Study On Itching Symptoms Relieving Of Non-neoplastic Epithelial Disorders Of Vulva By Focused Ultrasound

BackgroundNon-neoplastic epithelial disorders of vulva(NNEDV)is a group of common gynecological diseases,including chronic vulvar lichen simplex(LSC),lichen sclerosus(LS),lichen planus(LP)and so on.The pathogenesis of this group of diseases is slightly different,and the exact etiology is unknown,but the symptoms and treatments are almost similar.The group of diseases are characterized by intense vulvar itching,seriously affecting the patient's physical and mental health.The disease is difficult to cure and the main purpose of the treatment is to control the symptoms of the disease.The current treatment commonly used in clinic include of general treatment,drug therapy,physical therapy and surgical treatment.Each treatment has its advantages and disadvantages and there is no uniform standard at present.No matter what kind of treatment,there is the risk of recurrence.A large number of studies have confirmed that focused ultrasound is a safe and effective therapy for NNEDV,and can significantly reduce the patient's genital itching.But it is few reported how to alleviatethe itching symptoms and the influential factors of clinical efficacy of focused ultrasound.In this study,animal models of LSC were established with reference to oral leukoplakia animal model.The mechanism of focused ultrasound in the treatment of NNEDV was studied.The clinical data of patients with NNEDV were analyzed to find out the factors influencing the curative effect.Objective1.To establish a SD rat model of vulvar lichen simplex chronicus and investigate the effects of focused ultrasound on the expression of protease activated receptor 2(PAR2),substance P(SP)and neurokinin-1 receptor(NK1-R)in the genital skin of SD rats with vulvar LSC.To expore the mechanism of focused ultrasound in relieved itching symptom of LSC.2.To investigate the efficacy,safety and influential factors of focused ultrasound therapy for NNEDV.MethodsThe research is divided into three parts:1.Seventy female SD rats were randomly divided into A group(control group,n=10),B group(acetone solution group,n=10),C group(chronic mechanical irritation group,n=10),D group(experimental group,n=40).Group A serving as the negative control.Group B was painted with acetone solution only 3 times per week for 10 weeks.Group C was treated with chronic mechanical irritation 3 times per week for 10 weeks.Group Dwas topically treated with 0.5% 7,12-Dimethylbenzanthracene(DMBA)in acetone solution and chronic mechanical irritation 3 times per week for 10 weeks.The rat genital skin change was performed at 6,8,10,12 and 14 week in naked eye and microscopic.2.Forty female rat models of LSC were randomly divided into treatment group(n=20)and control group(n=20).The rats in the treatment group were treated by focused ultrasound,and those in the control group received sham treatment.After focused ultrasound intervention,the histological changes of vulva were observed by HE staining.The total number and the degranulated number of mast cells were identified by staining slides with toluidine blue.Immunohistochemistry was used to test the expression of PAR2,SP and NK1-R.Differences among the groups were compared.3.136 patients with pathologically confirmed NNEDV were treated by focused ultrasound.Patients were followed up on a regular basis after treatment.The efficacy was evaluated based on degrees of vulvar itching,physical signs and changes in pathological finding in local lesion.The relation between age,course,menopause status,pathological type,symptom score and curative was analyzed.Results1.57.5%(23/40)of the rats in group D showed LSC at 8 week;95%(38/40)of the rats in group D showed LSC at 10 week;20%(8/40)of therats showed papilloma at 12 week.Acetone and chronic mechanical irritation did not result in LSC.2.After 2 weeks of focused ultrasound treatment,the rate of normal in treatment group was 75% and that in control group was 10%.There was statistically significant between two groups(P<0.05).The total number and the degranulated number of mast cells in treatment group were significantly lower than those in control group,and the expression of PAR2,SP and NK1-R in treatment group was significantly lower than that in control group(P<0.05).3.The average follow-up period was 23.8 months(range 3 months to60 months).The complete remission occurred in 68 of 136 patients.The cure rate was 50%(68/136).59 were found much more improved.The effective rate was 93.38%(127/136).9 were ineffective and the inefficiency was 6.6%(9/136).7 cases recurred and the recurrence rate was5.51%(7/127).No severe side effects were found during treatment and no complications were observed during follow-up.The age,course and menopause status were related to the efficacy(Z=-2.229,P=0.026;Z=-2.003,P=0.045;Z=-2.039,P=0.041).Pathological types and symptom score weren't related to the efficacy(Z=-0.294,P=0.769;Z=-1.678,P=0.093).Conclusions1.0.5% DMBA in acetone solution and chronic mechanical irritationreliably produced LSC in female SD rats.2.Focused ultrasound could treat LSC through inhibiting PAR2,SP and NK1-R expression,decreasing the total number and the degranulated number of mast cells,reducing the inflammatory reaction of tissues and relieving itching symptoms.3.Focused ultrasound is safe and effective for the NNEDV and the efficacy is correlated with age,menopause status and course.