Organ transplantation, a significant 20th-century achievement, has seen remarkable progress in outcomes due to advancements in immunosuppression and surgical techniques, but faces ongoing challenges in organ availability and the long-term management of immunosuppression.
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okay thank you very much um that fidgety
thing took Amir about 3 weeks to do so
he's going to be very very upset that
was the highlight of the conference um
I'm Brian Davidson I'm I'm one of the
transplant surgeons here a liver
transplant surgeon uh and I've been
asked within 10 minutes to cover the
whole topic of progress and
transplantation organization and
research so um it's going to be fairly
superficial uh and it's going to be
please um it's been said that organ
transplantation is perhaps the greatest
achievement of the 20th century and when
you when you do Ponder on the subject I
think that that may well be the case um
I tried to sell that to my kids and I'm
afraid uh this come out in front of
transplantation but clearly
transplantation must be up there as one
of the great achievements for man in the 20th
century and just one little bit of
background information about when these
things started out uh just so we can put
our thoughts for today into context uh
we're really not talking about very far
back when we had the very first
procedures it suggested at 1933 was the
first renal transplant and that was done
uh without any understanding o of organ
rejection and not surprisingly the organ
failed within within minutes and it was
only when uh some twins uh were actually
transplanted that obviously didn't have
the problems with the immunological
barrier that there was actually a
successful outcome in transplantation
and was in the early
1950s and that preempted really the
understanding of of what organ rejection
was all about and uh it's attributed to
Peter medar uh for his work in the 60s
uh to understand the subject of
transplantation immunological rejection
and put in the strategies that we've
seen to prevent organ rejection and then
the early 60s that was followed by the
first uh human liver
transplant was because the results
progressively improved over the last 30
or 40 years uh you can see again this is
the European transplant registry results
uh we've got outcomes hereby uh time
period after transplantation and this
data is split into two cohorts uh one
cohort uh being here in the 70s and 80s
and the most recent cohort in the ' 80s
and '90s uh and into 2000 and you can
see that the transplantation results
have progressively improved improved and
too and it's not just been in Europe
that we've seen improvements in organ
transplantation this is the UK data uh
and this is the UK data separated into
cohorts of threeyear periods uh and this
is 10e outcomes and you can see that
there's been Progressive Improvement in
the outcomes of transplantation this is liver
liver
transplantation uh you can see that
there's now um over 90% one year
survival liver
transplantation and similarly with
kidney transplantation I see my
colleague bimbe in the audience of
course kidneys he tells me do far better
than livers and he's absolutely right
and that you can see that the outcomes
with Ral transplantation are even better
phenomenal success with over 90%
one-year uh Graft in patient survival
and a again Progressive Improvement um
over the last two
decades and that success has all uh been
due to a variety of things the first
thing obviously is is proper transplant
immun suppression uh back in the 60s
when transplants were started out the
were okay thank you very much um that
fidgety thing took here about 3 weeks to
do so he's going to be very very upset
that was the highlight of the conference
um I'm Brian Davidson I'm I'm one of the
transplant surgeons here a liver
transplant surgeon uh and I've been
asked within 10 minutes to cover the
whole topic of progress and
transplantation organization and
research so um it's going to be fairly
superficial uh and it's going to be
please um it's been said that organ
transplant ation is perhaps the greatest
achievement of the 20th century and when
you when you do Ponder on the subject I
think that that may well be the case um
I tried to sell that to my kids and I'm
afraid uh this come out in front of
transplantation but clearly
transplantation must be up there as one
of the great achievements for man in the 20th
century and just one little bit of
background information about when these
things started out uh just thought we
can put our thoughts for today into
context uh we're really not talking
about very far back when we had the very first
first
procedures it suggested at 1933 was the
first renal transplant and that was done
uh without any understanding o of organ
rejection and not surprisingly the organ
failed within within minutes and it was
only when uh some twins uh were actually
transplanted that obviously didn't have
the problems with the immunological
barrier that there was actually a
successful outcome in transplantation
and that was in the early
1950s and that pre emptied really the
understanding of of what organ rejection
was all about and uh it's attributed to
Peter medar uh for his work in the 60s
uh to understand the subject of
transplantation immunological rejection
and put in the strategies that we've
seen to prevent organ rejection and in
