Transvaginal ultrasound- and laparoscopy-guided percutaneous microwave ablation for adenomyosis: preliminary results.

Abstract Purpose: Adenomyosis is a relatively common disease among women of childbearing age. A minimally invasive alternative technique with low risks, faster recovery and decreased side effects is desired. We hypothesized that percutaneous microwave ablation (PMWA) under laparoscopic guidance would substantially reduce the risk of collateral thermal damage to the intestinal tract and relieve the pelvic adhesions. This study aimed to evaluate the feasibility, safety and efficacy of transvaginal ultrasound- and laparoscopy-guided PMWA for the treatment of adenomyosis. Materials and methods: From May 2015 to October 2017, a total of 70 patients with symptomatic adenomyosis who underwent transvaginal ultrasound- and laparoscopy-guided PMWA were included in this study. The technical efficacy and complications of PMWA were assessed. Meanwhile, the uterine volume, lesion volume, symptom severity score (SSS) and visual analog scale (VAS) score before PMWA and at 1, 6 and 12 months after PMWA were recorded. Results: PMWA was successfully performed with transvaginal ultrasound guidance and laparoscope assistance in all patients. No major complication was found after PMWA in any patients. The uterine volume, lesion volume, SSS and VAS were all decreased significantly at follow-up (p < .01). Conclusion: Transvaginal ultrasound- and laparoscopy-guided PMWA, which significantly decreased the uterine volume, lesion volume, SSS and VAS score, is a feasible minimally invasive technique for the treatment of adenomyosis.


Introduction
Adenomyosis is a relatively common disease among women of childbearing age with prevalence ranging from 8% to 27% [1][2][3]. Symptomatic patients often complain of dysmenorrhea, metrorrhagia, chronic pelvic pain, dyspareunia and infertility, which seriously influence the quality of daily life. Adenomyosis is often identified by uterine enlargement, and it is frequently found in the posterior uterine wall [4].
Medical therapy may relieve symptoms of adenomyosis to a certain degree, but medical therapeutic approaches may be ineffective in the long run, and relapse of symptoms frequently occurs.
UAE is considered safe and effective, but its effects on ovary function and fertility is still under evaluation [13][14][15]. A minimally invasive alternative technique with low risks, faster recovery and decreased side effects is desired.
HIFU with ultrasound or magnetic resonance imaging (MRI) guidance is safe and effective in the treatment of adenomyosis, but the technical eligibility limits its wide range of applications [9]. RFA is also an effective minimally invasive treatment, but it has low thermal efficiency and relatively long treatment time. MWA has gained increasing attention because of its high thermal efficiency. Moreover, ultrasound-guided percutaneous microwave ablation (PMWA) for adenomyosis can relieve symptoms of adenomyosis and reduce uterine volume [12,16,17], and it does not affect ovary function [11,12,18]. However, PMWA has the potential risk of collateral thermal damage to the nearby intestinal tract, and a percutaneous approach is technically challenging because of bowel interference. PMWA performed with artificial ascites may improve access for treatment of adenomyosis [16], while it is still limited for patients with pelvic adhesions.
We hypothesized that PMWA guided with laparoscope would substantially reduce the risk of collateral thermal damage to the intestinal tract and relieve the pelvic adhesions. Thus, this study aimed to assess the feasibility, safety and efficacy of transvaginal ultrasound-and laparoscopy-guided PMWA for adenomyosis.

Patients
From May 2015 to October 2017, 70 patients with diffuse adenomyosis who underwent transvaginal ultrasound-and laparoscopy-guided PMWA at our center were included in this prospective study.
The study was conducted according to the principles of the Declaration of Helsinki and approved by the Human Ethics Review Committee of the Central Hospital of Wuhan. Written informed consent for the procedure and study was obtained from all patients.
The inclusion criteria of the study were (a) adenomyosis diagnosed by imaging (transvaginal ultrasonography or MRI) and syndrome (e.g., dysmenorrhea and/or menorrhagia); (b) patients with a strong desire to preserve the uterus and fertility and (c) patients who accepted the PMWA technique voluntarily.
The exclusion criteria were (a) coexistence of severe disease of other important organs such as the brain, heart and liver; (b) patients with menopausal status and (c) patients with a history of other interventional treatment, such as UAE and high-frequency focused ultrasonography.

