The
format is wrong on the
papers from New Orleans, shall redo ASAP. Susan, May 10, 2005
DR. DANIEL FREY, Professor of Surgery:
Thank you, Dr. Woltering. What I'm going to try to do today is spend a
little time talking about what we have been involved in with the surgical
cytoreduction therapy. As you can see, we're going to talk about the
indications for surgery, indications for chemoembolization, and indications for
RFA. And then at the end, I'm going to talk a little bit about liver
transplantation, which has become more of an option when there is evidence of
disease in the liver that's not amenable to resection. Why does somebody want
to be operated on? You know, it's not something most people look forward to, no
matter what it is that you're having done, but from the point of view of the
carcinoid patient, there are really four reasons to think about having some form
of a cytoreduction or a surgical procedure. And I'm going to use those two
terms more or less interchangeably. Naturally, with all patients that have any
type of cancer, the first thing we want to do is we want to try to “cure” them
of their disease process. And the best treatment for that is a surgical
approach for patients with carcinoids.
Patients that have been operated on for surgical cure frequently are not
referred to me or Dr. Woltering or Dr. Anthony, and we don't see those patients.
Probably most of them are not sitting in this forum today. Because in their
aspect, they were operated on; the carcinoid was removed; it has not
metastasized, and therefore they're “cured” of the disease. At least for now!
From my perspective, the most common indication that I have to operate on
somebody is when they have a symptomatic disease process. As all of you in the
room know, carcinoid syndrome is a syndrome which is produced by excessive
hormone production. And it does cause significant symptoms. Those symptoms are
usually diarrhea, flushing, heart palpitations, but also it can be symptoms of
pain from the mass effect, i.e from the size of the tumor. You can also have
symptoms of obstruction, whether that be the obstruction of the intestinal tract
itself or biliary tract or of the blood vessels that lead to either the
intestines or the liver. So you can have a flux of symptoms that go along with
the individual person.
What we have been doing in our program is operating on people with the
intent to debulk them which improves the ability of the medical oncologist and
the radiation therapist to administer their therapies, i.e. if you've got 100
tumors and I get 50 of them out, well, then they only have 50 tumors that they
need to deal with. So it facilitates the medical therapy and we refer our
approach as adjuvant surgical therapy.
So I see the patient; I take out part of the tumor. I hope that this
decreases their symptoms, and we then use
either
Sandostatin LAR, radioactive
pentetreotide or chemoembolization on the remaining tumor.
And naturally as most patients that have carcinoids know, one of our big
reasons to operate on somebody is to improve the quality of life. Instead of
going to the bathroom 25 times a day, they may have to go to the bathroom 4 or 5
times a day. And though we may not be able to prolong your life expectancy,
which with carcinoid is fairly good anyway, the time that you do have to live is
a much better quality of life. You can go out of your house; you can go out to
dinner; you can go take trips and you're not tied by a 10 foot long cord to your
toilet.
So what's a big indication for the types of therapy that I'm going to talk
about over the next 40 to 45 minutes?
Just a little differently in scope and perspective and most of you-all
heard my talk last time, probably recognize these slides. But prior to the
introduction of Sandostatin, the only real treatment for carcinoid was surgery.
And when I was a resident 20, 25 years ago, the few carcinoid patients that I
had would come in periodically and we would pluck out some of their nodes to
control their symptoms. And they would go home, and they would come back 6 to
12 months later with carcinoid again until the disease overwhelmed them.
And if you look at the Sabiston Textbook of Surgery that was published in
1991, here were the statistics that they were
quoting. They
quoted with liver
mass, the average
five-year
survival was 20 percent but remember that this was
in the pre-Sandostatin era. In the late '80's and early '90s Sandostatin
probably became more popular and was used more. In fact, surgery fell “out of
vogue” and patients treated their symptoms with Sandostatin.
Surgeons were consulted kind of as part of a last ditch effort. And I
know of one of the patients that I was seeing had had his tumors treated for
three, four, five years with just Sandostatin. And then when they'd get
breakthrough, they'd elect surgery.
Well, here's the difference. Looking at the 20 percent five-year survival
and now that we – this slide is two years old -- We have a 67 percent five-year
survival with liver mets in the Sandostatin era. So Sandostatin has certainly
done a wonderful job of contributing
to the length of time that patients survive
as well as improving
their
quality of life the patient had with carcinoid.
The thing about carcinoid syndrome and carcinoid tumors that other
speakers may not have talked about just briefly. This is a picture of a
carcinoid primary. You can see how small it is. You can see that some of these
tumors were in a regional location and can be less than a centimeter in size.
And, in fact, there are some patients that have overwhelming metastatic disease
and we cannot find the primary source or a primary location.
And this can be an example of what an Octreoscan looks like on somebody
that has a tumor this size that has multiple masses in the liver and throughout
the abdomen on Octreoscan. So small tumors can be asymptomatic and the small
tumors can be hard to locate. For many patients, it's a metastatic disease that
is originally diagnosed, and it's usually the metastatic disease that gives the
most symptoms. Most patients that are symptomatic are symptomatic from
metastatic disease.
Where are small carcinoids located? You heard a little bit from Dr.
perspective of the surgeon. I'm an abdominal surgeon so most of what you're
going to hear about in my talk pertains to patients that have tumors that are
located in the GI tract and are metastatic tumors.