the early 60s that was followed by the
first uh human liver
transplant was because the results
progressively improved over the last 30
or 40 years uh you can see again this is
the European transplant registry results
uh we've got outcomes here by uh time
period after transplantation and this
data is split into two cohorts uh one
cohort uh being here in the 70s and 80s
and the most recent corot in the 80s and
'90s uh and into 200 you can see that
the transplantation results have
too and it's not just been in Europe
that we've seen improvements in organ
transplantation this is the UK data uh
and this is the UK data separated into
cohorts of threeyear periods uh and this
is 10e outcomes and you can see that
there been Progressive Improvement in
the outcomes of transplantation this is liver
liver
transplantation uh you can see that
there's now
um over 90% onee survival liver
transplantation and similar with kidney
transplantation I see my colleague bimby
in the audience of course kidneys he
tells me do far better than livers and
he's absolutely right in that you can
see that the outcomes with renal
transplantation are even better
phenomenal success with over 90% one-ear
uh graft and patient survival and a
grand Progressive Improvement um over
the last two decades
and that success has all uh been due to
a variety of things the first thing
obviously is is proper transplant
immunos suppression uh back in the 60s
when transplants were started out the
transplantation drugs were very limited
uh but cyclos sporn really brought in in
the mid '70s has been the main stay uh
of transplantation immunos supression
and only recently we have we had a few
other Smarties in the bag that can be
combined to try and improve further the
transplantation but perhaps we shouldn't
dwell on what's been there in the past
because we have to look forward and
looking forward we probably want to
avoid immun suppressive drugs and we
want to get our organ transplant
patients uh to be tolerant of the organs
so that we can take all immunos
suppression off immunos supressive drugs
damage other organs and really in the
long term we want a an immunosuppressant
free Pro protocol and I just pulled out
for interest this very recent paper
where this has been achieved in renal
transplantation and this is perhaps what
we'll be looking at in the next decade
is these very complex ways of modifying
both the donor and recipient to tolerate
the organs uh just to give you a very
brief outline this was a small study
based on eight patients undergoing live
donor renal
transplantation uh the recipient was
conditioned by giving them a short
course of chemotherapy and then total
body radiation they then had a stem cell
transplant they then had their kidney
transplant and shortly after the kidney
transplant they had uh again some stem
cell uh transplant with facilitating
cell enrichment along with some tea
cells uh and they all were discharged in
their third postop of day and the vast
majority of these patients are
completely free of immunos supression so
they are have full immunological Toler s
it's complex procedure but obviously it
can be achieved and I think clearly this
is what we're going to be dealing with
years the other major hdle has been
preserving organs uh and I'll just very
briefly mention two advances one is in
the use of preservation Solutions uh
University of Wisconsin solution in the
late 80s revolutionized liver
transplantation uh but really we've seen
very little progress really because it
it's so difficult to Market a new
transplant solution because the
transplantation results already are
excellent and therefore there's concern
always to introduce something new uh
without extensive trialing and then
machine profusion the concept of trying
to store the transplant organ in a
better condition or actually even
improve the condition of the organ
during that time period between
retrieval and implantation it's already
been shown to be satisfactory for the
kidney and way and others are doing work
liver but all these things taken
together is clearly not quite good
data okay thank you very much um that
fidgety thing took Amir about 3 weeks to
do so he's going to be very very upset
that was the highlight of the conference
um I'm Brian Davidson I'm I'm one of the
transplant surgeons here a liver
transplant surgeon uh and I've been
asked within 10 minutes to cover the
whole topic of progress and
transplantation organization and
research so um it's going to be fairly
superficial uh and it's going to be highly
highly
please um it's been said that organ
transplantation is perhaps the greatest
achievement of the 20th century and when
you when you do Ponder on the subject I
think that that may well be the case um
I tried to sell that to my kids and I'm
afraid uh this come out in front of
transplantation but clearly
transplantation must be up there as one
of the great achievements for man in the 20th
century and just one little bit of
background information about when these
things started out and just thought we
can put our thoughts for today into
context uh we're really not talking
about very far back when we had the very first
first
procedures it suggested at 1933 was the
first renal transplant and that was done
uh without any understanding o of organ
rejection and not surprisingly the organ
failed within within minutes and it was
