who have been treated. The use of the MOQ addresses this issue. The MOQ was originally developed and validated for use in women who had had a hysterectomy (Lamping et al., 1998Go). Comparison was made with an historic control group of patients who had undergone hysterectomy for symptomatic uterine fibroids. The total outcome score was better in the hysterectomy group (P = 0.02) while the quality of life/satisfaction score was similar between the groups (P = 0.06). Since the MOQ was originally validated using patients who had undergone hysterectomy, rather than MR guided laser ablation, it may be more sensitive to the outcomes that improve with hysterectomy. It is encouraging that MR guided laser ablation is achieving scores with this questionnaire that are comparable with hysterectomy given that hysterectomy is known to score very highly in patient satisfaction studies (Kjerulff et al., 2000Go). MR guided laser ablation of uterine fibroids is a minimally invasive, uterine sparing, day-case procedure after which patients rarely require analgesia compared with an average of 25 days of pain (Carlson et al., 1994aGo) reported following abdominal hysterectomy.

We have presented three independent outcome measures from patients treated with MR guided laser ablation of fibroids. We believe that we have shown that this is a promising treatment for symptomatic uterine fibroids and that these outcomes form the basis for continued development of this technique. The reduced morbidity and the potential fertility-sparing nature of MR guided laser ablation of fibroids could potentially make it a reasonable, future alternative to traditional surgery in selected patients. A randomized controlled trial involving MR guided laser ablation of fibroids would be helpful in further assessing the place of this new treatment.


    Notes
 
5 To whom correspondence should be addressed at: Interventional MRI, Clarence Wing, St Mary’s Hospital, London W2 1NY, UK. E-mail: w.gedroyc{at}ic.ac.uk Back


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Agency for Healthcare Research and Quality, Rockville, MD (2001) Management of Uterine Fibroids. Summary, Evidence Report/Technology Assessment: Number 34. AHRQ Publication No. 01-E051.

Carlson, K.J., Miller, B.A. and Fowler, F.J. (1994a) The Maine Women’s Health Study: I. Outcomes of hysterectomy. Obset. Gynecol., 83, 556–565.

Carlson, K.J., Miller, B.A. and Fowler, F.J. Jr. (1994b) The Maine Woman’s Health Study II: Outcomes of the non-surgical management of leiomyomas, abnormal bleeding and chronic pelvic pain. Obstet. Gynecol., 83, 556–572[Abstract]

Crosignani, P.G., Vercellini, P., Meschia, M., Oldani, S. and Bramante, T. (1996) GnRH analogues before surgery for uterine leiomyomas. A review. J. Reprod. Med., 41, 415–421.

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Gunderson, H.J. and Jenson, E.B. (1987) The efficiency of systematic sampling in stereology and its prediction. J. Microsc., 3, 229–263.

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Submitted on March 1, 2002; resubmitted on May 15, 2002; accepted on July 10, 2002.