I may touch a little bit on some of the bronchial tumors and others just
as a sidelight, but that's not going to be what the thrust of my talk is as
far as the indications for surgery. But as Dr. Linares said, it's a very rare
tumor. It doesn't matter if it's a rare tumor because each of you have it. So
it doesn't matter how rare it is; if it's yours, it's your disease.
Forty percent of carcinoids arise in the appendix; 30 percent of them are
in the small intestines and 10 percent in the rectum; and the other 20 percent
are in other various locations, like the pancreas or the stomach or the lungs.
Metastatic risk is associated in some ways to two factors: the size of the
tumor at presentation -- but as I already showed you in my very first slide, a
very small tumor can metastasize. So it doesn't mean because they told you your
tumor was less than one centimeter, you can never end up with a metastatic
tumor. Certainly, the smaller the tumor, the less likely it is to metastasize.
Site is somewhat important as far as the clump of carcinoid tumors to be
looked at in the intestinal tract.
Now, when you come to the doctor, no matter who the doctor is -- me, Dr.
Woltering, or other doctors -- when you start talking about surgery, you have to
have in mind or the doctor has to have in mind what is going to be the purpose
of the operation that we are about to undergo.
I'm going to give you a little bit of my philosophy. But my philosophy is
that my first goal is to take care of whatever you're presenting to me for that
day. So if your complaints have been related to obstructive-type symptoms:
nausea, vomiting, abdominal distention, bloating all the time, loss of appetite,
and you've got a carcinoid tumor of your small intestines, then that's generally
what I'm going to recommend to you to approach first. Even if you don't have a
lot of metastatic
disease in the
liver, because once again, my goal is to
improve your quality
of
life. So my approach to you as a pateint
is to try to
improve what your problem is.
If the problem is related to hormonal condition: diarrhea 25 times a day,
flushing that is uncontrolled, palpitations, then my recommendation would be to
deal with those symptoms first. There are different types of incisions and
there are different surgical approaches depending on what your complaint is. If
you have an obstruction of the bowel or if you've never been explored before and
if you've never been surgically staged by somebody, then I generally recommend a
midline exploration, removal of the primary tumor and staging: evaluate the
liver, evaluate the mesentery adenopathy, evaluate your pancreas and the
ligaments that attach the liver to the duodenum, and depending on how the first
surgery goes, maybe or maybe not do some or all of that the first go round.
Frequently, I will recommend that we explore somebody to get a good idea
of how much of the disease we have to deal with. Because the CT Scans and
OctreoScans underestimate the amount of disease that's present in the abdominal
cavity or the liver, small lesions will be referred to as milliary – and that's
in millimeters in size -- can be present throughout the peritoneal cavity or
throughout the liver.
And they won't show up on the
OctreoScan, or on
the CTs
because they are so small. So part of the question that you have to ask your
doctor is: What's going to be the goal of my therapy? And you need to kind of
have an idea in your mind of what it is that you're looking for as we go down
the treatment path that we're going to embark on.
Most of the time, by the time you see me, most of the time you've got the
workup done: CT Scan, the Octreoscan -- as Dr. Linares indicated is crucial -- I
don't do any preoperative ultrasounds, but just about every patient that I
explore I will do an intraoperative ultrasound because of small lesions within
the liver, and then the basic laboratory panel, 5-HIAA and chromogranin-A.
I do get a liver panel on most patients to find out what the status of
their liver reserve function is. Then I have an idea of how much work I can do
on the liver while I'm in there. If the patient has any type of cardiac
abnormality, then they get a cardiac workup. I assume most of you know that
carcinoid generally can affect the valves of the heart. So we may get an
echocardiogram if there's a murmur or they complain of fatigue or if they have
any associated symptomotolgy. And naturally, any patient that has another
type of co-morbid condition may need to have extra tests. If you're a diabetic
for 30 years or if you've got other types of complaints, then they have to do
more extensive testing. But from the carcinoid perspective itself, we do a very
limited pre-op workup to decide to get you ready for surgery.
There is a little bit of a difference between the various surgeons that
you're going to go see as far as how they manage patients intraoperatively. And
what I'm going to go through is my approach.
We use a continuous Sandostatin infusion that is started before we put the
patient to sleep. Some physicians feel that as long as you have the Sandostatin
available to give as an IV push then that is sufficient. They know what
carcinoid crisis is, and if one develops, they’ll treat it.
I am more comfortable with preventing it than having to treat it in the
middle of an operation and have to deal with blood pressures of 240 or 250 or a
heart rate of 170. If I can prevent it from happening, I'd just as soon do it.
Most of the patients are already on Sandostatin. And as most of you know, the
complications from utilizing Sandostatin is so minimal that I personally feel
more comfortable having the infusion going and having the base line level of
Sandostatin on board.
I also use a technique that's called low central venous filling pressure.
And so I don't like to give patients a lot of fluid and to blow them up and to
get their livers and intestines all swollen. So all of my patients that I treat
with carcinoid get what's called a central line placed, usually in a large vein
in the neck. And we then monitor their heart pressure and keep their heart
pressures on the low side. And we're going to use other types of drugs to keep
their blood pressure up instead of giving IV fluids.
And then, the last thing that I do if I'm dealing with liver problems –
and this just applies to liver problems -- is I use a technique that's called
“portal vein hepatic artery inflow occlusion”. What we do is we put a clamp on
the blood that's going from the intestines into the liver while we're working on
the liver. And that way we cut down on our blood loss and we cut down on any of
the other problems that may occur with a liver resection presenting itself.
