Nanomedicine | Applications of Nanotechnology in Interventional Oncology
Nanomedicine | Applications of Nanotechnology in Interventional Oncology
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the particular usage of nanotech

nanoparticles in medicine and the reason that we think it fantasia's is it's really the size of of things in nature and things in medicine so you can see red blood cells are in the order of nanometers and antibodies

these are all sort of in that same size range there's nano nano particles come in different flavors to liposomes if you think of a cell it has a by lipid layer membrane layer and that's just what a lysosome is and we can create these in

the lab we can create dendrimers it's basically like roots of a tree where we can grow them out to be different sizes that gold nanoshells is just a particle of gold and the reason we like gold is that you can heat it up in it it makes

things hot and then there's some other types of nanoparticles so it's not just one thing it's just a bunch of different structures that we can develop that are

over this paper here mr. Keane I had the privilege to meet at one of our conference this this guy Oliver Oliver

Burke I'm of the first author the very brilliant young 28 yield ND PhD students who got that first day besides man likely on the in- image on some professors all their life I trying to get a paper into that girona and now you

haven't said that would never accept I just went to my professor and asking for a project guide thistle and he said well you did all the words you might as well be the first author your is going to be cited in a hundred years so they

basically pitched within within six hours they pitched iv+ IV and I a you know Ivy versus ibni a and the outcome was that you had more recanalization you had a smaller in fact volume and you had a modified ranking

scale of 0.2 which is minimal disability no or minimal disability thirty-three percent versus nineteen percent which is a seventy percent relatively percentage increased chance of a good functional outcome you see here the shift analysis

with intervention and the control group how everything shifted to the right except for that some reason some other studies that also did but here that was there was a pivotal moment in installed medicine medicine altogether I don't

think we see very many such impactful trials during the Scientific careers so

A very excellent speaker and has been a very loyal loyal supporter of AVIR for years. So he usually does our radiation safety talk but he was getting burned out on it so we came up with his next topic. Now so today he's going to talk about burnout and productivity in the

workplace. His background...he did do some training up at the SUNY system in New York. He was originally in the as an ER doctor and then did his a IR fellowship and he is at the University of North Carolina at Chapel Hill. They

did win the other night against Duke so he's very happy. And it's amazing I don't know how he does it. But in his spare time apparently he develops golf balls. And I don't know why they're different but this is the Dixon golf

ball. And they are eco-friendly which fits in very nicely with the Chapel Hill world. And yes he did not know I was going to say this part of the presentation so he's not happy with me right now. But it is my pleasure to introduce

Dr. Dixon. You're fired. Ok so thanks. So this is a much different talk than what you just heard. You just heard three outstanding talks and most of your time here will be spent

talking...learning about procedures that we do and things like that and Dana's correct I usually talk to you about radiation safety and I've done that we think for about forty seven years so I decided not to do that. And

the...your leadership encouraged me to present on this. So I'm gonna tell you a story of how I ended up here. I feel that in a way i'm an expert on burnout and I'll explain why. So Dana touched on the idea that I was an emergency

medicine physician for a decade. And I did I got absolutely torched. And the reason is you see a lousy cross-section of the world and you have to see them and be really nice to them and it wears on you. It's a young person

sport and so I left when I discovered interventional radiology. Now most most radio...most emergency medicine doctor who leave emergency medicine and go into radiology and there's there's a handful of us...they do something smart they

go into MSK or they go into to neuro and they have a nice calm life. Maybe they learn how to do tendon repair work and and they have a very cush quiet life. I am not that smart. I went from one sort of intense chaotic

universe into another chaotic intense universe. So there's something wrong with me. So I burned out once on that specialty but I've worked hard not to burnt out on an interventional radiology. And the way this talk came to be

my division chief Charles Burke and I were speaking at another meeting and I did 30 minutes on burnout and he did 30 minutes on productivity and people came up to us afterwards and it was just like the two were meant to be together.

I couldn't persuade Dr. Burke to come speak with with me today so we're going to...I'm going to present both halves. I wasn't smart enough to look and see how change slide...the green. Ok I do some consulting work for Cook that's my

only disclosure. And those of you who have seen me I'm going to keep moving like this it depends how agitated I get. I may come down and tap you on the shoulder but I want to try to keep you awake.

