The Use of Fluorescent Imaging for Intraoperative Cholangiogram During Laparoscopic Cholecystectomy

The purpose of this study is to evaluate whether systemically injected ICG, when fluorescing
in response to NIR illumination, can assist with the identification of the CBD (common bile
duct)during laparoscopic cholecystectomy. This finding may assist surgeons to perform
laparoscopic cholecystectomy in less time and with less morbidity than standard laparoscopic
cholecystectomy.It is expected that a successful outcome to such a trial will result in less
time in the operating room and less morbidity following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is indicated for cholecystitis, biliary colic, resolved biliary
pancreatitis, and symptomatic cholelithiasis. Laparoscopic cholecystectomy involves the
introduction of surgical instruments through a number (usually 4) of small incisions
measuring about 5-12 mm each with visual guidance being provided by means of a camera
attached to an endoscope introduced through a similarly small access port. Laparoscopic
techniques offer numerous benefits including a decrease in postoperative pain, some
improvement in time to tolerance of food and return of bowel function, shorter hospital stay
and more rapid return to normal activity.

Laparoscopic cholecystectomy is one of the most frequently performed surgical procedures in
the United States. Iatrogenic bile duct injuries are a serious complication and patients
undergoing the laparoscopic type of cholecystectomy are at increased risk for this
complication. To minimize risk of injury, techniques such as "critical view" (dissection and
visualization of the cystic duct and cystic artery) have been developed. However, adhesions,
inflammation and anatomical variation can make surgical dissection and identification of
significant structures difficult. In addition significantly longer operative times are seen
when attempting to obtain the critical view. Some advocate the routine use of cholangiography
(IOC) but the national standard of care remains to only perform IOC selectively. IOC requires
cannulation of the cystic duct, injection of iodinated dye, and fluoroscopy which adds
significantly to the operative time and morbidity especially in centers where routine IOC is
not performed.

The present study will investigate whether the use of NIRF after injection of ICG will make
identification of the Biliary structures and CBD clearer and decrease the time required to
dissect out critical structures and perform safe cholecystectomy.

The SPY® Intraoperative Imaging System is cleared for use in Canada, Japan, Europe and the
US. SPY was originally developed for applications in cardiac surgery and allows cardiac
surgeons to visually assess bypass graft quality in real-time while the patient is still in
the operating room. Subsequently, SPY has received clearance from the FDA for use in plastic
and reconstructive surgery and in solid organ transplant.

The SPY Intraoperative Imaging System was originally developed for open surgical procedures
using ICG, which is an FDA approved drug. ICG is a fluorescent compound, which can be
administered intravenously or intra-arterially. The dye absorbs light in the near infrared
(NIR) region at 806 nm, and emits light at a slightly longer wavelength, 830 nm. When
injected intravenously, ICG rapidly and extensively binds to plasma proteins and is confined
to the intravascular compartment with minimal leakage into the interstitium under normal
conditions. ICG is taken up by the liver and then excreted into the biliary system where it
can be imaged. The SPY System has been the subject of numerous peer reviewed publications
demonstrating its safety .

SPY scope, the endoscopic version of SPY, is an endoscopic visible (VIS) NIR imaging system
consisting of:

1. An endoscopic light source that provides illumination for visible light imaging and NIR
fluorescence excitation to the endoscope via a flexible light guide

2. Rigid endoscopes optimized for illuminating the field of view and transmitting images in
the visible and NIR spectrum, and

3. A high definition (HD) endoscopic camera system connected to the endoscope eyepiece and
acquiring high resolution visible and NIR fluorescence images The ICG (25 mg per vial)
will be reconstituted according to the manufacturer's instructions using the entire
contents (10 ml) of the sterile diluent supplied, yielding a 2.5 mg/ml solution of ICG
or using half of the diluent supplied (5 ml) yielding a 5 mg/ml solution.

ICG Diagnostic Procedure: 3ml of 2.5 mg/ml solution (Akorn product, US Monograph) The ICG may
be administered through a peripheral venous access. Based on our prior experience in
colorectal cases 1.0 ml of a 2.5 mg/ml solution of ICG (flushed with 10 ml saline) will be
administered.

Our study will include patients undergoing laparoscopic cholecystectomy for both acute
cholecystitis and non-acute symptomatic cholelithiasis. The standard operating technique will
be used for all patients including the critical view technique and fluoroscopic IOC if
clinically indicated.

Our primary endpoint will be operative time measured as the time from the beginning of the
dissection until the gallbladder is separated entirely from the gall bladder fossa.

Secondary endpoints will be time to identification of structures and safety of the operation.
Other endpoints such as CBD injury and postop bile leak will be included if identified.

Inclusion Criteria:

- Subject is willing and able to provide an informed consent

- Subject is willing and able to comply with the study procedures

- Subject speaks English and is able to understand the study procedures

- A pregnancy test for women of childbearing potential prior to surgery

- Subject is scheduled for laparoscopic cholecystectomy

Exclusion Criteria:

- Subject has uremia, serum creatinine >2.5 mg/dl

- Subject has a previous history of adverse reaction or allergy to ICG, iodine,
shellfish or iodine dyes

- Subjects in whom the use of x-ray dye or ICG is contraindicated including development
of adverse events when previously or presently administered

- Subject has any medical condition, which in the judgment of the Investigator and/or
designee makes the subject a poor candidate for the investigational procedure

- Subject is a pregnant or lactating female

- Subject is actively participating in another drug, biologic and/or device protocol