Ultrasound-guided percutaneous cryoablation under local anesthesia: a promising treatment method for symptomatic adenomyosis

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Ultrasound-guided percutaneous cryoablation safely and effectively reduced dysmenorrhea and uterine volume in symptomatic adenomyosis patients, offering a promising uterine-sparing treatment.

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This retrospective study evaluated ultrasound-guided percutaneous argon-helium cryoablation under local anesthesia in 8 patients with symptomatic adenomyosis who requested conservative uterine-sparing therapy; adenomyosis was diagnosed using MRI, ultrasound, and symptoms, and treated by inserting 1–2 cryoprobes under real-time ultrasound with ice-ball targeting and CEUS to confirm immediate nonperfusion of the lesion. All procedures were completed without significant intraoperative pain or major complications, and dysmenorrhea/menorrhagia pain measured by VAS decreased progressively, with a 6-month median VAS reduction and improvements in an adapted UFS-QOL score. Ultrasound follow-up showed marked reductions in both uterine and lesion volumes by 6 months, with an emphasized short-term primary endpoint (6-month pain reduction), but the authors note the preliminary nature, small sample size, and short follow-up. This paper is centrally about endometriosis and adenomyosis — it is centrally about endometriosis-adjacent conservative cryoablation therapy for symptomatic adenomyosis, including explicit comparison context that all patients received targeted freezing for adenomyosis lesions.

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Abstract

BACKGROUND: Adenomyosis is characterized by ectopic endometrial tissue, which causes dysmenorrhea, menstruation, and infertility, significantly impairing quality of life. Current treatments-including medications, surgery, and interventional methods-all have limitations. Cryoablation, a technique that induces tissue necrosis through ultra-low temperature exposure followed by rapid thawing, has demonstrated efficacy in treating solid tumors (e.g., liver and kidney cancer). However, its application in adenomyosis remains in the exploratory phase. This study aims to evaluate the feasibility and efficacy of ultrasound (US)-guided percutaneous cryoablation for adenomyosis. METHODS: A retrospective study was conducted on symptomatic adenomyosis patients seeking uterine and fertility preservation who underwent US-guided percutaneous cryoablation at the Shengjing Hospital of China Medical University from January 2024 to September 2024. Follow-up assessments were conducted at 1, 3, and 6 months postoperatively. Dysmenorrhea severity was evaluated using the Visual Analogue Scale (VAS). The quality of life was quantified using the Uterine Fibroid Symptom and Quality of Life Questionnaire (UFS-QOL) score. Treatment efficacy was assessed based on changes in uterine volume and lesion volume measured by US. Intraoperative and postoperative complications were recorded to evaluate safety. RESULTS: A total of 8 patients with adenomyosis underwent cryoablation under local anesthesia. The median VAS score was 8.5 [interquartile range (IQR), 7.75-9] postoperatively, 5.5 (IQR, 4.75-6; P<0.05) at 1 month, 4 (IQR, 4-4; P<0.05) at 3 months, and 3 (IQR, 2.75-3.25; P<0.05) at 6 months. Six months postoperatively, the median UFS-QOL score decreased from 132 (IQR, 121.5-138) preoperatively to 93 (IQR, 87.5-98, P<0.05). US revealed a 68% uterine volume reduction from 334.89 cm3 (IQR, 259.22-410.52 cm3) to 106.49 cm3 (IQR, 72.91-185.16 cm3, P<0.05). Adenomyosis lesion volume decreased from 134.93 cm3 (IQR, 122.94-196.07 cm3) to 20.58 cm3 (IQR, 19.60-69.61 cm3, P<0.05). No intraoperative complications were reported. Within 2 hours postoperatively, 5 out of 8 patients (62.5%) reported abdominal pain, but all pain resolved on the same day. CONCLUSIONS: US-guided percutaneous cryoablation under local anesthesia is safe and effective in the short-term follow-up for treating adenomyosis, offering a promising uterine-sparing alternative for symptomatic patients.
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Intro

