{"paper_id":"a14bd7a9-430e-422e-b7ab-8caead119e0c","body_text":" Corresponding author: Vincent YT Cheung \nDepartment of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong. \nCopyright © 2022 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. \nEfficacy and safety of ultrasound-guided high-intensity focused ultrasound for \nuterine adenomyosis: Preliminary experience from a case series  \nVincent Y.T. Cheung 1, *, Tina P.W. Lam 2 and Shuk Wan Lam 3 \n1 Department of Obstetrics and Gynecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong. \n2 Department of Diagnostic Radiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong. \n3 Department of Anesthesiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong. \nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \nPublication history: Received on 11 January 2022; revised on 12 February 2022; accepted on 14 Februar y 2022 \nArticle DOI: https://doi.org/10.30574/wjarr.2022.13.2.0158 \nAbstract \nObjective: This prospective cohort study was to evaluate the efficacy and safety of ultrasound -guided High-Intensity \nFocused Ultrasound (HIFU) in the treatment of uterine adenomyosis. \nMethods: Ten premenopausal women with symptomatic adenomyosis underwent ultrasound -guided HIFU therapy. \nTheir symptoms were compared using symptom severity scores before and at 3, 6 and 12 months after treatment. The \nsizes of their uteri and adenomyotic lesions at 6 months after treatment were compared with those of pre-treatment as \ndetermined by magnetic resonance imaging. \nResults: The menstrual pain scores were reduced by 45.5% (-83.3–100%) at 3-month, 57.3% (-83.3–100%) at 6-month \nand 27.9% (-100–100%) at 12-month after treatment. The modified Uterine Fibroid Symptom and Quality of Life scores \nwere reduced by 50.0% (9.1 –69.7%) at 3-month, 40.9% (27.3–66.7%) at 6-month and 39.5% (0 –70.0%) at 12-month \nafter treatment. The uterus and adenomyosis volumes were reduced  by 24.4% (1.2–42.0%) and 46.3% (2.1-78.4%) at \n6-month after treatment, respectively. Two patients (20%) had significant treatment -related complications and three \npatients (30%) required subsequent surgical interventions.  \nConclusions: Although ultrasound -guided HIFU appears to provide symptomatic relief to most patients with \nadenomyosis, its long-term effectiveness and safety require further evaluation in a larger cohort of patients, and may \nimprove with clinical experience.  \nKeywords: Adenomyosis; Focused ultrasound; HIFU; Ultrasound-guided \n1. Introduction\nUterine adenomyosis is a common disorder in women of childbearing age. It is commonly associated with uterine \nenlargement, due to the presence of ectopic endometrial glands and stroma within the myometrium. It can give rise to \nsignificant symptoms, most commonly menorrhagia and dysmenorrhea [1]. Hysterectomy is used to be the definitive \nand standard treatment. However, nowadays more and more women prefer uterine preservation, especially for women \nwith future fertility wish. Medical treatment mainly allows the control of symptoms, whereas uterus -sparing surgeries \nor interventions, such as electrocoagulation of the involved myometrium, excision of adenomyotic foci or uterine artery \nembolization are associated with variable degree of success and risk of recurrence [1-3]. \n\n\nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \n360 \nRecently, high-intensity focused ultrasound (HIFU) therapy has been used as a safe and effective uterine -sparing \nalternative in the treatment of uterine adenomyosis  [4-6]. HIFU can be performed u nder either magnetic resonance \n(MR) or ultrasound guidance for target localization and treatment monitoring, causing focal thermo -ablation of the \nadenomyotic lesions [6-10]. While ultrasound-guided HIFU (USg HIFU) has been increasingly popular in China for  the \ntreatment of adenomyosis [11,12], this treatment modality is not available in many other countries. At our center, with \naccumulating experience in using USg  HIFU in the treatment of uterine fibroids  [13], we have started a prospective \ncohort study on the use of this treatment for adenomyosis in a small series of women since 2016. This article reports \nthe first local experience in Hong Kong, in evaluating the efficacy and safety of USg  HIFU in treating adenomyosis.  \n2. Methods \nThe followings were the eligi bility criteria for enrolment: (1) premenopausal women, over 35 years of age, with no \nfuture childbearing plans; (2) significant symptoms related to adenomyosis, intractable to standard medical therapy;  \n(3) uterine size less than 22 weeks’ gestation; (4) localized adenomyotic lesion or adenomyoma  as judged by contrast \nMR imaging, involving only anterior or posterior uterine wall, and not both; (5) abdominal wall thickness of less than 5 \ncm from MR imaging measurement; and (6) no history suggestive of possible extensive pelvic adhesions such as history \nof major open pelvic surgery, pelvic inflammatory disease or pelvic endometriosis.  \nResearch ethics approval was obtained from the Institutional Review Board of the University of Hong Kong / Hospital \nAuthority Hong Kong West Cluster. Written informed consent was obtained before treatment from all women.  \n2.1. HIFU Treatment \nFollowing a detailed medical history and a gynecological examination, women eligible for HIFU treatment would have \na cervical smear and an endometrial sampling if needed, and a pelvic ultrasound assessment. All women had MR imaging \nto confirm the diagnosis, to establish the extent and location of adenomyosis, to assess the accessibility of the lesions to \ntreatment, and to exclude other associated uterine or ovarian pathology. \nThe JC HIFU system (Chongqing Haifu Technology, Chongqing, China; Figure 1) consisted of a 0.8 MHz therapeutic \nultrasound transducer of 15 cm in focal length and 12 cm in diameter, and a real -time 3.5 MHz diagnostic ultrasound \nscanner integrated in the centre of the therapeutic transducer (Figure 2). Both transducers were submerged in a \ndegassed water reservoir system and were controlled by a master computer unit.  \n \nFigure 1 JC high-intensity focused ultrasound system \nIn order to familiarize the patients with the treatment process, they would need to go through a pre-treatment planning. \nAlso, during the planning, the treatment target was carefully located. The depth and the proximity of the target to th e \nadjacent structures were determined. At the same time, the likelihood of the presence of a bowel loop along the path of \nsonication was evaluated. \n\n\nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \n361 \nAll patients had pre -treatment mechanical bowel preparation. The lower abdominal skin was degassed with suction, \ndegreased with alcohol and shaved . The urinary bladder was catheterized to allow adjustment of the bladder volume. \nAll patients were placed in prone position, with the lower abdominal skin put in contact with degassed water. The target \nadenomyotic lesion and the important anatomical points (bladder, uterine fundus, sacrum and sacral promontory) were \nlocated with the diagnostic ultrasound. This was to ensure that no normal structures such as bowel loops were in the \nacoustic pathway. \n \nFigure 2 Real-time diagnostic ultrasound scanner integrated in the centre of the therapeutic ultrasound transducer  \nAll treatments were performed by the principal author (VYTC). The details of the HIFU treatment have been described \nin previous articles  [6,8,9,13]. The treatment of adenomyosis is similar to that of uterine fibroid. However, due to the \nlack of a pseudocapsule in adenomyosis, the ablation energy and ablation areas for adenomyosis are generally less than \nthat of fibroid treatment in order to minimize the risk of extensive tissue damage. \nDuring treatment, all patients were put under monitored anesthetic care, which was administered by our \nanesthesiologist (SWL). The desired volume of the target adenomyotic lesion was identified and was ablated in slices of \n5 mm, from deep to shallow region under real -time ultrasound monitoring, using a therapeutic acoustic power output \nof 300–350 W. Treatment was limited to the inside of the adenomyotic lesion, with 10 to 15 mm margin at all borders. \nFrom real-time ultrasound monito ring, the adequacy of ablation was determined by the degree of grey scale changes  \n[14]. Paracetamol and diclofenac were given for post-treatment pain relief if needed. Patients were discharged the next \nmorning. \n2.2. Follow-up \nAt 3, 6 and 12 months after treatme nt, all women had assessment of their symptoms by completion of the symptom \nseverity scores. At 6 months, all women had MR imaging to evaluate the sizes of their uteri and adenomyotic lesions.  \n2.3. Effectiveness \nTreatment effectiveness was evaluated using two symptom severity scores including the menstrual pain score and the \nmodified Uterine Fibroid Symptoms Quality of Life questionnaire (UFS -QOL) [15]. The menstrual pain score assessed \nthe degree of pain during menstruation using a 10-point Likert scale from 1 (not at all) to 10 (a very great deal). The \neight-item UFS -QOL used a 5 -point Likert scale to assess both menstrual bleeding and bulk -related symptoms  [15]. \nResponses were scored from 1 (not at all) to 5 (a very great deal) with total scores ranging from 8  to 40.  \nAs secondary outcome measures, t he volumes (V) of the uteri  and the adenomyotic lesions  were measured in \nlongitudinal (D1), anteroposterior (D2), and transverse (D3) dimensions and were calculated using the following \nformula: V = 0.5233 X D1 X D2 X D3.  \n2.4. Complications \nComplications were reported according to the Society of Interventional Radi ology (SIR) Standards of Practice \nCommittee Classification of Complications by Outcome  [16]. Major complications were defined as Class C, which \nrequired minor therapy or hospitalization of less than 48 hours; Class D, which required major therapy, unplanne d \nincrease in the level of care, or prolonged hospitalization of more than 48 hours; Class E, which having permanent \nadverse sequelae; and Class F, which resulted in death [16]. \n\n\nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \n362 \n2.5. Statistical Analysis \nData were expressed as median and range or mean ± standar d deviation (SD), when appropriate. The paired Student t \ntest or the Wilcoxon rank sum test was used to compare differences between outcome measures, when appropriate. A \np value of less than 0.05 was considered statistically significant.  \n3. Results  \nTen patients underwent HIFU treatment between July 2016 and March 2020. The median age at the time of treatment \nwas 45.5 years (range 37–50 years). All patients had heavy and painful menses. The median treatment time (time from \nthe first to the last sonication) wa s 95 minutes (range 62 –178 minutes). The median sonication time (time of ablation \nwhen energy was being delivered to the target) was 1,396 seconds (range 419 –2,006 seconds). The median energy \ndelivered was 516,503 joules (range 111,897–771,356 joules). All patients completed the follow-up at 12-month. \nTable 1 Changes in Menstrual Pain Score (MPS) after HIFU treatment  \n MPS Reduction in MPS (%) p* \nPre-treatment 5.5 (3-7.5) NA NA \n3-month 2.75 (0-5.5) 45.55 (-83.3-100) 0.0065 \n6-month 2.25 (0-5.5) 57.25 (-83.3-100) 0.0076 \n12-month 4.25 (0-6) 27.95 (-100-100) 0.0222 \nData are given as median (range).    \n*Compared to pre-treatment.   \nNA: not applicable   \n \nTable 2 Changes in modified Uterine Fibroid Symptoms Quality of Life Questionnaire (UFS -QOL) after HIFU treatment \n UFS-QOL Reduction in UFS-QOL (%) p* \nPre-treatment 28 (21-33) NA NA \n3-month 14 (10-20) 50 (9.1-69.7) 0.0003 \n6-month 13.5 (10-24) 40.9 (27.3-66.7) <0.0001 \n12-month 16 (9-28) 39.5 (0-70) 0.0015 \nData are given as median (range)    \n*Compared to pre-treatment.   \nNA: not applicable   \n \nThe menstrual pain scores before and after treatment are summarized in Table 1 and Figure 3; and the modified UFS -\nQOL scores in Table 2 and Figure 4. Two patients (20.0%) had adenomyosis in the anterior  uterine wall and 8 (80.0%) \nin the posterior wall. The volumes of the uteri and the adenomyotic lesions measured from MR imaging before and 6 -\nmonth after treatment, and the corresponding percentage volume reduction are summarized in Table 3. The MR images \nof one of the patients are illustrated in Figure 5.  \nThree patients (30%) required additional intervention after HIFU treatment. Two patients had hysterectomy 36 and 15 \nmonths after HIFU due to persistent heavy menses. One of these patients had the largest uterus volume (1488.6 cm3) in \nthis series but she strongly preferred uterus preservation.  One patient had repeat HIFU 18 months after her first \ntreatment. She had improvement of her symptoms during the first 6 months of the treatment but symptoms worsened  \nafter 12 months.  \n\nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \n363 \nTable 3 Changes in uterus and adenomyosis volume after HIFU treatment  \n Pre-treatment 6-month \nUterus volume (cm3) 441.85 (240.0-1488.6) 321.7 (166.8-1170.9) \nUterus volume reduction (%) NA 24.4 (1.2-42.0) \np NA 0.0029 \nAdenomyosis volume (cm3) 144.55 (43.7-1130.3) 64.45 (17.2-249.4) \nAdenomyosis volume reduction (%) NA 46.3 (2.1-78.4) \np NA 0.0129 \nData are given as median (range).    \nNA: not applicable   \n \n \nFigure 3 Menstrual pain scores (y-axis) of each patient before and after treatment \n \n \nFigure 4 Modified Uterine Fibroid Symptoms Quality of Life Questionnaire (UFS-QOL, y-axis) of each patient before \nand after treatment \n \n\n\nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \n364 \nA.   B.  \nFigure 5 Magnetic resonance (MR) images from a 43-year-old woman with adenomyosis. (A) Pre-treatment MR \nimage shows adenomyosis at posterior wall. (B) MR image 6-month after HIFU shows a 5.5x6.2x6.9 cm ablated area \n(arrows) \n \nTwo patients had major complications. One patient had thermal bowel injury requiring small bowel resection, which \nhad been reported previously [17], and was suspected to be due to overly extensive ablation of the adenomyotic lesion \n(SIR Class D).  The other patient had prolonged nerve injury with buttock pain and bilateral lower limb weakness \nrequiring physiotherapy and w alking support, which completely recovered after 6 months (SIR Class C). None of the \npatients reported menopausal symptoms or became amenorrheic after treatment.  \n4. Discussion \nUterine adenomyosis can cause significant morbidity, and its management is still ch allenging, particularly in women \nwith fertility wishes  [1]. Although various uterine -sparing interventions have been described for the management of \nadenomyosis, including myometrial or adenomyoma reduction or excision, uterine artery embolization, or myom etrial \nelectrocoagulation, there are not enough studies in the literature to support the efficacy of one treatment modality over \nthe other  [1,2]. The findings from this study suggest that HIFU can be effective in relieving the symptoms of \nadenomyosis, including menorrhagia and dysmenorrhea.  \nAlthough it is increasingly popular to use HIFU in China for the treatment of adenomyosis  [10-12], this treatment \nmodality is still considered a novel technology in many other countries. We believe sharing our findings from this small \ncase series is important to enhance experience, and to make this treatment more generalizable and universally \nacceptable. This study is the first local experience of USg  HIFU for adenomyosis in Hong Kong, which can serve as \nbackground information for the potential expansion of this treatment in the management of adenomyosis, both locally \nand nationally. \nThe treatment outcomes from our series were similar to those reported previously [6,11,12], with over 80% of patients \nshowed improvement of symptoms. Also mentioned in our previous study on uterine fibroids  [13], due to limitation of \nMR imaging resources, the post -treatment non-perfused volume was not available as part of our outcome measures. \nHowever, we believed that the degree of symptomati c relief and the need for subsequent intervention were more \nimportant indicators of treatment success. Nevertheless, our findings suggested the potential of HIFU as an alternative \nminimally invasive treatment modality for adenomyosis. \nIn our series, the re-intervention and complication rates were 30% (3/10) and 20% (2/10) respectively, both of which \nseemed higher than our own experience in treating uterine fibroids  [13], and other image -guided HIFU studies for \nadenomyosis [6,9,11,12]. While it was apparent that the number of cases in our series was too small for us to make a \ndefinitive conclusion, we also believed that treatment success would likely improve with growing experience on the \ntechnique and utilization of this technology. \nIt is expected that HIFU will continue to grow in popularity as a uterine-sparing option in treating adenomyosis because \nof its minimally invasive nature. The main limitations of this study clearly are the small number of cases, the relatively \nshort follow-up duration and the lack of information on the post-treatment