the newest breakthrough in cancer surgery
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The newest breakthrough in Cancer surgeryDr. Quyen Nguyen
Transcribed by Jos Roberto SimesSydney - Australia
I want to talk to you about one of the biggest myth in medicine,
and that is the idea that all We need are more medical breakthroughs
and then all of our problems will best solved.Our society loves to romanticize the idea of the single, solo inventor
who , working late in the lab one night, makes an earthshaking discovery,
and voila, overnight everything's changed.That's a very appealing picture; however, it's just not true.
in fact, medicine today is a team sport.
And in many ways, it always has been.I'd like to share with you a story about how I've experienced this
very dramatically in my own work.
I'm a surgeon, and We surgeons have always had this special
relationship with light.When I make an incision inside a patient's body, it's dark.
We need to shine light to see what we're doing.
And this is why, traditionally,
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surgeries have always started so early in the morning
to take a advantage of daylight hours.
And if you look at it historical picturesof early operating rooms, they have been on top of buildings.
for example, this is the oldest operating room in the Western world,
in London,
Where the operating room is actually on the top of the churchwith the skylight coming in.
and then this is a picture one of the most famous hospital in America.
this is Mass General in Boston.
and do you know where the operating room is?
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here it is on the top of the building
with plenty of windows to let light in.
So nowadays in the operating room,
We no longer need to use sunlight.
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and because We no longer need to use sunlight,
We have very specialized lights that are made for theOperating room.
We have an opportunity to bring in other kinds of lights
lights that can allow us to see what
We currently don't see.
And this is what I think is the magic of fluorescence.
so let me back up a little bit.
When We are in medical school, We learn our anatomy fromillustration such as this
where everything's color-coded.
nervers are yellow, arteries are red,
veins are blue.
That's so easybody could become a surgeon, right?
However, when We have a real patient on the table,
this is the same neck dissection
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not so easy to tell the difference between differentstructures.
We heard over the last couple days what an urgent
Problem cancer still is in our society.what a pressing need it is for us to not have
one person die every minute.Well if cancer can be caught early,
enough such that someone can have their cancer taken out,
excised with surgery.
I don't care if it has this gene or that gene,or if it has this protein or that protein,
it's in the jar.
it's done, it's out, you're cured of cancer.This is how we excise cancers.
We do our best, based open our training
and the way the cancer looks and the way it feelsand its relationship to other structures and all our experience,
We say, you know what, the cancers gone.
We've made a good job, weve taken it out.That's what the surgeon is saying in the operating room
when the patient's on the table.
But then we actually don't know that it's all out.
We actually have to take samples from the surgical bed,what's left behind in the patient,
and then send those bits to the pathology lab
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In the meanwhile, the patient's on the operating room table.
The nurses, anesthesiologist, the surgeon,
all the assistants are waiting around.
and we wait, the pathologist take that sample,freezes it, cuts it, look in the microscope one by one
and then calls back into the room.
and that may be 20 minutes after per piece.so if your sent three 3 specimens,
it's an hour later.
and very often they say," You know what, point A and B are okay,
but point C, you still have some residual cancer there.
please go cut that piece out".So We go back and do that again, and again.
And this whole process:
"Okay you're done.
We think the entire tumor is out."
We think we've done a good job but very ofter several days later
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had three parts.
The main part of it is the blue part,polycation,and it's basically very sticky to every tisssue in your body
so imagine that you make a solution full of this sticky material
and inject it into the veins of someone who has cancereverything's going to get lit up Nothing will be specific.
There's no specificity there.
So they added two additional components.the first one is a polyanionic segment which basically acts as no stick backing
like the back of a sticker.
so when those two are together, the molecule is neutral and the two pieces are
then linked by something that can only be cut
if you have the right molecular scissorsfor example, the kind of protease enzymes
that tumors make.so here in this situation, if you make a solution full of this three-
part molecule along with the dye, which is shown in green,
and you inject it into the vainof someone who has cancer, normal tissue can't cut it.
the molecule passes through and gets excreted
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However, in the presence of the tumor,
now here are molecular scissors can break this molecular apartright there at the cleavable site.
And now, boom, the tumor labels itself and it gets fluorescent.
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so here's an example of a nerve that has tumor surrounding itCan you tell where the tumor is?
I couldn't when I was working on this.
but here it is, it's fluorescent.
see, so every single one in the audience can tell where the
cancer is.We can tell in the operating room, in the field.
at a molecular level, where is the cancer and what
the surgeon need to do and how much more work theyneed to do to cut that out.
And the cool thing about fluorescence
is that it's not only bright,
it actually can shine through tissue.The light that the fluorescence emits
can go through tissue.
So even if the tumor is not right on the surface,you'll still be able to see it.
in this movie, you can see that the tumor is green. ok
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There's actually normal muscle on top of it. See that?
And I'm peelig that muscle away.
But even before I peel that muscle away.you saw that there was a tumor underneath.
So that's the beauty of having a tumor
that's labeled with fluorescent moleculesThat you can, not only see the margins
right there on a molecular level,
but you can see it even if it's not righton the top, even if it's beyond your field of view.
