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ORIGINAL ARTICLE
Year : 2023 | Volume
: 12
| Issue : 1 | Page : 15-25
High-intensity focused ultrasound for the treatment of fibroids: A single-center experience in Singapore
Smita Jindal1, Jacqueline Jung2, KeenWhye Lee3, Bernard Chern4
1 Associate Consultant, Department of Minimally Invasive Surgery, KK Women's and Children's Hospital, Singapore
2 Consultant, Department of Minimally Invasive Surgery, KK Women's and Children's Hospital, Singapore
3 Consultant, Gleneagles Hospital, Singapore
4 Head of Department, Department of Minimally Invasive Surgery, KK Women's and Children's Hospital, Singapore
Correspondence Address:
Dr. Smita Jindal
Associate Consultant, Department of Minimally Invasive Surgery, KK Women's and Children's Hospital
Singapore
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/gmit.gmit_102_22
Objectives: Uterine fibroids and adenomyosis are common gynecological conditions that often require surgical treatment. Minimally invasive interventions such as ultrasound-guided high-intensity focused ultrasound (USgHIFU) are gaining popularity as they avoid surgical morbidity and conserve the uterus. We present a single-center experience on the use of USgHIFU for the treatment of fibroids and adenomyosis.
Materials and Methods: This was a retrospective study of 167 patients who underwent USgHIFU for uterine fibroids and adenomyosis between July 2018 and December 2020. Relevant demographic data and pre- and post-intervention fibroid volume, symptom severity scores (SSS), and health-related quality of life (QOL) scores were collected and compared. The paired t-test or Wilcoxon signed-rank test was used to compare the difference before and after treatment. P < 0.001 was considered statistically significant.
Results: One hundred and sixty-seven patients with fibroids or adenomyosis were included in this study. The mean age of the cohort was 42-year-old. USgHIFU treatment led to a reduction in mean fibroid volume, improvement in SSS, and health-related QOL scores. The average reduction in mean fibroid volume was 68% and 75% at 6 and 12 months, respectively. There was a significant reduction in SSS (46.9 [pre] vs. 15.6 [post], P < 0.001) and improvement in health-related QOL scores at 6 months (58 [pre] vs. 86 [post], P < 0.001). The re-intervention rate following USgHIFU was 7.7% and successful pregnancy post USgHIFU was reported in 6 patients.
Conclusion: USgHIFU is safe and effective. In women who desire fertility or are not suitable for surgery, it is a good alternative option. It should be included in the armamentarium for the treatment of uterine fibroids and adenomyosis.
Keywords: High-intensity focused ultrasound, noninvasive, ultrasound, ultrasound-guided high-intensity focused ultrasound, uterine fibroid
Uterine leiomyomas, or fibroids, are the most common benign gynecological tumor, prevalent in up to 20%-50% of women in the reproductive age group.[1] Half of the women with fibroids are symptomatic, with complaints of menorrhagia, pelvic pain, urinary frequency, or pressure symptoms. Depending on the position and size, fibroids can also affect fertility and lead to pregnancy losses.[2] Medical treatment such as gonadotropin-releasing hormone analogue and selective estrogen receptor modulators may be used to control symptoms and fibroid growth. However, these treatments often fail or have side effects that limit their long-term usage.[3] On the other hand, surgical treatments for fibroids such as hysterectomy and myomectomy while efficacious, are associated with surgical complications in up to 10% of patients.[4],[5],[6],[7] There is also a concern for risk of uterine rupture in subsequent pregnancy after myomectomy, with a reported incidence of around 0.5%.[8]
This has spawned increasing interest in noninvasive gynecological interventions to mitigate surgical morbidity and preserve fertility. One such modality entails the use of high-intensity focused ultrasound (HIFU). This technology focuses the beams of ultrasound waves at a small target volume and deposits this to tissues deep within the body. This extracorporeal source of focused ultrasound energy can induce thermal coagulative necrosis, without damaging overlying and surrounding vital structures.[9],[10] Since the 1980s, HIFU has been used in the management of solid tumors in the breast, liver, pancreas, kidney, prostate, and thyroid.[9],[10]
In the last two decades, HIFU has been an emerging option for the treatment of uterine fibroids and adenomyosis. It has been demonstrated to be safe and effective. Most studies demonstrate overall fibroid volume shrinkage ranging from 18% at 3 months to 84% at 36 months.[11],[12],[13],[14],[15],[16],[17],[18],[19] Systematic reviews and meta-analysis report promising data on fertility and pregnancy rates after HIFU, making it an attractive option for fertility-desiring women.[20],[21]
HIFU can be performed under either magnetic resonance imaging (MRIgHIFU) or ultrasound (USgHIFU) guidance.[3],[12] A previous study on MRIgHIFU done at our center reveals that it is safe and effective.[22] However, to date, there remains no local data on USgHIFU. In this study, we aim to assess the efficacy and safety of USgHIFU in the treatment of uterine fibroids and adenomyosis in our local population.
