Abstract
Background:
Intraoperative blood loss has an unfavorable impact on the outcome of patients undergoing liver surgery. Today, the use of devices capable of minimizing this risk with high technical performance becomes mandatory. Into this scenario fits the CUSA® Clarity Ultrasonic Surgical Aspirator System. This prospective survey involving five liver surgery centers had the objective of investigating whether this innovative ultrasonic surgical aspirator is safe and effective in the transection of the liver parenchyma.
Materials and Methods:
This clinical study was a prospective, multicenter, single-arm Post-Market Clinical Follow-up study investigating 100 subjects who underwent liver surgery using the CUSA Clarity Ultrasonic Surgical Aspirator System at five centers during a period of 1 year and 8 months. After collecting all the patient's clinical information and instrument usage details, surgeons completed a brief survey giving their opinions on the performance of CUSA. Therefore, safety and efficacy outcomes were evaluated.
Results:
Surgeons had a 95% success rate in complete removal of the mass with an average overall operative time of 4 hours and 34 minutes. Overall, there were no complications or device deficiencies.
Conclusion:
The CUSA Clarity Ultrasonic Surgical Aspirator System performs well during liver surgery with a low complication rate.
ClinicalTrials.gov Identifier: NCT04298268.
Introduction
A
Today parenchymal dissection techniques are available, which are safer and can prevent or minimize blood loss thanks to the identification and preservation of blood vessels.7–9 Advances in technology have provided surgeons with many different tools, including those that require an energy source: electricity, ultrasound, laser, argon gas, microwave, or radio frequency waves. 10 Ultrasonic surgical aspirators, such as CUSA® Clarity Ultrasonic Surgical Aspirator System, use ultrasonic frequencies to fragment, emulsify, and aspirate tissue. Ultrasonic aspirators used in surgery typically include a longitudinally vibrating annular surface with a central channel providing suction, which contacts tissue enabling fragmentation via various mechanisms, such as mechanical impact (momentum), ultrasound propagation, and cavitation.
The need for removal of soft tissue is commonly noted in many types of procedures. Ultrasonic aspirators present an alternative, safe, tissue-selective method for soft tissue removal. Based on the principle of ultrasonic vibration, they work by emulsifying the contacted tissue with minimal heat and minimal risk of injury to surrounding tissues. They have applications in general surgery for the removal of benign or malignant tumors or other unwanted soft tissue in open or minimally invasive general surgical procedures and urological surgery applications for the removal of renal parenchyma during nephrectomy or partial nephrectomy.11–13
The purpose of this study was to demonstrate that the CUSA Clarity Ultrasonic Surgical Aspirator System is safe and effective when used for soft tissue removal, specifically in liver resection, with the aim of investigating clinical performance and surgeon preferences.
Materials and Methods
This study was carried out at four sites across Italy and one site in Germany. The site locations are listed in Table 1. The investigative sites were selected by the clinical team; site selection was based on professional reputation, history of scholarly activity, and academic credentials of the principal investigator (PI). This clinical study was a prospective, multicenter, single-arm Post-Market Clinical Follow-up study investigating subjects who underwent removal of soft tissue with the CUSA Clarity Ultrasonic Surgical Aspirator System, specifically during hepatobiliary surgery. The enrollment period was from the point of consent through the study index surgery and the duration of the study was 1 year and 8 months.
List of Site Investigators
Subjects were exited from the study immediately following the study index surgery, provided there were no safety issues for which the investigator felt that it was necessary to continue to follow the subject. There were no scheduled follow-up visits related to the study and enrollment ended when 100 subjects were enrolled. Patients who met the eligibility criteria were enrolled in the study, for which the inclusion and exclusion criteria are listed in Table 2.
Inclusion and Exclusion Criteria
IRB/EC-approved, Institutional Review Board/Ethic Committee-approved.
Protocol deviations were identified by site investigators, delegated personnel, study monitors, and the data management group. In the entire study, there were 49 protocol deviations that occurred in 48 subjects. All protocol deviations were reviewed by medical affairs. No major deviations were identified.