Adenomyosis is a common gynecologic disorder characterized by the presence of endometrial glands and stroma within the myometrium ( 1 ). Its clinical symptoms manifest as dysmenorrhea, menorrhagia, secondary anemia, infertility, and so on. Although it is a benign gynecological disease, it seriously affects patients’ physical and psychological well-being ( 2 ). The treatment of adenomyosis remains a significant challenge for clinical physicians. Current treatment options include medical therapy, surgical intervention, and interventional treatment ( 3 , 4 ). Pharmacological treatments, including gonadotropin-releasing hormone agonists, are clinically recommended for symptom improvement. However, their utility is limited due to side effects and high recurrence rates post-treatment. Hysterectomy remains the only definitive treatment, but is unsuitable for women seeking uterine preservation or fertility retention ( 4 ). Conservative surgeries such as laparoscopic partial endometrial resection and endometrial ablation are also potentially effective treatment options. Nevertheless, these procedures demonstrate variable success rates, carry risks of ectopic endometrial spread, with recurrence in approximately 50% of patients during long-term follow-up ( 5 ). In recent years, treatments such as uterine arterial embolization ( 6 ), high-intensity focused ultrasound (HIFU) ( 7 ), microwave ablation (MWA), and radiofrequency ablation (RFA) ( 8 ) have shown promise in reducing lesion volume and alleviating symptoms. However, many questions remain unanswered, necessitating more robust randomized controlled trials to confirm the efficacy and safety of the aforementioned therapies. For symptomatic adenomyosis patients prioritizing uterine conservation and fertility potential, conservative treatment is crucial, highlighting the need for further exploration of minimally invasive, repeatable, and affordable treatment options. Argon-helium cryoablation is a medical technology for minimally invasive ultra-low temperature freezing and ablation of tumors ( 9 ). Utilizing the Joule-Thomson effect, argon gas rapidly expands through the needle tip, creating a throttling effect that rapidly cools the needle tip. Within 15 seconds, target tissues can reach a freezing range of −140 to −170 ℃, leading to microvascular thrombosis and intracellular ice crystal formation, which ultimately leads to coagulative necrosis. Subsequent activation of helium gas rapidly heats the tissue to 20 and 40 ℃, inducing cellular rupture during thawing ( 10 ). Argon-helium cryoablation is suitable for treating solid tumors outside of hollow organs, particularly large-volume tumors. It is currently used for patients in the advanced stages of diseases such as lung cancer ( 11 ), liver cancer ( 12 ), and kidney cancer ( 13 ). For small renal masses, cryoablation has been recommended as a validated alternative to partial nephrectomy, with comparable efficacy and favorable safety profiles. Currently, cryoablation in the field of gynecology is limited to small-scale case reports. In a recent study ( 14 ), cryoablation treatment was performed on 52 symptomatic abdominal wall endometriosis (AWE) lesions, achieving complete symptom resolution in 80% of cases at 1-year follow-up. Research on cryoablation for adenomyosis is still in the exploratory stage. This study introduces a new approach for ultrasound (US)-guided percutaneous cryoablation therapy of adenomyosis, aiming to provide a novel conservative treatment option for symptomatic adenomyosis patients. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2159/rc ).

