Selective Indocyanine Green Injection of a Segmental Hepatic Artery Followed by Near-Infrared Fluorescence
Guided Anatomical Liver Resection: A Feasibility Study

Anatomical liver resections for hepatocellular carcinomas (HCCs) reduce tumor
recurrence and may reduce blood loss and bile leakage. Intraoperative
Indocyanine green (ICG) injected through the portal vein combined with
fluorescent near infrared imaging has proven to improve precision of anatomical
resection. However, intraoperative portal vein administration of ICG can be
challenging, especially in laparoscopic procedures. Recent feasibility studies
showed promising results for intra-arterial selective ICG injection followed by
embolization of the segmental artery using intervention radiology and hybrid
operating rooms. Unfortunately, hybrid operating rooms are not available in all
hospitals. Therefore, our intent is to perform the interventional radiological
procedure separately, before the operation to facilitate access to the
procedure, logistics, safe precious personnel and time. This approach is based
on the results published in a case report recently.

Primary objective: To investigate the feasibility of using intraarterial ICG
preoperatively to allow for liver segment visualization during anatomical liver
resection.

Secondary Objective(s):
1. To investigate the dosage which provides sufficient contrast index of ICG in
the liver segment compared to normal liver tissue.
2. To investigate the optimal timing of administration of the ICG-mixture
without being washed out of a liver segment.

Prospective, single center, open-label, non-randomized phase II trial. Total of
12 patients receiving the same treatment.

Patients will receive preoperative angiography at least three hours before the
operation, during which the artery of the segment(s) containing the tumor will
be selectively catheterized with a microcatheter. Angiography and cone-beam CT
are then performed to confirm that the correct segment has been catheterized. A
mixture of ICG and lipiodol can then be injected to stain the segment. Lipiodol
causes temporary vessel occlusion as recanalization of the artery usually
occurs several days to weeks after the injection. After injection of this
mixture, gel foam (Cutanplast®) will be injected to avoid wash-out of ICG.
Segmentectomy of the targeted liver segment(s) will then be performed using
near infrared cameras for identification of the segment(s).

The burden for patients is low. In the first part no extra visits are necessary
for this study, since both the interventional radiology procedure and the
surgery will be performed on the same day. In the second part of the study, the
interventional radiology procedure will take place one day prior to surgery;
thus leading to one additional admission day. Moreover, no extra blood samples,
physical examinations, questionnaires or other tests will take place. However,
in addition to the standard surgical procedure, the interventional radiologist
will insert a femoral artery line in order to administer ICG, lipiodol and gel
foam. Percutaneous transarterial angiography and embolization both carry the
risk of mild complications like hematoma of the inguinal region or an aneurysma
spurium as a result of the femoral artery puncture. With the use of a vascular
closure device, the risk of puncture site complications is approximately 1%. In
rare cases a dissection of the femoral, iliac or hepatic artery can occur.
According to literature the chance is less than 2%.

ICG has been safely used for over 60 years for different indications. Only mild
allergic reactions have been seen. Patients with a known allergic reaction to
ICG or a substance related to ICG are excluded. Patients meeting one or more of
the contraindications for ICG are excluded from this study.
Lipiodol is an oil-based radiopaque contrast agent of iodine combined with
ethyl esters of fatty acids of poppy seed oil. Lipiodol is indicated for
hysterosalpingography in adults, lymphography in adults and children and for
selective intra-arterial use for imaging hepatocellular carcinoma. Patients
with a known allergic reaction to lipiodol or a substance related to lipiodol
are excluded from participating in this study. Patients meeting one or more of
the contraindications for lipiodol are excluded from this study.
The combination of ICG and lipiodol has been studied in renal cancer and
pulmonary cancer patients, without any reported adverse events.