{"paper_id":"915bb6b4-b5f8-406b-aded-8f6ede443275","body_text":"© 2016 The Korean Academy of Medical Sciences.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) \nwhich permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.\npISSN 1011-8934\neISSN 1598-6357\nEffects of High-Intensity-Focused Ultrasound Treatment on \nBenign Uterine Tumor\nIn this study, the effects of high-intensity-focused ultrasound (HIFU) treatment on benign \nuterine tumor patients were examined. A total of 333 patients diagnosed with fibroids or \nadenomyosis using diagnostic sonography, treated with HIFU between February 4, 2010 \nand December 29, 2014 at a hospital in Korea, and followed up for three or six months \nwere selected for this study. Their benign uterine tumor volume was measured, and the \neffects of HIFU treatment on the volume were analyzed according to age, disease, fertility, \nand treatment duration. The volume of benign tumors of the uterus changed by age in all \nage groups after conducting HIFU treatment for 3 and 6 months, respectively. The rate of \ndecrease in individuals’ in their twenties was the largest, at 64.9%. When the decreasing \nvolume of benign tumors of the uterus was analyzed by type of disease, the treatment \nefficacy for adenomyosis was the best, with a decrease of 164.83 cm3 after 6 months. \nMyoma had the fastest decreasing rate, at 68.5%. When evaluated on the basis of fertility, \nthe volume of benign tumors of the uterus continued to decrease until 6 months after \ncompleting all procedures. The volume has continued to decrease for 6 months after all \nprocedures. This study showed that HIFU treatments for uterine fibroid and adenomyosis is \nan effective non-invasive therapy via reducing the benign uterine tumor volume. \nTherefore, the HIFU method might replace other conventional treatment methods.\nKeywords: High-Intensity-Focused Ultrasound; Benign Uterine Tumor; Treatment Effects\nJaeyoon Park,1,4 Jae Seong Lee,2  \nJae-Hwan Cho,3 and Sungchul Kim4\n1Department of Radiology, Incheon Christian \nHospital, Incheon, Korea; 2Department of Obstetrics \nand Gynaecology, Aegis Womanmed Clinic, Seoul, \nKorea; 3Department of Radiological Technology, \nAnsan College, Ansan, Korea; 4Department of \nRadiological Science, Gachon University Medical \nCampus, Incheon, Korea\nReceived: 18 January 2016\nAccepted: 11 May 2016\nAddress for Correspondence:\nSungchul Kim, PhD\nDepartment of Radiological Science, Gachon University Medical \nCampus, 191 Hambangmoe-ro, Yeonsu-gu, Incheon 21936, \nKorea\nE-mail: ksc@gachon.ac.kr\nhttp://dx.doi.org/10.3346/jkms.2016.31.8.1279 •  J Korean Med Sci 2016; 31: 1279-1283\nINTRODUCTION\nThe uterus, which is associated with sex and childbirth, has been \nsocioculturally recognized as a symbolic organ of mature wom-\nen (1). According to the 2011 in-depth analysis of the results of \na patient survey in South Korea, 329.6 in every 100,000 women \nhad undergone hysterectomy, the highest rate among the OECD \ncountries (2). Fibroids and adenomyosis are the most common \nindications of hysterectomy, accounting for approximately 30% \nand 20% of the total, respectively (3). According to the National \nHealth Insurance Service of South Korea, 237,000 patients were \ndiagnosed with fibroids in 2009, and the number increased to \n293,000 in 2013 for a mean annual increase of 5.5%. The num-\nber increased in all age groups except the 20s or younger (4). \n The fundamental method of benign uterine tumor treatment \nis hysterectomy or myomectomy, but it requires general anes-\nthesia, hospitalization, and a long recovery period. Furthermore, \nwomen who want pregnancies or want to preserve their uterus \nrequire non-invasive treatments (5). High-intensity-focused ul-\ntrasound (HIFU) is a non-invasive and non-hazardous method \nof preserving organs. It can be used repeatedly and is not affect-\ned by the lesion size. The treatment process can be monitored \nin real time for evaluation of its performance. Physical trauma \ncan be minimal because no incision or resection of tumors is \nperformed. The normal functions of the uterus could be main-\ntained (6,7). However, few fundamental studies on HIFU treat-\nments have been conducted in South Korea. \n In this study, the effects of HIFU on fibroids and adenomyo-\nsis patients treated in a Hospital in South Korea were analyzed.