So this is kind of our technique. There are many other techniques and if
you get to the point of wanting to know that much detail, then you need to talk
to your particular surgeon about the operation, but this is kind of what we do
from interoperative management perspective.
A little bit on the extent of the disease. Naturally we talk about CT
scans. Everybody gets CT scans. Everybody gets an Octreoscan. And then we
operate on them. And this is frequently what we will find at the time of
surgery. There's a big tumor; that's a patch of the intestines. Okay?
Here we're doing intraoperative ultrasound. This is the ultrasound being
utilized. It shows a big tumor in the posterior portion. And this one is
actually in the process of being burned. Here is the probe going down through
the liver, burning the tumor and the tumor's turning white.
When the tumor turns white as you burn it, that's an indication that the
tumor is dying. And there's the specimen with a piece of intestine and a whole
piece of liver attached. I want to shift here just a little bit and talk about
two separate subgroups of patients that we've operated on at LSU.
Unfortunately, I do not yet have a database put together on all the patients
that I've operated on that I can give you a complete evaluation. But what we
have been following over the last five years is we've been following two
subgroups of patients that we operated on, and I'm going to give you an update
on that. Those are the patients that have advanced liver involvement. So I'm
not talking about just a single liver lesion. It's somebody that's got a lot of
tumor in their liver and most are involving cancer that's wrapped around the
mesentery which many surgeons would have declared: There's nothing can be done
and it's not resectable.
And in fact, both of the groups of patients we've operated on have
actually been operated on by other surgeons with that finding. They're operated
on and they're either bypassed or they're closed and told that there's nothing
that can be done. Well, we're going to talk a little bit about those two
classes of patients. From the historical perspective, we would try to get an
idea from our patients on what causes cannot be performance scaled. And this is
a scale that I've talked a lot about. This is the scale that measures how well
you're getting along with your quality of life. A hundred being normal, zero
being before long you're dead. And you can see in the 50 range, patients need
considerable assistance in caring for themselves or in their life. We would say
anything below 50 would be a poor quality of life. Anything above 60 would be,
depending on the patient, an okay quality of life.
Somebody does fine if they can care for themselves or they're able to
work, their quality of life of that patient may be okay. But certainly, below
50 would be a poor quality of life. As you can see, the scale goes down death
is zero, near death is 10; very sick a lot or hospitalized to be around 20
range. So I'm just giving you that as a kind of benchmark for what we're
talking about.
What do we want our patients -- This is going to be old stuff. Because
this has not been updated on the parts I'm talking about right now. The next
part that I talk about will be updated. But this is the old stuff. We had 45
patients with various complaints, and you have to remember that these are
patients that are complaining
of
symptoms i.e. they are coming to me to be
operated on. So this is not the common presenting complaint for carcinoid
patients. But these are our patients that had advanced liver disease. And you
can see that there's -- there's the syndrome was present in 66 percent; pain and
small bowel obstruction was present in our entire percentage, but this is a –
this is a selected group of patients that are coming to us because they have
these symptoms.
And here is what the outcome is of our surgery. As you can see, the mean
score pre-op, before we operated on them, was 55. And remember, I told you
between 50 and 60 would kind of be needing considerable assistance or needing a
little assistance. But most of them were in that range.
Post-operatively their scores went up to 85, which is almost self-
sufficient, doing well with no complaints. So from our perspective, with a mean
follow-up of over a year we feel that operating on this particular group of
patient greatly improved their quality of life.
Here's the updated series from those same patients and the additional
patients that we've operated on in the last two years. We've got 53
patients with advanced liver disease. The syndrome was present in 45 patients,
but we've done more patients with the syndrome. We've had to do multiple
surgeries and multiple radiofrequencies in lot of our patients. It looks like
about 65 percent of our patients are now on what we're calling the “Staged
Surgical Treatment Plan”. You do a little bit this time. Six to twelve
months later, you bring them back; you do a little bit more. We have found that
the patients have tolerated this better. And also as a patient that you just
want to follow a hormone level. Our chromogranin-A level would be decreased by
almost 57 percent. So from that perspective we've had improvement in our total
amount of hormone production in this group of patients.
We have had complications. These complications include abcess formation.
In four patients, three of the four were associated with patients that also had
bowel surgery done at the same time. So they either had a small bowel and/or a
colon resection associated with a liver operation. So because of those four, I
now make sure that I tell the patients that if you want to have it all done as a
one stage operation with your liver the incidence of you getting an infection or
abcess goes up. And I let the patient decide if they want to take the increased
risk or if they want to do it in two separate surgeries.
We've also had a couple wound infections. Most patients will get what's
called a pulmonary effusion. Some doctors don't even consider this to be a
complication. They consider this to be an expected outcome from the surgical
procedure. Because of the fact that the liver is attached to the right
diaphragm and because of the fact that we have to take that apart and then work
along that area, there's a lot of irritation to the diaphragm, especially if we
do RFA. And so if we do radio frequency oblation at the same time, they get a
lot of swelling and a lot of edema.
What I tell most of my patients is most of us at some point in time have
burned ourselves. And when you burn yourself, you get a blister. You get fluid
that leaks and you get a big swollen finger that hurts. So that’s what effusion
is in those patients.
We have had two develop a bile fistula. And this is one of the problems
that occurs anytime you operate on the liver, and that is that when the liver is
being transected, little bile ducts that would normally be draining that segment
of liver can be left open. You try to keep an eye open and sew them off, but
these are multiple small ducts that are present in that cut surface of the
liver. And because of that, you can release bile, instead of going into the
intestine, it then leaks into the abdominal cavity.