PMWA procedures
To avoid inter-operator variability, PMWA and ultrasonography were performed by the same operators during the study period. PMWA was performed in an outpatient operating room. The patient was placed on the supine lithotomy position, and laparoscopy (OLYMPUS HD EndoEYE, Japan) was performed under general anesthesia. Artificial pneumoperitoneum widened the distance between the uterus and surrounding organs. The surface color and shape of the uterus could be seen clearly. Pelvic adhesions (if existed) were loosened and treated with laparoscopy first. Under real-time monitoring of laparoscopy and transvaginal ultrasound (4-9 MHz, Philips IU22, Netherlands), a 16-gauge needle (BARD, Tempe, AZ, USA) was inserted into the lesion for biopsies, avoiding important blood vessels. A cooled-shaft microwave tumor coagulator (ECO-100, Yigao Microwave System Corp., Nanjing, China) consisting of a 15-gauge needle antenna with a 1.0 cm exposed tip was used for PMWA, and it can produce 150 W of power at 2450 MHz.
According to the location and size of the lesion, MWA needle insertion was made with the 'moving shot' technique, the lesion was divided into multiple, small conceptual ablation units, and WMA was performed unit-by-unit by moving the electrode until the lesion was ablated completely. The antenna was percutaneously inserted across the abdominal wall and was placed close to the serosa of the uterus under laparoscope monitoring; then, avoiding large vessels, it was inserted into the planned site of the lesion under transvaginal ultrasound guidance (Figure 1). A power output of 60 W was used during PMWA. The lesions were ablated unit-by-unit by moving the antenna tip. The distance between two units was approximately 1.5-2.5 cm, and each unit was ablated for 2.5-3.5 min. On transvaginal ultrasonography, once the hyperechogenic signal covered the entire lesion or reached 3-5 mm near the margin of the serosa or uterine endometrium, the ablation procedure was halted and the needle was withdrawn ( Figure 2). Laparoscopy showed the color of the lesion surface changing from bright red to dark red and finally to pale, which suggested that the ablation effect was satisfactory. Contrast-enhanced ultrasonography (CEUS, SonoVue, Bracco, Italy) was immediately performed trans-abdominally to assess the effectiveness of WMA, and necrotic areas were shown as nonenhanced areas on CEUS (Figure 3).

Complications and follow-up
The complications of all patients during and after the procedure were recorded. The patients were asked to return to the hospital at 1, 6 and 12 months after the ablation procedure for follow-up. Measurements of uterine volume and lesion volume based on MRI were obtained. A symptom severity score (SSS) questionnaire and a visual analog scale (VAS) questionnaire [16] were completed before PMWA by all patients and 1, 6 and 12 months after the PMWA by patients who returned to hospital for follow-up. The SSS questionnaire included the following eight items: amount of menstrual blood loss, menstrual blood clotting, prolonged menstruation, menstrual disorders, pelvic pressure, frequency of urination at day and night and fatigue. The VAS was used to assess the extent of dysmenorrhea.

Statistical analysis
SPSS 19 (SPSS Inc., Chicago, IL, USA) software was used for statistical analysis. Normally distributed data were expressed as mean ± SD. Student's t test was used to compare data with normal distributions. The Wilcoxon signed rank test was used to compare data with skewed distributions. Fisher's exact tests were used to compare the proportions. p < .05 was considered statistically significant.

Patient information
A total of 70 patients (age range 32-49 years, 42 ± 6 years) underwent transvaginal ultrasound-and laparoscopy-guided PMWA for adenomyosis were evaluated. All women included in the study were premenopausal patients, and patients' baseline information is summarized in Table 1.

Technical feasibility
The technique of transvaginal ultrasound-and laparoscopyguided PMWA was feasible in all 70 adenomyosis patients,  with a success rate of 100%. On laparoscopy, pelvic adhesions between the uterus and surrounding organs were found in 36 patients (51%) and were detached with laparoscope for safe ablation. If the adhesions are extensive and severe, they were detached at least to the level of the cervix. The mean operation time was 29.4 ± 7.6 min.

Safety
No major complication was found during and after the procedure. Vaginal discharge was found in 11 patients (16%), which spontaneously disappeared in 2 weeks. Nine patients (13%) experienced abdominal pain, which spontaneously disappeared within 3 days.

Technical efficacy
Of the total 70 patients, 51 patients returned to the hospital for reevaluation at 1, 6 and 12 months after ablation. As shown in Table 2, the uterine volume and lesion volume measured on MR images decreased statistically from the baseline of 213.5 ± 88.6 cm 3 and 73.7 ± 35.4 cm 3 to 95.5 ± 44.6 cm 3 and 16.5 ± 8.6 cm 3 at 12 months after ablation, respectively (p < .01; Figure 4). Patient VAS scores for dysmenorrhea showed a significant reduction from the baseline of 7.1 ± 0.8 to 1.3 ± 0.4 at 12 months after the ablation procedure (p < .01). The SSS significantly decreased from 21.6 ± 6.3 to 8.6 ± 3.7 at the 12-month follow-up (p < .01).