non-perfused volume. Nevertheless, despite \n\n\nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \n365 \nthese shortcomings, HIFU is a potential advancement in treatment of adenomyosis. Although USg  HIFU appears to \nprovide symptomatic relief to most of our patients, its long -term effectiveness and safety in treating adenomyosis \nrequire further evaluation in a larger cohort of patients, and may improve with clinical experience, as suggested in \nstudies from larger treatment centers [10-12]. \n5. Conclusion \nUSg HIFU appears to be an effective minimally invasive modality in treating adenomyosis. With more evidence available \non its safety and long -term outcomes, this treatment can be a potential preferred uterine -sparing option for women \nwith symptomatic adenomyosis.  \nCompliance with ethical standards \nAcknowledgments \nThe authors wish to thank Ms. W.K. Choi for her assistance in data collection.  \nDisclosure of conflict of interest \nAll authors declare no conflict of interest. \nStatement of informed consent \nInformed consent was obtained from all individual participants included in the study. \nReferences \n[1] Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clinical review of a challenging gynecologic condition. J Minim \nInvasive Gynecol. 2016; 23(2): 164–185. \n[2] Grimbizis GF, Mikos T, Tarlatzis  B. Uterus -sparing operative treatment for adenomyosis. Fertil Steril. 2014; \n101(2): 472–487. \n[3] Popovic M, Puchner S, Berzaczy D, Lammer J, Bucek RA. Uterine artery embolization for the treatment of \nadenomyosis: a review. J Vasc Interv Radiol. 2011; 22(7): 901–909. \n[4] Dong X, Yang Z. High -intensity focused ultrasound ablation of uterine localized adenomyosis. Curr Opin Obstet \nGynecol. 2010; 22(4): 326–330. \n[5] Liu L, Wang T, Lei B. Image -guided thermal ablation in the management of symptomatic adenomyosis: a \nsystematic review and meta-analysis. Int J Hyperthermia. 2021; 38(1): 948-962. \n[6] Cheung VYT. Current status of high -intensity focused ultrasound for the management of uterine adenomyosis. \nUltrasonography. 2017; 36(2): 95-102. \n[7] Al Hilli MM, Stewart EA. Magnetic resonance -guided focused ultrasound surgery. Semin in Reprod Med. 2010; \n28(3): 242–249. \n[8] Cheung VYT. Sonographically guided high -intensity focused ultrasound for the management of uterine fibroids. \nJ Ultrasound Med. 2013; 32(8): 1353–1358. \n[9] Cheung VYT. High-intensity focused ultrasound therapy. Best Pract Res Clin Obstet Gynaecol. 2018; 46: 74 –83. \n[10] Zhang L, Zhang W, Orsi F, Chen W, Wang Z. Ultrasound-guided high intensity focused ultrasound for the treatment \nof gynaecological diseases: a review of safety and efficacy. Int J Hyperthermia. 2015; 31(3): 280–284.  \n[11] Shui L, Mao S, Wu Q, Huang G, Wang J, Zhang R, et al. High-intensity focused ultrasound (HIFU) for adenomyosis: \nTwo-year follow-up results. Ultrason Sonochem. 2015; 27: 677-681. \n[12] Zhang L, Rao F, Setzen R. High intensity focused ultrasound for the treatment of adenomyosis: selection criteria, \nefficacy, safety and fertility. Acta Obstet Gynecol Scand 2017; 96(6): 707-714. \n[13] Cheung VYT, Lam TPW, Jenkins CR, Lam SW, Cheung GKI, Chan SSY, et al. Efficacy and safety of ultrasound-guided \nhigh-intensity focused ultrasound for uterine fibroids: a preliminary experience. J Obstet Gynaecol. 2019; 39 (6): \n833-839. \n\nWorld Journal of Advanced Research and Reviews, 2022, 13(02), 359–366 \n366 \n[14] Rabkin BA, Zderic V, Vaezy S. Hyperecho in ultrasound images of HIFU therapy: involv ement of cavitation. \nUltrasound Med Biol. 2005; 31(7): 947–956. \n[15] Spies JB, Coyne K, Guaou  NG, Boyle D, Skyrnarz -Murphy K, Gonzalves SM. The UFS -QOL, a new disease -specific \nsymptom and health -related quality of life questionnaire for leiomyomata. Obstet Gyne col. 2002; 99 (2): 290–\n300.  \n[16] Omary RA, Bettmann MA, Cardella JF, Bakal CW, Schwartzberg MS, Sacks D, et al. Quality improvement guidelines \nfor the reporting and archiving of interventional radiology procedures. J Vasc Interv Radiol. 2002; 13 (9): 879–\n881. \n[17] Ko KYJ, Seto TYM, Cheung VYT. Thermal bowel injury after ultrasound-guided high-intensity focused ultrasound \ntreatment of uterine adenomyosis. Ultrasound Obstet Gynecol 2018; 52(2): 282-283.","source_license":"CC0","license_restricted":false}