Evaluation of ultrasonic energy for sealing 5–7 mm blood vessels in thoracoscopic surgery: a noninferiority randomized controlled trial

Introduction

Thoracoscopic surgery, including video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS), is the recommended treatment strategy for resectable thoracic malignancies (1,2). Although thoracoscopic surgery is associated with better perioperative outcomes compared with open surgery (3,4), significant complications can still occur. One of the most severe intraoperative complications is pulmonary vascular injury, which may lead to conversion to open surgery or even death (5). Traditionally, hemostasis of the blood vessels is achieved using vascular endostaplers. However, these staplers are large and bulky, making them difficult to be maneuvered in the tight spaces around the pulmonary vasculature, particularly during thoracoscopic surgery.

Energy-based coagulation and tissue fusion techniques have been effectively utilized in various minimally invasive surgeries (6). Compared to vascular endostaplers, these devices have a smaller and finer footprint which can decrease the manipulation and dissection required for sealing blood vessels. In the last decade, numerous studies have confirmed the safety and efficacy of these vessel-sealing devices in thoracoscopic surgery (7-14). A prospective clinical trial demonstrated that there was no difference in bleeding between vessels sealed with ultrasonic devices and those sealed with endostaplers (14). In this study, most surgeons reported that using ultrasonic energy devices made lung resections significantly easier. However, despite previous research, no randomized controlled trial has been conducted to directly compare the safety and efficacy of different ultrasonic energy devices in sealing 5–7 mm blood vessels.

The HARMONIC ACE +7 Shears with Advanced Hemostasis (ACE+7; Ethicon, Cincinnati, USA) is the most frequently studied ultrasonic energy devices in prospective trials and has shown good safety and efficacy in sealing pulmonary arteries (12-14). The SOUND REACH SR7 Shears (SRB; Reach Surgical, Tianjin, China) is a newly designed ultrasonic energy device in China. This is an investigator-initiated trial to directly compare the safety and efficacy of SRB versus ACE+7 in sealing 5–7 mm blood vessels in thoracoscopic surgery. We present this article in accordance with the CONSORT reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-433/rc) (15).

Methods

Trial design and participants

This single-blinded, multicenter, randomized, noninferiority trial was conducted at four hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio to the experimental group (SRB) or control group (ACE+7). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by ethics board of Ruijin Hospital on March 30, 2023 (approval No. 2022-89), the First Affiliated Hospital, Zhejiang University School of Medicine on July 20, 2023 (approval No. 2023-342), the Second Affiliated Hospital, Zhejiang University School of Medicine on May 16, 2023 (approval No. 2023-215), and Shanghai Ninth People’s Hospital on June 1, 2023 (approval No. SH9H-2023-C23-2). Written informed consent was obtained from all participants following individual counseling sessions by an independent research coordinator. The study protocol was published before (16), and was also available in Trial Protocol (doi: 10.1186/s12893-024-02497-x). A total of 17 surgeons in four hospitals took part in this study: three at Ruijin Hospital, four at Ninth People’s Hospital, seven at the First Affiliated Hospital, Zhejiang University School of Medicine, three at the Second Affiliated Hospital, Zhejiang University School of Medicine. The trial was registered at ClinicalTrials.gov (NCT06002737).

Eligible patients were aged 18 to 75 years and underwent thoracoscopic surgery with at least one blood vessel that required sealing, as determined by preoperative computed tomography (CT) images. The diameter of the blood vessels should be greater than 5 mm but less than or equal to 7 mm on CT images. Patients with a prothrombin time longer than 5 s were excluded. Patients with a body mass index (BMI) ≥ 35.0 kg/m² were excluded because it could bring additional difficulty in dissecting blood vessels caused by the adipose tissue. Patients were also excluded if the blood vessel was involved by tumor, or there were anatomic variations, malformations or calcifications of the blood vessels, which could affect the dissection or ligation of the blood vessels. Preoperative chemotherapy or radiotherapy was not allowed in enrolled patients. Other exclusion criteria were patients with a fasting plasma glucose ≥11.1 mmol/L, hypertension patients with poorly controlled blood pressures and a stable pressure of 140/90 mmHg or above after taking medications, pregnant or lactating women, or women planning to get pregnant during the clinical study. Hyperglycemia can impair tissue healing and microvascular integrity, potentially increasing bleeding risk and confounding our primary endpoint (17,18). Therefore, patients with a fasting plasma glucose ≥11.1 mmol/L were excluded. The detailed eligibility criteria are listed in the study protocol (16), which is available in Trial Protocol (doi: 10.1186/s12893-024-02497-x).

