2:32 Liver transplants 4:04 How effective is surgery for liver tumors? 7:18 Who can and who cannot have liver surgery? 8:45 What are the different surgical …
I'm going to talk about liver surgery
for neuroendocrine tumors and I know that
some of my patients are sitting in the
audience here and some of my patients
had had surgery so I hope I'm not going
to bore you too much because you've
probably heard this talk before however
let's talk about neuroendocrine tumors
and liver metastases so the liver is the
most common organ where neuroendocrine tumors
will metastasize to. and about
40 to 50 and sometimes here like you see
up to 70 or 80% of patients have liver
metastases when they present to us and
interestingly with small bowel
neuroendocrine tumors and with pancreatic
neuroendocrine tumors alike unlike other
cancers we often see actually a small
primary tumor like Jim described before
in this talk for small bowel and open
tumors. these tumors can be so small you
can't even see them but then a larger
lymph node package and a usually
relatively large amount of metastatic
burden it's often the opposite then we
see with other types of cancers now
there's one take-home message that I
think is extremely important and and I
think we we should all remember that is
that the number one cause of a
diminished lifespan in patients with neuroendocrine tumors is liver failure due to
overwhelming liver tumor burden I think
it's important because it helps us as as
a physician understand where the
priorities should be so we have two
treatment options for liver metastases
and we talked about that throughout the
entire day Andy gave a fantastic talk as
well about it but essentially there's
systemic therapy so any therapies that
target any tumor in your body
we have octreotide analogs we have
targeted chemotherapy with chemotherapy
and we have PRRT and then we have those
liver-directed therapy so these are
therapies that specifically go towards
the liver and as already gave a great
talk about the liver directed therapy is
that the interventional radiology uses
but as surgeons we also use liver
directed therapy and that is actually
removing the tumor
of the liver and in liver transplant I'm
not going to touch on that today it is a
question I quite commonly get liver
transplant we rarely use for metastatic
neuroendocrine tumors and the reason for
that is that even though there are some
studies out of the US and out of you of
data shown like occasionally it can be
helpful most of the time because you
have to go an immunosuppressive regiment
after after having had a liver
transplant the tumour tends to come back
in the liver and then you are in an even
more challenging space so it's it's not
a cure unfortunately but there there's
research that's ongoing and perhaps that
will be more and more important than on
the line okay so this is a paper
published with Thor and Jim and a couple
of other people but essentially what we
are specifically pointing to in this
paper is saying you know we have
systemic therapies for neuroendocrine
tumors but none of them works
particularly well or we just don't have
any data so we don't know whether they
work particularly well specifically
specifically for liver metastases this
is an area that I think we need a lot
more research in because we really want
to try to understand how well do these
systemic therapy work for liver disease
and especially at shrinking liver tumor
burden because as we heard before they
are good at stabilizing disease but
ultimately the tumor continues to grow
at some point and again we don't want to
be in that situation where you have
overwhelming liver tumor burden so so
much tumor in your liver that your liver
doesn't work properly anymore so why
surgery for limited tasks is now the
first point is an important point that I
want to make when the tumor has spread
to the liver it is exceedingly rare that
with an operation where we'll cure you
5% chance or so we always say 95% the
tumor is gonna come back even if we
operate and remove it out of your liver
however we do think and there are some
retrospective study that you we do
provide a survival advantage by
operating on your liver and removing the
liver tumor burden and that is because
of our famous surgical debulking concept
which is we're resetting the time clock
so these are slow-growing tumors they
are not like other types of cancers that
rapidly spread and rapidly grow and so
if you think about it it comes down to
the point that if you have a slow
growing tumor by the time you're
diagnosed that you will probably have
the tumor already for many years and if
we can at that point remove all the
tumor that we can see we kind of put you
back in time we go back in time to a
time point where you know maybe three
four or five years ago you didn't have
that much tumor and ideally it would
take that as much time again until the
tumor comes back so it's really this
resetting the time cock like paradigm
that is very important for us now we can
achieve major tumor burden removal and
deliver that Jim has been one of the the
surgeons that have done this for a long
time and and and and I've follow up in
this footsteps and this many studies
that have shown that we could do it
without having a lot of complications
and the concepts I'll talk to you about
that in a minute it's not to remove huge
chunks of tumors but just picking these
tumors out one by one or burning them
like ours did and then there is an
interesting intriguing question that we
are asking ourselves more and more is
that surgery actually helped other
therapies to work better and that's a
really really fascinating field so as I
said many studies although retrospective
thousands of patients that I had sought
a reduction in the literature and we
think that there's some survival
advantage as you can see here compared
to other therapies these are Jim's data
I'm not going to go too long over this
because of of you know time constraints
but traditionally we always wanted to
take out 90% of the tumor burden in the
liver turns out that maybe if we do 70%
we're still significantly helping
patients so it's not because we can't do
90% that you should not have an
operation the overall survival is quite
good whether you remove greater than 10
lesions or 1 to 5 lesion so again the
number of lesions not necessarily
restraining us in terms of what we can
do surgically and then the survival the
long-term survival is very good for
… patient excuse me those patients
that have achieved greater than 70%
debulking that's a slide that Jim showed
before compared to other data so it's
liver surgery safe that's a very
important question because we the last
thing we want to do remember you can
live a long time with this tumor the
last thing we want to do is you never
leave the hospital that would be the
worst-case scenario for as a surgeon so
we have to pick out our patients
properly we have to make sure that they
can go through a surgical site a
reductive operation so if you're 90
years old and you had the three heart
attacks probably not the best candidate
to undergo liver surgery but if you are
young or or if you are if if we think
that you can get through surgeries then
definitely you should do it in certain
situation because we have shown that the