Methods

This study retrospectively enrolled patients diagnosed with symptomatic adenomyosis who presented to our hospital from January 2024 to September 2024. They requested conservative treatment for adenomyosis and agreed to undergo cryoablation at our center. This study was approved by the Institutional Review Board of Shengjing Hospital of China Medical University (No. 2024PS1253K). The intervention details and potential risks were explained to the patients, and written consent was obtained. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The diagnosis of adenomyosis was confirmed through a combination of magnetic resonance imaging, US, and clinical symptoms. General information, clinical symptoms, and imaging data of the patients were recorded before and after the procedure. All procedures were performed by the same interventional radiologist under real-time US guidance. The schematic diagram of the surgery is shown in Figure 1 . Before the surgery, US was used to determine the uterine location, the position and volume of the planned ablation lesions, as well as the status of surrounding blood vessels and intestines. Artificial ascites ( 15 ) may be established if necessary to protect vital organs in the abdominal cavity. Meanwhile, the arrangement of the cryoablation probes was planned according to the lesion size and shape, and its relationship to the endometrium and the plasma layer. Figure 2A,2B illustrate two approaches that can be taken with the probes. Patients were positioned in a supine position. A mixture of 10 mL of 2% lidocaine and 10 mL of 0.75% ropivacaine was diluted to 120–140 mL for local anesthesia of the pelvic plexus and subplasma of the uterus. Vital signs, including blood pressure, oxygen saturation, and respiratory rate, were continuously monitored during the procedure. Schematic diagram of the percutaneous cryoablation of adenomyosis. (A) Preprocedural ultrasound evaluation of lesion and adjacent tissue for approach planning. (B,C) Insertion of 1–2 cryoablation probes into the adenomyosis lesion based on size and morphology. (D) Activation of the argon gas freezing mode, real-time monitoring of ice ball formation, and cessation of freezing when the ice ball covers the entire lesion. Cryoablation probe configurations. (A) Two probes are arranged in a nearly parallel fashion via two subcutaneous approaches. (B) Two probes are arranged in a crossing fashion through a single subcutaneous approach. The Cryoablation System AH-22 (Beijing Sunshine Yibang Medical Technology, Ltd.) was used for the cryoablation procedure. Before the cryoablation, uterine volumes and lesion volumes should be recorded ( Figure 3A ). One or two argon-helium cryoablation probes (K-17S, diameter 1.7 mm) were percutaneously inserted into the lesion through the anterior abdominal wall ( Figure 3B ). The argon gas freezing mode was activated, forming an ice ball visible as a hypoechoic ice ball area on real-time US ( Figure 3C ). Subsequently, the helium gas rapid rewarming mode was initiated, completing one “freeze-rewarm” cycle. The duration of the cryoablation cycle was adjusted based on lesion size. Throughout the procedure, real-time US was used to ensure proper ablation by coordinating the layout of 1–2 cryoablation probes to achieve adequate coverage of the lesion with ice ball, while preventing the ice ball from reaching the uterine serosa or endometrium. Contrast-enhanced ultrasound (CEUS) was used to assess the immediate cryoablation efficacy, with success defined as no perfusion area covering the lesion. When CEUS indicated incomplete ablation, supplementary ablation should be performed. After completion of the cryoablation, patients were monitored for 2 hours to check for any complications. Patients were discharged on the same day of treatment. Patients undergo regular US examinations to monitor recovery progress ( Figure 3D ). Changes in ultrasound images before, during, and after cryoablation in a 36-year-old patient with adenomyosis. (A) Preoperative transabdominal scan reveals an enlarged uterine body measuring approximately 8.10 cm × 6.97 cm with rough and uneven echogenicity on the anterior wall (VAS score: 9). (B) After local anesthesia, insertion of two cryoablation probes (one indicated by the arrow) into the lesion. (C) During cryoablation, the ice ball appears as a hyperechoic line with posterior acoustic shadowing. (D) At 6-month follow-up, ultrasound reveals a reduction in uterine body size to approximately 5.63 cm × 5.12 cm (VAS score: 2). VAS, Visual Analogue Scale. Follow-up was performed at 1, 3, and 6 months after cryoablation. Since there is no specific questionnaire for adenomyosis, the Uterine Fibroid Symptom and Quality of Life Questionnaire (UFS-QOL) was adapted to quantify quality of life scores, which includes general information, past medical history, dysmenorrhea severity, menstrual bleeding volume, 8 symptom severity items, and 29 health-related quality of life items. The specific content of the questionnaire is presented in Supplementary file ( Appendix 1 ). Dysmenorrhea severity during menstruation was assessed using the Visual Analogue Scale (VAS) ( 16 ). Uterine volumes and lesion volumes were assessed using US. The volume was calculated using an approximate ellipsoid formula that employs the three largest diameters apparent on the US image: Due to the preliminary nature of this study, the primary endpoint focused on the short-term clinical efficacy of cryoablation, defined as the percentage reduction in pain scores at 6 months postoperatively. One secondary endpoint was to review the US data to evaluate the rate of reduction of uterine volumes and lesion volumes. Categorical variables were expressed as raw numbers, proportions, and percentages. Quantitative variables were expressed as medians, first (Q1) and third (Q3) quartiles. VAS scores, UFS-QOL scores, uterine volumes, and lesion volumes before and after cryoablation (1, 3, and 6 months) were compared using the Wilcoxon signed-rank test for repeated measurement data. A P value <0.05 was considered statistically significant. Statistical analysis was performed using GraphPad Prism (V9.0.0).

