0:25 okay thank you very much um that fidgety
0:27 thing took Amir about 3 weeks to do so
0:29 he's going to be very very upset that
0:32 was the highlight of the conference um
0:35 I'm Brian Davidson I'm I'm one of the
0:36 transplant surgeons here a liver
0:38 transplant surgeon uh and I've been
0:40 asked within 10 minutes to cover the
0:42 whole topic of progress and
0:43 transplantation organization and
0:46 research so um it's going to be fairly
0:48 superficial uh and it's going to be
0:55 please um it's been said that organ
0:57 transplantation is perhaps the greatest
0:59 achievement of the 20th century and when
1:02 you when you do Ponder on the subject I
1:05 think that that may well be the case um
1:07 I tried to sell that to my kids and I'm
1:09 afraid uh this come out in front of
1:11 transplantation but clearly
1:13 transplantation must be up there as one
1:15 of the great achievements for man in the 20th
1:21 century and just one little bit of
1:23 background information about when these
1:26 things started out uh just so we can put
1:29 our thoughts for today into context uh
1:32 we're really not talking about very far
1:34 back when we had the very first
1:38 procedures it suggested at 1933 was the
1:41 first renal transplant and that was done
1:43 uh without any understanding o of organ
1:46 rejection and not surprisingly the organ
1:49 failed within within minutes and it was
1:52 only when uh some twins uh were actually
1:53 transplanted that obviously didn't have
1:55 the problems with the immunological
1:57 barrier that there was actually a
1:59 successful outcome in transplantation
2:02 and was in the early
2:05 1950s and that preempted really the
2:07 understanding of of what organ rejection
2:10 was all about and uh it's attributed to
2:13 Peter medar uh for his work in the 60s
2:15 uh to understand the subject of
2:18 transplantation immunological rejection
2:19 and put in the strategies that we've
2:23 seen to prevent organ rejection and then
2:26 the early 60s that was followed by the
2:28 first uh human liver
2:30 transplant was because the results
2:33 progressively improved over the last 30
2:36 or 40 years uh you can see again this is
2:39 the European transplant registry results
2:42 uh we've got outcomes hereby uh time
2:45 period after transplantation and this
2:48 data is split into two cohorts uh one
2:51 cohort uh being here in the 70s and 80s
2:53 and the most recent cohort in the ' 80s
2:56 and '90s uh and into 2000 and you can
2:58 see that the transplantation results
3:00 have progressively improved improved and
3:06 too and it's not just been in Europe
3:07 that we've seen improvements in organ
3:10 transplantation this is the UK data uh
3:13 and this is the UK data separated into
3:16 cohorts of threeyear periods uh and this
3:18 is 10e outcomes and you can see that
3:20 there's been Progressive Improvement in
3:23 the outcomes of transplantation this is liver
3:23 liver
3:25 transplantation uh you can see that
3:29 there's now um over 90% one year
3:32 survival liver
3:34 transplantation and similarly with
3:35 kidney transplantation I see my
3:37 colleague bimbe in the audience of
3:39 course kidneys he tells me do far better
3:41 than livers and he's absolutely right
3:43 and that you can see that the outcomes
3:45 with Ral transplantation are even better
3:48 phenomenal success with over 90%
3:51 one-year uh Graft in patient survival
3:53 and a again Progressive Improvement um
3:56 over the last two
3:59 decades and that success has all uh been
4:01 due to a variety of things the first
4:04 thing obviously is is proper transplant
4:07 immun suppression uh back in the 60s
4:08 when transplants were started out the
4:28 were okay thank you very much um that
4:30 fidgety thing took here about 3 weeks to
4:33 do so he's going to be very very upset
4:35 that was the highlight of the conference
4:38 um I'm Brian Davidson I'm I'm one of the
4:40 transplant surgeons here a liver
4:42 transplant surgeon uh and I've been
4:44 asked within 10 minutes to cover the
4:45 whole topic of progress and
4:47 transplantation organization and
4:50 research so um it's going to be fairly
4:51 superficial uh and it's going to be
4:59 please um it's been said that organ
5:01 transplant ation is perhaps the greatest
5:03 achievement of the 20th century and when
5:05 you when you do Ponder on the subject I
5:08 think that that may well be the case um
5:10 I tried to sell that to my kids and I'm
5:12 afraid uh this come out in front of
5:14 transplantation but clearly
5:17 transplantation must be up there as one
5:19 of the great achievements for man in the 20th
5:25 century and just one little bit of
5:26 background information about when these
5:29 things started out uh just thought we
5:31 can put our thoughts for today into
5:33 context uh we're really not talking