Randomization and masking

In this clinical study, a stratified block randomization method was used, with the center serving as the stratification factor. A statistician independent of the study generated the random assignment table, which was automatically created using the Statistical Analysis System software (version 9.4, SAS Institute Inc., Cary, USA). The subjects were randomized in the experimental group and the control group at a ratio of 1:1. The investigators checked the subjects against the eligibility criteria and then randomly assigned the subjects into the treatment groups with the corresponding numbers. The investigators were not allowed to modify the generated randomization numbers and the groups that the subjects were assigned to throughout the study. Because of the infeasibility of blinding to the investigators, the study was only blinded to the enrolled patients.

Interventions

All the enrolled patients received thoracoscopic pulmonary or esophageal surgery. The surgery types included lobectomy, sleeve resections, segmentectomy, and esophagectomy. The surgeries were carried out following standard procedures, with the exception of the method used for sealing the blood vessels. The two ultrasonic energy devices used in this study were shown in Figure 1. Both devices had a vibration frequency of 55 kHz. The ACE+7 (control group) was designed with 3 buttons, and the SRB (experimental group) was designed with two buttons. Both devices had one lateral button. The ACE+7 had an additional slow-coagulation button located at the front, which was absent in the SRB. However, the slow-coagulation function in the SRB could be performed using the lateral button, ensuring effective coagulation while freeing up the front button for other uses. This two-button design of the SRB provided a more ergonomic and comfortable operation experience. A detailed description of the SRB was available in the Trial Protocol (doi: 10.1186/s12893-024-02497-x). For each enrolled patient, the decision to divide an artery or vein was made intraoperatively by the operating surgeon. During the surgery, the diameter of the target blood vessel was measured using a sterile ruler. In the experimental group, SRB was used for the sealing of the target blood vessels while ACE+7 was used in the control group. The representative process of sealing blood vessels using SRB and ACE+7 is shown in Video S1 and Video S2, respectively. For the sealing of the blood vessels other than the target blood vessels, we would first ligate both ends of the severed vessel using silk threads or titanium clips and the sealed the vessels by using the ultrasonic energy device.

Figure 1 Two ultrasonic energy devices used in this study. (Top) SOUND REACH SR7 Shears. (Bottom) HARMONIC ACE +7 Shears with Advanced Hemostasis.

To ensure the consistency of the sealing techniques, all participating surgeons were instructed on the steps and technical tips for using the two devices and completed simulation training before operating on patients. During the surgery, the suitability of individual blood vessels for sealing using ultrasonic energy devices was assessed based on the surgeons’ judgement, considering factors such as anatomy, dissection, and patient-specific conditions. The reasons for not using ultrasonic energy devices were recorded. Enrolled patients received standard postoperative care.

Outcomes

Sealing was deemed successful if there was no bleeding from the target blood vessel before the chest or abdomen was closed. Minor bleeding that did not require intervention beyond compression was also considered a successful sealing. If the target blood vessel rebled and needed to be treated with other hemostatic methods such as a stapler, a vascular clamp, or suturing, the sealing was regarded as failure. The secondary outcomes included postoperative rebleeding, volume of intraoperative bleeding, drainage volume, surgical duration, operational performance, and stability of the ultrasonic energy devices. In cases where a secondary surgery was needed due to postoperative rebleeding, the correlation between the bleeding vessel and the initially operated blood vessel was examined. All patients were followed up until 30 days after surgery.

Statistical analysis

According to a previous study, the success rate of sealing pulmonary artery branches of 7 mm or less using ultrasonic energy devices was 98.7% (14). Based on literature reports and our clinical practice, we estimated a success rate of 96% for sealing target blood vessels with ultrasonic energy devices in both the experimental and control groups. A sample size of 61 patients per group was determined to achieve 80% power with a −10% noninferiority margin and a one-sided significance level of 2.5%. To account for a 15% loss to follow-up, the final sample size was increased to 72 patients per group.