What the heck is that. So we're five minutes in and I've got golf balls and r2 d2 or something here. Ok so Charles Burke is a was part of the original yin-yang presentation and I was actually asked to present last year at SIR

once somebody saw that presentation by both of us. So we'll we'll cover the burnout side and then we'll turn around and try to cover the productivity side. And at first glance you might think that's not really

the way to solve burnout but it is part of of the solution. And the other person I want to acknowledge is a psychiatrist at UNC named Samantha Meltzer-Brody and Samantha has been doing work on burnout

maybe for a decade or so and if you're were interested in this and and google her you'll come up with a few papers including of a paper about burnout amongst residents at our

billion dollars annually on nanotechnology and research if you can

imagine that so nanotechnology is not just in the lab it's everywhere I was giving a lecture and they I was at I should say that I was at a national meeting and they're talking about biomimicry and actually the stuff they

spray on your windshield to make the water beat up that's nano technology so it's a part of your everyday life you just don't know it but that's that

does the nanoparticle nanoparticles are

just a description of a very small entity so so just to put it in perspective imagine me holding a marble and it's a marble to the size of the earth that's how small it is when we think about things one nanometer is a

billionth of a mirror that doesn't mean anything to me that's why i used the marble in that analogy but two nanometers would be the diameter of a DNA helix a very very tiny size that we're talking about so what's the

history of nanoparticles Richard Feynman wrote a book called there's plenty of room at the bottom in 1959 and he sort of imagined a world where we could sort of take atoms and manipulate them and create new things the term

nanotechnology was coined by nereo taniguchi in 1974 and then Eric Drexler wrote this engines of creation book where he where he imagined a world where we could have the entire library of congress on something the size of the

sugar cube and we're there right we have these teeny tiny little microchips in your computer that can have tons of information so we spend about ten

was in our lab and she developed the Saracen and microspheres so why is that you know why is that important what does that mean why can't you just give her the drug patients the drug well it turns

out that this drug is very poorly tolerated patients get sloughing of their skin on their hands in their feet so they can't walk but maybe they get the benefit of the drug the other difficulty with this drug is why can't

you just infuse it like we do for key memorization what's lipophilic so it's that right so if you infuse fat it's just going to come out it's not going to go it needs to be so she dances she developed these

very fancy nanoparticles that would go into the bloodstream they wouldn't precipitate out they wouldn't be fat globules and we could inject them into tumors and what we found is you know she put iron on them so that we could see

and this is just images from the MRI showing you that as we go up in concentration the images go from white to black that means we can see them and we know that as the concentration goes up it gets darker and darker and so does

it work so we tested it in vitro so that's just in a petri dish we put it in with a petri dish and does it kill cell so it actually does kill cells which is good what we want and then we delivered it into the into the liver this is just

a tumor before we embolize this is after you see pruning of the vessels and on an MRI you can see again it goes from white the dark now it's not completely dark you're getting that speckled appearance but that means that those nanoparticles

are actually getting to the tumor we do histology so we take it out iron iron turns blue on particularly Prussian blue staining so we know that the iron actually got to the tumor but it didn't look like if you look at that last slide

it didn't look like it penetrated the tumor so that big clump in the center that's the actual tumor but it sort of looks like it went around the tumor so how can we get it into the tumor how can we get it to penetrate more into the

And,...of...a good morning everybody so I want to ask a question anybody doing one day care at all. All right so we have a few here ok. And, I want to talk a little bit more about myself about whom the...I'm not an expert actually just started doing one to care about nine months ago so I'm internal medicine I used to do internal medicine for twenty two years out of the twenty two years they used to do and patient and outpatient care

and then about seven years or six years ago I start to do an outpatient on here I start doing out in patient. And, using this time I was ...actually...was in an office. I wasn't going anywhere I just am solo practitioner so I have no other physician have contact with and

about nine months ago somebody asked me to do someone to care. Side the site to do it and I did the training and. Went to florida...thought I would have a long vacation but it was a very fall week of things I think and the same. ...did many years before me and came back to do on the care and actually one to get as people who do it.

