Fluorescent Evaluation of Colorectal Anastamoses

The purpose of this study is to evaluate whether systemically injected ICG, when fluorescing
in response to NIR illumination, can assist with the assessment of perfusion at a bowel
anastomotic site. This finding may assist surgeons to minimize the occurrence of leaks at
the anastomotic site following this surgical procedure. The present study is a preliminary
investigation to determine if this imaging modality will yield information regarding
perfusion that is likely to be clinically relevant and so determine if a larger, multi
center trial that correlates perfusion to clinical outcome is warranted. The results of the
present study will also assist in the design of a larger scale study. It is expected that a
successful outcome to such a trial will result in less morbidity following laparoscopic
colectomy.

Laparoscopic bowel surgery is indicated for colon cancer, rectal cancer, diverticulitis,
inflammatory bowel disease (including ulcerative colitis or Crohn's disease) and infarcted
bowel. Prophylactic colectomy is also indicated for certain forms of polyposis to mitigate
the risk of progression to colon cancer. The portion of colon resected during a colectomy is
dependent upon the nature of the disease and its location and extent. Traditionally,
colectomy has been performed by means of laparotomy, a standard abdominal incision. In
recent years, beginning in the early 1990s, there has been increasing interest in, and
utilization of, minimally invasive techniques for surgical procedures involving the colon
and rectum. Laparoscopic surgery involves the introduction of surgical instruments through a
number (usually 2-3) of small incisions measuring about 10-12 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.

Irrespective of the type of procedure performed (open or laparoscopic), anastomotic leakage
following colorectal resection and primary anastomosis is a major clinical problem. The
incidence of intraperitoneal anastomotic leaks reported in the literature may be as high as
30%. Anastomotic leaks leads to increased length of hospital stay, and may progress to
abscess formation, sepsis, multi organ failure and even death.

The cause of anastomotic leakage is multifactorial with the following factors appearing to
impact upon leakage; adequacy of blood flow to the anastomosis, contamination, the presence
of a pelvic drain, anastomotic tension, anastomotic technique and the distance from the anal
verge . The present study will investigate the first factor listed above, adequacy of blood
flow to the anastomosis. At present there is no reliable and easy-to-perform modality that
can be used to assess adequacy of perfusion at the anastomosis during colorectal procedures.
This study will investigate the potential for the SPY scope to fill this clinical need.

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 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. This property makes it an ideal agent for the acquisition of high quality images
of the vasculature. Intraoperative images are acquired during the first pass of a bolus of
ICG through the area of interest. The SPY System has been the subject of numerous peer
reviewed publications demonstrating its safety and efficacy .

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

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

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

- 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.

Inclusion Criteria:

- Candidates for this study must meet ALL of the following 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 low anterior resection

Exclusion Criteria:

- Candidates for this study who meet any of the following criteria at the time of the
baseline visit are NOT eligible to be enrolled in this study:

- 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