mortality rate is low and the
complications are low as well if it's
done in experienced hands now when not
to surgically cytoreduce as a nice
slide from Jim you know you see this
liver here that is chock full of tumors
so there's so much tumor that I can
almost not tell where the normal liver
is that's something that I can't take
out that's a 60, 70 ,80 % of replacement
that's something that where you would
see our medical oncologist for a
systemic therapy or ours actually that
can help with some of his liver directed
therapy even in those complex situation
so when not to cytoreduce obviously we
got to make sure that you don't have a
ginormous amount of liver that's
replaced by tumor we we want to make
sure that we rule out carcinoid heart
disease before we do an operation
because you may need a valve replacement
before we take you to the operating room
and obviously if you have poor
performance status you're not a good
candidate for surgery and high grade
tumors also so this is an example of a
liver here that you could see these
black dots are tumors what do we look
for preoperative and when do we decide
how to resect well we got a look on
where where are these tumors compared to
the blood vessels that are mentioned
that go in and out of the liver are they
on both lobes one lobe well do we have a
liver tumor burden it's overwhelmingly
arch or not 25% is probably a good
number where we could say if it's less
than 25% you're probably a good surgical
candidate and then my little drawing
said I took to the operating room is a
map these tumors out there's fancy
technologies that you could also do it
but I do it by hand the night before and
I and I basically show where all these
tumors are in relationship to the
structures so I remember which one I
need to take out because if you have 40
tumors in your liver I got to remember
which one I need to take out and then I
have a marker that's sterile and I
checked them off one by one and I work
in a clockwise manner so it takes a
little bit of time you have to be
patient but you could definitely clear
this livers out of a lot of tumor this
is an example everything that's right
here is actually tumor and then some
important structures not too far away
the patient was told to be non operative
candidate because close to bile ducts
and close to some of the important veins
but actually not that close so we were
able instead of taking can you press
play please
taking out the entire big chunks of the
liver we actually can you press play we
actually do it by by literally it's like
a golf ball we we basically carved these
tumors out one by one and we stayed
close to the tumor because there's no
point of taking big chunks of out of the
liver remember the liver is the most
important organ we want to keep it nice
and healthy so we're not gonna take
large amounts of liver out we're gonna
take everything out that's around the
tumor all right and when we're done it
looks like this can you press pray one
more time the Swiss cheese liver like we
like to call it so that's a liver that
we're lifting it up here you have a
bunch of holes all over the place
right and those are all the tumors that
we actually remove and the liver is an
amazingly strong organ you can beat it
up pretty hard and it's gonna do
fantastic and grow back very very
quickly now another example press play
again one more time please is that we we
combine these resections with ablation
so I don't know if you can see that very
well on the screen here
if you plus play they're coming
no it's not coming but anyway so what
this would show you is a video of an
ablation how we do an ablation like ask
say this we like stick a catheter into
one of these tumors and we burn it with
heat usually I don't know what it's not
popping up but so this are some of the
tumors that we end up removing in this
particular patient you know this is the
scan about a month later
these are ablation zones here you can
see this little holes in the third in
the liver this is where we resect it and
a year later you can see the livers
contracted here but there's no tumor
that showed back up this is what I
mentioned before where the big lesion
was the liver kind of you know grows in
itself and outside of itself and
contracts a little bit but that's a
tumor free liver so I'm just gonna not
take a lot of time to go over this but
this is these are the decision-making
trees that we need to take right so if
you have a tumor that has spread to the
liver usually how is the disease tumor
burden do we think we can take it out or
not do we think you need to go on
systemic therapy or not and that's why
we have these famous tumor boards like
you saw this morning now the last two
slides one of them is repetitive slide
this that Andy showed but essentially in
the NETTER one trial remember the trial
that tested PRRT four in small bowl
neuroendocrine tumors interestingly you didn't do necessarily worse if you were in the
PRRT arm if you had a lot of tumor burden
but you did worse if you had larger
lesions like like we saw this morning so
that's an interesting concept and we
don't know why is it because you know
tumors that have larger lesion are more
aggressive we don't know because we
think that probably if you wait long
enough the tumor will reach a certain
size or is it perhaps truly because PRRT
is not able to like penetrate larger
lesions as well and that's an
interesting point that we're going to
actually study in a phase three trial
here at the University of Chicago
with Jim and also with OHSU me at
OHSU where for peanuts we're gonna open
up a protocol for pNETs where we're
gonna open up cytoreduce patients and them give them PRT before surgery and see
whether that is gonna make a difference
in terms of progression-free survival so
can surgery be helpful in taking out the
large lesions and let PRRT do the rest
for the smaller lesions and another
study which is also an interesting study
was published this year came out out of
Europe where they actually looked at
patients that underwent PRRT and who had
their primary tumor removed right so
most of them did not have liver surgery
but they had the primary tumor removed
and you could see that the chance of
actually having an event meaning that
you're progressing is actually less if
you had your primer tumor removed when
you got PRRT that's almost a thousand
patients so that's a really interesting
study because what it shows you is that
perhaps removing a primary tumor even
even if you can't remove the liver
metastases may help PRRT to work better
so these are two like interesting new
piece of data that we saw this year that
may play into what we believe is a
really exciting times ahead and trying
to understand what is the role of
systemic therapy and liver directed
therapy and I don't see them as two
completely different aspects of treating
the tumor but I actually see them as
working hand-in-hand and perhaps you we
are going to help PRRT by cytoreduction
or perhaps PRRT for example can help us
to cytoreduction so I think really
exciting times I had for this and and
and I hope that the important message
that came across was that you should
cherish your liver it's a very important
organ all right my favorite organ to by
the way

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