It's a it's totally different than what I thought it would be so I thought in the beginning it's actually more like. A piece of...and wrapping and that's all but it came to be bigger, bigger than what they thought it would be...very interesting... And, the and starting once made me more aware how serious even the medical condition...my own office as...

So, I hope they will give you an idea about what ...the care is and how big the problem is ok?

vein sandpoint right so remember what I talked about when there's a that narrowing it turns out hormones to the kidney the kidneys will send out hormones or aldosterone we can also measure those in the renal vein to see

if there's differences in them and help isolate one side to the other just in case the Renard nose is too small and we can't see but mainly we want to do the Instagram so we can treat alright so there's different forms of treatment of

renal a hypertension and children one is medical management just given medicine it's not on the single medicine you can't get much better than that you know and it's it controlled unfortunately I like an adult we get hypertension at the

age of 60 and if we have to take medicines for the next 20 years or probably I diet with it you know if a child is at nine years old they have to take medicine we don't know what's the effects of taking medicines for the next

60 or 70 years are going to be so it's imperative that we at least try to diagnose why they have hypertension you can do surgical revascularization or a nephrectomy which is much more in days and or in our case in our profession

percutaneous catheter and SRAM so the

let's move on to the gold standard and geography remains the gold standard it gives us high resolution right we're able to directly identify the rarest roses but more important what what's the

utility of diagnosing something if you can't do anything about it so really its utility is that when we see it we have an intent-to-treat so where we can perform an angioplasty it also allows us flow dynamics as well as its resolution

is superior allows us to see the second third and fourth level branches so some limitations of angiography the main one is that it's invasive that's the main limitation of our specialty unfortunately I are is that it's

quote-unquote invasive invasiveness is all relative okay so I'm doing a Perkins puncture is invasive compared to doing nothing but certainly much less invasive and opening up the abdomen so we always have to put things in perspective right

so what's the yield right the yield of a positive angiography of finding an abnormality is at least fifty percent when those various factors are identified with what we talked about

there's a bunch of different types of drug delivery we know that they're

systemic which is what we're all used to so we just injected into the IV and the patient gets all of these systemic side effects right they lose their hair they get nauseous they have all these other issues or we can do passive targeting

which is where we basically injected in a particle and we hope that the EPR effect works these are the clinical trials going on with nanoparticles today you probably don't know it but a lot of the chemo therapeutic agents that we

deliver to patients are nanoparticles they're liposomal components and that's just because we think they are more effective and have less systemic side effects but really in the lab we can do lots of fancy things we can make them

actively targeted to tumor so we can put antibodies on them so they go directly to the tumor we can we can put antibodies on them so they go to the blood vessels and the other thing we can do is trigger drug release so we can

inject them and then we can say you're only going to release your drug where I tell you to release it because I'm going to trigger you to release and I'll show you an example of that so this is triggered triggered drug

release so this is an example of a nanoparticle that's basically a microbubble so all it is is its air with a core and what happens if you insulate it with ultrasound you put also ultrasound on top of the blood vessel on

top of the tissue that you want it will come down and what will happen to the microbubbles is they will expand contract expand contract well they don't particularly care to do that then they explode when they explode they become

nano shards to become these teeny tiny little shards that are small enough to get through that leaky blood vessel the hole right that we talked about with cancer those nano shards will go into the tissue and then they will deposit

their drug if we have coded these micro bubbles with drug so does it work it does and this is pictures from our lab these are the micro bubbles that we created again here on the image be you just see it's it's hollow there's

nothing in it but air and we need that air for the ultrasound image Steve just shows that it's coated with doxorubicin which is red when we look on it under fancy cameras and we like doxorubicin because it is red we don't have to put

some special marker on it and then image d it's just a picture after it's exploded so it's in these teeny tiny pieces it explodes and that's what goes into the tissue and will help kill the tumor these are our ultrasound images of

tumors and you can see the micro bubbles are sort of swarming around we can see them it's an ultrasound contrast agents we can see it the image that says free ducks is just when we infuse doxorubicin directly into the vein so you're not

going to see it because it's not a contrast agent on the bottom it just shows you that you see a means that that's the ultrasound contrast agent it's what we termed it that just means that it's getting to the tumor it's

depositing and the tumor when we take the tumor out there's a lot of drugs it gets in there versus free doxorubicin there is drugs that will get there it's just not as concentrated as if we do it that way so does it work it slows the

tumor growth the blue line shows of the tumors are growing more slowly the purple line shows that the tumors continue to grow more rapidly if they're not triggered and they have it so nanoparticles offer this great site

targeted drug delivery and we're all interventional radiologists so should we all go home or unemployed let's just find a new job well thankfully no right because we talked about sites elective