An intention-to-treat analysis was performed. All statistical analyses were performed using SPSS Statistics (version 22.0, IBM, New York, USA), R software (version 4.3.2, R Foundation for Statistical Computing, Vienna, Austria), and GraphPad Prism (version 8.0.1, GraphPad Software, San Diego, USA). For categorical variables, we utilized Pearson χ² test or Fisher’s exact test to compare the two groups. As for continuous variables that followed a normal distribution, they were presented as mean ± standard deviation (SD), and the Student’s t-test was used for comparison. In cases of noncompliance with the normal distribution, continuous variables were presented as medians [interquartile range (IQR)] and compared using the Wilcoxon rank-sum test between the groups. The significance level for testing differences between the two groups was set at α=0.05 (bilateral), and differences with a P value less than 0.05 were considered statistically significant.

Results

Patients

Between August and December 2023, 156 patients were assessed for trial eligibility, and 144 patients were enrolled for randomization. A CONSORT diagram of the study is provided in Figure 2. Seventy-three patients were assigned to the SRB group while 71 patients were assigned to the ACE+7 group. Eleven patients were excluded from the full analysis set (FAS) because eight patients had an intraoperative change of surgical plan, two patients did not have suitable vessels, and the target vessel could not be isolated in one patient. Finally, there were 67 patients included in the FAS analysis in the SRB group and 66 patients included in the FAS analysis in the ACE+7 group (Figure 2).

Figure 2 CONSORT diagram. ACE+7, The HARMONIC ACE +7 Shears with Advanced Hemostasis; FAS, full analysis set; SRB, SOUND REACH SR7 Shears.

The characteristics of patients at baseline were similar in the SRB and ACE+7 group (Table 1). Patients in the SRB group had a median age of 59 (IQR, 49–69) years and included 23 males (34.3%) and 44 females (65.7%). Patients in the ACE+7 group had a median age of 57 (IQR, 52–65) years and included 28 males (42.4%) and 38 females (57.6%).

Trial outcomes

A total of 71 lobectomies, 60 anatomic segmentectomies, and two esophagectomies were conducted in this study. In the SRB group, there were 37 lobectomies and 30 anatomic segmentectomies. A total of 67 blood vessels were sealed in the SRB group: 62 arteries and five veins (Table 2). The mean and median diameters of the sealed vessels in the SRB group were 6.1 mm (SD, 0.59 mm) and 6.0 mm (range, 5.0–7.0 mm). In the ACE+7 group, there were 34 lobectomies, 30 anatomic segmentectomies, and two esophagectomies. A total of 66 blood vessels were sealed in the ACE+7 group: 61 arteries and five veins. The mean and median diameters of the sealed vessels in the ACE+7 group were 6.1 mm (SD, 0.63 mm) and 6.0 mm (range, 5.0–7.0 mm). The success rate of intraoperative sealing was 100% in both groups with an absolute difference of 0% (95% confidence interval: −5.5% to 5.4%) that did not cross the prespecified noninferiority margin of −10%. In all the included patients, both SRB and ACE+7 successfully sealed the blood vessels without bleeding before the chest or abdomen was closed.

No mechanical events related to the ultrasonic energy devices occurred during the operation in either group. There was no conversion to thoracotomy in either group. The patient postoperative outcomes are listed in Table 3. No significant difference was found in surgical duration [88 (IQR, 75–115) vs. 96 (IQR, 75–116) min, P=0.52], intraoperative bleeding [50 (IQR, 20–60) vs. 50 (IQR, 20–70) mL, P=0.37], or drainage [220 (IQR, 100–450) vs. 275 (IQR, 124–525) mL, P=0.44]. No complication was related to the use of ultrasonic energy devices in either group. All the included patients completed the follow-up until 30 days after surgery. Within 30 days after surgery, no patient required reoperation because of bleeding. There was no mortality at 30 days in either group.

Discussion

In this multicenter, noninferiority, randomized controlled trial conducted in four hospitals in China, we found that the use of SRB was not inferior to ACE+7 in sealing 5–7 mm blood vessels. To our knowledge, this is the first randomized controlled trial to compare the use of two ultrasonic energy devices in sealing blood vessels.

Thoracoscopic surgery, including VATS and RATS, is the recommended approach for resectable thoracic malignancies (1,2). However, the relatively confined operative space in thoracoscopic surgery presents challenges for the dissection and sealing of blood vessels, which was traditionally accomplished using bulky and rigid endostaplers. Ultrasonic energy devices, with a smaller and finer footprint, allow for a decreased manipulation during thoracoscopic surgery. ACE+7 is one of the representative ultrasonic energy devices that is widely used around the world. Previous studies have confirmed the safety of using ACE+7 in sealing pulmonary artery branches for vessels with a diameter ≤7 mm (11-14). However, there is still a lack of evidence from a randomized trial. SRB is a newly designed ultrasonic energy device available in Chinese market. Therefore, this study allowed us to have a deeper understanding about the safety profiles of ACE+7 and SRB in blood vessel sealing in a randomized trial setting.

