Organ Transplants for Cancer Treatment

Dr. Sukru Emre, Organ Transplants for Cancer
Treatment
 January 16, 2011Welcome to Yale Cancer Center Answers with doctors Francine
Foss and Lynn Wilson.  I am Bruce Barber.  Dr. Foss is a
Professor of Medical Oncology and Dermatology, specializing in the
treatment of lymphomas.  Dr. Wilson is a Professor of
Therapeutic Radiology and an expert in the use of radiation to
treat lung cancers and cutaneous lymphomas.  If you would like
to join the conversation, you can contact the doctors
directly.  The address is canceranswers@yale.edu and
the phone number is 1-888-234-4YCC.  This evening, Francine
and Lynn are pleased to welcome Dr. Sukru Emre to the program for a
conversation about transplantation.  Dr. Emre is Section Chief
of Transplantation Surgery and Director of the Yale-New Haven
Transplant Center.  Here is Francine Foss.Foss
Could you start us off by telling us what the transplant program
is, and what it does?Emre
For anyone who develops end-stage organ disease, we will be able to
change the organ, getting the organs from cadaveric donors, some of
the transplants are with living donors and we can change the organs
and handle the problem accordingly.Wilson
How did you become interested in transplantation and what are your
specific clinical interests?Emre
My subspecialty is hepatobiliary surgery and I was trained before
the 1980s.  At that time transplantation was just coming to
the surface, especially with the liver in those days, and we did
not have anything to do but hold the patient's hands while they are
dying, because when we diagnosed cirrhosis, we had very minimal
options to offer them. For someone who has bleeding we used to do
shunt surgeries or sometimes with the small tumors we had to do
resections in those days.  So for me transplantation was a
natural extension of the hepatobiliary surgery.Foss
Can you tell us what the most common organ is that is transplanted
in the United States?Emre
In the United States, the most transplanted organ, of course, is
the kidney, because we have two kidneys as opposed to one liver,
one heart, and one pancreas.  Therefore, the kidney is the
most common transplantation in the United States and around the
world.  There are now more patients waiting for kidney
transplantation.  To be exact, in the United States, a little
lower 100,000 patients are waiting for transplantation and among
them 70,000, are waiting for a kidney, and 17,000 are waiting for a
liver.  These are the two big groups.Wilson
So with these organs, when is a transplant typically done, say, for
a kidney patient and for a patient with a liver problem?Emre
For kidneys, we have two categories.  For children, we prefer
to do the transplant before they start dialysis.  On the other
hand, for adults, many times we do the transplant once they start
dialysis.  That is the indication for transplantation. 
For liver transplantation, we have a set system for allocating the
organs, which became the gold standard at this point, what we call,
MELD, the Model for End-Stage Liver Disease scoring system. 
We usually prefer not to transplant anyone with a MELD score less
than 15, because those individuals one-year survival, without
transplant, is4:00 into mp3 file 
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 almost 100%.  So the transplant is not justified.  There
are other signs we use to decide whether a patient is eligible for
transplantation or not, what we call degree of the illness, or
cirrhosis.  We categorize the cirrhosis into two types, one is
compensated cirrhosis.  Although a patient has cirrhosis,
their function is almost 100%, they are 100% functional, they go
work and do the work and so on and so forth.  As opposed to
de-compensated cirrhosis, those individuals develop serious side
effects of the cirrhosis, including what we call encephalopathy or
cloudy mind, esophageal variceal bleeding, muscle wasting, bone
disease, as well as spontaneous bacterial peritonitis and other
infections.  Those are the signs that will tell us that
patient is doing poorly, and we have to hasten the transplant
operation.Foss
Can you tell us a little bit about the team approach in
transplantation, what other physicians are involved and how does a
patient go through the process of getting a transplant?Emre
At Yale we have a real team approach from head to toe. When
patients come or are referred to us for transplantation, we have
our coordinators, we have our hepatologists and nephrologists, for
kidney, they see patients and they evaluate the patients. 
