Colon and Rectal Diseases Clinical Trial
Official title:
EnSeal Efficacy and Bursting Pressure in Human Vessels
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.
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.
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