The other thing to do is in this deep pelvis,

other ways to get around bony structures is to take a transgluteal approach. The mantra for transgluteal approach in my mind is to hug the sacrum and stay below the piriformis as much as you can, in which this case demonstrates.

In order to minimize the risk of vascular injury to gluteal vessels, as well as entry into the cyatic nerves so hug the sacrum, and stay below the piriformis not quite below the piriformis here, but based on the anatomy this is where we had to go, and this allowed us to get to the small collection in the deep pelvis again, we're anteriorly, and posteriole/g [INAUDIBLE] Would

have been blocked by bone, and a variant to this technique, or an extension of this technique if you will. Is to utilize the power of the angled gantry. And as radiologists we always tend to think in 90 degrees. AP or lateral, frontal or lateral, but

we don't have to think. This gets us a little bit closer to ultrasound real time imaging we have a wide variety of angles to which you can approach lesions. With most CT scanners you can get about a 20 to 25 degree angulation. And sometimes anything within that range is enough to create a window

that avoids ball, avoids vessel, avoids bone. And so in this example that we utilize that angle again, the technique to find a window that gives us what we though was the most optimal approach to these deep pelvic lesions.

So just a series of cases really to think a little bit outside the box, how to dissection, moving things away, creating different angles and different approaches to get out some deep pelvic lesions. And thank you for your attention. I'm happy if

to take questions. Okay [BLANK_AUDIO] One last section which is the other way to get access to these deep pelvic lesions are transrectal or transvaginal approaches. Demonstrating sort of a technique that we use, an ultrasound probe cover over a transvaginal or prostate ultrasound

probe. This is the sheath of a pillow. The sheath that we affix using some elastic rubber bands. And use it in the transrectal or transvaginal approach. We gain access to give us very close proximity to deep pelvic lesions, and here's a case here demonstrating a collection behind the uterus

and to the rectum. And by ultrasound imaging you can see a needle coming in and there's our catheter finally in place, running into that colder sack behind the uterus and enter into the rectum. And the thing to keep in mind

this technique is often utilized at least the transrectal approach in pediatric patients. For the transvarginal approach, one thing to keep in mind is that the vaginal cuff is very, very, thick very muscular and certainly require some force to get through that.

Discussing this case with Dr. Agostino a few days ago he emphasized the point of minimizing the use of a speculum if you can. Because the speculum often times displaces and pushes your target further away just adding another element of challenge. So hydrodissection angled entry transvaginal transgluteal approaches.

Things to keep in mind, when you are approaching [UNKNOWN] Often times it migrate down into the pelvis. Can we have our IT, are they available? Looks like we've lost our signal here. Let me see.

[BLANK_AUDIO] Sorry about that we'll find somebody here in a moment. [SOUND] Any questions or clarifications or disagreements? >> How many of you do transvaginal and rectal drainages? [SOUND]

Do you use speculum or you do it without speculum? Who does it with speculum? >> [INAUDIBLE] >> It cannot clean and you can clean the vagina, well, you're gonna clean this rectum.

>> [INAUDIBLE] [BLANK_AUDIO] >> They're trying to find somebody [INAUDIBLE] >> Okay. Any questions regarding any of the previous discussions?

>> [INAUDIBLE] So we suture all our tubes into the skin, and one of the advantages of having a big tube, and it's a little bit of a selfish reason, but sometimes they do fall out and they fall out we're usually

on call on a Saturday night and we happen to be in the ER and when you have a tract that has been occupied by 24 French tube for several weeks, that is unblood type tract. And so I've gone down to ER, taken the tube, it's usually straight shot into the cavity,

advanced the tube without a wire without anything straight into the tract. And then the pus starts coming, coming right out. But to answer the main question I do suture directly to the skin. We've evolved a little bit,

we do [INAUDIBLE] And switch it to the disk, butterfly, start lock devices and that sort of thing for all sorts of drain/g. Nothing is as reliable as a [INAUDIBLE] Although that's as you know not 100% reliable as well. >> [INAUDIBLE]

>> No, no. We just create a mesentery, just one strike through the skin, create a little mesentery and just wrap around. >> Question?