5:37 about very far back when we had the very first
5:38 first
5:41 procedures it suggested at 1933 was the
5:44 first renal transplant and that was done
5:47 uh without any understanding o of organ
5:49 rejection and not surprisingly the organ
5:52 failed within within minutes and it was
5:55 only when uh some twins uh were actually
5:57 transplanted that obviously didn't have
5:59 the problems with the immunological
6:00 barrier that there was actually a
6:03 successful outcome in transplantation
6:05 and that was in the early
6:08 1950s and that pre emptied really the
6:11 understanding of of what organ rejection
6:13 was all about and uh it's attributed to
6:16 Peter medar uh for his work in the 60s
6:19 uh to understand the subject of
6:21 transplantation immunological rejection
6:23 and put in the strategies that we've
6:27 seen to prevent organ rejection and in
6:29 the early 60s that was followed by the
6:31 first uh human liver
6:34 transplant was because the results
6:37 progressively improved over the last 30
6:39 or 40 years uh you can see again this is
6:43 the European transplant registry results
6:46 uh we've got outcomes here by uh time
6:48 period after transplantation and this
6:51 data is split into two cohorts uh one
6:55 cohort uh being here in the 70s and 80s
6:57 and the most recent corot in the 80s and
7:00 '90s uh and into 200 you can see that
7:02 the transplantation results have
7:09 too and it's not just been in Europe
7:11 that we've seen improvements in organ
7:14 transplantation this is the UK data uh
7:16 and this is the UK data separated into
7:19 cohorts of threeyear periods uh and this
7:22 is 10e outcomes and you can see that
7:24 there been Progressive Improvement in
7:26 the outcomes of transplantation this is liver
7:27 liver
7:29 transplantation uh you can see that
7:30 there's now
7:36 um over 90% onee survival liver
7:38 transplantation and similar with kidney
7:40 transplantation I see my colleague bimby
7:41 in the audience of course kidneys he
7:44 tells me do far better than livers and
7:45 he's absolutely right in that you can
7:47 see that the outcomes with renal
7:49 transplantation are even better
7:52 phenomenal success with over 90% one-ear
7:54 uh graft and patient survival and a
7:57 grand Progressive Improvement um over
8:01 the last two decades
8:03 and that success has all uh been due to
8:05 a variety of things the first thing
8:07 obviously is is proper transplant
8:10 immunos suppression uh back in the 60s
8:12 when transplants were started out the
8:14 transplantation drugs were very limited
8:17 uh but cyclos sporn really brought in in
8:19 the mid '70s has been the main stay uh
8:22 of transplantation immunos supression
8:24 and only recently we have we had a few
8:26 other Smarties in the bag that can be
8:28 combined to try and improve further the
8:36 transplantation but perhaps we shouldn't
8:38 dwell on what's been there in the past
8:40 because we have to look forward and
8:42 looking forward we probably want to
8:45 avoid immun suppressive drugs and we
8:47 want to get our organ transplant
8:50 patients uh to be tolerant of the organs
8:51 so that we can take all immunos
8:54 suppression off immunos supressive drugs
8:56 damage other organs and really in the
8:58 long term we want a an immunosuppressant
9:01 free Pro protocol and I just pulled out
9:04 for interest this very recent paper
9:06 where this has been achieved in renal
9:09 transplantation and this is perhaps what
9:11 we'll be looking at in the next decade
9:14 is these very complex ways of modifying
9:17 both the donor and recipient to tolerate
9:19 the organs uh just to give you a very
9:22 brief outline this was a small study
9:24 based on eight patients undergoing live
9:26 donor renal
9:28 transplantation uh the recipient was
9:29 conditioned by giving them a short
9:31 course of chemotherapy and then total
9:34 body radiation they then had a stem cell
9:37 transplant they then had their kidney
9:39 transplant and shortly after the kidney
9:42 transplant they had uh again some stem
9:45 cell uh transplant with facilitating
9:47 cell enrichment along with some tea
9:50 cells uh and they all were discharged in
9:53 their third postop of day and the vast
9:54 majority of these patients are
9:56 completely free of immunos supression so
10:00 they are have full immunological Toler s
10:02 it's complex procedure but obviously it
10:04 can be achieved and I think clearly this
10:06 is what we're going to be dealing with
10:12 years the other major hdle has been
10:14 preserving organs uh and I'll just very
10:17 briefly mention two advances one is in
10:21 the use of preservation Solutions uh
10:23 University of Wisconsin solution in the
10:25 late 80s revolutionized liver
10:27 transplantation uh but really we've seen
10:29 very little progress really because it