Materials and MethodsThis is a retrospective analysis of the initial experience of HIFU performed in the first HIFU center in Singapore. All patients provided their informed consent in writing to be included in this study and the datae was audited and analysed by APAGE HIFU committee. The data in this study is not available to the public but it can be made available on request from researchers who meet the criteria upon approval from APAGE HIFU Committee.
Patients
From July 2018 to December 2020, 167 patients with symptomatic uterine fibroids and or adenomyosis were included in this study. All patients were seen by a gynecologist who elicited relevant gynecological and medical history and assessed symptoms according to the uterine fibroid symptom and QOL questionnaire (UFS-QOL).[23]
UFS-QOL is a validated questionnaire-based tool for the assessment of symptom severity and health-related QOL for women with fibroids. The UFS-QOL, (Appendix A), was designed as two scales: A symptom severity scale and a health-related QOL scale. The scales are scored separately (Appendix B) and may be used either separately or together.
The UFS-QOL consists of 37 questions, of which the initial 8 related to menstrual flow and pressure symptoms were used to calculate the (SSS).
The inclusion criteria were as follows: (i) women in good general health, older than 21 years old, and able to give independent consent for the procedure, (ii) uterine fibroids or adenomyosis assessed by ultrasound or magnetic resonance imaging (MRI) to be accessible to HIFU, (iii) ability to communicate with nurse or physician during the procedure, and (iv) agreeable for follow-up.
In general, patients were excluded if they had foreign objects or extensive abdominal scars that lie within the proposed pathway of the ultrasound beam. Women with significant comorbidities (cardiac, renal, or liver disease and history of stroke), history of lower abdominal radiotherapy, acute pelvic inflammatory disease, or suspected gynecological malignancy were also excluded.
Pre-HIFU simulation
All eligible patients underwent a pretreatment simulation on the HIFU machine, where ultrasonography was performed without ablation. During the simulation, the patient was made to lie prone while ultrasonography assesses the position of the uterus in relation to its surrounding pelvic organs. The number, location, type (intramural, submucosal, subserosal, and pedunculated), size, and volume of uterine fibroids and/or adenomyosis were also determined. The images were analyzed alongside MRI images to determine the patient's suitability for HIFU.
PRE-HIFU preparation
All patients were required to have bowel preparation. They were advised to have a semi-liquid diet 2 days before and a liquid diet 1 day before the procedure. They were required to be kept fasted 12 h before. In addition, an enema was given on the day of the procedure to ensure the optimum bowel preparation.
On the treatment day, the skin was prepared by careful shaving from the level of the umbilicus to the upper margin of the symphysis pubis, degreased and degassed. This is to optimize ultrasound imaging. An indwelling urinary catheter was also inserted to control the bladder volume through injection of normal saline.
Ultrasound-guided HIFU treatment
USgHIFU treatment was performed under intravenous conscious sedation and analgesia. During the procedure, an anesthesiologist was present and monitored the patient's vital signs continuously. The patient was also in direct visual and voice contact with the attending gynecologist. A nurse was also assigned to accompany the patient by the HIFU machine at all times to monitor the patient's symptoms.
The JC model of focused ultrasound tumor therapeutic system (Chongqing Haifu Medical Technology, Co., Ltd., Chongqing, China) was used in this study [Figure 1]. This system has a transducer diameter of 20 cm, the focal length of 17 cm, and a frequency of 1 MHz [Figure 2]. Real-time monitoring of the patient was performed using HIFU-GOLD79 type B ultrasonic equipment (product of the Esaote Group, Italy).