\nMATERIALS AND METHODS\nStudy subjects\nOf the 1,168 patients diagnosed with fibroid or adenomyosis \n(546 fibroids patients and 622 adenomyosis patients) 333 pa-\ntients (141 fibroid patients and 192 adenomyosis patients) who \nunderwent HIFU treatment between February 4, 2010 and De-\ncember 29, 2014, and followed for three- and six-month follow-\nups were selected for this study. To enhance the accuracy of the \nvolume measurements, the subjects were followed up for up to \nsix months. \nHIFU treatments and the tumor volume measurement \nmethod\nBefore HIFU treatment, the size and location of the fibroids and \nadenomyosis were confirmed using transvaginal ultrasound, \nand the feasibility of the HIFU procedure was assessed through \nsimulation. The strength of the ultrasound was adjusted from \nORIGINAL ARTICLE\nUrology\n\n\nPark J, et al. •  Ultrasound Treatment on Benign Uterine Tumor\n1280  http://jkms.org http://dx.doi.org/10.3346/jkms.2016.31.8.1279\n300 W to 400 W considering the subject’s pain level and the trans-\nmutation level of the fibroid and adenomyosis shown in the ul-\ntrasound. The clinician determined the treatment duration. The \nmedian room time was 102 minutes, and mean time for sonica-\ntion was 20 minutes 11 seconds.\n ACCUVIX V10 (Samsung Medison, Seoul, Korea) was used \nto measure the tumor volume. A single gynecologist measured \nthe horizontal, vertical, and longitudinal lengths of the fibroids \nand adenomyosis using the transvaginal ultrasound method \nbefore the HIFU procedure was performed, and the process \nwas repeated three and six months later (Fig. 1). In patients with \ntwo or more fibroids or adenomyosis, the largest one was mea-\nsured, and their volume was calculated using the following el-\nlipsoid volume equation.\n Volume = π/6 × H × V × L -------------------------- Equation 1\n H: Horizontal Length, V: Vertical Length, L: Longitudinal Length\n SPSS ver. 18.0 was used for the statistical analyses. ANOVA \nwas used for the analyses according to the subject’s age, fertility, \nand treatment duration, and the independent t-test was used \nfor the analysis by disease. The significance test was used to ver-\nify the significance of the volume reduction and the reduction \nrate of the fibroids and adenomyosis. Statistical significance was \naccepted at P < 0.05.\nEthics statement\nThe study protocol was approved by the institutional review \nboard of Inchon Christian Hospital (2015-01), and written in-\nformed consent was provided by all subjects.\nRESULTS\nTreatment effects according to the subject’s age\nIn all age groups of the subjects who underwent the HIFU pro-\ncedure, decreases in the benign tumor volume were measured. \nThe 30s group showed the greatest reduction of 158.36 cm3, but \nthe differences among all age groups were statistically insignifi-\ncant. In terms of the reduction rate of the benign uterine tumor \nvolume, all age groups showed changes three and six months \nafter HIFU treatment. The 20s groups showed the highest re-\nduction rate of 64.9% six months later, but the difference was \nstatistically insignificant (Table 1).\nTreatment effects according to the subject’s disease\nThe adenomyosis volume decreased by 164.83 cm3 six months \nlater, which was the most statistically significant treatment ef-\nfect. The myoma showed a statistically significant 68.5% volume \nreduction rate (Table 2).\nFig. 1. Measurement of the adenomyosis by ultrasound scanning. (A) Horizontal & vertical length. (B) Longitudinal length. (C) Horizontal and vertical length. (D) Longitudinal length. \nA\nC\nB\nD\n\nPark J, et al. •  Ultrasound Treatment on Benign Uterine Tumor\nhttp://jkms.org  1281http://dx.doi.org/10.3346/jkms.2016.31.8.1279\nTreatment effects according to the subject’s fertility\nThe reduction of the benign uterine tumor volume was statisti-\ncally significant up to six months after treatment in all fertilities. \nThe volume reduction rates were sustained for up to six months \nafter treatment, but the difference was statistically insignificant \n(Table 3).