Nanomedicine | Applications of Nanotechnology in Interventional Oncology
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

purpose of our study was to assess the safety and feasibility of CDT in the settings MSP so we had a single-center retrospective review performed on 24 consecutive patients with some massive

PE who referred for CDT between jun 2014 january 2016 all patients were actually evaluated by a multidisciplinary pulmonary embolism response came apart this team is comprised of pulmonary medicine critical-care bathroom medicine

cardiothoracic surgery hematology and interventional radiology treatment algorithms were four patients were determined by / consensus just borrowed a flowchart actually from Mass General Hospital which is one of the first p

response teams institute in the country kind of show how it is for our technique

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

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

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

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 own office as...

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

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

tumor so there's something called a lecture of nano therapy which is essentially using electroporation so if you've ever heard of this you know there's a bunch of people that do electroporation essentially what it is

is your electrocuting the tissue you have to have two probes in and there's a signal that goes from one probe to the other and at electrocute thing if you've ever seen us in real life it's very eye-opening it's shocking because you're

justyou're electrocuting a person so the whole little patient will go like this so they have to give you paralytic so you don't do that in animals we don't give them paralytics and it's very shocking the first time you do it

because the whole animal chicking around on the table and kind of freaks me out but any event what happens is the cells instead of if you do reversible electroporation what will happen is the cells instead of being the membranes

instead of being tight they'll loosen up and they'll actually they'll actually be pores within the membrane if you do it irreversibly the pores open and what happens is the things around it will go in and the cells can explode or those

shrivel up if things go move out of the cell so the cytoplasm depending on which direction and you ph and all these other factors they can either explode the cells will explode of the shrivel up when they'll die and so

that's if we couple that with nano nano technology it actually works and we can get more penetration of drug and nanoparticles into the tumors and this is just an example where we did electroporation followed by a

nanoparticle injection and you can see that it turns from light to dark as we want to see and the tumors okay this is just a color map a different way of looking at the white to dark the other thing we can do is photo thermal

ablation I talk to you about gold nanoparticles so we can essentially inject nano particles that have gold in them as soon as gold sees light we have lasers that we can use you put a laser and it hits the gold and the gold makes

it hot you can increase your ablative

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

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

i'll be talking about evidence gaps in chronic venous insufficiency ok so many of you have heard the buzz words you know precision medicine or personalized medicine and and you know it's sort of a big fake trim you see written in newspaper articles and all

that relating to big big picture initiatives but what does that really come down to really comes down to predicting in advance who is going to benefit or be harmed by a particular treatment based on individual

characteristics of the specific patient if you think about something easy that's been incredibly well studied like the use of aspirin for acute MI what you find is that it's very consistently shown that aspirin reduces mortality

from acute MI but it's not about 7% to maybe six percent or something like that which tells you that even for something as well studies as that six out of seven patients were treating actually aren't

really getting anything out of it and so in a similar way when you apply that to other treatments we really do have a big challenge the idea is that can we use genomic markers imaging biomarkers patient demographics to predict who will

succeed and you know the presence of big data approaches on the information technology revolution obviously is the core central element in all of that now

when cancer cells grow they don't grow normally I talked about they sort of

send out these signals that say I need to grow I need to grow well they don't grow normally normal cells have time cancer cells don't they want to go quickly and so when they grow they don't have the tight junctions that you would

see in a normal cell ok so it's and we can use that to our benefit by getting by penetrating tumors by giving drugs that way it's called the EPR effect so because they don't have these tight junctions they're sort of leaky we

anticipate that if we inject nanoparticles intravenously those nanoparticles will deposit into the tumors because it's a different different structure than the normal cells there's no gap there's a gap in

tumor cells so the nanoparticles will preferentially go into the tumor and that's called the enhanced permeability and retention affect the EPR effect now

get them there in sort of a creative way you know we're interventional

radiologists and we like to you know pave the way you saw dr. Walton he paves away so this group looked at nanoparticles and they put a magnetic component in it and then they put a magnet over the side of the tumor and

look at that the nanoparticles will actually go to where the tumor is it's fascinating right all you have to do is put a magnet on your belly and now all of a sudden I'm getting treated for cancer and I'm decreasing the amount of

systemic drug that's floating around my body so that's sort of a creative way this is just again nano therapeutics and I are image-guided delivery is how we think we can do it better than just putting a magnet on your belly okay we

don't have to do that we can actually get into those arteries and deliver it locally so you all are very you know adept at conventional team mobilization this is just an image of an HTC and it's the tumor is on a stock and you can

imagine if i have a nanoparticle i could inject it directly into that tumor and have a good effect the other types of things that we do and I are you guys know this thermal ablation this is an image of an ultrasound probe going into

a liver and the image on the screen right is image from my lab this is when we did cryoablation of a tumor and a rat and the reason I show you this is that it when we all do cryoablation we never see it right we just suit sort of this

defect on CT you never could see the ice ball so when I did this for the first time I thought this is the coolest thing at everything's been like oh my god have to see what the ice boat looks like turns out that before I got this I froze

the whole mouth because you have to use mouse settings or not human settings but nonetheless here is a nice bowl after much after much going back and forth

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