Protocol deviations categorized as informed consent were the most common type of protocol deviation site-wide (n = 45), followed by “other” (no source available; n = 4).
The required information was collected through a review of the patient chart or electronic medical records by the PI or delegated personnel. The delegated staff member collected all demographic information and significant medical/surgical history as outlined by the investigator, as well as any diagnoses or prior surgical treatments, such as prior scarring, prior chemotherapy, or radiation, which may have resulted in degradation of tissue integrity, be pertinent to soft tissue removal, and/or affect the results of the study. Any prior treatment within the surgical area was also documented.
Information regarding the study index procedure was collected from the operative Case Report Form (CRF). Some information about the surgical procedure was electronically accessed via download from the CUSA system and did not need to be entered on the operative CRF. Information that was collected during the procedure included, but was not limited to:
Operating room (OR) Time Settings and performance of the CUSA Clarity Ultrasonic Surgical Aspirator System Device Malfunctions Any additional tools/technology used during soft tissue removal Location and volume/size of soft tissue removed Speed of soft tissue removal Utilization of CUSA during any other procedures Success in the desired outcome of the procedure Instrument handling abilities and design appreciation Overall outcome of the surgery
Surgeons completed a brief survey giving their opinions on the performance of CUSA during the procedure. Endpoint Analysis was based on 9 surgeon survey questionnaires and information collected from an operative evaluation form.
The primary efficacy endpoint was the effectiveness of soft tissue removal as per surgeon assessment, evaluated by surgeon confirmation of complete mass removal. Other exploratory endpoints were as follows:
Precision of soft tissue removal
Speed and efficiency of soft tissue removal
Noted safety concerns
Device malfunctions
Overall surgical success in the desired surgical outcome
Preferred CUSA settings
Overall OR time
Overall CUSA performance acceptability in removing soft tissue
Instrument handling abilities and design appreciation
Safety endpoints were assessed through reports of adverse device effects (ADE) and serious ADE. For the purposes of this report, an ADE means any untoward medical occurrence, unintended disease or injury, or any untoward clinical signs (including an abnormal laboratory finding) in subjects that can be deemed by an investigator to be at least possibly related to the investigational medical device and/or study index surgery.
The investigator was responsible for performing the study in full accordance with the protocol and ICH E6: Good Clinical Practice (R2), and any applicable national and local laws and regulations, including but not limited to the European Union General Data Protection Regulation (EU GDPR).
Integra was responsible for adequate study monitoring at each site to ensure the protection of the rights and safety of subjects, and the quality and integrity of the data collected and submitted.
Statistical methods
For the final statistical analysis plan (Version 1.0, dated January 11, 2019), statistical analyses were conducted using SAS® for Windows, version 9.4 or later. This study was a single-arm, open-label study whose objective was to assess the clinical performance of and surgeon preferences for CUSA for soft tissue removal during surgical procedures. No comparison was performed for endpoints; therefore, no statistical hypothesis testing was performed in the study. Descriptive statistics were used to summarize the study outcomes. For categorical data, frequencies and percentages were provided. For continuous data, descriptive statistics, including sample size, mean, median, standard deviation, and range of values (i.e., minimum and maximum values) were provided. No formal statistical testing was performed. All statistical analyses were performed by the Integra Clinical Biostatistics Department.
Results
This study was conducted in accordance with Good Clinical Practice (ICH-GCP E6) and the principles of ISO 14155:2020 for the clinical investigation of medical devices for human subjects.
The first site was initiated and the first patient was enrolled on March 31, 2020. The last subject for this study was enrolled on November 24, 2021. A total of 5 sites were initiated and a total safety population of 100 subjects was enrolled in the study for screening. All subjects were treated with the CUSA Clarity Ultrasonic Surgical Aspirator System during hepatobiliary surgery.
Demographics and medical history
The mean age of the study subjects was 64.8 years, with a standard deviation of 11.4. The majority of the study subjects were male (65 [65%]; 35 [35%] were females). A relevant medical history was reported for 70% (70/100) of the subjects. Table 3 lists the relevant medical history reported for these subjects. There was a total of 186 relevant medical conditions encompassing 15 body systems with 141 (76%) that were still ongoing at the time of the enrollment.