\nBenign uterine tumor change according to the treatment \nduration \nIn all treatment durations, the benign uterine tumor volume \ndecreased with statistical significance up to six months post-\noperatively. The volume reduction rate were unchanged up to \nsix months after treatment, so the difference was statistically in-\nsignificant (Table 4).\nDISCUSSION\nMost recently, HIFU has been widely applied in clinical cases, \nand an increasing number of hospitals are using HIFU equip-\nment. HIFU is recognized as a more conservative and safe meth-\nod with a faster recovery time than surgical methods, thereby \ndrawing the attention of patients with benign uterine disease. \nHowever, its treatment effects and safety have not yet been ade-\nquately studied.\n In previous studies, only the reduction rates of fibroids and \nadenomyosis--no other factor of the benign uterine tumor size-\nTable 1. Changes in the benign uterine tumor volume according to the subject’s age\nPeriod Age group, yr No. Volume (cm3)\nMean ± SD P value Reduction rate (%)\nMean ± SD P value\nBefore treatment 20-29\n30-39\n40-49\n50-59\n  22\n134\n154\n  23\n249.35 ± 211.45\n277.91 ± 188.05\n256.59 ± 159.93\n260.54 ± 144.57\n0.733\n3 months after 20-29\n30-39\n40-49\n50-59\n  22\n134\n154\n  23\n114.95 ± 107.57\n136.16 ± 94.28\n124.81 ± 83.44\n123.13 ± 74.60\n0.606 57.02 ± 10.73\n50.40 ± 14.83\n51.67 ± 13.68\n53.90 ± 16.72\n0.194\n6 months after 20-29\n30-39\n40-49\n50-59\n  22\n134\n154\n  23\n103.25 ± 113.32\n119.55 ± 86.36\n104.44 ± 78.05\n104.33 ± 63.00\n0.443 64.86 ± 14.47\n57.98 ± 15.73\n60.52 ± 15.19\n61.39 ± 15.85\n0.188\nSD, standard deviation.\nTable 2. Changes in the reduction rate of the benign uterine tumor volume according to the subject’s disease\nPeriod Disease No. Volume (cm3)\nMean ± SD P value Reduction rate (%)\nMean ± SD P value\nBefore treatment Myoma\nAdenomyosis\n141\n192\n218.23 ± 175.50\n299.28 ± 165.12\n< 0.001\n3 months after Myoma\nAdenomyosis\n141\n192\n97.77 ± 91.85\n151.25 ± 79.73\n< 0.001 57.35 ± 13.39  \n47.50 ± 13.43  \n< 0.001\n6 months after Myoma\nAdenomyosis\n141\n192\n77.74 ± 81.90\n134.45 ± 75.86\n< 0.001 68.54 ± 13.50 \n53.45 ± 13.58\n< 0.001\nSD, standard deviation.\nTable 3. Changes in the reduction rate of the benign uterine tumor volume according to the subject’s fertility\nPeriod Fertility No. Volume (cm3)\nMean ± SD P value Reduction rate (%)\nMean ± SD P value\nBefore treatment 0\n1\n2\n3\n147\n  49\n124\n  13\n295.85 ± 201.77\n253.21 ± 141.72\n222.60 ± 130.49\n364.15 ± 216.05\n0.001\n3 months after 0\n1\n2\n3\n147\n  49\n124\n  13\n140.33 ± 98.89\n128.29 ± 82.31\n110.89 ± 70.19\n166.24 ± 130.66\n0.036 53.08 ± 12.42\n49.14 ± 12.82\n50.65 ± 16.67\n55.02 ± 11.89\n0.176\n6 months after 0\n1\n2\n3\n147\n  49\n124\n  12\n126.36 ± 97.61\n105.30 ± 65.88\n90.47 ± 60.83\n140.14 ± 114.03\n0.005 59.56 ± 16.45\n58.69 ± 14.39\n60.55 ± 14.81\n60.63 ± 14.96\n0.811\nSD, standard deviation.\n\nPark J, et al. •  Ultrasound Treatment on Benign Uterine Tumor\n1282  http://jkms.org http://dx.doi.org/10.3346/jkms.2016.31.8.1279\n-were investigated (8,9). In addition, the factors of the treatment \neffects according to the patient’s age, disease, fertility, and HIFU \ntreatment duration were not investigated. In this study, the ef-\nfects of HIFU treatments according to the patient’s age, disease, \nfertility, and treatment duration were examined. \n During HIFU treatment, the necrotized benign tumor is ab-\nsorbed via the nearby micro-blood flow. Thus, this study was \nconducted to prove the hypothesis that younger patients with \nan active blood flow experience better treatment effects. In our \nresults, the treatment effects in the 20s age group were the great-\nest, and those in the 30s age group were the lowest, but the be-\nnign uterine tumor volume reduction and its reduction rates \ndid not show a statistically significant difference among the age \ngroups.