And we've had two of those, one of which required a repeat operation to
sew it off. The other one was able to just be treated with a drain, that kept
a drain until it closed off on its own. We've had two deaths that have been
related to surgery itself. These were unexpected deaths that were patients that
should not have died from their carcinoid process.
And we've had four early deaths that were related to early carcinoid
disease. In retrospect, those four early deaths probably should not have been
operated on. We probably should have accepted that the patient had such an
advanced level of disease that it was beyond our ability to help, but at the
time we knew it was their only chance. And so we went ahead and proceeded with
it.
Overall, our results have been good. And we feel that our patients, for
the most part, have had improvement in their quality of life. And I have to
emphasize that a lot of these patients were getting them, more or less, as a
last resort.
Here's the other big group that I just want to spend a little bit of time
on. And this is actually a group that we've seen -- I guess more frequently, at
least in my mind. I didn't see any of these prior to two years ago; a year ago
we had seen four of them and then in the last two months we've seen two more.
These are patients that have disease in the mesentery that involves that part of
the mesentery where all of the blood vessels come up from the aorta and go up to
the intestines.
So this is the area that all of the blood vessels run through. And it's
also the area involved where lymphatics drain from the intestine back into the
portal vein area. So it's called the root and it looks like a tree on the –
when you look at the patients on the operating table. It's where all the
blood vessels come out, all the blood vessels and all the lymphatics return.
And this is one of the areas that because I'm seeing these patients, I'm
actually treating my patients that I'm doing bowel resections a little bit
differently. And I'll talk about that a little bit. But all of these patients
were explored elsewhere. They were all declared nonresectable by what I deem to
be very competent surgeons. I actually know personally two of these surgeons
that were involved in these cases. And I think that both of these surgeons are
very competent, qualified surgeons who felt that there was nothing to be done.
However, after they were closed, the patients simply either got worse or
they lost weight so even the patients felt that they were on a downward spiral
and we operated on them as a second approach. We were actually able to resect
five of the six patients. One of them, who was unable to be resected, actually
died in the early postoperative period.
Four of the five have had marked improvement in their symptomotology.
Now, none of these patients were cured. They still had residual disease from
other areas. But at least their presenting complaints having a bowel
obstruction, or what's called mesentery ischemia, that part of the intestine
wasn't getting enough blood flow to it and was giving them severe pain, had been
relieved.
Just a few more points on surgery before I switch over to
chemoembolization. What I have done to surgically relieve the mesentery is I
now do a complete node resection all the way down to the root of mesentery on
any patient that I am getting with a carcinoid primary. Like I said, a lot of
times patients with carcinoid are operated elsewhere. And one of the things
that some of the other surgeons do when the see a liver full of metastatic
disease is they say: Well, we're just going do a limited operation to try to
just get this part out. And they'll leave residual disease behind because they
think it's going to be cancer in the liver that's going to kill them.
With Sandostatin now and with chemoembolization and the other techniques,
patients are living long enough that the primary disease in the root of the
mesentery and/or primary lesions are now giving them problems. So I actually
have become much more aggressive in my surgical treatment of the primary disease
and in the liver and the mesentery to try to remove all those lymph nodes to get
any possible carcinoid remnant out of it even if you've got liver disease. I
know we can treat the liver disease, and I know we can continue to whittle away
at that and treat with other modalities. And if you're going to talk about
liver transplantation, I also know that if there's no disease outside of the
liver, then a liver transplant makes a lot more sense than if I've left residual
disease in the liver. But my current approach when I do resections primarily,
is that we do a fairly generous resection and try to get out all of the
lymphatic and all of the draining vein from that tumor to try to minimize any
recurrence within the liver.
Okay. We're going to kind of shift gears a little bit and talk about
other methods of cytoreductive therapy. Chemoembolization is the -- what I
refer to as -- the "second line."
The theory behind chemoembolization is that malignancy initiates new blood
vessel formation. These new tumor cells need to have blood and oxygen so that
they can survive. And so if we can do something to get rid of that blood
supply, then we will cut down on
the growth of the tumor. Importantly the liver
has two main blood
supplies—one
to thenormal parts of the liver(portal vein)and
another one to the
tumor( hepatic
artery). The embolization is done
through the
hepatic artery and
thus hits the
tumor hard while leaving the normal liver
relatively untouched.
And so
that's the theory.
The other part of the theory is that chemoembolization by injecting high
doses of chemotherapy and then cutting off the blood supply to the tumor, the
tumor will die or necrose. Here's a rather large tumor (pointing) in the
right lobe of the liver. There's a small one over here. There's another small
one there; there's some little ones here. And there's some over here. So this
would be what we would refer to as bilobar disease with a large dominant lesion.
There are two ways to approach this lesion. One approach would be to
resect it. And the other approach would to embolize it. Different patients
may have different preferences about how they would want this to be treated. A
lot of it may depend on how old they are, what their risk factors are, how
many other surgeries they've had. But that’s a large lesion.
Here's what it looks like on an angiogram. Now, an angiogram of the liver
is just like an angiogram of the heart. The radiologist sticks a needle in the
blood vessel, the artery of the leg, threads a catheter from the leg, up into
the blood vessel that goes to the liver. And that would be this artery right
here (pointing). And here it is coming off, going up into the liver. And
here are the big tumor vessels. This is filling up this whole big tumor.
o they get a catheter, then, they injected it and thread a catheter all
the way out to right there. And right at this point when they get the catheter
to right here (pointing), they hook up an infusion device where they can infuse
chemotherapy into this. And then they take what are called some portal -- or
some kinds of embolic material and they just close it off. So that now that
tumor is loaded up with chemotherapy material and there's no more blood flow to
it.
