Clinical trial NCT01312246: EnSeal Efficacy and Bursting Pressure in Human Vessels
Official title: EnSeal Efficacy and Bursting Pressure in Human Vessels
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Colon and Rectal Diseases
Keywords: vessel ligation
colon resection
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: Ethicon Endo-Surgery
First posted: 2011-03-10
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: In this study the investigators will include adult patients who are not part of a vulnerable patient population. Inclusion criteria include patients who will be undergoing resection of part of their colon that will require dividing the IMA. The investigators will use the resected surgical specimens for our project. The investigators will use the EnSeal on all major vessels in our procedure. The investigators will use the EnSeal 5 mm round head model. Due to the nature of the project, we will apply for IRB approval prior to beginning our research. The investigators plan to include 60 total patients in the study, 30 at the University of Illinois and 30 at Lutheran General Hospital.

Prior to resection, the investigators will use a sterile caliper to take an in-vivo measurement of the IMA and IMV. Immediately after resection, the investigators will remove the sealed proximal end of the IMA and the 3 cm distal to it from the surgical specimen. The investigators will similarly prepare the IMV. The investigators will inspect our vessels for any iatrogenic traumatic tears. If the vessels are suitable, the investigators will then gentle apply manual traction to remove any blood or clots within the lumen. The investigators will measure the outer diameter of the vessels using a digital caliper. If there are small branches, the investigators will tie them off with suture. The unsealed end will then be attached to the burst pressure tester with suture and it will be tested for the bursting pressure. The device measures pressure continuously as it infuses the segment with normal saline at a steady rate (50 ml/hr). A leak will be determined by a decrease in intra-luminal pressure of 100 mm Hg or a visible leak. A failure to seal the vessels will be determined by a bursting pressure of less than 100 mm Hg. It should be noted that each section would only be pressure-tested once. All of our data will be collected on the enclosed data sheet we have created for use in this protocol. The investigators will then place the vessels with the original surgical specimen where it will be submitted for routine pathological examination of surgical specimens. Twenty five specimens at each site will undergo the testing, whereas 5 specimens will be sent to pathology without testing.

Our pathologist will analyze the submitted specimen for extent of seal, disruption of vessel smooth muscle, gas bubbles, and will stain for elastin to analyze the disruption in the vessel wall. In addition, the seal will be measured and we will obtain digital images. The specimens submitted for pathology will be 5 burst specimens as well as 5 un-burst specimens taken from the pool of 25 patients at UIC.

For our human component, the investigators have estimated the standard deviation and width of the confidence interval to be 100 mm Hg each. With a 95% confidence level, the investigators expect to require 16 measurements for human specimens from 16 patients although the investigators will use 50 patients to allow for errors in obtaining pressures.

Our timeline for the completion of the projects is 6 months. The investigators plan on being able to complete the human burst pressure testing within 6 months.

Detailed description: Introduction

Multiple new cautery devices are used to perform quicker and safer surgeries. These devices are able to seal vessels without need of ties or adjunct maneuvers and produce a minimal thermal spread to adjacent tissues. We have found that the EnSeal is a reliable, versatile, and effective device for sealing vessels.

Currently, the EnSeal is approved for vessels as large as 7 mm in diameter. We believe, based on prior clinical experience, that the EnSeal can safely seal vessels of a larger diameter. Current data shows that the bursting pressures obtained in 7 mm vessels are five times the physiological normal pressure in animal models.1, 2 We have demonstrated that all of the mesenteric vessels encountered in a human colectomy can be safely divided with EnSeal. However, neither we nor other researchers have measured the bursting pressure of these seals in human patients.

We propose to examine the bursting pressures of vessels taken in colectomies in an ex-vivo fashion. After we use the EnSeal to divide the inferior mesenteric artery at its origin, we will then use assess the bursting pressure of this seal. We will similarly assess the inferior mesenteric vein. We will measure the diameter of the vessels both in-vivo and ex-vivo. Finally, we will conduct histopathological examination of the sealed vessels to determine the effects of the EnSeal device on the structure of the vessels.