Results

From January 2024 to September 2024, a total of 8 patients with adenomyosis underwent percutaneous cryoablation at our center. All patients presented with dysmenorrhea and menorrhagia, with one patient experiencing prolonged menstruation. Table 1 provides the patients’ baseline characteristics and lesion descriptions. The median age of the patients was 39.5 years (range, 37.5–42.75 years). In 8 patients, 1 (12.5%) had concomitant ovarian endometriosis, 1 (12.5%) deep infiltrating endometriosis, and 6 (75%) isolated adenomyosis. Five patients had diffuse adenomyosis, and 3 focal adenomyosis. All patients successfully completed the cryoablation procedure without significant intraoperative pain or complications. Within 2 hours postoperatively, 5 (62.5%) patients reported abdominal pain similar to dysmenorrhea, with 3 (60%) achieving relief after the administration of scopolamine for smooth muscle spasm control. The pain resolved on the same day, and all patients were discharged within 24 hours postoperatively. The median follow-up period was 8.5 months [interquartile range (IQR), 6–10.5 months]. Quantitative variables are expressed as medians followed by first (Q1) and third (Q3) quartiles in parentheses. Qualitative variables are expressed as n (%). The median preoperative VAS score was 8.5 (IQR, 7.75–9). At 1 month follow-up, the median VAS score decreased to 5.5 (IQR, 4.75–6; P<0.05). By 3 months postoperatively, the median VAS score further declined to 4 (IQR, 4–4; P<0.05), reaching 3 (IQR, 2.75–3.25; P<0.05) at 6 months. All patients showed a reduction in VAS score postoperatively ( Figure 4A ). The UFS-QOL score decreased from a preoperative median of 132 (IQR, 123.5–138) to 93 (IQR, 87.5–98, P<0.05) at 6 months postoperatively, which means that cryoablation has a positive impact on symptoms related to adenomyosis ( Figure 4B ). Comparison of (A) VAS scores, (B) UFS-QOL score, (C) uterine volume and (D) lesion volume before and after cryoablation. *, P<0.05; **, P<0.01. UFS-QOL, Uterine Fibroid Symptom and Quality of Life Questionnaire; VAS, Visual Analogue Scale. US measurements revealed reductions in both uterine and lesion volumes across all patients during follow-up ( Figure 4C,4D ). The median preoperative uterine volume was 334.89 cm 3 (IQR, 259.22–410.52 cm 3 ), which decreased to 106.49 cm 3 (IQR, 72.91–185.16 cm 3 ) at 6 months, representing a median volume reduction of 68%. The median volume of adenomyosis lesions decreased from 134.93 cm 3 (IQR, 122.94–196.07 cm 3 ) preoperatively to 20.58 cm 3 (IQR, 19.60–69.61 cm 3 ) at 6 months. The follow-up data postoperatively are presented in Table 2 . Quantitative variables are expressed as medians followed by first (Q1) and third (Q3) quartiles in parentheses. *, pre-cryoablation vs. 1-month follow-up; # , pre-cryoablation vs. 3 months follow-up; ^, pre-cryoablation vs. 6 months follow-up. UFS-QOL, Uterine Fibroid Symptom and Quality of Life Questionnaire; VAS, Visual Analogue Scale.