We're going to talk a little bit about it in a minute, but sometimes they
will actually do in this what is called "multiple chemoembolization" procedures.
So instead of trying to kill this whole tumor, the can actually thread the
catheter all the way out to here, and they can just inject the top part. They
can then come back six weeks later and do the middle part and then come back and
do the bottom part. And we'll talk a little bit about why that would be
indicated.
And here's what a tumor like that would look like after its been
embolized. So this is all dead, necrotic tissue all the way here.
Chemoembolization is a useful technique for people that have a lot of
disease in the liver that are not amenable to surgery or as an adjunct to
surgery, but it does have its limitations. Any time cells in the body die, they
release those byproducts into your blood vessel system.
So when you get big cell death, those cells get released. The byproducts
get released into the blood stream and they circulate throughout your body.
Naturally, the bigger the tumor and the more cells that you kill, the larger
these properties that they release. So the size of the tumor can be a limiting
step and sometimes depending on the patient, we would do multiple embolizations
instead of trying to do it all at once.
It is also related to how good the rest of the liver is working. If
somebody already has cirrhosis from another cause, like Hepatitis C, or if
they have so much tumor in the liver that they are already borderline on liver
failure, then chemoembolization may be enough to tip them over into liver
failure. So the risk with liver failure increases as the amount of liver
reserve decreases.
And then, finally, not all livers are created the same. And there are
some technical variances. There are some arteries that sometimes prevent the
radiologist from threading a catheter into that spot. So there are some
technical problems that sometimes can occur in the chemoembolization process.
And an offshoot of chemoembolization is a new technique that we've
actually started here at LSU in the last six months called "Direct
Chemoinfusion." I don't know if anybody has talked to you about this or
not, but chemoinfusion is a process where you put some chemotherapy material in
over a period of a few minutes, 30 to 45 minutes, and then you block off the
blood supply immediately. The amount of chemotherapy that gets into that tumor
and/or stays into that tumor is unknown, but it's probably limited to a small
amount.
Dr.
Pommier up
at
this technique, and we've actually started doing it here within the last six
months. And this is high dose chemoinfusion of 5 FU directed into that artery
that leads to the liver tumors (the hepatic artery).
The way we're trying to do this now is when we operate on patients that
have liver disease that is in both lobes, that is overwhelmed, if we can't deal
with it with a local RFA or local resection, this is our backup plan.
We put a catheter directly into the artery that goes into the liver. The
patient ends up with is a small little what is called a "port" buried under the
skin that allows us to put a needle in. And then over a
period of five days, we
give them five days worth of 5 FU chemotherapy.
And then we follow this with chemoembolization. So instead of their just
getting a small amount of therapy into the liver, they get a high dose amount of
chemotherapy into the liver tumor and then we go in and we block off the blood
supply.
Dr. Pommier has reported excellent results with this with a lot of
improvement in quality of life as well as decrease in the size of the tumor.
We've just started it within the last six months, and I really don't have any
information that I can give you on our experience yet. But so far the patients
seem to be doing very well except for one patient that developed an infection
and we had to take the port out. So he never got the treatment and I removed
his port. But this is a new technique.
Switching gears again, from cytoreductive therapy to radiofrequency
ablation, most of us will say it's RFA or the other word that we use is called
cooking; we cook the tumor. RFA is basically high energy microwave frequencies
that are administered to the tumors to burn them. I like to explain to the
patients that it would be the equivalent of putting a piece of liver in the
microwave at home, cranking it on high and turning it on for 30 minutes, and
then coming back and seeing what that liver looks like. It looks like charcoal.
It started being used in 1996 and 1997 as an adjunct, and it has now
become pretty much a mainstay therapy to where -- once again, some progams will
use this as their preferred method to treat patients with carcinoid. So some
centers will -- if you go there and you have a liver scan and carcinoid, they'll
use this as their preferred method because in their mind the complication rate
is lower than doing a resection.
Here is what it looks like (holding up). Here is the probe. The probe
goes into the liver; it's collapsed when it goes in, and you then push on it
here and it comes out and it looks like a little umbrella. So you open it and
it looks like an open umbrella. When you're trying to prevent yourself from
getting sunstroke or rained on and just pours itself into the tumor and then it
gets hooked up to a microwave generator.
And you just sit there until the generator tells us that everything in
here is dead. You know, it's pretty simple. The machine tells us when the
electric impulses throughout here can no longer be transmitted, then that means
there's no more live tissue in there to transmit microwave energy. And it's
considered to be cooked at that stage.
It takes about 15 minutes per each lesion that you want to cook. So if
you wanted to try five or six lesions on somebody the operation would still take
a couple of hours to treat all of them. Here is an example of what an radio
frequency ablation would look like. Here's the lesion.
The question that has arisen is: can this be done without operating on
you? And the answer to that is yes. And this would be an ideal lesion to not
have to open your abdomen for. Here is the lesion. The radiologist can easily
go through the skin; put the probe right here on the ultrasound or CT guidance
and cook this lesion. And here is what it would look like after it's been
cooked. One of the down sides to that, if you're going to call this a down
side, is this does not go away. This is dead tissue, so therefore the liver
will not regenerate and will not fill this in. So you will always have a CT
scan that shows a hole here. Okay?