Medical History—Body System Summary
Subject C04-016 has three “Other” Body systems cases noted as “Thalassemia”, “major Secondary hemochromatosis” and “Extramedullary hematopoiesis” Subject C04-017 has one “Other” Body system case noted as “Iron-deficiency anemia”.
Among the enrolled subjects, 40% (40/100) had at least one previous surgical procedure related to the study index surgery. Almost half (44/100) of the subjects had received radiation, chemotherapy, or a combined treatment before study enrollment, while 56.0% (56/100) had no history of radiation or chemotherapy treatment at enrollment. Thirteen subjects had received two chemotherapy treatments in the past and one subject had received three treatments.
Device
Index surgery for all 100 subjects used the CUSA Clarity Ultrasonic Surgical Aspirator System. In more than half of all surgeries, 59% (59/100) utilized the 36 kHz Handpiece with the Curved Extended Standard Tip, while 52% (52/100) utilized the 23 kHz Handpiece with the Standard Tip and Nosecone.
During liver surgery, CUSA Clarity Ultrasonic Surgical Aspirator System was utilized predominantly with an amplitude setting frequency of 60 (69% of cases), an aspiration of 60 (69%) and an irrigation setting of 3 (51%). Often the tissue select used was 2 (69%) and most surgeons (93%) did not need to change initial CUSA settings during surgery. In the seven remaining cases, the reasons that prompted the surgeon to change the initial settings were either the proximity to major vascular structures or changes in the consistency of the liver parenchyma. In addition, the majority of surgeons (74%) did not need to use the CUSA electrosurgical Module Nosecone during surgery.
In 38% of cases, the type of surgical situation required the use of another energy device in association, and the preferred instrument in this sense was the Aquamantys, chosen in 66% (Table 4) of cases to optimize hemostasis in the parenchyma.
Summary of Additional Technologies Used
Nearly half (39%) of all study index surgeries were performed on tissue previously treated with chemotherapy and 2 of 100 on tissue with scar tissue/tissue adhesions.
Nearly 7 in 10 (73%) study index surgeries, furthermore, were performed on deep-seated tissue
Lesion Location
The surgeon-reported mean operative time of the study index surgery was 4 hours 34 minutes. The shortest time was 68 minutes, while the longest was greater than 13 hours 30 minutes.
Two ADE's happened during the study. Neither ADE was device-related and no device deficiencies occurred in this study.
Endpoint analysis
The primary efficacy outcome was evaluated by the rate of surgeon confirmation of complete removal of a mass: overall, 95.0% (95/100) of index surgeries (Table 6).
Overall Outcome of the Surgery
C03-002 and C03-018 had excess blood loss which are associated with ADE.
C04-014 and C04-022 had “Other” entered: “All that was planned to remove has been removed,” “A nonremovable lesion was treated with thermal ablation.”
C01-025 and C03-008 had partial removal of mass.
C04-020 had surrounding tissue trauma.
ADE, adverse device effects.
Device performance was assessed through the evaluation of information collected from case reports based on the device performance questionnaire. A surgeon questionnaire was completed by the sites for each subject enrolled. Table 7 summarizes the results of the surgeon survey and questionnaire.
Surgeon Survey Summary
As shown in the table, according to the surgeon survey, 97% strongly agreed or agreed that the CUSA Clarity was efficient and precise in the removal of soft tissue with an average overall operative time of 4 hours and 34 minutes, which they considered acceptable for an ultrasonic tissue ablation system. Surgeons had a 95% success rate in complete removal of the mass. Three surgeries resulted in the partial removal of the target mass while one surgery resulted in only the exploration of the tissue using CUSA with no mass removal, and another used thermal ablation to treat a nonremovable lesion. Depending on the surgical site and anatomic position, tissue removal and maintaining vascular integrity was more difficult due to the ergonomics of the instrument.
