The Clinic Study Of Focused Ultrasound Ablation For Type Ⅰ And Ⅱ Submucosal Uterine Fivroids

Uterine fibroids are the most common benign tumor,most happened in women of 30-50 years old, the incidence is about 20-50%。Most fibroids are without exact symptoms, so the exact incidence is unknown. According to location of fibroids in uterus, it can be divided into three types: submucosal, intramural and subserosal. The submucosal myoma, the incidence rate is only 5-10% of the total, it may cause some serious clinical symptoms: including excessive menstrual flow, menstrual period prolonged, menstrual cycles shortened, dysmenorrhea,etc and being secondary to anemia and infertility. In recent years, there are growing methods of conservative therapy for uterine fibroids, they have significance meanings of keeping uterus, improving the quality of life,the physical and mental health which compare with the traditional surgical methods. Hysteroscopy dominante the conservative surgical therapy of Uterine submucosal fibroids, however, the efficacy and risk highly depend on the type of the submucosal fibroids. Base on the standard of Uterine submucosal fibroids applying by ESGE(European Society for Gynaecological Endoscopy), for type 0, hysteroscopic treatment supplied a satisfied efficacy and safety. However, forⅠ,Ⅱ-type submucosal uterine fibroids (especially type II), the recurrence rates and risk are not neglectable. Focused ultrasound ablation of uterine fibroids has been applied as a conservative treatment currently which has proved its preliminary clinical efficacy, this method can be easier to control the ablation range precisely to ablate the myoma closed to mucosal which due to its features of non-invasive, conformal nature and real-time monitoring by the image, etc. This study would research the safety and efficacy of focused ultrasound ablation for typeⅠandⅡsubmucosal uterine fibroids prospectively, hoping to find another new conservative therapy for submucosal fibroids.1. Materials and Methods1.1 Patients1.1.1 Inclusion criteria:①in childbearing age with no requirement of procreation; initial diagnosis by ultrasound for non-pedunculated submucous myoma and defined the fibroids as submucous type if multiple fibroids exist;②undergoing obvious clinical symptoms associated with fibroids;③not in the menstrual period and without the IUD.1.1.2 Eliminating criteria:①cervical mucous myoma;②endometrial disease, combining with other serious or acute gynecological inflammation;③pregnant (pregnancy test is positive);③skin in the lower abdominal treatment area swell, infected or broken;⑤uterine adhesions with the surrounding tissues or organs;⑥severely abnormal liver and kidney function, blood coagulation disorder or evidence of bleeding tendencies and serious heart and brain diseases: such as sever hypertension and heart failure;⑦feeling and communication with barriers;⑧connective tissue disease or received high-dose radiotherapy in abdominal;⑨there is plain and enhanced pelvic magnetic resonance and ultrasonography contraindications (such as drug allergy);⑩the patients who can not maintain a prone position for a long time(not less than 2 hours).1.1.3 Choose patients who understand and inform consent to treat after explaining the principle, method, risk and disposal measures of focused ultrasound ablation fully to patients who meet the inclusion criteria.1.2 Instruments and reagentsFocused ultrasound ablation JC-type using focused ultrasound tumor therapy system (Chongqing Haifu [HIFU] Technology Co), the main treatment parameters: treatment of head and frequency of 0.8-0.9MHZ, focal length 150cm.MRI SIGNA EXCITE 1.5T GEMSGEMS system (GE, America).Sequence set: T1-weighted spin echo sequence (TR 420ms, TE 7.1ms, slice thickness 5.0mm, layer from 0mm); T2-weighted spin echo sequence (TR 3800ms, TE 137ms, slice thickness 5.0mm, layer from 0mm); Enhanced T1-weighted sequence (TR 4.2ms, TE 2ms, thickness 5.0mm, layer from-2.5mm), Coil: 8ch Body Array by GE. Ultrasound imaging systems Ultrasound equipment used Acuson Sequioa 512 (Siemens, USA) color Doppler, frequency 3.5-5MHz. Gray-scale ultrasound contrast imaging with low mechanical index gray-scale imaging of the contrast pulse sequence imaging (Contrast Pulse Sequencing, CPS) technology, angiography probe frequency 4MHz, Mechanical index 0.13-0.18 (MI).ReagentsMagnetic resonance imaging contrast agent Gadopentetic Acid Dimeglumine Salt Injection(Magnevist)0.5mmol/ml,20ml。Ultrasound contrast agent Sulfur hexafluoride microbubble injection: Sulphur Hexafluoride Microbubbles for Injection (SonoVue).1.3 Preparing for ablation1.3.1 Image①ultrasonography to know the perfusion of myoma;②Plain and enhanced pelvic magnetic resonance imaging(MRI) to:(1)diagnose as submucous myoma and numbers(;2)exclude the other pelvic disease;(3)know the relationship with myoma and organs closed to it;(4)measure the crossed lines of myoma;(5)classify myoma according to its features in MRI image。