And one of the other down sides -- and once again, it may not be a down
side -- but frequently after radio frequency oblation, the liver -- the lesion
will actually look bigger because we've cooked tissue that's normal around the
lesion. So it is not uncommon to see a follow-up patient or a radiologist to
say: gee, since we scanned you last time, it's doubled in size. Well, it didn't
double in size; it's just that we treated the other surrounding area too. And
so it looks like it's doubled in size. And the next time when you get another
x-ray, it's shrunk back down to its original size. So that's something I always
warn the patient about.
Here's another example of multiple lesions that were cooked. This was
done probably open. But that's what they look like and various amounts of
necrosis throughout them, depending on how well they cook throughout these
lesions. The closer the lesion is to the center of the liver, the harder it is
to cook because there are some structures down there that are dangerous: the
bile duct, the arteries, the veins. And for those reasons some are harder to
cook. The ones in the periphery are very easy to cook.
A little bit about what the limitations of RFA are. Once again, the size
of the lesion is a relative limitation. The biggest probe we have right now is
a 4 centimeter probe. So if the lesion is less than 4 centimeters, I can cook
that lesion with a 4 centimeter probe. If it's a 10 centimeter lesion, I then
have to cook that lesion five or six different places, 4 centimeters at a time,
rather than throughout so I can get the whole lesion treated. So we can still
do large lesions, but they don't do as well as the small ones.
If you tumor is near a major vascular structure, the blood flow through
the liver cools off the liver tissue. So if it's next to a main vein or a big
artery that's got a lot of blood flow to it, then it doesn't get as good of a
cook because it would be as if we're trying to microwave while you're running
water on the liver. It cools it off and you get less of a uniform burn
throughout.
nd then the last thing that is a limit and was a significant problem is
how close it is to the bile duct. If I burn the bile duct, the bile duct scars
down and we've actually not done you a favor; we've made you worse. Now you
have an obstruction; you now get problems where the liver doesn't drain; you
turn yellow.
So we've got to avoid any of the proximity of the bile duct. Within the
last six months, there's been reported a new technique that I've not tried yet –
- but I'm going to if I have these situations -- where they actually put a cold
saline solution -- they put a catheter into the bile duct and the irrigate the
bile duct continuously with an ice-cold saline solution. And that protects the
bile duct and prevents the bile duct from getting hot and therefore it doesn't
burn.
And they have reported a marked improvement in the ability to treat the
bile duct without damaging the bile duct. So that's a relatively new approach
for tumors that are in close proximity to the bile duct.
And then I'm going to end up talking a little bit about liver
transplantation. Liver transplantation, as most of you know, is the process
whereby we remove the old liver and we get a new liver from another source.
Usually it's somebody that has died of a car accident or a stroke and there is
brain death but we make sure that the liver is preserved. And we then
transplant it into the person that's waiting for the liver for whatever reason.
When to do a liver transplant on somebody with carcinoid is still not
well-defined. With the techniques that we use right now, we can actually
prolong the quality and the length of life of the patient for a significant
number of years. A liver transplant is a big operation. There's a real chance
that people will die from the transplant operation itself. That's in the range
of 5 to 10 percent death rate from the operation.
We also have to be aware that a lot of our carcinoid patients have
carcinoid disease elsewhere in the body that a liver transplant won't treat. If
you've got that disease in the bones, a liver transplant won't cure that. And
in fact, the suppressive medication that you would take for the rest of your
life may make that disease worse. So it may make the cancer grow faster because
your immune system is now not able to help protect you from that.
So if you have disease outside the liver, then that can be a
contraindication. But many centers that are doing liver transplantation are
reporting that they'll do it in face of extra hepatic disease and part of it is
because of the success rate involved. The reason is simply that most of the
carcinoid patients die of liver disease. I mean, that is ultimately what kills
a lot of our patients is overwhelming liver failure or an overwhelming liver
disease. And so that's why it's become an indication of why a lot more of the
programs that do a lot of carcinoids like us are considering it.
The interesting thing you're going to see about this most of them are
foreign centers. And the reason for that because of the way livers are
distributed in the
patients -- once again, 1 death. That's 10 percent. Okay?
However in that 4 years, 75 percent are alive. And, you know, going back,
right now at 5 years with what we're currently doing, we've got a 65 percent
survival rate. So carcinoid patients live a long time with their condition.
Fifty percent of you are still alive at 10 years, however, 75 percent of
those survivors have recurrent disease. So once again, with transplantation --
it is not being used so much to cure you of your disease but to improve your
quality of life and
prolong your
life. There is a fifty percent 10
year
survival for those that have gotten liver transplants.
These numbers are better than the average liver that gets transplanted.
The average liver transplant patient today at 5 years has about a 67 percent
survival rate and at 10 years has about a 40 percent survival rate.
A lot of the diseases that we do liver transplants for recur in the
transplanted liver, like Hepatitis C, which is the most common reason we do a
liver transplant today is Hepatitis C. Ninety percent of them recur within the
first two years of returning Hepatitis C.
Here's
another
report from
19 percent operative mortality rate. Fifty percent of their survivors died from
recurrent disease and they only reported a 5 year survival of 36 percent. So
this is not nearly as good as
multicenter reports don't usually do as good as a single center report because
you have too many variables that go into the mix.