\n In this study, the volume reduction and the volume reduc-\ntion rate of fibroids and adenomyosis were statistically signifi-\ncant. In a previous study on the changes in fibroids and three, \nsix, and 12 months after completion of HIFU treatment, the \nvolume was reduced by 58.1%, 66.2%, and 77.6%, respectively. \nRegarding adenomyosis, reduction rates of 44.0%, 47.0%, and \n54.0% were observed, respectively (10). Ren et al. (11) reported \nthe reduction rates of 27.2%, 47.9%, and 50.3% at 3, 6, and 12 \nmonths, respectively (11), and Wang et al. (8) showed 46.7%, \n68.2%, 78.9%, and 90.1% at 3, 6, 12, and 24 months, respectively.\n Since pregnancy and childbirth cause hormonal changes, \nfertility was thought to have affected the changes in the fibroid \nand adenomyosis. In this study, the subjects who had given birth \nthree times experienced the greatest treatment effects, and those \nwho had given birth only once experienced the least treatment \neffects. The volume reductions according to fertility were statis-\ntically significant, but no statistically significant reduction rate \nresult was obtained. The volume reductions according to the \nTable 4. Changes in the reduction rate of the benign uterine tumor volume according to the subject’s treatment duration\nPeriod Minute No. Volume (cm3)\nMean ± SD P value Reduction rate (%)\nMean ± SD P value\nBefore treatment 0-30\n31-60\n61-90\n91-120\n121-150\n151-\n    7\n  71\n127\n  79\n  37\n  12\n78.55 ± 40.10\n150.55 ± 87.66\n229.37 ± 121.51\n330.24 ± 165.33\n382.91 ± 178.35\n633.99 ± 223.60\n< 0.001\n3 months after 0-30\n31-60\n61-90\n91-120\n121-150\n151-\n    7\n  71\n127\n  79\n  37\n  12\n37.96 ± 26.40\n81.10 ± 55.45\n108.19 ± 65.13\n156.44 ± 83.36\n190.46 ± 96.32\n304.67 ± 117.69\n< 0.001 59.27 ± 19.64\n48.47 ± 18.33\n53.10 ± 13.44\n52.46 ± 11.44\n49.99 ± 12.61\n51.06 ± 11.07\n0.178\n6 months after 0-30\n31-60\n61-90\n91-120\n121-150\n151-\n    7\n  71\n127\n  79\n  37\n  12\n34.90 ± 24.94\n69.39 ± 56.85\n94.19 ± 60.79\n136.63 ± 84.13\n148.79 ± 89.76\n278.67 ± 104.65\n< 0.001 62.96 ± 20.86\n59.23 ± 20.23\n59.85 ± 15.01\n59.53 ± 11.81\n62.50 ± 14.44\n55.41 ± 7.42\n0.778\nSD, standard deviation.\ntreatment duration were statistically insignificant; but as a re-\nsult of ANOVA on the volume reduction rate, statistically signifi-\ncant results were obtained. What was unique about the treatment \nduration was that the subjects with 31-60 minutes and 121-150 \nminutes experienced lesser treatment effects three months lat-\ner, but at six months post-operatively, they showed a greater re-\nduction than the subjects with any other treatment duration. \nThis study had the following limitations. Although some pa-\ntients were followed up to 12 months after HIFU treatment, this \nstudy contains only short-term treatment (6 months) effect. The \ndiscrimination based on the contrast-enhancement ultrasound \nusing microbubbles might be more meaningful than the meth-\nod used in this study. In the case of two or more fibroid or ade-\nnomyosis, only the largest one was used for the analysis of treat-\nment effect. In addition, patients who underwent HIFU treat-\nment only at a Hospital were targeted. In future studies, patients \nfrom various hospitals may be targeted. Considering the size of \nthe benign uterine tumor, would be decreased up to 24 months \nafter completion of HIFU treatment, a longer follow-up period \nmight be needed. Next, HIFU can also cause complications but \ndata related to HIFU complications were not collected in this \nstudy. For HIFU treatment, however, it is known that the gener-\nal complications are as follows: subcutaneous edema can occur \non the patient’s skin. In addition, pain similar to that experienced \ndue to a slight burn can occur. Although HIFU treatment does \nnot cause bleeding because it is an extracorporeal treatment, it \ncan cause damage to the surrounding organs (i.e., heart, stom-\nach, and intestine). In cases of liver cancer, there is a low possi-\nbility of nerve damage. However, if nerves exist in adjacent re-\ngions like uterine myoma, some transitional disabilities have \nbeen reported. There is also the possibility of infection in the \ntissues with coagulation necrosis (12). In cases of uterine myo-\n\nPark J, et al. •  Ultrasound Treatment on Benign Uterine