EnSeal Efficacy and Bursting Pressure in Human Vessels

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.

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.