only when uh some twins uh were actually
transplanted that obviously didn't have
the problems with the imun ological
barrier that there was actually a
successful outcome in transplantation
and that was in the early
1950s and that preempted really the
understanding of of what organ rejection
was all about and uh it's attributed to
Peter medar uh for his work in the 60s
uh to understand the subject of
transplantation immunological rejection
and put in the strategies that we've
seen to prevent organ rejection and in
the early 60s that was F followed by the
first uh human liver
transplant was because the results
progressively improved over the last 30
or 40 years uh you can see again this is
the European transplant registry results
uh we've got outcomes here by time
period after transplantation and this
data is split into two cohorts uh one
cohort uh being here in the' 70s and 80s
and the most recent corot in the ' 80s
and '90s
and into 2000 and you can see that the
transplantation results have
too and it's not just been in Europe
that we've seen improvements in organ
transplantation this is the UK data uh
and this is the UK data separated into
cohorts of threeyear periods uh and this
is 10year outcomes and you can see that
it's been Progressive Improvement in the
outcomes of transplantation this is
liver transplantation uh you can see
that there's now um over 90% onee
survival liver
transplantation and similarly with
kidney transplantation I see my
colleague bimby in the audience of
course kidneys he tells me do far better
than livers and he's absolutely right
and that you can see that the outcomes
with renal transplantation are even
better phenomenal success with over 90%
oneyear uh Graft in patient survival and
a grand Progressive Improvement um over
and that success has all uh been due to
a variety of things the first thing
obviously is is proper transplant
immunos supression uh back in the 60s
when transplants were started out the
transplantation drugs were very limited
uh but cyclosporin really brought in in
the mid '70s has been the main stay uh
of transplantation immunos supression
and only recently we have we had a few
other Smarties in the bag that can be
combined to try and improve F the
transplantation but perhaps we uh
shouldn't dwell on what's been there in
the past because we have to look forward
and looking forward we probably want to
avoid imun supressive drugs and we want
to get our organ transplant patients uh
to be tolerant of the organs so that we
can take all immunos supression off
immun suppressive drugs damage other
organs and really in the long term we
want a an immun supress free protocol
and I just pulled out for interest this
very recent paper where this has been
achieved in renal
transplantation and this is perhaps what
we'll be looking at in the next decade
is these very complex ways of modifying
both the donor and recipient to tolerate
the organs uh just to give you a very
brief outline this was a small study
based on eight patients undergoing live
donor renal
transplantation uh the recipient was
conditioned by giving them a short
course of chemotherapy and then total
body radiation they then had a stem cell
transplant they then had their kidney
transplant and shortly after the kidney
transplant they had uh again some stem
cell uh transplant with facilitating
cell enrichment along with some tea
cells uh and they all were discharged in
their third postop of day and the vast
majority of these patients are
completely free of immunos supression so
they are have full immunologic iCal
tolerance it's complex procedure but
obviously it can be achieved and I think
clearly this is what we're going to be
years the other major hurdle has been
preserving organs uh and I'll just very
briefly mention two advances one is in
the use of preservation Solutions uh
University of Wisconsin solution in the
late ' 80s revolutionized liver
transplantation uh but really we've seen
very little progam really because it's
so difficult to Market a new transplant
solution because the transplantation
results already are excellent and
therefore there's concern always to
introduce something new uh without
extensive trialing and then machine
profusion the concept of trying to store
the transplant organ in a better
condition or actually even improve the
condition of the organ during that time
period between retrieval and
implantation it's already been shown to
be satisfactory for the kidney
liver but all these things taken
together is clearly not quite good
enough this H is again UK transplant
data over a 10year period down here and
you can see the number of patients
waiting for transplantation at the top
and the number of patients actually
transplanted down here and you can see
that there's this huge gap between the
need and what's actually available and
many of these transplants are actually
not um CTIC transplants these are live
here and Adrian barely commented in the
fact that perhaps one of the things that
would be most useful would be to has
change the concept of of donation uh and
the whole system for donation and this
is just showing you that in different
countries in Europe there's an enormous
difference between the organ donation
rates and you can see Spain uh which
takes the lead right up at the top here
and the UK is
down somewhere here yes Britain in here
we have about half the donation rate of