Discussion

Our study presents a novel surgical approach for adenomyosis. Percutaneous cryoablation significantly reduces adenomyosis-associated pain (VAS score) and achieves marked uterine volume reduction. Cryoablation performed under US guidance allows real-time visualization of the ice ball coverage area and dynamic adjustment of probe positions based on lesion morphology. This short-term follow-up study demonstrates that percutaneous cryoablation is a safe, effective, and minimally invasive option, which can be considered as one of the conservative treatments for symptomatic adenomyosis. Hysterectomy remains the definitive treatment for adenomyosis, but for patients with fertility needs and a desire to preserve the uterus, more alternative therapies are being chosen by patients, including local resection and interventional treatments ( 17 ). Thermal ablation of adenomyosis has been performed in recent years using several modalities, including HIFU ( 18 ), MWA ( 19 , 20 ), and RFA ( 21 ). All thermal ablation techniques result in a significant relief rate of dysmenorrhea, with 84.2% for HIFU, 89.7% for MWA, and 89.2% for RFA ( 22 ). Our cohort achieved 100% dysmenorrhea relief after cryoablation, which may be related to the limited sample size. Compared to thermal ablation, cryoablation has its unique advantages. Real-time US visualizes the sharply demarcated ice-ball boundary, enabling dynamic monitoring of lesion coverage ( 23 ). Cryoablation using multiple probe combinations is more adaptable to the morphology of the lesion. Cryoablation induces cellular structural damage via intracellular and extracellular ice crystal formation, resulting in minimal injury to the surrounding tissues. In contrast, thermal conduction may lead to occult tissue damage ( 9 , 24 ). Another advantage is that cryoablation is well tolerated by patients ( 25 ). Its cryogenic effect can provide nerve blockade, relieving pain ( 26 ). All patients in this study underwent the procedure under local anesthesia with conscious sedation, with no intraoperative pain reported. In contrast, patients undergoing MWA for adenomyosis in our center often reported intolerable intraprocedural pain. It is important to note that before performing cryoablation, a careful distinction needs to be made between benign and malignant lesions (e.g., uterine sarcomas). When adenomyosis coexists with specific fibroid subtypes, overlapping imaging features increase misdiagnosis risks. Such misdiagnosis carries profound clinical consequences, necessitating preoperative multidisciplinary evaluation (e.g., enhanced imaging, tumor marker analysis, and biopsy) ( 6 , 27 ). Since its clinical application, cryoablation has been less commonly used in gynecology. Currently, several teams have utilized cryoablation to treat AWE ( 14 , 28 - 30 ), achieving safe and effective long-term pain relief. Adenomyosis and AWE are both manifestations of endometriosis in different locations ( 31 ). Cryoablation can effectively alleviate pain in both conditions. In addition to inducing necrosis in the diseased tissue and reducing local compression to alleviate pain, it is unclear whether cryoablation also reduces pain through certain molecular mechanisms, such as decreasing the release of inflammatory factors or inhibiting nerve conduction. To our knowledge, this is the first attempt to treat adenomyosis under local anesthesia with percutaneous cryoablation. A recent study described cryoablation of adenomyomas under US and laparoscopic guidance ( 32 ). Our US-guided percutaneous approach enables outpatient procedures. Patients remain conscious during the procedure and achieve rapid postoperative recovery, enabling discharge after a 2-hour observation period. Compared to laparoscopic surgery, this method demonstrates superior cost-effectiveness. There are some limitations in this study. This single-center pilot study with a small cohort preliminarily confirms cryoablation’s efficacy in alleviating adenomyosis-related dysmenorrhea and improving quality of life. However, for patients who are struggling with infertility, the recovery of the uterus after cryoablation, its impact on embryo implantation, and future obstetric outcomes still need to be verified by prospective trials. The application of cryoablation in adenomyosis is still in its preliminary stage, and due to the small sample size and lack of a control group, we cannot definitively state that cryoablation is superior to drug therapy and other minimally invasive treatments. However, this preliminary study confirms the safety and short-term efficacy of cryoablation. Future work will extend follow-up and the design of large-sample case-control studies to provide stronger evidence.

Conclusions

In conclusion, US-guided percutaneous cryoablation under local anesthesia may offer a promising alternative treatment for symptomatic adenomyosis, addressing the demand for uterine preservation. Cryoablation is well-tolerated with minimal intraprocedural pain, achieves well-defined ablation margins, and maintains a favorable safety profile. We look forward to more large-scale prospective comparative studies to further validate the benefits and limitations of cryoablation compared to other minimally invasive interventions.

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