10:31 it's so difficult to Market a new
10:33 transplant solution because the
10:36 transplantation results already are
10:38 excellent and therefore there's concern
10:40 always to introduce something new uh
10:43 without extensive trialing and then
10:45 machine profusion the concept of trying
10:48 to store the transplant organ in a
10:50 better condition or actually even
10:52 improve the condition of the organ
10:54 during that time period between
10:56 retrieval and implantation it's already
10:58 been shown to be satisfactory for the
11:00 kidney and way and others are doing work
11:06 liver but all these things taken
11:08 together is clearly not quite good
11:29 data okay thank you very much um that
11:31 fidgety thing took Amir about 3 weeks to
11:33 do so he's going to be very very upset
11:36 that was the highlight of the conference
11:39 um I'm Brian Davidson I'm I'm one of the
11:40 transplant surgeons here a liver
11:42 transplant surgeon uh and I've been
11:44 asked within 10 minutes to cover the
11:46 whole topic of progress and
11:47 transplantation organization and
11:50 research so um it's going to be fairly
11:52 superficial uh and it's going to be highly
11:53 highly
11:59 please um it's been said that organ
12:02 transplantation is perhaps the greatest
12:04 achievement of the 20th century and when
12:06 you when you do Ponder on the subject I
12:09 think that that may well be the case um
12:11 I tried to sell that to my kids and I'm
12:13 afraid uh this come out in front of
12:15 transplantation but clearly
12:17 transplantation must be up there as one
12:19 of the great achievements for man in the 20th
12:25 century and just one little bit of
12:27 background information about when these
12:29 things started out and just thought we
12:32 can put our thoughts for today into
12:34 context uh we're really not talking
12:37 about very far back when we had the very first
12:38 first
12:42 procedures it suggested at 1933 was the
12:45 first renal transplant and that was done
12:47 uh without any understanding o of organ
12:50 rejection and not surprisingly the organ
12:53 failed within within minutes and it was
12:56 only when uh some twins uh were actually
12:57 transplanted that obviously didn't have
12:59 the problems with the imun ological
13:01 barrier that there was actually a
13:03 successful outcome in transplantation
13:06 and that was in the early
13:09 1950s and that preempted really the
13:11 understanding of of what organ rejection
13:14 was all about and uh it's attributed to
13:17 Peter medar uh for his work in the 60s
13:19 uh to understand the subject of
13:22 transplantation immunological rejection
13:23 and put in the strategies that we've
13:27 seen to prevent organ rejection and in
13:30 the early 60s that was F followed by the
13:32 first uh human liver
13:34 transplant was because the results
13:37 progressively improved over the last 30
13:40 or 40 years uh you can see again this is
13:43 the European transplant registry results
13:46 uh we've got outcomes here by time
13:49 period after transplantation and this
13:52 data is split into two cohorts uh one
13:55 cohort uh being here in the' 70s and 80s
13:57 and the most recent corot in the ' 80s
13:59 and '90s
14:01 and into 2000 and you can see that the
14:02 transplantation results have
14:10 too and it's not just been in Europe
14:11 that we've seen improvements in organ
14:14 transplantation this is the UK data uh
14:17 and this is the UK data separated into
14:20 cohorts of threeyear periods uh and this
14:22 is 10year outcomes and you can see that
14:24 it's been Progressive Improvement in the
14:27 outcomes of transplantation this is
14:29 liver transplantation uh you can see
14:33 that there's now um over 90% onee
14:36 survival liver
14:38 transplantation and similarly with
14:40 kidney transplantation I see my
14:41 colleague bimby in the audience of
14:43 course kidneys he tells me do far better
14:45 than livers and he's absolutely right
14:47 and that you can see that the outcomes
14:49 with renal transplantation are even
14:52 better phenomenal success with over 90%
14:55 oneyear uh Graft in patient survival and
14:58 a grand Progressive Improvement um over
15:04 and that success has all uh been due to
15:05 a variety of things the first thing
15:08 obviously is is proper transplant
15:11 immunos supression uh back in the 60s
15:13 when transplants were started out the
15:15 transplantation drugs were very limited
15:17 uh but cyclosporin really brought in in
15:20 the mid '70s has been the main stay uh
15:22 of transplantation immunos supression
15:24 and only recently we have we had a few
15:27 other Smarties in the bag that can be
15:29 combined to try and improve F the
15:36 transplantation but perhaps we uh
15:38 shouldn't dwell on what's been there in
15:40 the past because we have to look forward