Spain and I think further in this
meeting we'll be discussing some of the
this surgeons like to innovate and some
of the surgical things have been done to
try and improve organ uh availability for
for
transplantation um I don't think that
these have really made a remark able
dent on the requirement for organ
transplantation but Innovation is good
and Innovation can be developed uh first
of all there's the concept of splitting
organs for transplantation and it's
quite straightforward to split the liver
because it really has a unilateral uh
blood supply so you can use the small
left portion of the liver for a child's
transplant and the big right lob of the
liver for an adult transplantation so
you get two organ donations out of one liver
liver
and the other uh big development is live
donor transplantation which has really
maintained uh renal transplantation
activity at the level it is because uh
there's now far more live donor
transplants in the kidney than there is CTIC
CTIC
transplants and that's taken on because
of the improved techniques for
retrieving the uh the kidney from the
healthy donor uh showing that it can be
done very safely and effectively but we
have a big problem in the liver because
removing sufficient liver for
transplantation involves in the majority
of cases removing the right lob of the
liver which is certainly not a small
operation and it's certainly not one
without risk of morbidity and also
potential mortality in the donors and as
you know there's been some very um
publicized cases where the donor has
died after donation of a right lobe of the
liver so one of the other areas that
have been expanded uh and is expanding
rapidly is the use of non-heartbeating
donors and for those of you that are not
um familiar with this concept or or
donation after cardiac death uh these
are organs that have come from patients
where the there's been a decision made
to withdraw life support and the organs
are retrieved after the heart stops and
this has been a big Source uh of donor
organs huge opportunity but there has
been a price to pay and the price being
paid is that these patients have a
prolonged period of hypotension low
blood pressure and low oxygen supply
during the time period that they are
their support is withdrawn and these
produce very marginal graphs they might
work but they might not they certainly
have far higher instance of
complications and also problems that we
see only very rarely uh with a brain dead
donor and if we use these
non-heartbeating donor organs
you can see that the outcomes are poorer
if you compare this with the slide I
showed earlier you can see we're dipping
down with uh survivals uh at 80 or 70%
this is kidney kidneys from non-he
heartbeating donors and it's exactly the
same message from livers from non-he
heartbeating donors where the results
are significantly worse than organs that
have been retrieved from somebody that's
brain dead so it has maintained our
supply of donor organs
price and this is obviously of some
concern when you look at the big picture
in the UK because this slide shows the
big picture of what's Happening uh these
are living donors and this is over the
last 10 years and you can see the number
of living donors has increased
enormously with risk to the donor
obviously uh the nonheartbeating donors
the the donors after cardiac death uh
you can have have um sorry that's this
dark blue have increased progressively
and these are relatively poor quality
organs and the good quality organs from
brain dead donors have actually dipped
down over this period of time so we have
had the um situation where we've
maintained transplantation activity at
organs so I think that that um
background really gives you some idea of
where I think that we have to go in the
way of challenges uh now and for the
future I I think that we have to accept
that we have to reduce the risks for
live donors by every means possible and
there are many means to do that some of
which we'll discuss
today I think that we are using more and
more marginal graphs where they're not
going to function as well or as quickly
as before and we have to have strategies
to try and improve those or orans or
certainly make sure that they don't
deteriorate further and one opportunity
is to try and improve the organ between
the time of retrieval and
transplantation whether that's by
perusing it through my machine or
conditioning the organ and we're going
to hear shortly from Sarah about how you
can do organ conditioning which is one
of our research interests and you can
use pharmacological strategies as well
to try and to mop up the the damaging
molecules during the preservation period
we'll see more about M Min minimizing
immunos suppression because the imun
supressive drugs are damaging to the
body and clearly the best way of doing
that is to produce tolerance uh and the
small series that I showed on the kidney
I I think marks the way ahead of how
we're going to produce tolerance in our
transplant recipients it's going to be
complex it's going to be expensive but I
think that that's going to be the way
we're going to go and then lastly we're
going to hear something today uh about
the options to try and fill the gap of
the shortage of organs either by the use
of animal organs or tissue engineering organs
organs
denov thank you very much [Applause]
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