1.3.2 Other Check the ECG,test the blood,urine and the function of liver,kidney, take the low-residue,less flatulence food three days before ablation, fast and take laxatives 12 hours before ablation, enema with warm water 1 hour before ablation, shave the hairs, degreased and degassed on the skin in the acoustic pathway, build intravenous access, insert and place the urinary catheter。1.4 Ultrasound ablation1.4.1 Focused ultrasound ablation carries out on the basis of conscious sedation and analgesia and monitoring of basic vital signs of patients under the non-invasive ECG. Conscious-sedation is 3-4 grade by ramsy and control the pain scale less than 4 points by VIS.1.4.2 Ablation①Ablation range:treat region limited within pseudo-capsule,slice-slice distance:5mm; point-point distance:5mm;②Ablation procedure: focused Ultrasound in the form of 3-dimentional fulfilled the process of ablation. The focus is 1-1.5 cm to the edge of fibroid, the rapid increase of echo at the treatment zone demonstrate the success and finish of the area. In order to understand patients'feeling and avoid the irradiation point might cause nerve stimulation, communication with patients in the process was required, and also, the time and intensity of ultra sound could be reset to prevent burning.③Patients were supervised after treatment for 2 hours.1.5 Follow-up The follow-up was perfoemed before the treatment and at 3, 6, 12, 24 months after the treatment. Contents:①to value the improvement of clinical symptoms;②to research the change of volume of fibroids;③to access the contact of adverse events and ablation based on the data in and after the ablation.1.6 Effect valuation Ultrasound was applied to value the effect. The none-perfusion area in the arterial phase and parenchymatous phase indicates the ablation part. The volume was measured to calculate the ablation rates (ablation rates=volume of none-perfusion area/volume of fibroid before treatment*100%). The elements (types, location, intensity of MRI T2 signal, volume) were analyses to reveal the relationship between ablation rates and improvement of clinical symptoms.1.7 Safe: SIR was applied to category the adverse events. (A: no need of treatment, no Adverse consequences; B: Base treatment required, no Adverse consequences; C: limited hospilazation (<48h); D: important treatment required, care levels increase, prolonged hospitalization; E: Permanent sequelae; F: death), and SIR scores was calculated (as A=1, B=2,C=3,D=4,E=5,F=6,no AE=0) to analyse the difference of SIR scores between types, location, intensity of MRI T2 signal and volume, then access the contact between ablation rates and adverse events.1.8 Statistical analysis SPSS 13.0 was applied for statistical analysis.2. Results2.1 Clinical data 74 patients with 76 submucosal fibroids accepted treatment from October 2006 to august 2009. The mean age of them is(39.19±6.38), which range from 24 to 50. these cases consist 72 Mono-fibroids, 2 multi-fibroids; 8 type-Ⅰand 68 typeⅡ; the mean diameter is (6.02±1.98)cm, the mean treatment time is (90.58±30.89)min, range from 23 to 196 min. Ablation rates of volume of myoma is (76.59±16.69)%.2.2 Follow–up: the mean follow-up time is 22.5 months, (22.84±9.44)month, range from 6 to 44 months. 2 were lost at 6 and 12 months respectively. no skin burns, blisters, acute abdomen symptoms, acute pelvic infections, intestinal perforation, sacral plexus and sciatic nerve injury was observed. varying degrees of vaginal discharge occurred in 36 cases (48.65%), which relieved after 3 to 4 menstrual cycles.2.3 SIR analyze: the adverse events obsreved after ablation are all SIR A. no SIR B to F exist. According the feature images on the MRI, the comparison found that different myoma location,MRI T2WI signal intensity and sizes of SIR scores showed no significant difference (P>0.05). the levels of ablation rates have no linear relation with the SIR scores of adverse events.2.4 Ablation rates of different types of submucous myoma: the comparison found that different locations and singal intensity in MRI T2WI of ablation rate show no significant difference(P>0.05); the comparison found that different sizes of ablation rate showed significant difference(P<0.05), the bigger of fibroids, the lower of ablation rate.2.5 Change of clinical symptoms: there is significant difference at SSS and menstrual cycle scores between before and 3, 6, 12, 24 months after the ablation(P<0.05). the most obvious symptoms improvement was observed at 3-6 moths after the ablation(P<0.05), the improvement was stable at the 6-24 months period. A proportional relation was obtained between the ablation rates and the changes of clinical symptoms(0