During this evaluation process, there are many other disciplines
that help us out, including cardiac evaluation, pulmonary
evaluation, dental evaluation, colonoscopies, other endoscopies if
it is necessary, psychologic evaluation, social work evaluation, so
on and so forth, and there are specific cases where we ask for more
evaluation, for example, patients with bone problems, and there we
can talk with orthopedics or endocrine people, especially metabolic
bone diseases, and patients with liver tumors, and we always
discuss with a medical oncologist about what to do with that, and
plus we ask anesthesia intensive care units and other
disciplines.  For example, for pediatrics, we work with the
child psychiatric services for their psychologic evaluation or
whether they have any post-traumatic stress.  We do some
studies to decrease the post-traumatic stress of these
patients.  We have a special program with the psychiatrists,
especially for adult patients with substance abuse, called the
liver SMART study that we do group therapies for
these patients in order to increase their sobriety and insight
about drinking and other problems so they will become better
candidates for transplantation.  After transplant, definitely,
they do better.  Therefore, it is a perfect setup before
moving to this team approach, and in inpatient, after
transplantation or in a patient before a transplant, they get sick,
requiring admission to the hospital, so we have social workers, we
have pharmacists, we have nutritionists, and they work with them
and if there is a problem, we address those issues, and our job is
just to make sure that we take care of every aspects of the care of
our patients.Wilson
I know that you have a very robust and busy surgical service, where
do your patients come from? Are they from Connecticut, the region,
other states, other countries?Emre
We have a mix of everything. The first thing is to help our local
patients, especially citizens of Connecticut, but we have other
patients and they are from Chicago, from Oklahoma, from Puerto
Rico, from Turkey and Italy and Gulf countries and many different
patients, and they come to us because of our reputation and because
of our good results.8:15 into mp3 file 
http://yalecancercenter.org/podcast/jan1611new-cancer-answers-emre.mp3Foss
Can you talk to us a little bit about the complications that can
happen with a transplant?Emre
Transplantation is a very difficult operation.  First of all,
we are crossing the line and we are doing certain things against a
modern nature, so there are many hurdles to overcome, and in
pre-transplant for livers a major problem is development of
esophageal variceal bleeding or what we call spontaneous bacterial
peritonitis, because of the severe portal hypertension, patients
develop fluid in the abdomen, what we call ascites that ascites may
get infected, and therefore, we have to deal with this infectious
problem, and the other thing is muscle wasting related
issues.  Fractures are more common with patients with
cholestatic liver diseases, such as PSC, PBC and we need to take
care of that and we communicate with the bone metabolism experts to
make their bones sturdier.  For kidney transplant patients
with dialysis, although we are very grateful that at least we have
some remedy while they are waiting for a transplant to alleviate
the degree of toxins in the body, dialysis is not an easy process
for the patients.  In every dialysis episode, the patient's
blood sugar comes down to 35-40, and blood pressure is always down,
and they really feel bad after every dialysis session; it is not
ideal.  As a result, especially in patients more than age 50
with kidney diseases and cardiovascular problems, complications are
more common leading to their demise.  So that is the major
problem for the kidney.  The second problem is bone problems,
and because of the dialysis they lose their bone minerals and their
bones are very weak as well.  Post-transplant, early after
transplantation, there are many problems, for example, clotting in
the vessels, what we call hepatic arteriothrombosis, portal vein
thrombosis or hepatic vein thrombosis.  When we look at the
nationwide data, the incidence of these complications is around 5%
to 7%, in our case, it is 0%.  We have bile duct
complications, or what we call bile duct stricture or bile leaks
after surgery.  Nationwide it is somewhere around 20%, ours is
15% here, and also we have infectious complications.  I am
really grateful to the hospital because we have a very robust
infection control system, hand washing, wearing gowns and gloves
before touching the patients.  Therefore, our infection rates
overall are really, really low, somewhere around 2% to 3% after
transplant operations.  As opposed to nationwide, this number
goes to 30% to 35%.  For me, the most important problem in
early post-operative period is the infection, because in order to
treat the infection, we have to decrease the
immunosuppression.  On the other hand, in order to make the
liver function or kidney function, we have to give
immunosuppression.  In a way that pushes us into a corner and
it makes the case very difficult for us.  Late complications,
especially in pediatric patients, are opportunistic infections,
what we call major culprits such as CMV and EBV infections. 
