Near-Infrared fluorescence imaging in open and laparoscopic hepatectomy: improving safety of the extra-glissionian approach?

Liver resection is the accepted treatment for various benign and malignant
indications. Several techniques can be applied to resect one or more segments
of the liver. In anatomic resections two main techniques to transect the main
portal pedicles are generally used. Traditionally the hilar dissection
technique is being used most but this technique is time consuming. A faster but
potentially more risky technique to damage the remnant bile duct is the
(extra)glissonian approach. Takasaki described the glissonian sheet that
envelopes the hepatic artery, het biliary duct and the portal vein extra
hepatic as well as intrahepatic. Because these structures are all enveloped
together, they can be approached and transected together without dissecting
Glisson*s sheet, making this surgery faster and easier when experienced. The
en-bloc transection of the hilar structures is called the *extra glissonian
approach*. This includes the dissection of the whole sheet of the pedicle
directly after division of a substantial amount of the hepatic tissue to reach
the pedicle, which is surrounded by a sheet derived from Glisson*s capsule. The
use of vascular staplers in this situation allows simultaneous ligation of the
entire right or left portal pedicle. Using this approach, the hilary dissection
is faster. However, the extra-glissonian approach is being associated with an
increased rate of biliary fistula, and described disadvantages of the approach
are accidental ligation of the biliary confluence when stapling the right
pedicle, presenting postoperatively as obstructive jaundice or portal vein
thrombosis. These complications can possibly be prevented easily by a clearer
view of enhanced hilar anatomy and visualization of the exact location of the
left and right biliary confluence. For minimal invasive liver resections, the
Glissonian approach has been further popularized by Machado (5) and Topal (6).
They both use intraoperative fluoroscopic (i.e. guided by X-ray)
cholangiography to avoid the aforementioned complications. The fluoroscopic
cholangiography however is cumbersome, time consuming and costly since it
necessitates extra equipment and a radiologic team being present in the OR.
Also, the patient is exposed to X-rays.

Several clinical feasibility studies have shown the potential benefit of
near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) for
enhanced (and even earlier) biliary anatomy visualization during laparoscopic
cholecystectomy with the aim to reduce the number of vascular and biliary
injuries (7-11). The same technique can be used to visualize the central bile
ducts when performing a hepatectomy to visualize the biliary anatomy. NIRF is
easily applicable and less cumbersome than fluoroscopic intra-operative imaging.

The aim of this study is to investigate the feasibility of the use of NIRF
fluorescence imaging for visualizing the biliary anatomy during partial
liver-resection using the hilar dissection as well as the glissonian approach.
Is the fluorescence imaging helpful for the surgeon? We hypothesize that by
visualizing the bile ducts by using near infrared fluorescence imaging, this
technique will be easier to perform and the surgeon can be more sure about the
exact location of the left and right biliary confluence. where to transect the
glissonian envelope.

An additional benefit of using this technique might be that the hepatic
metastasis can be visualized according to the study by van der Vorst et al.
Therefore, the second hypothesis is that the use of NIRF fluorescence imaging
will help identifying liver metastases.

The main objective of this trial is to investigate the ability to visualize the
exact location of left and right confluence of the bile ducts and thereby
distinct between right and left hepatic ducts and the common hepatic duct using
NIRF imaging. This will be scored by the operating surgeon on a scale from 1-5
in which 1 is no visualisation of the structures in fluorescent light, and 4 is
excellent visualisation. Also, the target to background ratio will be
calculated to quantify the fluorescence intensity of the cystic ducts compared
to the liver.

Secondary Objectives:
- To establish when the ICG should be given for optimal visualisation of the
bile ducts with minimal background fluorescence.
- To assess whether the use of ICG can help identify the location of the liver
metastases.
Also, bile duct injury, total surgical time, postoperative length of hospital
stay and complications due to the injected contrast agent will be recorded.

A single center trial with two randomization arms:
- Early administration group: ICG is being administered the day before surgery
(12-24 hours before surgery), in a dose of 0,15mg/kg intravenously
- Late administration group: ICG is being administered just after induction of
anesthesia, in a dose of 0,05mg/kg intravenously.

Planned duration of this project: 1 year

The included patients will undergo NIRF-assisted liver surgery with the use of
ICG. ICG will be administered 12-24 hours before surgery in a dose of 0,15mg/kg
or just after induction of anesthesia in a dose of 0,05mg/kg. The fluorescence
mode on the (laparoscopic) equipment will be used.

Compared with standard care, patients participating in this pilot study will
receive one intravenous injection of ICG. This is the only additional
(minimally) invasive action for the patient. The administration of ICG (FDA
approved and used for several clinical diagnostic indications, previously used
in related NIRF-LC studies (NL 38521.068.11 en NL 47718.068.14)) and the
fluorescence imaging system are not related to additional risk for the patient.