Therapeutic Efficacy Evaluation And Pathological Study On Extracorporeal Ablation Of Uterine Leiomyomas With High Intensity Focused Ultrasound

Part One Pathological study on extracorporeal ablation of uterine leiomyomas treated with high intensity focused ultrasoundObjective: To evaluate the therapeutic efficacy of uterine leiomyomas treated with high intensity focused ultrasound (HIFU) by using pathological examination and microvessel density (MVD) calculation.Methods: From May 2004 to June 2005, 119 patients with 187 uterine leiomyomas were treated with HIFU in Xijing hospital. From these patients, ultrasound guided needle puncture biopsy was performed in 64 patients one week before and after HIFU treatment to analyze HIFU therapeutic response pathologically using light microscope and transmission electron microscope. Microvessel density (MVD) of these 64 uterine leiomyomas was counted by using immunohistochemical staining of anti-CD31 antibody. The result of MVD was compared before and after HIFU treatment.Results: Microscopic examination showed homogeneous coagulative necrosis in the treated region with distorted cells, shrinkage of nuclei, cell debris and hyalinization. Also, H&E staining showed that small vascular vessels, including branches of arteries and veins, were heavily damaged. Electron microscopy showed in the specimens of treated tumor tissues, at low magnification, overall cell debris was observed. Higher magnification showed disruption of cytomembrane, pyknotic nuclei and caryorrhexis. And implosion cysts were present. MVD was 60.3±17.0 in pre-treatment uterine leiomyoma specimens while it was 12.1±16.3 in post-treatment specimens. MVD was significantly lower in post-treatment specimens than in pre-treatment specimens(P<0.001).Conclusions: HIFU can extracorporeally induce tissue necrosis and destroy tumor vessels in uterine leiomyomas. The histopathologic evidence directly validates HIFU ablation as an effective treatment of uterine leiomyomas. Part Two Value of real time contrast-enhanced ultrasonography in evaluating the therapeutic efficacy of uterine leiomyomas treated with high intensity focused ultrasoundObjective: To study the contrast-enhanced sonographic characteristics of uterine leiomyomas and to evaluate the clinical value of real time contrast enhanced ultrasonography (CEUS) in evaluating the therapeutic efficacy of uterine leiomyomas treated with high intensity focused ultrasound (HIFU).Methods: Sixty-four patients with uterine leiomyoma and 29 with endometrioma were enrolled in our study and all the patients were confirmed by ultrasound-guided needle puncture biopsy. New contrast agent SonoVue was injected intravenously as a bolus in 2.4 ml and real time contrast enhanced ultrasound was performed to observe the enhanced pattern and characteristics. From May 2004 to June 2005, 119 consecutive patients with 187 uterine leiomyomas were treated with HIFU. 2DUS, CDFI and CEUS were performed and analyzed respectively one week before and after HIFU treateatment. From these patients, 64 patients received ultrasound guided needle puncture biopsy and contrast-enhanced MRI (ceMRI) was performed one week before and after HIFU treatment respectively. CEUS results were compared with ceMRI results.Results: 1. CEUS characteristics of uterine leiomyoma and endometrioma: After the administration of SonoVue, 62 patients with uterine leiomyoma showed peripheral globular enhancement pattern and centripetal filling immediately. There was a clear border between the tumor and the adjacent uterine parenchyma in 60 patients. All the 29 patients with endometrioma showed intratumor enhancement pattern and remained isoechoic with respect to the surrounding tissue. There was no clear border between the tumor and the adjacent uterine parenchyma. There was no significance comparing the parameters of peak intensity, initiation time of enhancement, time of reaching peak intensity and enhancement duration between two groups.2. 2DUS and CDFI change of uterine leiomyoma after HIFU ablation: One hundred and seventy four leiomyomas of the 187 leiomyomas showed obvious acoustic enhancement in 2DUS after HIFU treatment. 152 leiomyomas showed the blood supply disappeared and 24 leiomyomas showed the blood supply decreased obviously after HIFU treatment. While 8 leiomyomas showed no CDFI signal change.3. CEUS result after HIFU ablation: After HIFU ablation, on the CEUS, complete tumor ablation was observed in 53 (82.8%) of the 64 uterine leiomyomas and residual unablated tumors were found in three leiomyomas (4.7%). Eight leiomyomas (12.5%) showed diffuse enhancement indicating failed treatment.4. Comparison of CEUS and ceMRI: CEUS and ceMRI got the same result. In post-HIFU ceMRI, it was common to observe the absence of contrast enhancement in the treated region and a thin peripheral rim of enhancement surrounding the coagulative necrosis. ceMRI revealed there was an absence of contrast enhancement within the treated region in 53 of 64 leiomyomas, the same as in CEUS. As to those 8 leiomyomas which showed failed treatment on CEUS, diffuse enhancement still could be found on ceMRI in 6 patients and complete tumor ablation was found in 2 patients after a second HIFU ablation. As to the 3 leiomyomas which showed residual unablated tumor portions on CEUS, the same result was found in ceMRI. Of the one ablated leiomyomas with residual tumor on the CEUS after the initial HIFU ablation, a residual vessel was found on the CEUS, while on the ceMRI, the residual vessel was not found.Conclusions: CEUS can effectively differentiate uterine leiomyoma from endometrioma and it can help to assess the therapeutic efficacy of HIFU treatment. It is also useful to identify minute foci early after HIFU ablation, thus it helps to establish proper protocol in further treatment. Part Three Clinical follow-up study on extracorporeal ablation of uterine leiomyomas treated with high intensity focused ultrasoundObjective: To evaluate the therapeutic efficacy and clinical long term results of ultrasound guided high intensity focused ultrasound (HIFU) in the treatment of uterine leiomyomas by following up the volume change and symptom relief after HIFU treatment.Methods: From May 2004 to November 2005, 145 consecutive patients (mean age, 40.0±5.4 years; age range, 26-58 years) with 220 uterine leiomyomas were treated with HIFU. The leiomyomas were 1.5-9.8 cm in mean diameter (mean, 4.3±2.0 cm). Ultrasound guided needle puncture biopsy was performed to assess the early therapeutic efficacy. Immediate therapeutic effects were assessed at follow-up with 2DUS and CDFI. All patients were followed up to observe long-term therapeutic effects and complications. Leiomyoma mean diameters, volumes and reduction rates 1, 3, 6 and 12 months after HIFU treatment were calculated and compared by using one-way ANOVA and Student-Newman-Keuls tests.Results: All patients were followed up for 12-28 months (mean, 20.7±4.4 months). No severe complication was observed after HIFU ablation. Follow-up images showed absence or reduction of blood supply in the lesions after HIFU ablation. Results showed that the volumes began to decrease one month after HIFU ablation and the decrease of leiomyomas was obvious 3 months after HIFU ablation. Median reductions in tumor size as a percentage of initial tumor volume at 1, 3, 6, and 12 months after HIFU treatment were 22.2%, 27.2%, 47.9% and 50.3% respectively. 85.5% of women in our study declared significant relief from previous symptoms 12 months after HIFU treatment and 59.3% reported completely asymptomatic after HIFU treatment.Conclusions: HIFU ablation appears to be an effective treatment of uterine leiomyomas in reducing the volume and treating the symptoms.