lymphatics you know I have this nice lymph angiogram image on the right side

of the screen here you see a plethora of lymph nodes you see a lot of fine detail not an easy image necessarily to get historically and that's for a few reasons one lymphatic fluid unlike your blood is clear right we can all look at

somebody's hand and you can look at the veins and you can see the hand an IV can go right in you can't see what the lymphatics aren't and beyond that beyond it just having clear fluid it's also has relative to blood not that many cells

which makes it hard to see and the vessels are pretty small so I've magged up on just one lymph node there and you see that one little lymph node has about 28 faire and efferent vessels going to it

so each the size of each one of those vessels is less than a millimeter in size so you can imagine if they just do a surgical biopsy and excise one of these lymph nodes in one patient they've damaged at least 20 different vessels

and if they take out multiple lymph nodes you can imagine the damage to the circulation to that particular extremity and that's why the patients end up having some of these complications the lymphatics are driven by valves

predominantly you see all these little sac you lations inside and that's where the valves are but we don't really have a good grasp for how many valves is normal with the distribution of valves and patients etc there's no central pump

so unlike the circulatory system which is dependent on the heart the lymphatics are dependent on skeletal and smooth muscle to help move things along the first method to image lymphatics historic who's actually limb for

scintigraphy and the first the first actually marker that was used was a gold base did a scintillation camera and they had some images you know it's not something we do commonly now for the purposes of detection we actually use it

as a functional scan to help guide some degree of therapy the spatial resolution is fairly poor particularly compared to fluoroscopic images but the current uses are still there particularly for sentinel lymph node

mapping breast cancer melanoma patients and/or lymphedema this is an example of a patient who had a melanoma on their back or this could easily just as well be a breast cancer patient you do an injection around the tumor and you see

what lymph node the the tracer drains to so this is a functional imaging test which can be very useful in guiding therapy when you compare that to a peripheral lymphedema you see what it looks like in this case you see one

patient in five and sixty minutes and within 60 minutes the tracer has gone from the feet where you inject all the way up to the neck that's actually a normal lymph flow centigram and that patient you look at their extremities

they're fairly symmetric you look at the second patient and you see that one leg the left leg is asymmetrically swollen compared to the right you see that the injection at five hours on that swollen extremity has not gone up above the knee

and you see it really going to the skin surface so that's a typical appearance for somebody who has lymphedema okay so it exaggerated but a fairly typical appearance you see that once the contralateral extremity is actually

traversed and gone all the way up to the thoracic duct up into the neck so we certainly see the that lymphedema is useful but the detail really isn't there

one pain geography as we know it was first described in 1955 by Kenneth in

the UK and I always find it interesting that you know we sit here we talk about how not fun it used to be but he said well lymphatic vessels at least the normal ones are much smaller than our deserve Eanes they're hard to see they

contain colorless lengths etc so this is something that has not been a state secret for for a long time but in this case he actually I used the microscope you see a needle he's doing hand injection and he did a surgical incision

across the foot and when he did that he was able to generate these images so one of them is a normal empathic you see a very fine vessel with a hemostat at the bottom of the image and the other one that has his tortuous winding vein or

vein appearance or varicose vein appearance is actually an abnormal lymphatic so this technique was described in fifty five seven years later was described in Pediatrics very similar about

much more difficult as well and they were able to get some very nice images you see these examples of abnormal lymphatics and these pediatric patients so in my fellowship at Brigham we were still doing PETA limp angiography during

my training and usually whenever we started and sat around talk with our text and nurses in the morning you could hear the groans and you could see the frowns but basically we knew that we closed down a room for one day and it

would start by us injecting a freezing solution in the inners web spaces of the toes and then injecting this methylene blue dye we would then milk the foot up until the dorsum of the foot had a blue streak and that's where we knew the

lymphatic vessel was we'd make this vertical incision and skeletonize the vessel we tie it off with some silk we tape it down and then we would get to work trying to catheterize this little skinny vessel with a 30 gauge needle now

this process alone would usually take a couple hours and a lot of patience and then we'd fix our catheter up and attach it to a pump and it would go at a rate of five to eight CC's an hour it'd take a couple hours to get the pictures

through the leg a couple more hours to go from the leg to the rest of the retroperitoneum etc so now you've talked now you're talking six plus hours and you haven't even really done the case yet elegant images you see how fine and

wispy these vessels are we have many more lymphatics than you do any other vessel in your body we don't really have a good grasp with the distribution of of all the different variants that you have from person to person but there's a lot

of variation obviously a technically challenging procedure to have high-quality peda lymph angiography it's time-consuming invasive to patients you have this incision that would take several mattress sutures and a couple

weeks to heal but the images have good resolution it was diagnostic it was therapeutic in some cases of lymphatic injury leaks as well no to lymph

angiography came along towards the tail end of my fellowship so around 2011-2012

actually a children's Boston initially and then subsequently done in Penn in adults and this really became as simple as doing a lymph node biopsy basically sticking it on a lymph node while it seems novel it's really