In this study, we reported an excellent success rate of 100% in both groups. The high success rates suggest that both ultrasonic energy devices are safe and effective in sealing blood vessels during thoracoscopic surgery. Our results are similar to a previous phase 2 clinical trial, where three sealing failures occurred in 239 pulmonary artery branches divided with ultrasonic energy devices, with a success rate of 98.7% (236/239) (14). Also, the surgeons participating in the current clinical trial were all familiar with the operation of the two devices. As reported previously, technical details are important when manipulating these devices (13,14). In this study, we performed adequate dissection of the blood vessels, which allowed for safer positioning of the ultrasonic blade around the blood vessels. This prevented surrounding tissue from becoming interposed between the ultrasonic blade and blood vessel wall which could interfere with the quality of the sealing. This also ensured sealing without much tension. Proper positioning of the target blood vessels in the middle of the blade is important. In addition, there are other technical tips summarized in previous articles, which we considered important when using ultrasonic energy devices (13,14). For example, to ensure proper closing of the instrument on the blood vessels, the tip should be cleaned by wiping with a surgical sponge if necessary. All the complications in this study were minor and were not related to the use of ultrasonic energy devices.

The current trial is the first and largest randomized controlled trial comparing two ultrasonic energy sealing devices for sealing blood vessels during thoracoscopic surgery. However, there are some limitations. First, we excluded patients who received any anti-tumor treatment before surgery, such as chemotherapy and radiotherapy. Currently, preoperative treatment is becoming more common for patients with lung cancer or esophageal cancer. Preoperative treatment has an impact on the blood vessels, which may affect vessel sealing (19,20). We also excluded hypertensive patients whose blood pressure exceeded 140/90 mmHg after medication which may affect the generalizability of the results of this study. Second, there were only two esophagectomy cases—by chance both were randomized to the ACE+7 arm—to assess systemic (non-pulmonary) vessel sealing. This influences the generalizability of our findings to blood vessels under systemic pressures. Third, we enrolled both arteries and veins without differentiating between them in our inclusion criteria. The arteries and veins differ in their histological structure and hemodynamic pressures, so this heterogeneity may have influenced our findings.

Conclusions

In conclusion, this single-blinded, multicenter, noninferiority, randomized controlled trial confirmed that SRB was non-inferior to ACE+7 in terms of success rate of sealing blood vessels. Both ultrasonic energy devices demonstrated excellent safety profiles and efficacy in sealing 5–7 mm blood vessels. SRB could be considered an alternative to ACE+7 for sealing 5–7 mm blood vessels in diameter in thoracoscopic surgery.

Acknowledgments

We thank all the patients and their families, as well as the study coordinators and investigators in 4 participating hospitals for their support in preparing the report and data management.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-433/rc

Trial Protocol: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-433/tp

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-433/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-433/prf

Funding: This study was supported by National Natural Science Foundation of China (Nos. 82372855 and 82072557, to H.L.), Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2023ZD04, to H.L.), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (No. 2022JC023, to H.L.), Shanghai Municipal Education Commission - Gaofeng Clinical Medicine Grant (No. 20172005, the 2nd round of disbursement, to H.L.), National Key Research and Development Program of China (No. 2021YFC2500900, to H.L.), and Natural Science Foundation of Shanghai Municipal (No. 22ZR1439200, to H.L.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-433/coif). H.L. reports that this study was supported by National Natural Science Foundation of China (Nos. 82372855 and 82072557), Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2023ZD04), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (No. 2022JC023), Shanghai Municipal Education Commission - Gaofeng Clinical Medicine Grant (No. 20172005, the 2nd round of disbursement), National Key Research and Development Program of China (No. 2021YFC2500900), and Natural Science Foundation of Shanghai Municipal (No. 22ZR1439200). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by ethics board of Ruijin Hospital on March 30, 2023 (approval No. 2022-89), the First Affiliated Hospital, Zhejiang University School of Medicine on July 20, 2023 (approval No. 2023-342), the Second Affiliated Hospital, Zhejiang University School of Medicine on May 16, 2023 (approval No. 2023-215), and Shanghai Ninth People’s Hospital on June 1, 2023 (approval No. SH9H-2023-C23-2). Written informed consent was obtained from all participants following individual counseling sessions by an independent research coordinator.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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