>> [INAUDIBLE] At the time [INAUDIBLE] >> Yeah our usual protocol at the time of drainage is to evacuate everything that we can and then flush with three or four [UNKNOWN] Of normal saline just to clean things up. And then for the period of time the catheter remains,

we'll flush at least twice a day about 10 CCs. Of that 10 CCs about 5 go into keeping the catheter clear and the

in cancer research well you can use them

in a bunch of different ways you can use them in drug screening you can use them to deliver genes i have an example in my lab we're working with an ophthalmologist who is trying to figure out how to treat diabetic retinopathy

and so he's developed a gene vector and if he gives it through through the IV it never makes it to the eye because it gets sequestered out by all the other cells and so what we do is we go up into the artery that supplies the eye and we

deliver this gene locally and it actually helps prevent diabetic retinopathy and so that's just a way of using nanotechnology particles are very tiny we can use it for diagnosis so if if these nanoparticles will hone to

tumor cells we can say yep that's a tumor that's not a tumor we can deliver drugs there an we're going to talk a lot about that because that's what we do particularly in my lab again detection where are these things we can track them

we can say how much drug was delivered and then diagnosis and monitoring so patients coming for follow-up do they have two more don't they have ten where we can use it that way so how does cancer work since I am a cancer doctor

there's a bunch of different things that cells have to be able to do to be cancerous they have to evade apoptosis so those signals that the cells are telling them I you have to die you have to diet has to say I don't care I'm not

going to die you can tell me that but I'm not going to they have to be self-sufficient so they don't have to rely on their surroundings to survive because they have to move they have to go from their site of origin and

metastasize elsewhere they also have to be insensitive to those anti growth signals so when the body says you know it's not time for me to replicate they have to say you know what I don't care i'm going to replicate

they have to be able to invade and metastasize so that's sort of what I voted to earlier and they have to be able to continue to reproduce over and over and over again because what good would a cancer cell be if it couldn't

reproduce itself and then they have to be able to sustain angiogenesis or what that means is that they have to be able to get nutrient and how do they get nutrient they send out signals that say I need blood you need to develop blood

blood vessels so I can continue to grow so this is sort of a six hallmark of what cells have to do to be able to do

so how do we get its site selectively there well we can just do enter to Merle

injections if we can just inject directly into the tumor we an interventional radiology or leaders and how to you know get something through a needle somewhere and they showed in this study that if you do inject it directly

into the tumor it gets there first of all and second of all it's high concentrations it stays there and sort of all it decreases the growth of the tumor so that's really amazing these images are from actually dr. omaree's

lab and thanks to them for giving me these images but this is essentially nano embolisation where we're doing just what I talked about on that conventional chemo Malaysian slide where we're injecting nanoparticles directly into

the tumor and this is a rabbit liver it allows us to get high concentrations it circumvents that sequestration so they're not going to be sucked out by the spleen or the lymphatics and you can actually see where they're going you can

visualize where they're going the other fancy thing we can do is we can put some iron in it and when we image iron on MRI it changes what color it looks like so tumors look like they're bright so they're sort of whitish that's what's

outlined on by the red and the after picture you can see it turns dark so that's what iron does then we say oh we actually nailed the tumor because the tumor went from white to dark if you have non-target or two or nanoparticles

to go to the liver you'll see the liver double turn Burke as well and so some of the things that happen in humans after we do chemo Malaysian is that angiogenic factors get turned on now this is in human safety test date they drew the

blood and these are angiogenic factors so those are the factors that to tumor says I need more blood supply I need more blood supply and we tested that in humans and it turns out that those angiogenic factors get elevated so is

there a way that we can with nanotechnology get these levels decrease because we don't want those signals turned on we want the cells to be dead we won't don't want them to be saying I need more blood supply how can I get it

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