Figure 2: Real-time diagnostic ultrasound integrated with the therapeutic transducerPatients were positioned prone on the HIFU table, with their anterior abdominal wall in contact with a degassed water balloon placed over the ultrasound transducer used in the ablation. This water balloon also aids to push the bowel away from the treatment pathway. The sagittal view mode of the ultrasound scan was selected and lesion(s) analyzed. The target lesion(s) was divided into different slices each with a thickness of 5 mm. The treatment plan was mapped out, usually starting posteriorly to anteriorly and from caudal to cranial. A safety distance of 15 mm was maintained from the ablation focal point to the endometrium and uterine serosal surfaces. The power setting was set at 300-400 watts. An initial low energy test power was aimed within the target lesion to confirm the focal point and patient's response, before therapeutic levels of sonications were used.
During the entire course of HIFU treatment, real-time ultrasonography was used to monitor the ablation pathway to ensure a margin of safety from surrounding organs like the bladder or bowel. Ultrasonography was also used to monitor treatment response where grayscale changes suggest coagulation necrosis and successful ablation. The ablation focal point, therapeutic energy, and sonication time were adjusted based on the patient's real-time feedback.
Adverse events and the number of sonications were recorded. The patients were monitored for 24 h following USgHIFU treatment and were discharged if there were no complications.
Follow-up
After the completion of treatment, an ultrasound was performed immediately to determine the changes in the uterine fibroid. Patients were also followed up through telephone consult over the next few days, and subsequently a week later at the outpatient clinic.
Further follow-up assessments were carried out at 6 months and 12 months after HIFU, where surveillance ultrasound was performed. A change in fibroid volume was recorded. Information about the fibroid-related symptoms, symptom severity, and side effects from treatment was also recorded using the UFS-QOL questionnaire. Reduction in SSS score and improvement in QOL was used as an indication of symptom improvement.
Statistical analysis
Kolmogorov-Smirnov test and Shapiro-Wilk test were used to test for the normality of the data. For normal distribution data, the comparisons of means were assessed by paired t-test. Otherwise, the Wilcoxon signed-ranks test was used to evaluate the difference between before and after USgHIFU treatment. A two-sided P value of 0.01 was considered statistically significant. Data are reported as the median and interquartile range for skewed distribution data or mean ± standard deviation for normal distribution data.
Data analysis was performed using SPSS 20.0 (Statistical Package for the Social Sciences: SPSS Inc., Chicago, IL, USA).
*100
ResultsPatient characteristics
One hundred and sixty-seven patients with single or multiple fibroids or adenomyosis/adenomyomas were treated by USgHIFU in this retrospective study. The mean age of the patients was 41.9 years old and their median body mass index was 22. The demographic characteristics of the study cohort are summarized in [Table 1]. The most common presenting complaint was menorrhagia followed by pain, as shown in [Figure 3].
Table 1: Demographic characteristics of patients with uterine fibroids/adenomyosis treated with ultrasound-guided high-intensity focused ultrasoundClinical outcomes
Change in fibroid volume
The changes in fibroid volume before and after treatment are illustrated in [Figure 4]a and [Figure 4]b. There was a significant reduction in fibroid volume at 6 months (22 cm3 vs. 95 cm3, P < 0.001) and at 12 months postintervention (14 cm3 vs. 95 cm3, P < 0.001). The percentage reduction in fibroid volume at 6 months and 12 months was 68% and 75%, respectively.
Figure 4: (a) Comparison of fibroid volume medians before and after treatment at 6 months and 12 months. The number in the bars represents the number of patients. (b) The percentage changes in fibroid volume median after treatment at 6 and 12 months. The number in the bars represents the number of patients. Bars represent median percentage changes in fibroid volumeImprovement in symptoms and quality of life
There was a significant improvement in SSS at 6 months of follow-up (SSS 46.9 [pre] vs. 15.6 [post], P < 0.001) [Figure 5]a. This was also accompanied by significant improvements in health-related QOL scores (58 [pre] vs. 86 [post], P < 0.001) [Figure 5]b.
Figure 5: (a) Comparison of Symptoms Severity Score before and after USgHIFU treatment at 6 months. (b) Comparison of Health-Related Quality of Life Score (b) before and after USgHIFU treatment at 6 months.Adverse events
All patients were discharged home after 24 h of observation in the hospital. They were subsequently followed up with phone calls on alternate days for a week.
There was one patient who presented with left lower limb weakness and foot drop after USgHIFIU and was diagnosed with L4 nerve radiculopathy. This was conservatively managed and pregabalin was prescribed. She achieved full recovery in 3 months with no long-term sequelae.
