Near-infrared Fluorescence Cholangiography assisted Laparoscopic Cholecystectomy versus Conventional Laparoscopic Cholecystectomy (FALCON): a multicenter randomized controlled trial

Laparoscopic cholecystectomy (LC) is one of the most commonly performed
laparoscopic procedures in gastrointestinal surgery. Bile duct injury during
this procedure is rare but constitutes a serious complication (0.3-0.7%).
Misidentification of the extra-hepatic bile duct anatomy during laparoscopic
cholecystectomy is the main cause of bile duct injury.

The Critical View of Safety (CVS) technique was introduced to reduce the risk
of bile duct injury. To establish CVS, two windows need to be created: one
window between the cystic artery, cystic duct and gallbladder, another window
between the cystic artery, gallbladder and liver. The CVS technique is
especially aimed at mobilizing the gallbladder neck from the liver, in order to
obtain a circumferential identification of the cystic duct.

Intraoperative cholangiography has been advised to reduce the risk of bile duct
injury. However, this radiological imaging of the biliary tree is only used
selectively, as the process takes time, radiation exposure is involved and
additional equipment and manpower for the procedure are required. Therefore,
worldwide consensus about implementation of intraoperative cholangiography is
still lacking.

Near-infrared fluorescence (NIRF) imaging after intravenous injection of
indocyanine green (ICG) is a promising new technique for easier intraoperative
recognition of the biliary anatomy. It may help improve the outcome of
laparoscopic cholecystectomy. ICG is cleared quickly and exclusively by the
liver after intravenous administration. Neither radiological support nor
additional intervention, such as opening the biliary tree, is required. The
NIRF laparoscopy technique using ICG has been evaluated in various animal
models and in open, laparoscopic, and single-incision laparoscopic
cholecystectomy. Promising results were presented for successful intraoperative
identification of the common bile duct and the cystic duct, compared to
conventional laparoscopic imaging. Another clinical study showed that the NIRFC
technique provides significantly earlier identification of the extra-hepatic
bile ducts during the CVS dissection phase: up to 10 minutes earlier
identification of cystic duct and common bile duct could be obtained. Real-time
simultaneous imaging of the hepatic and cystic arteries can also be obtained.

Despite the encouraging results from these (pre)clinical feasibility studies,
wide clinical acceptance for the routine use of ICG fluorescence laparoscopy is
still lacking due to the absence of reliable clinical data. Therefore, a
multicenter randomized clinical study is desirable to assess the potential
added value of the fluorescence imaging technique during laparoscopic
cholecystectomy in order to perform an even more safe procedure leading to a
reduction in the vascular and bile duct injuries. This study will compare NIRF
assisted laparoscopic cholecystectomy to conventional laparoscopic
cholecystectomy.

The main objective of this study is to evaluate whether earlier establishment
of Critical View of Safety can be obtained during laparoscopic cholecystectomy,
by applying NIRF laparoscopic imaging as an adjunct to conventional
laparoscopic imaging versus conventional laparoscopic imaging alone.

A multicenter randomized controlled trial, with two randomization arms:
- NIRF-LC group: this group of patients will undergo near-infrared fluorescence
cholangiography assisted laparoscopic cholecystectomy;
- CLC group: this group will undergo conventional laparoscopic cholecystectomy.

Planned duration of the project: 2 year

This study is being performed by the Departments of Surgery of three University
Medical Centers and two large peripheral training hospitals in the Netherlands,
one University Hospital in Italy, a clinic in Germany and two potential centers
in Belgium and the United Kingdom.

- Maastricht Universitair Medisch Centrum + (MUMC +, Maastricht, the
Netherlands)
- Leids Universitair Medisch Centrum (LUMC, Leiden, the Netherlands)
- Catharina-ziekenhuis Eindhoven, the Netherlands;
- IRCCS - Ca' Granda, Policlinico hospital, Milan, Italy;
- Clinic for general, visceral and vascular surgery, Asklepios Westklinikum
Hamburg, Germany
- Colchester University Hospital, Colchester, United Kingdom

The NIRF-LC group will undergo near-infrared fluorescence cholangiography (in
combination with one preoperative and one per-operative intravenous injection
of contrast agent ICG) assisted laparoscopic cholecystectomy.
The CLC group will undergo conventional laparoscopic cholecystectomy (CLC).

Compared with standard care, patients in the NIRF-LC group have to receive one
preoperative and one per-operative intravenous injection of ICG. This is the
only additional (minimally) invasive action for the patient. Initially,
patients participating in this study will not benefit from the application of
NIRFC during the surgical procedure. The administration of ICG (FDA approved
and already used for several clinical diagnostic indications, previously used
in the NIRFC-LC pilot study: NL38521.068.11) and the laparoscopic fluorescence
imaging system are not related with any kind of additional risk for the
patient.

Despite the encouraging results from several (pre)clinical feasibility studies,
wide clinical acceptance for the routine use of ICG fluorescence laparoscopy is
still lacking due to the absence of reliable and validated clinical data. A
randomized clinical study is desirable to assess the potential added value of
the NIRF imaging technique during laparoscopic cholecystectomy. The FALCON
trial will provide evidence on the benefit of standard application of NIRF
imaging during laparoscopic cholecystectomy. Strong evidence in favor of
routine implementation of this new imaging technique during laparoscopic
cholecystectomy, the most commonly performed laparoscopic procedure worldwide,
will probably lead to worldwide routine application of the NIRF technique.
Therewith long term sustainability of this research project is guaranteed.