Natural Orifice Translumenal Endoscopic Surgery (NOTES) Transvaginal Cholecystectomy

Introduction: Natural Orifice Translumenal Endoscopic Surgery (NOTES) describes a new field
of investigational surgery which uses the endoscope as the primary operative tool. The
insertion sites for the endoscope include natural orifices such as the mouth, anus, vagina,
or urethra. Multiple animal studies utilizing similar techniques are ongoing at several
institutions, including Baystate Medical Center. These multidisciplinary teams consist of
surgeons and gastroenterologists who are collaborating to develop safe and effective
surgical techniques via the natural orifice route in order to avoid surgical incisions.

The NOTES team at Baystate began animal studies in May, 2006. Multiple procedures, including
but not limited to uterine horn resection (simulating appendectomy), cholecystectomy,
nephrectomy, splenectomy, distal pancreatectomy, small bowel resection, mediastinal
exploration, and sleeve gastrectomy have been completed successfully by the team. This work
has led to a separate, IRB-approved protocol to perform NOTES pancreatic
pseudocystgastrostomy in human patients. To date, 2 patients have successfully undergone
entirely transluminal, endoscopic cystgastrostomy with a third case upcoming. The focus of
much of our research (as well as that of many other investigators), is to develop a secure
closure method for the stomach. Unfortunately, key scientific questions remain regarding
this technique and thus have limited human trials to date. Given this, we have begun to
explore other access techniques.

Gynecologists have long considered transvaginal access to the peritoneum as a safe route of
entry into the abdomen. Transvaginal hysterectomy and transvaginal tubal ligation have
indeed become a regular part of the gynecologic armamentarium. NOTES surgeons have learned
from this access approach and have begun to employ it as a safe route into the abdomen. In
fact, investigators in New York1,2; San Diego3; Strasbourg, France4; Mallorca, Spain5;
Hamburg, Germany6, Milan, Italy7; and Rio de Janeiro8,9 and São Paulo10, Brazil have all
announced transvaginal NOTES procedures involving the gallbladder. All of these approaches,
to date, have utilized one or more laparoscopic trocars for safety reasons.

Primary Objective: The primary objective of this pilot study is to demonstrate that the
Natural Orifice Translumenal Endoscopic Surgery (NOTES) transvaginal cholecystectomy
technique is as safe and effective as standard laparoscopic surgical technique for the
resection of gallbladder.

Hypothesis: Patients who undergo Natural Orifice Translumenal Endoscopic Surgery for
treatment of their gallbladder disease will experience effective treatment with less
discomfort and with quicker recovery than standard surgical techniques.

Introduction: The NOTES team (surgeon and gastroenterologist) at Baystate has extensive
experience with animal work in developing novel techniques with commercially available
products. Despite performing cholecystectomies in porcine models both through a transgastric
and transvaginal approach, we have yet to perform a human case. The surgeons on the team
have performed well over a thousand laparoscopic cholecystectomies; the gastroenterologist
is a recognized advanced therapeutic endoscopist; and the gynecologist is an expert in
transvaginal surgery. We believe that our combination of human experience and animal
research will lead to safe attempts to perform the procedure described herein.

Methods: There will be a total of 3 patients undergoing this experimental surgical procedure
once meeting all entry criteria and subsequent to obtaining informed consent These patients
will be recruited from the Baystate ambulatory surgery clinics.. Preoperative laboratory
testing, such as blood work (liver function tests, amylase and lipase, a white blood cell
count, and a pregnancy test), as well as ultrasound of the liver to document gallbladder
disease will be performed as is the standard for patients undergoing surgical removal of the
gallbladder. In this procedure, after the induction of general anesthesia and creation of a
culdotomy, a sterile endoscope would be inserted into the vagina and then into the abdomen.
Following the insertion of the endoscope, a retraction stitch will be passed through the
abdominal wall and into the gallbladder to retract the fundus of the gallbladder in a
cephalad direction. A 5-mm trocar will be placed in the umbilicus and will serve two
functions: one, to allow for a laparoscope in case the view becomes compromised or
substandard; and two, to allow a clip applier to be placed in the abdomen for clipping the
cystic artery and cystic duct. Dissection of the gallbladder can commence using endoscopic
tools and removal of the specimen will be directly through the culdotomy and out through the
vagina. Utilizing this technique, as many as three surgical incisions can be avoided.

Postoperatively, the patient will be kept in the hospital overnight. After discharge,
follow-up examination will be conducted at 3-5 days (by telephone), 1 week, and 6 weeks
following the procedure to determine the success of the procedure. Longer term follow-up
will be determined by the patient's overall condition. For at least the first 3 procedures,
a laparoscopic camera will be available on the sterile field and at least one laparoscopic
trocar will be employed. As with any operation, we would revert to the next least invasive
modality should patient safety and/or degree of difficulty dictate that it be so. In this
case, should we encounter difficulties during transvaginal cholecystectomy, we would have a
low threshold to revert to laparoscopic cholecystectomy or even to open cholecystectomy as
needed.

Safety Monitoring: Due to the novelty of the procedure, safety information will be monitored
on a continuous basis. Complications that deviate from expected outcomes from standard
laparoscopic cholecystectomy would result in, the study being terminated prematurely or
temporarily suspended while we assess the events. A member of the general surgery department
will be appointed as a safety monitor and will review all the cases and report to the IRB
after the first and third case.

Risks and Benefits: The anticipated risks associated with this type of surgery include:

Bleeding, infection, need for open surgery, bile leak, bile duct injury, and bowel injury.
Risks specific to the transvaginal NOTES approach include infection of the vagina,
dyspareunia. A vaginal incision has no known adverse effects on either fertility or
subsequent childbirth, even within a few weeks of the procedure. The anticipated benefits
include a decrease in the amount of pain experienced with laparoscopic cholecystectomy, as
well as a more cosmetically acceptable result.

Statistics: As this is a purely descriptive study of feasibility of a new technique, there
are no specific statistics to be monitored.

Data Storage: The identifiable data collected will be kept in a locked filing cabinet in the
primary investigator's office. Only the PI will have access to this file.

It is anticipated that there will be more similar "natural orifice-type" surgeries in the
future for a variety of procedures and a multitude of reasons (no incision, less pain, and
less time in the hospital). These surgeries will be some of the first transvaginal
cholecystectomies performed in the world.

Inclusion Criteria:

1. Adult female (18 years old or over) patients who are able to provide informed consent
for this surgical procedure

2. Patients scheduled to undergo non-emergent surgical removal of the gallbladder

Exclusion Criteria:

1. Inability to provide informed consent

2. Patients who have a history of prior pelvic surgery (excluding Caesarian sections,
tubal ligations, or non-operative pelviscopy)

3. Patients who have acute cholecystitis, gallstone pancreatitis, or who have had a
percutaneous cholecystotomy tube placed

4. Patients with a BMI > 40 kg/m2

5. Pregnancy

6. Male gender

7. History of PID