Other devices, such as Aquamantys, bipolar forceps, and LigaSure were used to provide hemostatic sealing in 38% of the procedures. The occurrence of residual heat generation with the handpiece was reported in 3% of the procedures performed. Overall, there were no major complications or difficulties and no device deficiencies related to the use of the CUSA Clarity Ultrasonic Surgical Aspirator System, and the device performed as intended with a very low complication rate.
Discussion
Dissection of the liver parenchyma is the most essential step during liver resection and may cause considerable blood loss 14 ; intraoperative bleeding is one of the main causes of surgical complications and perioperative deaths. 15 How to reduce bleeding during parenchymal resection in liver surgery, therefore, is a challenge that surgeons have been posed with for many years.
Nowadays, there are advanced parenchymal dissection techniques which can prevent injury to blood vessels and appropriately and promptly stop bleeding, hence, these techniques are fundamental to performing a safer hepatectomy.
In 2014, at the second International Consensus Conference on Laparoscopic Liver Resections, an important clinical question was raised, which was: what is the most suitable instrument for performing a laparoscopic liver resection? According to the recommendations, the most important factor to consider when deciding is the depth of liver resection: parenchymal transection in the superficial layer can be performed safely using ultrasonic dissection; however, care must be taken in the transection of the deeper parenchyma and this can be best achieved using liver dissection techniques, such as CUSA.16,17
CUSA is the most appropriate tool for parenchymal transection during open liver resection 18 and is recommended especially for deep layer dissection, which depends most upon its working principles. The Cavitron Ultrasonic Surgical Aspirator (CUSA) is particularly suitable for parenchymal dissection close to major vascular structures since it guarantees a meticulous parenchymal dissection with minimal vascular injury 19 : It can attain a precise cross-sectional plane and protect the biliary ducts, as well as blood vessels.20,21 In a 2018 report from France (> 4000 patients), CUSA was the most frequently used tool (64.6% of cases) in laparoscopic liver resections. 22
The purpose of this study was to demonstrate that the CUSA Clarity Ultrasonic Surgical Aspirator System is safe and functional during parenchymal transection in resective hepatic surgery in a prospective population, and the results of this study reinforce what was already known from the literature on the safety and performance profile of the instrument during liver resection. These products have been on the market for a very long time; indeed, surgeons are adept at using this system safely and effectively.23–25 Most of the data points in this study showed no major complications or difficulties, and no device deficiencies while performing soft tissue removal.
Overall, 97% of surgeons surveyed strongly agreed or agreed that the CUSA Clarity was efficient and precise in the removal of soft tissue. In the 100 patients studied, removal of the entire mass was achieved in 95% of the surgeries performed. Due to the ergonomics of the instrument, some procedures were more difficult to perform considering the surgical site and anatomic position. Out of the two (2%) ADE reported, it was determined that neither was due to the use of the CUSA Clarity Ultrasonic Surgical Aspirator System. Two patients had excessive bleeding that was not related to the device used but to the complexity of the resection and, therefore, related to the index procedure; a condition well known in the literature and whose etiological factors are multiple and often independent of the devices used during surgery. 26 The results of this survey, therefore, describe a useful, safe tool in resective liver surgery.
Conclusions
In conclusion, this study demonstrates that the CUSA Clarity Ultrasonic Surgical Aspirator System performs well during liver surgery with a low complication rate, which makes it a recommended tool for surgeons in the late phase of their learning curve. The goal of minimizing blood loss during liver surgery remains fundamental to improving postoperative outcomes in hepatic surgery patients, and necessitates the continued use of tools that can overcome the limits of human capabilities.
Footnotes
Acknowledgment
A heartfelt thank you to the operating room staff of all the centers involved in the realization of this survey.
Authors' Contributions
C.A. and S.G. wrote the article. F.G., S.G., L.D., M.S., and S.A. managed the patients. A.A., V.B., F.A., and P.M.M. revised the article. All authors read and approved the final article.
Disclosure Statement
No competing financial interests exist.
Funding Information
The article was sponsored by Integra Lifesciences Corporation, 1100 Campus Road, Princeton, NJ 08540, USA.