Other than this, there were no other serious adverse events during the treatment period. There were minor complaints like mild lower abdominal pain or discomfort, which all resolved spontaneously. Except for the patient with L4 nerve radiculopathy, all the other patients returned to their normal activities within a few days after the procedure.
No skin burn event was reported, and no blood transfusion was needed in any of the HIFU cases.
Re-intervention rate
Thirteen of 167 patients (7.7%) required further intervention after USgHIFU treatment. Of the 13 patients, three patients underwent re-treatment with USgHIFU, three patients underwent a hysterectomy, one patient underwent myomectomy and three underwent hysteroscopic endometrial ablation for symptomatic relief. Of these, one of the patients who underwent re-treatment with USgHIFU was a patient who was planning to have 2 sessions of USgHIFU from the beginning. Hence, in this patient, the re-intervention interval was 3 months. For the rest of the 9 unplanned cases, the median re-intervention interval was 12 months (range 6-16 months). Three patients continued to have abnormal uterine bleeding after USgHIFU and opted for medical treatment with Mirena.
Pregnancy outcome
Six patients had successful pregnancy post-USgHIFU and all were delivered successfully by cesarean section. None of them had any uterine complications such as uterine rupture. Out of the six patients, three underwent USgHIFU for treatment of fibroids while the other three underwent USgHIFU for the treatment of adenomyosis. The median duration from USgHIFU treatment to pregnancy was 5 months (3-15 months).
DiscussionUterine fibroids are the most common benign gynecological tumors, causing symptoms in up to 50% of patients. Historically, surgical management in the form of hysterectomy is considered definitive management for large or symptomatic fibroids. In younger women and those desirous of fertility, myomectomy is usually considered the alternative option and is currently accepted as the standard of care in this population. However, there remains limited evidence for myomectomy in effectively addressing the symptoms of uterine fibroids in the long-term. It is also associated with surgical morbidity which can be as high as 10% [4] and also carries the risk of recurrence, with repeated intervention conferring even higher surgical morbidity. This has spawned an interest in various noninvasive or minimally invasive treatment options. USgHIFU is one of these options. In Singapore, it was first introduced and performed in 2018. This is the first and only study reviewing USgHIFU in our population.
In our study, there was a significant reduction in fibroid volume and an improvement in symptoms and QOL score. Most studies showed a decrease in fibroid volume ranging from 18% at 3 months to 84% at 36 months.[10],[11] These findings were similarly mirrored in our study (68% and 75% reduction in fibroid volume at 6 and 12 months respectively). It is important to emphasize that reduction in fibroid volume was accompanied by improvements in symptoms (SSS 46.9 [pre] vs. 15.6 [post], P < 0.001) and QOL scores (58 [pre] vs. 86 [post], P < 0.001). This has been consistently demonstrated in a vast majority of studies, although the extent of improvement varies.[10]
In any novel treatment modality, adverse events are always closely monitored. When HIFU was first introduced, adverse events such as skin burn, nerve injury, deep-vein thrombosis, and bowel injury were often reported. The majority of studies report the overall incidence rate of major adverse events to be around 0.3% to 0.4%.[24],[25],[26] Amongst these, the most commonly reported complication is skin burn. In the largest multicenter cohort study comprising 27,053 patients, the rate of skin burns was reported to be 0.14%.[24]
The rate of adverse events in our study (0.59%) is comparable with other larger studies. It has demonstrated low morbidity associated with HIFU. Of note, there were zero cases of skin burns reported. These findings could be explained by appropriate case selection and stringent treatment protocols. There was only one reported adverse event involving a nerve injury. In this patient, the nerve injury was due to oversedation, which allowed for better patient comfort at the expense of real-time feedback from the patient resulting in over ablation. As sedation protocols are further optimized, we expect such complications to be averted. It is encouraging to note that these results were achieved during the initial learning curve of HIFU. As the learning curve is gradually mounted and further operative experience is gained, the rate of an adverse event is likely to decline further as illustrated in a large multicenter study [Figure 6].[24] Compared to conventional treatment modalities such as surgery, HIFU was also associated with lower morbidity and shorter length of stay.[27],[28] The reintervention rate was 7.7% in our study which was also consistent with a rate of 8.1% based on a meta-analysis by Yu et al.[29]
Figure 6: A multicenter study demonstrating the annual rate of major adverse effects in patients undergoing HIFU for benign uterine disease. Liu Y et al. International Journal of Hyperthermia 2018. Rate of major adverse effectsThe reintervention rate should be compared to laparoscopic myomectomy.