Tumor\nhttp://jkms.org  1283http://dx.doi.org/10.3346/jkms.2016.31.8.1279\nma, the follow-up observation of 7 pregnant women who expe-\nrienced unplanned pregnancies showed that all women had a \nfull term delivery and did not have any specific complications \nrelated to the pregnancy within 1 year (range: 5-32 weeks, aver-\nage: 20 ± 8.85 weeks) after receiving HIFU treatment. Although \nit is considered safe for women to get pregnant 1 year after HIFU \ntreatment, the need for a large-scale study on the topic has been \nmentioned (13). However, Bohlmann et al. (14) mentioned that \nthere has yet to be any prospective research on the effects of \nHIFU treatment on pregnancy; therefore, they recommend that \nHIFU treatment be conducted selectively only for the following \ntypes of patients: patients at high risk of undergoing surgery, \npatients who refuse surgery, or infertile patients. Complications \nobserved have been predominantly of Society of Interventional \nRadiology class A (no medical intervention required), with a \nsmall number of Society of Interventional Radiology class B \n(nominal therapy, no consequence). Class A adverse effects \nhave included abdominal pain, mild sciatic/buttock pain, geni-\ntal bleeding/increased discharge, and a prolonged next period \n(15). Zhang et al. (9) reported a slightly increased frequency of \nabdominal pain (64% vs. 71%) and skin reaction (0.8/2.4%) in \npatients with diffuse adenomyosis compared with those with \nfocal disease. In their recent large analysis of 346 cases, Lee et \nal. (10) reported a range of more unusual complications, includ-\ning foot drop (one case), transient unilateral leg weakness (one \ncase), tumor lysis syndrome with transient acute prerenal fail-\nure (one case), sleep apnea due to a sedative agent (one case), \nfirst degree skin burn (five cases), second degree skin burn (three \ncases), and transient hematuria (ten cases) (10). Research on \nHIFU complications is planned in the future.\n HIFU is a relatively effective method of treating benign uter-\nine tumors. It can be used for patients who cannot undergo the \nconventional surgical methods due to their poor medical con-\ndition. In conclusion, HIFU might replace existing methods of \ntreating benign uterine tumors.\nDISCLOSURE\nThe authors have no potential conflicts of interest to disclose.\nAUTHOR CONTRIBUTION\nConcept and design: Park J, Lee JS, Cho JH, Kim S. Data collec-\ntion and analysis: Park J, Lee JS, Cho JH. Interpretation of the \ndata and critical review: Park J, Lee JS, Cho JH, Kim S. Revision: \nPark J, Lee JS, Cho JH, Kim S. Approval of final manuscript and \nagreement of submission: all authors.\nORCID\nJaeyoon Park http://orcid.org/0000-0001-7212-7391 \nJae Seong Lee http://orcid.org/0000-0002-3988-1496 \nJae-Hwan Cho http://orcid.org/0000-0001-7112-3866\nSungchul Kim http://orcid.org/0000-0002-4195-1297\nREFERENCES\n1. Kim YL. The quality of life in hysterectomy women and social support. \nKorean J Fam Welf 2010; 15: 49-71.\n2. Ministry of Health and Welfare (KR); Korea Institute for Health and Social \nAffairs. For 2011, Patient Survey In-Depth Analysis: Policy Rreport 2013-\n11. Seoul: Korea Institute for Health and Social Affairs, 2013.\n3. Raedah A, Togas T. Treatment options for uterine myoma. Int Congr Ser \n2004; 1266: 197-201.\n4. National Health Insurance Service (KR). Uterus for more than 50 female \npatients the latest four years increased emphasis [Internet]. 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Outcome of unintend-\ned pregnancy after ultrasound-guided high-intensity focused ultrasound \nablation of uterine fibroids. Int J Gynaecol Obstet 2012; 117: 273-7.\n14. Bohlmann MK, Hoellen F , Hunold P , David M. High-intensity focused ul-\ntrasound ablation of uterine fibroids - potential impact on fertility and \npregnancy outcome. Geburtshilfe Frauenheilkd 2014; 74: 139-45.\n15. Fukunishi H, Funaki K, Sawada K, Yamaguchi K, Maeda T, Kaji Y. Early \nresults of magnetic resonance-guided focused ultrasound surgery of ad-\nenomyosis: analysis of 20 cases. J Minim Invasive Gynecol 2008; 15: 571-9.","source_license":"CC0","license_restricted":false}