MR-guided Focused Ultrasound Surgery Etiology Preliminary Clinical Studies And Uterine Fibroids Treatment Of Uterine Fibroids

BackgroundUterine leiomyomas (UL), benign tumors of human uterus, are the most common disease diagnosed among reproductive women. They are clinically apparent in up to 20～35% of women and about 20～50% cause significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pressure, and, recently realized, reproductive dysfunction. The traditional treatments for leiomyomas are hysterectomy or myomectomy. Recently, people try to find non-surgical alternatives for surgeries. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive thermoablative technique. The waves pass through the anterior abdominal wall, and 65～85℃heating occurs where the waves converge at the focus. The heating causes coagulative necrosis of the neoplasm. ExAblate(?) was the first MRgFUS equipment approved by FDA for treating symptomatic uterine leiomyomas.Uterine leiomyoma is a multifactorial disease, established risk factors include age, Africal American Heritage, early age of menarche and et al. Estrogen and progesterone can promote the growth of UL, but the etiology has remained elusive. Luteinizing hormone (LH) and human chorionic gonadotropine (hCG) bind to the same receptor. Recently study discovered that LH/hCG receptor exist in non-gonadal tissues. In black women health study (BWHS), PCOS was associated with a 65% increase in the risk of uterine leiomyomas. Baird found that LH showed significantly accelerated tumor onset but little evidence of effects on tumor growth. ObjectivePart IThis study was conducted to describe early results regarding safety and efficacy of MRgFUS for the treatment of symptomatic uterine leiomyomas among a population of Chinese reproductive women.Part IITo test the LH/hCG receptor expression in leiomyomas and myometrium of patient and that in myometrium of control group by immunohistology and Western blot.MethodsPart I1. In this prospective study, premenopausal women with symptomatic leiomyomas who were willing to participate in this study were screened treatment eligibility through clinical and MRI criteria.2. Patients were treated by MRgFUS and followed up on time. Their subject feelings, objective examination and adverse events were recorded.3. Uterine Fibroid Symptoms Quality of Life (UFS-QOL) were filled in by patients each time they were followed up.Part II1. Immunohistochemical (IHC) staining was done to 6 cases for LH/hCG receptor, with 3 cases in research group and 3 cases in control group. Cytoplasm expression is regarded as positive.2. Western blot was done to all the samples, greyscales were calibrated byβ-actin and statisticly analyzed.ResultsPart I1.64 patients were willing to participate in the study, among those,60(93.75%) passing the clinical screening and 21 (35%) passing the MRI screening.2. No serious or unexpected adverse events arose during the study.7 patients with abdominal scar were treated safely. Most patient were treated with a expected non-perfused volume ratio (NPV%) except one. Average NPV%was 61.4%±24.5% (6%～93%)o3. At half-year follow up, average uterine volume reduced by 26.5%±11.4%, average uterine fibroids volume reduced by 34.9%±22.2%. Pressure symptoms were mostly relieved by one month, and bleeding symptoms were mostly relieved by three months. Scores of UFS-QOL were improved. 4. Most common adverse events were abdominal cramp, vaginal discharge and numb of legs, which could be improved just by conservative following up.Part II1. Positive staining of IHC is detected in muscularis propria and leiomyoma of secretory phase as well as spiral arteries in research group, however, large vessels shows negative. Endometrium in proliferative phase shows weakly positive both in research and control group. Muscularis propria in control group shows negative.2. Western blot shows that LH/hCG receptor expression is a little higher in the myometrium than that in UL, without statistic significant; no difference was showed among four subgroups.3. LH/hCG receptor expression is higher in myometrium of secretory phase than that of proliferative phase; during proliferative phase, the LH/hCG receptor expressed with no difference between UL and myometrium in research group, while in secretory phase, myometrium expresses more LH/hCG receptor than UL does.ConclusionsPartⅠ1.MRgFUS is a effective non-invasive treatment of symptomatic leiomyomas, patient treated by MRgFUS should be screened by clinical and MRI criteria.2. The adverse events were rare when operated strictly by the protocol.3. Short term follow up results showed that patients'symptoms relieved effectively after MRgFUS treatment, long term follow up was needed. PartⅡ1. Uterine myometrium expressing LH/hCG receptor is significantly higher in secretory phase than proliferative phase.2. LH/hCG receptor expressions in research group and control group are with no difference. LH/hCG receptor in UL was less influenced by steroid hormones.3. GnRHa can down-regulate the LH/hCG receptor express in myometrium.4. It is not yet to conclude that LH/hCG receptor is not relevant with etiology of UL...