One of the purported benefits of HIFU lies in its ability for fertility preservation. After myomectomy, the patients are at risk of uterine rupture, miscarriage, preterm birth, and intrauterine adhesions that can affect the chances or outcome of pregnancy.[30] Patients are also often advised to withhold conception for 6-12 months to allow myometrium healing. This interval could prove significant in the fertility desiring population, particularly those with advanced maternal age. HIFU, which has a shorter downtime thus maximizes the window for conception in this population. More importantly, the avoidance of a myometrial scar, which is inevitable in a myomectomy, obliterates the risk of a uterine rupture. This risk is estimated to be approximately 0.5%-0.75% which is associated with significant maternal-fetal morbidity and mortality.[8],[31] A retrospective study by Wu G, et al. showed similar pregnancy rates when HIFU was compared to myomectomy (68.4% for ultrasound-guided HIFU vs. 66.7% for myomectomy).[32] However, average times to pregnancy were statistically significantly higher after myomectomy (18.9 ± 7.3 months vs. 13.6 ± 9.5; P < 0.05) as compared to post-HIFU treatment. Spontaneous vaginal delivery was also more frequent after HIFU (51.1% HIFU vs. 36.4% myomectomy) and the cesarean section rate was lower (41.6% HIFU vs. 54.9% myomectomy). Pregnancies have been reported as early as 3-5 months of HIFU treatment.[33] Studies have shown uneventful vaginal deliveries after HIFU treatment with no cases of uterine rupture.[34] This illustrates the potential benefits of HIFU in fertility desiring patients.
Uterine artery embolization, is another minimally invasive modality that has been accepted as an effective alternative treatment for uterine fibroids and adenomyosis in place of surgery.[35] However, due to complications like uterine necrosis and infection leading to emergent hysterectomy, ovarian failure, amenorrhoea, and vaginal dryness related to nontarget embolization or over-embolization, this has limited application in patients desirous for future fertility.[36]
Myomectomy is the preferred surgical treatment for women who wish to conserve their uterus, but fibroid recurrence after myomectomy can be up to 12.4% at 12 months to 46.0% at 24 months.[37] Some studies show recurrence rates as high as 62% at 5-10 years post myomectomy.[38],[39],[40] After a first myomectomy, approximately 10%-25% of patients will undergo a second major surgery.[40],[41],[42],[43],[44] The recurrence rate with HIFU is approximately 15%, which is lower or at least comparable with myomectomy. HIFU can be a good option for patients with recurrent symptomatic fibroids after myomectomy, thus avoiding recurrent surgery and morbidity associated with surgery.
This is the first study on USgHIFU in our local context. Our results are consistent with many other studies and have demonstrated the safety and efficacy of HIFU in the management of uterine fibroids. There are however certain limitations to our study. In our study population, a significant proportion of patients were lost to follow-up. In mitigation, as patients who defaulted follow-up were more likely to be less symptomatic, our results may have underestimated the effects of HIFU rather than the contrary. Nonetheless, we acknowledge that further studies on HIFU would be invaluable.
In conclusion, we have demonstrated that HIFU is a safe and effective treatment modality for uterine fibroids with promising initial results. It may offer benefits to selected patient groups such as those desiring fertility. HIFU for fibroids and adenomyosis avoids postoperative complications like adhesions, severe blood loss, uterine rupture, and hysterectomy. Further studies encompassing elements of economic analysis would be invaluable to guide treatment decisions. However, considering these results from our study and various other studies, it's imperative to include HIFU in the arsenal of treatment for fibroids and adenomyosis.
Acknowledgment
The authors thank the following doctors for their contribution to the study:
Dr. Lee Keen Whye, Dr. Fong Yoke Fai, Dr. Peter Chew, Dr. Beh Suan Tiong, Dr. Hong Sze Ching, Dr. Tan Yew Ghee, Dr. Anthony Siow, Dr. Clara Ong.
Conflicts of interest
Dr. Bernard Chern, an editorial board member at Gynecology and Minimally Invasive Therapy, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
Appendix A:
Adapted from: Spies JB, Coyne K, GuaouGuaou N, Boyle D, Skyrnarz-Murphy K, Gonzalves SM. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. ObstetGynecol 2002;99:290-300
Adapted from: Spies JB, Coyne K, GuaouGuaou N, Boyle D, Skyrnarz-Murphy K, Gonzalves SM. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. ObstetGynecol 2002;99:290-300
References
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