Discussion
Adenomyosis is a common uterine pathological change. Hysterectomy is the standard treatment, but it is more invasive. In recent years, patients prefer some less invasive treatment options. As such, PMWA is a minimally invasive treatment for adenomyosis by inducing regional tissue necrosis through heat energy. However, PMWA may damage the nearby intestinal tract, and the percutaneous approach is also technically challenging because of bowel interference. Therefore, finding a feasible and safe method is necessary to avoid potential risk of PMWA. Laparoscopy could observe the surface of the uterus and movement of the bowel and could combine with PMWA to reduce potential risk.
The results of this study showed that transvaginal ultrasound-and laparoscopy-guided PMWA is a feasible technique with a 100% success rate without severe side effects, and it is also an effective technique. The uterine volume, lesion volume, SSS and VAS score of each patient all decreased significantly in the 1-year follow-up period.
In 2011, Zhang et al. reported the transabdominal ultrasound-guided PMWA technique for the treatment of adenomyosis [22]. Transabdominal ultrasound-guided PMWA can effectively relieve symptoms, and it provides high microwave thermal efficiency and short treatment time. In another study, the efficacy of treatment and effect on ovarian function have been evaluated in 142 women with adenomyosis [11]. As an advantage, this technique only needs local anesthesia and the technique is simple and easy. However, it has some drawbacks. The intestine may interfere with antenna insertion, and thermal ablation under transabdominal ultrasound guidance alone may cause severe complications such as penetration or thermal injuries of other pelvic organs and abdomen hemorrhage, especially in patients with adhesion between the uterus and surrounding organs. Several studies  have reported bowel perforation after hepatic or renal thermal ablation with image guidance alone [23][24][25]. In addition, many adenomyosis lesions are located in the posterior wall of the uterus, and the antenna has to pass through the endometrium to enter the posterior wall of the uterus, which may damage the endometrium. To achieve a clear antenna path in some cases and avoid damaging the surrounding organs during PMWA, Hai et al. [16] introduced artificial ascites during the procedure. However, artificial ascites could not separate the adhesions between the uterus and surrounding organs and could not reduce the heat conduction from the uterus to other organs through adhesions. In our procedure, we introduced laparoscopy to separate pelvic adhesions and provide a visually wide antenna path. In our study, pelvic adhesions between the uterus and surrounding organs were found in 51% of the patients (36/70), which could be detached with laparoscope at least to the level of the cervix.
Laparoscopy also has the following roles in the procedures: (1) it could remove subserosal uterine fibroids before ablation; (2) the blood vessels on the surface of the uterus could be seen during antenna insertion, which is useful to avoid bleeding; (3) laparoscopy could observe the color change of the surface of the uterus to evaluate the ablation effect; (4) the cavitas pelvis and uterine surface could be cleaned with the laparoscope, which may reduce the possibility of pelvic adhesions after the ablation and (5) the operator could find the hemorrhagic spots in the abdomen and stop bleeding with laparoscope immediately.
In this study, the antenna tip was clearly displayed on transvaginal ultrasound screen and was inserted into the optimal site in the lesion of all patients. On transvaginal ultrasonography, once the hyperechogenic signal covered the whole lesion or reached 3-5 mm near the margin of the serosa or uterine endometrium, the MWA procedure was halted. Meanwhile, the operator could observe the color change of the uterine surface on the laparoscope screen during ablation. The procedure was stopped when the color of the uterine surface changed from bright red to dark red or pale to avoid damage to the uterine serosa. No bowel Table 2. Uterine volume, lesion volume, SSS and VAS score before and after microwave ablation of group 1.  perforation or severe hematuria was found in any patients in our study. CEUS was used immediately post ablation to assess the range of ablation. If the nonenhanced areas were much smaller than the lesion evaluated with transvaginal ultrasonography or MRI before ablation, further ablation was needed. In addition, the nonenhanced areas after ablation corresponded to the hyperechogenic signal areas from transvaginal ultrasonography during ablation.
In this study, MRI was used to measure the uterine volume and lesion volume before ablation and at 1, 6 and 12 months after ablation. The volume decreases of the uterus and lesions after ablation and in follow-up were both significant. The SSS and VAS scores were also significantly reduced, indicating the effectiveness of this method.
This study has several limitations. First, this was a prospective study, not a randomized controlled study. Second, the short-term efficacy (1 year) after ablation of adenomyosis was assessed, but long-term efficacy (3 years and longer) needs further observation. Third, the border of the lesion was unclear, and subjective factors influenced the judgment of the extent of ablation.
In conclusion, transvaginal ultrasound-and laparoscopyguided PMWA is a feasible minimally invasive technique for the treatment of adenomyosis. It has some obvious advantages and no severe side effects. The uterine volume, lesion volume, SSS and VAS score decreased significantly in the follow-up period. Therefore, transvaginal ultrasound-and laparoscopy-guided PMWA is an effective technique and could be an option for the treatment of adenomyosis.