15:42 and looking forward we probably want to
15:45 avoid imun supressive drugs and we want
15:49 to get our organ transplant patients uh
15:51 to be tolerant of the organs so that we
15:53 can take all immunos supression off
15:55 immun suppressive drugs damage other
15:57 organs and really in the long term we
16:01 want a an immun supress free protocol
16:03 and I just pulled out for interest this
16:05 very recent paper where this has been
16:07 achieved in renal
16:09 transplantation and this is perhaps what
16:12 we'll be looking at in the next decade
16:15 is these very complex ways of modifying
16:17 both the donor and recipient to tolerate
16:20 the organs uh just to give you a very
16:22 brief outline this was a small study
16:25 based on eight patients undergoing live
16:26 donor renal
16:28 transplantation uh the recipient was
16:30 conditioned by giving them a short
16:32 course of chemotherapy and then total
16:35 body radiation they then had a stem cell
16:37 transplant they then had their kidney
16:39 transplant and shortly after the kidney
16:42 transplant they had uh again some stem
16:45 cell uh transplant with facilitating
16:48 cell enrichment along with some tea
16:50 cells uh and they all were discharged in
16:53 their third postop of day and the vast
16:54 majority of these patients are
16:57 completely free of immunos supression so
16:59 they are have full immunologic iCal
17:02 tolerance it's complex procedure but
17:04 obviously it can be achieved and I think
17:06 clearly this is what we're going to be
17:13 years the other major hurdle has been
17:15 preserving organs uh and I'll just very
17:18 briefly mention two advances one is in
17:21 the use of preservation Solutions uh
17:23 University of Wisconsin solution in the
17:26 late ' 80s revolutionized liver
17:28 transplantation uh but really we've seen
17:29 very little progam really because it's
17:32 so difficult to Market a new transplant
17:34 solution because the transplantation
17:37 results already are excellent and
17:39 therefore there's concern always to
17:41 introduce something new uh without
17:44 extensive trialing and then machine
17:47 profusion the concept of trying to store
17:49 the transplant organ in a better
17:51 condition or actually even improve the
17:53 condition of the organ during that time
17:55 period between retrieval and
17:57 implantation it's already been shown to
17:59 be satisfactory for the kidney
18:06 liver but all these things taken
18:08 together is clearly not quite good
18:11 enough this H is again UK transplant
18:14 data over a 10year period down here and
18:16 you can see the number of patients
18:19 waiting for transplantation at the top
18:21 and the number of patients actually
18:23 transplanted down here and you can see
18:26 that there's this huge gap between the
18:28 need and what's actually available and
18:30 many of these transplants are actually
18:34 not um CTIC transplants these are live
18:41 here and Adrian barely commented in the
18:43 fact that perhaps one of the things that
18:44 would be most useful would be to has
18:48 change the concept of of donation uh and
18:50 the whole system for donation and this
18:52 is just showing you that in different
18:54 countries in Europe there's an enormous
18:56 difference between the organ donation
18:59 rates and you can see Spain uh which
19:01 takes the lead right up at the top here
19:03 and the UK is
19:06 down somewhere here yes Britain in here
19:09 we have about half the donation rate of
19:10 Spain and I think further in this
19:12 meeting we'll be discussing some of the
19:19 this surgeons like to innovate and some
19:21 of the surgical things have been done to
19:24 try and improve organ uh availability for
19:25 for
19:27 transplantation um I don't think that
19:29 these have really made a remark able
19:31 dent on the requirement for organ
19:33 transplantation but Innovation is good
19:35 and Innovation can be developed uh first
19:37 of all there's the concept of splitting
19:39 organs for transplantation and it's
19:41 quite straightforward to split the liver
19:44 because it really has a unilateral uh
19:46 blood supply so you can use the small
19:49 left portion of the liver for a child's
19:51 transplant and the big right lob of the
19:54 liver for an adult transplantation so
19:57 you get two organ donations out of one liver
19:59 liver
20:01 and the other uh big development is live
20:03 donor transplantation which has really
20:06 maintained uh renal transplantation
20:08 activity at the level it is because uh
20:10 there's now far more live donor
20:12 transplants in the kidney than there is CTIC
20:14 CTIC
20:16 transplants and that's taken on because
20:18 of the improved techniques for
20:21 retrieving the uh the kidney from the
20:24 healthy donor uh showing that it can be