Background

With the increased preference for laparoscopic surgery, new instruments are needed to safely replicate and, where possible, improve upon the techniques used in open surgery. Visualization is eminently important and dependent on multiple factors, including bleeding and smoke from coagulation and cautery. Therefore, there is a high demand for devices that can safely coagulate tissue with low heat and little smoke. Resection of tissues in a safe and haemostatic fashion in laparoscopic colorectal surgery depends upon good control of mesenteric vessels. Ideally, the thermal spread should be minimal and travel in a predictable pattern. Various new devices have been created and used for the purposes of vessel sealing, with some of the more popular being Ligasure (Valleylab), Harmonic (Ethicon), Gyrus (Gyrus ACMI), and EnSeal (Ethicon). Multi-purpose instruments are preferable because the surgeon can avoid frequent exchange of instruments and thus reduce operative time. The previously mentioned vessel-sealing devices work with two jaws and can also be used to manipulate some tissue. Of particular interest to our group of colorectal surgeons is the finding that along with decreased operative time, these devices have been shown to contribute to decreased blood loss during laparoscopic colectomies.3 These modern vessel-sealing devices work by varying methods. The Harmonic Scalpel is an ultrasonic shear that breaks hydrogen bonds and cause tissue coagulation and vessel sealing.4 The Ligasure device works by coagulating the tissue in the jaws of the device with high-current/low-voltage flow and then using high-pressure jaws to seal it.5 The nano-particle technology of the EnSeal device aims to lower the temperature of the instrument to minimize heat transfer to adjacent tissue and allows for different temperatures within different parts of the jaws. It turns off when collagen denatures, at approximately 100 degrees Celsius.6 These sealing systems have been widely used in many surgical disciplines and surgeons continue to try to find new uses for these innovative devices. They have been compared to conventional methods such as clips and ties and found to be as effective when applied properly.7 The Gyrus PK system has been used in urological and robotic surgery.8, 9 The Harmonic Scalpel has been used in major abdominal operations and also in otolaryngology operations.10, 11 Ligasure has perhaps been the most widely adopted and is used in gynecological, otolaryngology, and colorectal specialties.12-15 The EnSeal device is newer than the others and while it is gaining popularity in its use, it has not been as extensively studied at this time.

Currently, the USA FDA has approved the EnSeal device for vessels up to 7 mm in diameter. This is equal or greater to other vessel sealing systems that are widely used such as Ligasure (7 mm) and Harmonic Scalpel (5 mm). Porcine studies done by SurgRx as well as research groups from Cleveland Clinic - FL and Carolinas Medical Center demonstrate the safety of this device in its approved size range when compared to other devices. In these studies, they find that the EnSeal has significantly higher burst pressures on sealed vessels than other sealing systems (678 mm Hg for EnSeal vs 489 mm Hg for Ligasure) or that there is no statistical difference, but that it seals at supra-physiologic pressures (891 mm Hg EnSeal vs 884 mm Hg Ligasure).1, 2 These measurements are obtained by securing the open end of a vessel to a device that fills the lumen with fluid. Once the seal on the other end bursts, the machine records the final pressure reading within the lumen of the vessel. Other notable findings of the EnSeal include less adventitial damage to the vessels on histopathologic evaluation and minimal failure rates (only 1/39 vessels failed to seal).1, 2 A study completed from Turkey used EnSeal on rat liver parenchyma and compared it to Ligasure and conventional methods for liver resection. Sahin and colleagues found that EnSeal was at least as effective as conventional techniques and that there was less inflammation and damage due to thermal spread to the rat liver parenchyma when compared to Ligasure.16 In a comparison of two ultrasonic devices on human vessels, Ching found that veins have a decreasing burst pressure as the diameter of the vessels increase.17 These burst pressures are much lower than what is reported in porcine arteries. This finding makes it important to determine the seal bursting pressure in human vessels so that the relationship between experimental values in porcine models can be clinically correlated. Previous studies have analyzed the histopathologic effect of the EnSeal device on the blood vessels.2 We will also do an analysis of human tissue.