interesting because if you go back to 1931 that's actually when they started doing some of this work when they were actually injecting the lymph nodes with these different tracers and they could see so it's a combination of a little

bit of ingenuity and looking back at our history and we the way that made it a lot easier for everybody this is basically my little setup here and I used some Italian syringes a plastic opaque three way so

that the lapa doll doesn't dissolve through it the medallion syringes hold up a lot better than the typical day we used luer lock stuff I use long propofol type thin bore tubing I attached it to a nine

centimeter long 25 to 27 gauge spinal needle I take the inner styler out of that cheeba so that because it's such a skinny needle that it bends a lot and this way I can put it right into the lymph node without having to connect it

to the tubing and then I can start my injection right away the 2115 cheeba there and that scalpel are really the only other things that I need to get started to do a successful thoracic duct embolization other thing that's really

critical is I always ask my texts and nurses to slap SC D's on the patients and if once we have the SC DS it really speeds up the procedure by an hour to two because you have this constant compression of the Venus and the

lymphatics and the legs forcing more fluid to make your thing to make your case I move along more quickly so something that was more recently adopted at many medical centers and these are the type of images that you get so I

stick my needle into the lymph node and I start this injection you give this beautiful arborization of the lap I doll contrast as it continues to spread and move from one lymph node to another you see there's a central area there that

isn't filling that's actually the lymph node that's already transmitted the lap idol and this was the image that I showed you initially so same image injection injecting of different lymph nodes you can see the transit from one

area to the rest of the chain in the pelvis hepatic lymph angiography is not

something many of us think about but this is actually something that's been known about for many decades more recently we starting to look at some

therapeutic some therapeutic potential for this as well but if you go back to CUDA in the 1970s they actually looked at a bunch of PT PT C's if they were doing they noticed an in some proportion of those cases that they were able to

see hepatic lymphatics and it actually looked just the same see those same wispy vessels in the center of the level and it was going down to the portal system and from the portal into the thoracic

duct in the central emphatic circulation if you look hard enough on a non dilated ptc after you do all of these passes and as you go back and forth and if you're taking spots you'll actually notice it in there a cohort of 800 some patients

they saw at about 15% of the time not even trying to see it so you can imagine if we're trying to see and we know where to look how much more successful will be Konstantin cope published a technique in 2004 where he used a coaxial 25 gauge

needle inside of a 21 while he was doing his PTC's and in that proportion of patients he was able to see the lymphatics in 47 percent of patients so now we've actually gone up to one in every two times again he wasn't trying

to purposefully see them but he was able to do it so if we can see them on purpose what are the possibilities we're gonna talk to that what we're gonna talk about that a little bit later so we'll

talk about some more non-invasive ways

to image the lymphatics there's non-contrast at Marlon Payne geography this has been around for a greater than a decade we basically do a tea to fats at sequence and we basically really amplify the signal difference between

fluid and soft tissue and we really want to focus on fluid that's very slow moving so this is very good for people of lymphedema cirrhosis venous malformations etc you're gonna get very nice images it's non-invasive gives you

good spatial resolution but you can't see small structures and you don't have an idea of how things are flowing so just to kind of show you an image from my training and right there where the arrow is showing you the thoracic duct

right next to the aorta obviously fairly distended what I did actually in this patient as we were doing research to generate these images actually giving them didn't mr gave him a milkshake put him back in the mo and you see this

little thing plump up and is actually really cute dynamic a Marlon pan geography is a newer technique that's come along where basically we've combined what we do with nodal and faint geography where we put a needle into the

lymph nodes with what we do with regular mr which is to inject gadolinium we dilute the gadolinium we can inject it right into the lymph nodes and now you can have flow dynamics as well as faster mapping of what's going on with the

lymphatics a very useful technique that I use in complicated leaks in pediatric patients etc

and then getting back to really where the rubber hits the road you know we can do all of these fancy techniques why

does it matter well Constantin cope one of the fathers of IR is certainly the pioneer of lymphatic interventions and over subsequent five publications in the mid 90s really showed the the technical

build as well as the feasibility of imaging lymphatics putting a needle into them and then starting to be able to embolize them and functionally curing patients who had Kyle authorities and a potential morbidity or mortality of over

50% and how did he do it well as he did his lymph angiogram and it got up to the retroperitoneum and the structure started dilating into some of the central structures such as the cisterna chyli he would take that 21 gauge needle

and go after that structure put a needle into him pass a wire that wire would pass into the central lymphatic circulation and then he'd be able to put in a micro catheter Neff set machan visa or whatever inner inner

components and then do central and faint geography as well as potential and fame gia embolization so that would be the general antegrade trains abdominal access this was a traditional access that was done for over a decade more

recently a lot of authors have started focusing on doing retrograde trans venous access which you do basically a PICC line axis on the left arm and you take a sauce catheter to where the thoracic duct dumps into the veins and

you catheterize it backwards and just kind of showing you and get your sheath down or you can put a wire from below and then snare and come across it so that's a retrograde transvenous and finally the direct train cervical access

and some patients who you never see another target you can potentially access this under ultrasound or if you have fluoroscopy and some contrast in there in this case we put our wire retrograde and were able