And this works for metastatic lymph nodes also.
Sentinel lymph node dissection
has really changed the way that We manage breast cancer, melanoma.Women used to get really debilitating surgery
to excise all of the auxiliary lymph nodes.
But when sentinel lymph node
came into our treatment protocol,the surgeon basically looks for the single node
that is the first draining lymph node of the cancer.and then if that node has cancer,
the woman would go on to get
the auxillary lymph node dissection
so what that mean is if the lymph node did no have cancer.the woman would be saved from having unnecessary surgery
But sentinel lymph node, the way that We do it today.
is kind of like having a road mapjust to know where to go
So if you're driving on the freeway
snd you want to know where's the next gas station,you have a map to tell you that gas station s down the road.
it doesn't tell you whether or not
the gas station has gas.you have to cut it out, bring it back home cut it up, look inside
and say."Oh yes, it does have gas."
So that takes more time
Patients are still on the operating room tableAnesthesiologist, surgeon are waiting around.
That takes time.
So wit our technology, We can tell right away.You see a lot of little, roundish bumps there.
some of these are swollen lymph nodes
that look a little larger than others.Who amongst us hasn't had swollen lymph nodes with a cold?
That doesn't mean that there's cancer inside.
well with our technology.
the surgeon is able to tell immediately
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which nodes have cancer.
I won't go into this very much.
but our technology, besides being ableto tag tumor and metastatic lymph nodes with fluorescence,
we can also use the same smart three-part molecule
to tag gadolinium onto the systemso you can do this noninvasively.
the patient has cancer,
you want to know if the lymph nodes have cancereven before you go in.
well you can see this on a MRI.
So in Surgery.
it's important to know what to cut out.But equally important
is to preserve things
that are important for function.
So it's very important to avoid inadvertent injury.And what I'm taking about are nerves.
Neverves, if they are injured, can cause paralysis,can cause pain.
in the setting of prostate cancer,
up to 60 percent of men
after prostate cancer surgerymay have urinary incontinence
and erectile disfunction
that's a lot of people to have a lot problemsand this is even in so-called nerve-sparing surgery
which means that the surgeon is aware of the problem,
and they are trying to avoid the nerves.But you know what, these little nerves are so small,
in the context of prostate cancer,
that they are actually never seen.they are traced just by their known anatomical path
along vasculature.
And they're known because somebody has decided to study them,
which means that we're still learningabout where they are.
Crazy to think that we're having surgery.
we're trying to excise cancer, we don't know the cancer is.we're trying to preserve nerves; we can't see where they are.
So I said,wouldn't it be great if could find a way
to see nerves with fluorescence?And at first this didn't get a lot of support.
People said. " we've been doing it this ways for all these years.
What's the problem?
We haven't had that many complications"
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But I went ahead anyway.
And Roger helped me
And he brought his whole team with him.So there's that teanwork things again.
And We eventually discovered molecules
that were specifically labeling nerves.And When we made a solution of this,
tagged with the fluorescence
and injected in the body of a mouse,their nervers literally glowed.
here you're looking at a sciatic nerve of a mouse,
and you can see tht that big, fat portion can see very easily.
but in fact, at the tip of that where dissecting now,
there's actually very fine arborizations that can't really be seenyou see what look like little medusa heads coming out.
we have been able to see nerves for facil expression, for facial movement, forbreathing every single nerve nerves for urinary function around the porstate.
we've been able to see every single nerve.
when we put these two probes together...
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so here's a tumor.
Do you guys know where the margins of this tumor is?
now you do
what about the nerve that's going into this tumor?
that white portion there is easy to see.
but what about the part that goes into the tumor?
Do you know where it's going?
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now you do
Basically, we've come up with a ways to stain tissue
and color-code the surgical field.
this was a bit of a breakthrough.
I think that it'll change the way we do surgery
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We published our results
in the proceeding of the Naional Academy of Sciences
and in Nature Biotechnology.
We received commentary in Discover magazine.
and the economist.
And We shoed it to a lot of my surgical collegues.
They said. " wow!"
I have pacient who would benefit from this
I think that this will result in my surgerieswith a better outcome
and fewer complications."
What need to happen now is further development of our technology
along with development of the instrumentation
that allows us to see this sort of fluorescence in the operation room.the eventual goal is that we'll get this into patients.
However, We've discoveredthat there's actually no straightforward mechanism
to develop a molecule for one-time use.
Understandably, the majority of the medical industry
is focused on multiple-use drugs,
such as long-term daily medications.
We are focused on making this technology better.
We're focused on adding drugs, adding growth factors
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killing nerves that are causing problems
and not the surrounding tissue.
We know that this can be done and we're committed to doing it.I'd like to leave you with this final thought.
Successful innovation is not a single breakthrough.
it is not a sprint it s not an event for the solo runner.Successful innovation is a team sport, it's a relay race.
it require one team for the breakthrough
and another team to get the breakthrough accept and adopted.And this takes the long-term steady courage of day-in-day-out struggle
to educate, to persuade and win acceptance.
And that is the light that I want to shine on health and medicine today.
Thank you very much
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