20:26 done very safely and effectively but we
20:28 have a big problem in the liver because
20:30 removing sufficient liver for
20:33 transplantation involves in the majority
20:34 of cases removing the right lob of the
20:37 liver which is certainly not a small
20:38 operation and it's certainly not one
20:41 without risk of morbidity and also
20:43 potential mortality in the donors and as
20:46 you know there's been some very um
20:49 publicized cases where the donor has
20:51 died after donation of a right lobe of the
20:56 liver so one of the other areas that
20:59 have been expanded uh and is expanding
21:01 rapidly is the use of non-heartbeating
21:03 donors and for those of you that are not
21:06 um familiar with this concept or or
21:08 donation after cardiac death uh these
21:11 are organs that have come from patients
21:13 where the there's been a decision made
21:16 to withdraw life support and the organs
21:19 are retrieved after the heart stops and
21:22 this has been a big Source uh of donor
21:26 organs huge opportunity but there has
21:27 been a price to pay and the price being
21:30 paid is that these patients have a
21:32 prolonged period of hypotension low
21:35 blood pressure and low oxygen supply
21:38 during the time period that they are
21:40 their support is withdrawn and these
21:42 produce very marginal graphs they might
21:45 work but they might not they certainly
21:46 have far higher instance of
21:49 complications and also problems that we
21:52 see only very rarely uh with a brain dead
21:56 donor and if we use these
21:59 non-heartbeating donor organs
22:01 you can see that the outcomes are poorer
22:03 if you compare this with the slide I
22:05 showed earlier you can see we're dipping
22:10 down with uh survivals uh at 80 or 70%
22:12 this is kidney kidneys from non-he
22:14 heartbeating donors and it's exactly the
22:16 same message from livers from non-he
22:18 heartbeating donors where the results
22:21 are significantly worse than organs that
22:23 have been retrieved from somebody that's
22:27 brain dead so it has maintained our
22:29 supply of donor organs
22:35 price and this is obviously of some
22:37 concern when you look at the big picture
22:40 in the UK because this slide shows the
22:42 big picture of what's Happening uh these
22:45 are living donors and this is over the
22:47 last 10 years and you can see the number
22:49 of living donors has increased
22:52 enormously with risk to the donor
22:55 obviously uh the nonheartbeating donors
22:58 the the donors after cardiac death uh
23:01 you can have have um sorry that's this
23:04 dark blue have increased progressively
23:06 and these are relatively poor quality
23:09 organs and the good quality organs from
23:11 brain dead donors have actually dipped
23:14 down over this period of time so we have
23:17 had the um situation where we've
23:19 maintained transplantation activity at
23:27 organs so I think that that um
23:29 background really gives you some idea of
23:31 where I think that we have to go in the
23:34 way of challenges uh now and for the
23:37 future I I think that we have to accept
23:39 that we have to reduce the risks for
23:42 live donors by every means possible and
23:45 there are many means to do that some of
23:46 which we'll discuss
23:49 today I think that we are using more and
23:52 more marginal graphs where they're not
23:53 going to function as well or as quickly
23:56 as before and we have to have strategies
23:59 to try and improve those or orans or
24:00 certainly make sure that they don't
24:03 deteriorate further and one opportunity
24:05 is to try and improve the organ between
24:07 the time of retrieval and
24:09 transplantation whether that's by
24:12 perusing it through my machine or
24:13 conditioning the organ and we're going
24:15 to hear shortly from Sarah about how you
24:17 can do organ conditioning which is one
24:20 of our research interests and you can
24:22 use pharmacological strategies as well
24:26 to try and to mop up the the damaging
24:29 molecules during the preservation period
24:31 we'll see more about M Min minimizing
24:33 immunos suppression because the imun
24:36 supressive drugs are damaging to the
24:38 body and clearly the best way of doing
24:41 that is to produce tolerance uh and the
24:43 small series that I showed on the kidney
24:45 I I think marks the way ahead of how
24:48 we're going to produce tolerance in our
24:50 transplant recipients it's going to be
24:53 complex it's going to be expensive but I
24:54 think that that's going to be the way
24:56 we're going to go and then lastly we're
24:59 going to hear something today uh about
25:01 the options to try and fill the gap of
25:04 the shortage of organs either by the use
25:07 of animal organs or tissue engineering organs
25:10 organs
25:13 denov thank you very much [Applause]