In our practice, we routinely use the EnSeal device to seal the ileocolic vessels and the inferior mesenteric artery and vein (IMA, IMV). Data with good evidence of the diameter (external or internal) of the inferior mesenteric artery is not widely available. However, we were able to find some data that can provide a little information. In a study by Yekeler et al, the investigators used ultrasound technology to determine the internal diameter of the superior mesenteric artery (SMA). In their study, they found that in healthy patients the internal diameter average was 5.8 mm. Among their findings is a pattern of significantly increased internal diameter in patients with active inflammation compared to patients with quiescent disease.18 We have long suspected that in tissue experiencing acute or chronic inflammation the feeding vessel will be larger; their evidence supports this hypothesis. In a very small study examining the use of the IMA for coronary artery bypass grafts, researchers harvested two IMAs and measured one of them. This artery had a 4 mm diameter at its origin. The IMA is smaller than the SMA in the vast majority of patients. Therefore, the findings by Shatapathy are consistent with this expectation.19 In our practice, we have gravitated towards the EnSeal. We find that it is effective, reliable and its versatility is evidenced by its use as a grasper, dissector, scissors and vessel and soft-tissue sealer. The nano-particles that are within the jaws of the device to regulate current and heat distribution serve to protect the adjacent tissue from thermal injury. Such injuries from other devices have been documented and often present with late and serious complications.21 As part of our normal surgical practice, we use the EnSeal to divide and seal the inferior mesenteric artery and vein when their resection is indicated. In our experience with this device, it has a low failure rate. We have not experienced any post-operative bleeding that requires transfusion or re-operation. Even though we believe that the majority of IMAs we encounter are below the 7 mm size, most surgeons do not feel comfortable using the EnSeal to seal this vessel and will use staplers to divide them.

We intend to demonstrate that the bursting pressures in large vessels (IMA, IMV) sealed in colectomy of human patients are sufficiently high. Using the EnSeal device on larger vessels, we believe, would further reduce operating time, blood loss, and hasten post-operative recovery from less tissue manipulation.

Methods

In this study we will include adult patients who are not part of a vulnerable patient population. Inclusion criteria include patients who will be undergoing resection of part of their colon that will require dividing the IMA. We will use the resected surgical specimens for our project. We will use the EnSeal on all major vessels in our procedure. We will use the EnSeal 5 mm round head model. Due to the nature of the project, we will apply for IRB approval prior to beginning our research. We plan to include 60 total patients in the study, 30 at the University of Illinois and 30 at Lutheran General Hospital.

Prior to resection, we will use a sterile caliper to take an in-vivo measurement of the IMA and IMV. Immediately after resection, we will remove the sealed proximal end of the IMA and the 3 cm distal to it from the surgical specimen. We will similarly prepare the IMV. We will inspect our vessels for any iatrogenic traumatic tears. If the vessels are suitable, we will then gentle apply manual traction to remove any blood or clots within the lumen. We will measure the outer diameter of the vessels using a digital caliper. If there are small branches, we will tie them off with suture. The unsealed end will then be attached to the burst pressure tester with suture and it will be tested for the bursting pressure. The device measures pressure continuously as it infuses the segment with normal saline at a steady rate (50 ml/hr). A leak will be determined by a decrease in intra-luminal pressure of 100 mm Hg or a visible leak. A failure to seal the vessels will be determined by a bursting pressure of less than 100 mm Hg. It should be noted that each section would only be pressure-tested once. All of our data will be collected on the enclosed data sheet we have created for use in this protocol. We will then place the vessels with the original surgical specimen where it will be submitted for routine pathological examination of surgical specimens. Twenty five specimens at each site will undergo the testing, whereas 5 specimens will be sent to pathology without testing.

Our pathologist will analyze the submitted specimen for extent of seal, disruption of vessel smooth muscle, gas bubbles, and will stain for elastin to analyze the disruption in the vessel wall. In addition, the seal will be measured and we will obtain digital images. The specimens submitted for pathology will be 5 burst specimens as well as 5 un-burst specimens taken from the pool of 25 patients at UIC.

For our human component, we have estimated the standard deviation and width of the confidence interval to be 100 mm Hg each. With a 95% confidence level, we expect to require 16 measurements for human specimens from 16 patients although we will use 50 patients to allow for errors in obtaining pressures.

Our timeline for the completion of the projects is 6 months. We plan on being able to complete the human burst pressure testing within 6 months.

Budget

The budget PAF number has been included in this study. The budget also includes moneys for a concurrent study involving porcine vessels. We will harvest these blood vessels after pigs used for other research purposes are euthanized. I have included a letter from the BRL stating that this study does not require approval because we are using animals that were used for other purposes.

Eligibility criteria: Inclusion Criteria:

* Include patients who will be undergoing resection of part of their colon that will require dividing the colonic vessels. The use of the resected surgical specimens is included our project.

Exclusion Criteria:

* Patients who do not meet the the inclusion criteria.

Primary outcomes:
measure: EnSeal Efficacy and Bursting Pressures in Human Vessels
timeFrame: 21 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University Of Illinois Medical Center at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Leela M Prasad, MD
role: PRINCIPAL_INVESTIGATOR
References:
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