The reason I say pediatric patients are more of a problem is
because most of them are aged less than 5, their CMV and EBV titers
are negative.  Since we are doing split and living donor liver
transplants most of the organs come from the adult patient
population.  They are CMV and EBV positive, and that creates a
high-risk group for the patients and children can develop CMV and
EBV infections.  Especially EBV is really important because
EBV can lead to what we call post-transplant lymphoproliferative
disease, which is tumor development.  Therefore, we check out
patients routinely and we control monthly CMV and EBV titers and
make sure that everything is under control.13:03 into mp3 file 
http://yalecancercenter.org/podcast/jan1611new-cancer-answers-emre.mp3Wilson
What sort of cancer patients do you see?Emre
For adults the main cancers for liver are hepatocellular carcinoma
and cholangiocarcinoma.  Most of our patients have
hepatocellular carcinoma, the reason for that is underlying
cirrhosis.  We rarely see a patient with normal liver
functions. Normal liver structure without cirrhosis with
hepatocellular carcinoma may be 3% to 5% of our patient
population.  For the cancer development it may include
hepatitis C, as we know, hepatitis C is the major reason at this
point for development of liver cirrhosis and our estimates tell us
that up until year 2020 we are going to see increase in hepatitis C
cases.  Our calculations tell us that in someone who is
diagnosed with hepatitis C cirrhosis, approximately 20% will
develop hepatocellular carcinoma within 5 years. So this is a major
problem for us, and of course in pediatric patients we have another
tumor, what we call hepatoblastoma, which is a totally different
etiology without underlying liver injury.Wilson
Welcome back to Yale Cancer Center Answers.  This is Dr. Lynn
Wilson and I am joined by my co-host Dr. Francine Foss. 
Today, we are joined by Dr. Sukru Emre and we are discussing the
Yale transplant program.  Dr. Emre, could you talk to us a
little bit about the hepatobiliary cancer program?Emre
When I came to Yale and was developing and improving the kidney
program and developing the liver program, I thought that it was
wise to develop a hepatobiliary cancer program and that is the
program we have now. It is a multidisciplinary program and involves
a transplant surgeon and medical oncologists, hepatologists,
interventional radiologists, diagnostic radiologists and the
oncologic surgeons.  The advantage is providing comprehensive
care to our patients.  To give an example, someone with liver
cancer and underlying liver cirrhosis, this individual does not
need to go one place to another place and one consult to another
consult.  The patient will be prepared and presented in our
meeting and there will be only one decision made for this
patient.  They will of course reach a decision quickly without
wasting any time and also that will be the best decision for the
patient because it is coming from an expert panel and is based on
the patient's disease17:34 into mp3 file 
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 category, underlying cirrhosis and degree of cirrhosis.  The
treatments included are removing the tumor together with part of
the healthy liver, what we call a liver resection. In order to do
that the patient should have very good liver functions.  If
the patient has cirrhosis which is not treatable for resection,
those individuals will undergo what we call ablation techniques,
either radiofrequency ablation or what we call transarterial
chemoembolization.  Those techniques allow us to keep the
tumor in the liver and control the tumor; therefore, the patients
never lose the chance of transplantation later on.  And of
course, a patient with a liver tumor is still a candidate for
transplantation if they have living donor options. We preferto go
directly to a living donor or liver transplant patient. 
Transplant will take care of two problems, one it takes care of the
tumor, and two, it takes care of the underlying liver disease, but
the aim of this program is to provide our patients the best
possible care.Foss
You mentioned that in some cases you might resect only part of the
liver.  How often can patients with liver cancer expect to be
able to save their liver?Emre
If there is underlying cirrhosis, eventually these individuals are
going to need transplantation, there is no doubt
about that, but on the other hand, we have a shortage of organ
donors.  If we think that the patient has what we called
Child's A cirrhosis, early cirrhosis, compensated cirrhosis, with
normal liver enzymes including INR, bilirubin and a normal platelet
count, those are the patients suitable for liver resection. 
Unfortunately, many of our patients have advanced cirrhosis and as
a result performing liver surgery for them is really
difficult.  We also do resection for patients with different
liver diseases such as liver adenoma, liver hemangioma, and other
liver tumors such as liver hemangioendothelioma and liver agioma,
or angiosarcoma, and in some patients, we prefer liver surgery.Wilson
Obviously, these procedures are very complicated and complex and
require a tremendous amount of expertise and just for the benefit
of our listeners, this is obviously not the type of procedure that
is done in every hospital.  How many places in Connecticut,
for example, provide a service as comprehensive as yours, Dr.
