99mTc-mebrofenin Hepatobiliary Scintigraphy (99mTc-HBS) liver function stress test.

Surgical resection remains the only potentially curative treatment option for
patients diagnosed with primary or metastatic hepatic tumor. Liver resection,
when performed in the absence of sufficient FRL function inevitably leads to
post-resectional liver failure (PLF), a severe and potentially life threatening
complication.

Computed tomography (CT) volumetry is considered the gold standard in the
preoperative assessment of patients scheduled for major liver resection.
Though, FRL volume does not necessarily reflect liver function.
99mTc-mebrofenin hepatobiliary scintigraphy (HBS) is a validated quantitative
liver function test and in being used in the AMC for the preoperative
assessment of patients scheduled for major liver resection and patients who
undergo portal vein embolization.

Currently we use one single cut off value (2.69%/min/m2) for HBS in order to
decide if the measured liver function is sufficient for a patient to undergo
hepatic resection. Though, HBS is performed after 4 hours fast which could mean
that the liver function measured is the **rest liver function** in stead of
**maximum function** of the FRL.

We hypothesize that some patients have a great **reserve capacity**. This
information could be of crucial importance in the preoperative patient
selection process especially in patients considered *borderline* operable due
to their low liver function. Furthermore, we do expect young patients to differ
in their **hepatocyte reserve capacity** compared to elderly patients.

In this study we will explore changes in the hepatic function after stimulation
of hepatic cells with an oral food challenge, the **hepatocyte reserve
capacity**. Moreover, we will explore potential differences in the hepatocyte
reserve capacity between young (25-45 years) and elderly (*75 years) subjects.

In case of encouraging study results, the study will be continued in patients
who will undergo a hepatic resection.

This study is designed as a prospective observational pilot study in 24 healthy
subjects.

Radiation burden for the participants increases as a consequence of HBS, which
we want to reduce as much as possible. For this reason, HBS will be performed
without SPECT-CT, which is normally performed together with
99mTc-mebrofnine-HBS. This is possible because information that is obtained by
SPECT-CT is not relevant for our endpoints. In case of patients who undergo HBS
prior to liver resection of portal vein embolization, SPECT-CT is an essential
part of liver function measurement. This adjustment reduces the radiation
burden for the participants with 50%. Furthermore, we will reduce the dose with
another 50% by performing HBS with 100 MBq 99mTc-mebrofenin instead of 200 MBq
(200 MBq is the clinical routine for HBS-SPECT-CT). This reduction is also
possible due to the fact that HBS will be performed without SPECT-CT. The total
radiation burden for the participants in this study will be 3.4 mSv for both
scans (instead of 13.6mSv for both scans in case of routine HBS with SPECT-CT).
As already mentioned, this dose is in category IIb of ICRP (report ICRP62),
qualified as an intermediate risk. We will advise the subjects not to
participate in this kind of studies more often than once per 4 years. There are
no known complications related to HBS.

For this study we will include healthy volunteers. In order to insure reliable
measurements, we need to include healthy participants without underlying
parenchymal diseases. In this light, we are not able to include patients who
will undergo HBS as part of their clinical assessment. Liver malignancies are
often accompanied by parenchymal diseases such as cirrhosis, fibrosis or
cholestasis. Moreover, this patient population is often treated with
neoadjuvant chemotherapy which has a great impact on liver function.

Participants need to fast overnight prior to each scan, which is burdensome for
the subjects. Though, patients who undergo HBS as standard preoperative
assessment or because of portal vein embolization experience little discomfort
due to the fasting. HBS will be scheduled the next morning. For each scan,
participants will not need to fast longer than 4 hours during the day (4 hour
fast is the routine for patients who undergo HBS in the clinical setting). The
total time investment will be maximal 9 hours. Travel expenses for the extra
visits to the hospital will be reimbursed.

An i.v. canula will be placed prior to each HBS scan. In this way we are able
to reduce the burden as using the i.v. canula 1) we will draw blood in order to
obtain biochemical parameters and 2) subjects will be injected with 100 MBq
99mTc-mebrofenin.


Standard clinical assessment will be performed prior to the first HBS-scan
which will be done by means of a number of questions aimed at participant*s
medical history and current health status. These questions are necessary in
order to ensure our exclusion criteria.

The counterpart of the burden is the possible impact of this study on our
future preoperative patient selection. Each day we see patients who are
considered *borderline* operable due to their low FRL function. This is a
difficult situation for every patients as we need to decide between 1)
performing liver resection with a realistic chance on developing postoperative
liver failure, which has a mortality risk of 80% or 2) no resection, though
liver resection is the only potentially curative option. In our opinion, the
social benefits that can be achieved with this study should not be neglected.

In case of encouraging study results, the study will be prospectively continued
in patients who will undergo a hepatic resection.