The
main
limitation here in the
distribute organs for transplantation is on the basis of the person who is going
to die the soonest is first in line to get the organ. Once again, carcinoid is
slow disease process. So the good news for you is that you all are going to
live a long time before this disease is going to get you. The bad news if we're
going to do liver transplantation, is it's going to be real hard for me to get a
liver for you under our current distribution system.
And this is where the concept of the living related liver donation is
being investigated.
In fact, the
in carcinoid patients. That process would be that we would take part of a liver
from somebody else, somebody that's healthy, to take a liver from a person
that's healthy with no liver problems and give up half of your liver with a 3 to
5 percent chance that you're going to die in the process. We're going to use
half of that to treat somebody that's got a carcinoid.
So that's kind of where we're sitting right now with liver transplantation
with carcinoid. With liver transplantation, it looks like the living related
option might be the best approach for patients that have diseases that do not
qualify to get them on the cadaver list. And most of the big centers are
reporting that's what they're doing, the living related donation in patients
that have other cancers that can't be transplanted. And with that, I'm done.
I'll be glad to answer any questions.
QUESTION:
Comment on the extra hepatic use of RFA for unresectable tumors. In other
words, can you do RFA in small bowel? Can you do it in lung? Can you do
it in a node?
ANSWER:
You can do it in the lung. You can do it in extra hepatic nonhollow
viscous tumors so we've done it in pancreas. We've done it in
subcutaneous tissues for nodes. You can't do it in bowel because one of
the complications is when the bowel dies, it's going to perforate. So we
don’t do bowel.
QUESTION:
Are there any specific features that you look for in a liver mass
that helps you predict that the hepatic artery chemoemboliation is going
to be a big success? less of a success? The more vessels the better? The
less vessels the better? What's the word?
ANSWER:
I don't know the answer to that question. It's certainly the bigger
the lesion, the less the effect of the chemoembolization is. So the
lesions that are huge in size have less of a response. But I am not aware
if it's related to the number of the vessels or if there's any other
predictive values in them.
QUESTION:
Think chemoembolization is better than bland embolization or
does it make any difference?
ANSWER:
All we've done is the chemoembolization so I can't answer that. I
guess the chemoembo is better 'cause that's what we do.
DR. WOLTERING:
When there's a lack of randomized prospectives in a trial, a lot of
what we do as surgeons, as chemotherapists, as gastroenterologists is
based on how we read the literature, how we interact amongst ourselves. I
mean, we grow in out knowledge every year. And I truthfully
say
when I
hear
Richard Warner and Tom O’Dorisio, Lowell Anthony and Larry Kvols
talk, I learn something myself. And God willing, when they listen to me,
they learn something also.
QUESTION:
Do you do the entire liver at one time when you chemoembolize? Or
do you zap the right lobe this time and the left lobe next time? Touch up
on the third time? Why do you do that?
ANSWER:
We don't do the whole liver all at once. With the chemoinfusion, we
are now chemoinfusing the whole liver during the chemoinfusion process.
But we do so selective embolization. There are two techniques for
embolization, and I don't do the embolization. I let the radiologist do
it.
But there are two techniques. One is what's called selective
embolization where they actually go out put the catheter all the way up to
the lesion and then plug off just the blood supply that's going to that
tumor. The other is basically you block off the whole artery that's going
to that side of the liver. We have gravitated towards doing the super
selective embolization. We've try to salvage as much viable liver as we
can. But I do know a lot of programs that just embolize the whole artery,
come back embolize the whole artery on the other side.
DR. WOLTERING:
And I've got to say the more super
selective you
are, the more
effective and non toxic you become. The less normal tissue you hurt and
the harder you hit the tumor, the better off you are.
QUESTION:
Is there an advantage of using a laser. Can you do stuff with a
laser that you can't do with probe and the RFA gizmo?
ANSWER:
No.
QUESTION:
Have any experience with Theraspheres? I know Dr. Warner is one of
the gurus on that. Can we use that in the Yttrium glass beads?
ANSWER:
We have not used it with carcinoid patients, but that's actually in
the new material. We have our spheres program up and running. We have
done three metastatic study patients. The SCIDS program is radioactive;
you embolize with radioactive spheres. So the radiation deals with the
tumor versus chemotherapy dealing with the tumor.
QUESTION:
Could you chemoinfuse a mesenteric artery or give it radiolabeled
Somatostatin analog.
ANSWER:
We have not given anybody a direct infusion, but we have treated
some of the mesentery tumors with the systemic infusion. The problem with
the infusion is that the catheter has to be placed into the artery and
they are bedridden for 5 days. And so you basically can't get up and move
and do anything for that 5-day period.
DR. WOLTERING:
And I alluded to yesterday the fact that we have one patient who has
metastasized right down between the bladder and the rectum that tumor was
debilitating. She was the librarian at Tulane and was in a wheelchair.
And we took two catheters, one in each leg. This one coming across and
into the artery feeding the left side of the tumor and one over here
feeding the right side of the tumor and infused that in her pelvis. And
she got a great response and went back to work without a wheelchair.
QUESTION:
If the cells in the dead tumor remain in the liver, does it affect
liver function?
ANSWER:
Yes. We already talked about that. If we ablate somebody and we
leave the dead tumor tissue behind, the liver is not regenerated.
QUESTION:
Can you replace a bile duct with a mechanical or synthetic device or
can you transplant a bile duct?