Emre?Emre
Our program is really the number 1 in the country, not just in
Connecticut, but in Connecticut we have two liver transplant
programs and two kidney programs and one is in Hartford, one is
here at Yale.  If we look at the SRTR data which I will
explain a little bit, the Federal Government mandates all
transplant programs in the United States and they have to submit
the results to the Federal Government to what we call the
Scientific Register of Transplant Recipients.  Therefore, we
have center-specific data as well as nationwide data and
statistics.  Based on those statistics, when you look at our
one year survival in pediatric liver transplantation, it is 100%,
adult liver transplantation is 98%, and therefore our program is
not comparable with any program.  We have expertise, we have
resources, we have know how and plus that we have a
multidisciplinary team approach to serve our patient's in the best
possible way.22:00 into mp3 file 
http://yalecancercenter.org/podcast/jan1611new-cancer-answers-emre.mp3Foss
You also mentioned that there is a lot of care that goes into the
patient after the transplant, that the patient is on
immunosuppressive medications. Can you tell us little bit about
that?Emre
The organs are coming from another individual, therefore, the
recipient immune system is going to recognize the organ as a
foreign body and will try to get rid of, what we call
rejection.  In order to prevent rejection, we have to use
anti-rejection medications, in other words, the immunosuppressive
medications, and of course, those medications are heavy-duty
medications with a lot of complications that require all of the
expertise to run the immunosuppression.  I always give the
example to my patients that running the immunosuppression is
similar to tightrope walking, one side is rejection and one side
are all the side effects of all these medications, thus this
medical act to run the immunosuppressive medications.  If
anyone reads all the complications of these immunosuppressive
medications they definitely can freak out because there are many
complications.  On the other hand, we rarely see all these
complications because we follow our patients very carefully, and
for example, after we discharge the patients from the hospital, for
the first month we see them two times a week, and during these
visits we check their immunosuppressive blood levels, we examine
them, we check their kidney functions, liver function,
electrolytes, everything, and we make the adjustments
accordingly.  That will give us the best possible results for
our patients.  Those immunosuppressive medications make the
immune system very weak and that sets a stage for
development of opportunistic infections. 
Therefore, we have to follow our patients carefully.  We have
to cover our patients for certain bacterial infections, viral
infections, or fungal infections after surgery. Another note I
would like to make is early on we use high doses of
immunosuppressive medications but as we go we decrease the
immunosuppressive medications, dose-wise as well as the number of
immunosuppressive medications we use, and usually six months after
transplant, our patients are on only one immunosuppressive
medication with minimal dosage.Foss
Will they ever stop these medications or are they pretty much on
them for life?Emre
Based on our current knowledge, we tell our patients that they are
going to use those medications indefinitely. In my experience with
liver transplantation, which is 3000 transplants, I have maybe 50
patients where we were able to stop all the immunosuppressants and
they are doing very well, those are mainly pediatrics patients
actually.Wilson
What sort of changes have you seen in the field of transplantation
in the last decade, and as a second question, what changes have
happened here at Yale in the last 10 years?Emre
When I got involved in the transplant field in the beginning of the
1980s, it was difficult in every aspects of transplantation, in
terms of availability of different immunosuppressive medications,
where now-a-days we have great immunosuppressive medications. As a
result, I do not remember any patient I lost secondary to rejection
or chronic rejection, except non-compliance issues.  The
second issue is development of ICU, anesthesia care and development
of the field of hepatology and also technical expertise, performing
the liver transplantation, those are the general guidelines.
26:07 into mp3 file 
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 But specifically we also developed something that is very unique,
a multidisciplinary team approach, that is the major change and we
added it to all transplant fields.  When we do rounds, rounds
are done everyday, there is one transplant hepatologist, one
transplant surgeon, a hepatology fellow, a surgical fellow, a
transplant surgical fellow, residents, PAs, MPs, pharmacists,
social workers, nutritionists and nurses altogether.
 Therefore, we give our patients better care.  I
developed this methodology in our multidisciplinary team
approach.  It was in 1997, I was assigned to be at the
pediatric liver transplant program at Mount Sinai and at that time
I built the program in a multidisciplinary fashion.  Last
year, CMS mandated that all programs should be multidisciplinary.
 I had that vision, and because I knew what my patients at
that time needed, I followed my gut feelings and instincts. What
changed at Yale in the last 10 years? I cannot say in the last 10
years, but I can tell you in the last 3-1/2 years I have been here,
I believe that many things have changed.  The medical school
and hospital have come together to build excellent clinical
programs and there is a focus on developing translation of research
that the researching should be 100% meaningful that can be of use
for patient care and improving outcomes.Dr. Sukru Emre is the section chief of transplantation
surgery and Director of the Yale-New Haven Transplant
Center. If you have questions or would like to share
your comments, visit yalecancercenter.org where you can also
subscribe to our podcast and find written transcripts of past
programs.  I am Bruce Barber and you are listening to the WNPR
Health Forum on the Connecticut Public Broadcasting
Network.