Basic Investigation
Focused Ultrasound Therapy for Vulvar Intraepithelial Neoplasia in a Mice Model

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Abstract

Background

The purpose of this study was to determine the effectiveness and safety of focused ultrasound (FU) for the treatment of vulvar intraepithelial neoplasia (VIN) in a mice model.

Methods

Estradiol benzoate was subcutaneously injected into the abdomens of eighty 129/J mice. VIN was successfully induced in 56 mice and was divided into the FU group and the control group. Pathologic features and changes in vascular endothelial growth factor expression in the lesions were analyzed before and after treatment.

Results

Two months after treatment, lesions in 25 of the 56 mice showed restoration of normal skin. Nineteen of the 21 VINI and VINII lesions returned to normal and the other 2 VINII lesions were down graded to VINI, yielding a curative rate of 90.1%. In the control group, all 21 mice had persistent VIN (P < 0.0001). In the 14 mice with VINIII lesions, 6 returned to normal skin histology representing a curative rate of 42.9%, 5 were reclassified as VINI and 3 were reclassified as VINII. Thus, the total effectiveness rate was 100%.

Conclusions

The present study suggests that FU therapy is effective, noninvasive and safe in treating VIN in a mice model.

Section snippets

Experimental Animals

A total of eighty 6-week-old 129/J female mice, weighing 18–20 g, were used in this study. Mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd (Beijing, China) and maintained in specific pathogen-free environments.

Reagents and Equipments

Injectable estradiol benzoate was purchased from Shanghai General Pharmaceutical Co., Ltd. (Shanghai, China). CZF focused ultrasound therapy equipment was manufactured by Chongqing Haifu (HIFU) Technology Co., Ltd. (Chongqing, China). TES-1310

Gross Observation

In the 4 weeks after FU treatment, congestion and edema were observed on the skin surface of the vulva and bloody secretion was also present. After 6 weeks, some mice showed obvious tumor growth with ulceration and bleeding (Figure 1). During the period of induction of VIN, 5 mice died, all of which developed gross tumors on the vulva. The lesions were harvested in a timely manner and prepared as paraffin sections for HE staining and microscopic evaluation.

Histologic Evaluation

After 7 weeks, all lesions were

DISCUSSION

In the present study, we have successfully established a mice model of VIN at different stages. This model allowed us to test the efficacy of FU treatment for VIN. Our results suggest that this technique is effective and safe.

Many forms of treatment have been used for VIN. In a study of 405 cases of VINII and VINIII from 1962 to 2003, Kaushik et al10 found that patients undergoing surgical excision of vulvar lesions had relatively high rates of recurrence. In some cases, the margin for surgical

CONCLUSIONS

In summary, the treatment of VINI and VINII with FU for VINI and VINII lesions in a mice model appears to be effective and safe. Although it is less effective in treating VINIII lesions, further studies with larger samples and varying treatment parameters may provide more insights. The vulva has a unique anatomical location and biological function. Nonsurgical treatment such as FU without the disruption of form and function of this unique structure is an appealing and promising technology.

ACKNOWLEDGMENTS

The authors acknowledge all authors who contributed significantly to this study. We also thank Professor Zhibiao Wang and Wenzhi Chen from the Biomedical Engineering College of Chongqing Medical University who contributed significantly to this study.

REFERENCES (16)

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Cited by (0)

We state that all authors have no relationship with Chongqing Haifu (HIFU), Technology Co., Ltd. We also did not receive any honoraria or consulting fees or funds.

The authors have no other conflicts of interest to disclose.

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