ANSWER:
Well, no. But we can replace a bile duct depending on where it's
injured. We can bring up a loop of intestine directly to that bile duct
and that's the most common thing that we do.
The other thing that we can do is we can have the radiologist put a
plastic catheter through the artery blockage and put a stent similar to
what they do with the heart stent in patients that have heart disease. So
those are the two techniques that we can use in the bile obstruction.
QUESTION:
Okay.
I'll do this one.
At ERCP a patient was told that if they
had
bleeding, they would use epinephrine.
Would norepinepherine be better
for
a noid?
ANSWER:
No. And whenever you have an invasive procedure like ERCP, have
Sandostatin on board. And look in your handout; it tells you how to do
that to prevent crisis.
QUESTION:
If the entire liver is involved with many, many, many tumors, how
would you do chemoembolization? Would you do the entire liver at once?
ANSWER:
We've already answered that.
QUESTION:
Does chemoembolization cause kidney problems? And would low kidney
function keep you from doing chemoembo, and maybe make you do a bland embo
instead?
ANSWER:
No. I don't think -- The biggest problem that's going to cause you
to have kidney problems is the resulting tumor necrosis with the release
of the byproducts.
DR. WOLTERING:
I guess if you were going to use cis-platin in your chemoembo, you
might drop that agent out and pick a different agent to chemoembo with.
QUESTION:
Mesentery ischemia, how do you deal with an obstructed SMV or an
SMA? Tumor fibrosis and/or obstructed encircled?
DR. WOLTERING:
I think that's what Dr. Frey's whole talk was about. When people
tell you you can't do anything, see Danny or Phil Bourdeaux. I think
that's what he was telling you. Good competent surgeons don't do this
often. Why don't I do this myself? Because I don't have the patience to
sit there and dissect around in the root of the mesentery for 12 hours.
Drs. Frey and
Boudreaux will take whatever amount of time it takes to
dissect out all these little teeny tiny blood vessels. You know, there
are some of us who don't have that mentality and I'm one of them.
QUESTION:
As to success rate, difficulty, and risk please compare RFA,
chemoembo, chemoinfusion, and Theraspheres in the liver. You see any
difference in the difficulty in doing chemoembolizatin versus
chemoinfusion or is spheres --
DR. WOLTERING:
I don't see any difference in difficulty. I think the success rate
of serasphere are too early to tell in carcinoid. And RFA and
chemoembolization? Oh, good
question. That question actually
triggered
another one. I've always said that
this is therapy and its success is
guided by the concept of sequence, sequence, sequence.
QUESTION:
If you're going to think of somebody having a surgical option, does
prior chemoembolization make your life as a liver surgeon harder? Should
you do the liver surgery and RFA first followed by chemoembo, or should
you do the chemoembo followed by liver surgery, or it doesn't make a
difference?
ANSWER:
Well, it depends on where your liver lesions are. Chemoembolization
certainly makes my life as a surgeon difficult. Chemoembolization causes
the tumor to become inflamed. It becomes necrotic; it gets an intense
reaction of scar tissue.
DR. WOLTERING:
Sticks the liver to the diaphragm like superglue.
ANSWER:
Yes. It increases our work markedly. However, sometimes the
lesions are so big the only way that we can do it is to have them
treated to shrink it down first.
So my preference, if you're going to ask me what my preference is,
my preference is for me to do everything I'm going to do first. Operate
on
you, take out
the primary, take out the gall bladder, fix up the
liver,
or go
back into the liver at a later date. Then consider the
embolization. We frequently will take patients back two or three times
and work on different parts of the liver. And then when I have done what
I have done, all I can do from a surgical perspective, then I hand you off
to the interventional radiologist for embolization and/or Dr. Linares for
the radioactive therapy. And keep in mind, though, that as complications
from all this we may have you come back on an as needed basis.
QUESTION:
Is there a situation where you can have too many tumors to do RFA?
ANSWER:
Yes. You can have hundreds of
tumors—RFA works best if tumors
are
small
and discrete
QUESTION:
Do you recommend pancreas transplant --
ANSWER:
No. There are no indications for a pancreas transplant in a
carcinoid patient. Pancreas transplantation is strictly if you are a
diabetic, have had diabetes for a long time.
QUESTION:
Best treatment for liver mass discovered after removal of the
primary? If you could surgically resect something, should you do it?
ANSWER:
Well, that's where you're going to get these differences of opinion
that always end up in these discussions. My point is that we ought to be
aggressive up front early on as much as we can before it gets to the point
you're having debilitating symptoms.
QUESTION:
Some groups have talked about cluster transplants. For people like
noids, would they be considered for a cluster transplant where you had
transplanted the liver and the entire small bowel so that these people
could have normal bowel function again.
ANSWER:
A cluster transplant is the combination of multiple transplants
together from a single donor. And the most common cause for transplant
that's done right now is a combination of liver with duodenum and
pancreas and the entire small intestines up to the right colon. It has
been proposed to be used in patients that have root mesentery involvement
and you take out -- when you do the resection -- in the carcinoid patients
you take out the whole liver, the whole mesentery and pancreas. You take
the supramesentery off the aorta also. It has everything in the abdomen
out.
So, yes, it has been proposed. It has not yet been done. And once
again, cluster transplants are done for a number of other indications. To
our knowledge they are not being done in a carcinoid patient. And the
reason for that is the mortality rate on a carcinoid from cluster
transplant is even much, much higher than the mortality rate from a liver
transplant. We're looking at a mortality rate of probably 30 percent.