to complete the case and you see of the lymphatic fluid leaking out in this case as well so those are your three main ways to access the central lymphatics

where the rubber hits the road is how we and what we do with this and the first

entity that we started treating with skyla thorax and what kyla thorax is basically a milky pleural effusion you guys I'm sure I've seen this you're doing a thoracentesis on a the food that comes out actually pretty

thick it's not clear it's almost this milky color the patients are usually fairly ill they've had Safa geo surgery lung cancer surgery heart surgery etc we test the fluids for triglycerides and chylomicrons and if that's positive then

we know it's a kind of thorax historically these patients would be treated by not being fed given TPN and maybe octreotide they'd maybe go to surgery if they received no treatment they had 50% of them died six to 12

weeks later if they went to surgery 12 percent of them died if they went to surgery 40% of them had major complications so you can see if this was a major opportunity for us to step in and really change the outcome for these

patients as I said Constantine Koch did the first procedures on this but I'll show you what it looks like this is doing a central and fangy Graham and we're serial images you see that leak accumulating on the right side the

right pleural space we have our wire and catheter in all ready and all we're gonna do is we're gonna start coiling up at the area across the leak and put more coils and a little bit of glue at the end when we do that we have a very high

success rate you see four major studies that have been published from 2004 to the present you see the first ones doctor copes major study 42 patients from UPenn the second one is also from UPenn 109 patients the next ones from my

Hospital Brigham and Women's where I did my training and then the last ones from Pittsburgh there have been subsequent studies as well but this included over 400 patients between these there was a meta-analysis in jvi our last year

showing that the lymphatic interventions for Kyle thorax pretty successful looking even at old technology that were used for the embolization zhh 400 patients nine studies 80% success rate across all these different centers I

would say in experienced hands a success rate exceeds 95% for traumatic Kyllo thorax at the present so we know that this is a pretty respectable for the treatment of Kyle of thorax a CR has some guidelines out for how the thorax

treatment as well encourage you to take a look at them it can break it down between traumatic and non traumatic caudal thorax and gives you some recommendations of how to approach it

pediatric catholic's is a little bit slower to treat generally everything in peds is a little bit slow to be adopted we obviously want to be very careful with our most vulnerable patients so the types of disorders that pediatric

patients are slightly different because they can have congenital or idiopathic I authorities it can be from lymphatic malformations or from different syndromes it certainly be from congenital heart surgeries and other

issues that they may have going on there have been several reports published at our institution University of Michigan we publish the largest cohort of pediatric patients and it was only eleven but ultimately we showed that

thoracic duct embolization was just as effective just as safe in this population our youngest kid was only two weeks old our smallest kid was two kilograms so a very vulnerable very small structures but you can still do

and still have fantastic outcomes for

these kids just to show a couple cases from our study this was a three-month-old who'd had a congenital Kyle thorax as well as congenital ascites and you see that we're starting

be lymph angiogram it certainly looks very bizarre certainly not like anything else I'm showing you so far and you see if this child was actually born can generally without a thoracic duct or central lymphatic so this was a an

example of thoracic duct atresia unfortunately not compatible with life very rare thing that has published every couple years this was another child a little bit older 15 year old we wonder with scoliosis a corrective surgery lots

of screws had a great outcome from surgery unfortunately noticed right there that one of the screws went right through the thoracic duct so not a surprise this kid had recurrent Kyllo thorax we certainly didn't oblique here

to prove that it also went right through that structure we got our wire up and in all the way across and put our catheter up we'll put some coils right at the top and then place some glue across the whole thoracic duct and you see the two

areas where the site of injury were the two arrow heads at the bottom of the screen there so plastic bronchitis is a

more rare condition that some of you may not have heard of but certainly something that wasn't familiar to me a

few years ago but basically people present by coughing up these rubbery casts of their Airways and what these rubbery casts are basically is a collection lymphatic food that's dried out and it just slowly fills in the

airways and they cough up these big things obviously an embarrassing thing to happen have happened to you at dinner can certainly affect your quality of life but I had one patient who saved who

saved a napkin and brought it to me to show me it and the clinic and I was like wow that's impressive please throw that away I believe you but you'll see patients congenital heart disease with COPD asthma tuberculosis cystic fibrosis

etc any of these patients can present with this particular issue what we found out by doing some of these mr so if we embolize these lymphatic vessels or find a way to bypass them the patients will have resolution of their symptoms and

it's an amazing change in quality of life it's only been done in adults as well as pediatrics I'll show you guys an example from the University of Michigan we did lymph and geography this gentleman was actually 500 pounds so I

couldn't do a mr on him and you see this weird tuft of lymphatic vessels right around his airway there on the left side bronchoscopy had already shown that that's where he was having his casts I was able to actually puncture him from

his neck and go retrograde he was a bit too big for me to go through the abdomen but he sees lymphatic duct looks all really fairly standard normal-looking anatomy with exception of that tuft of vessels we actually went down with a

sheath we put a stent graft a vibe on stent graft across that area we excluded those or normal vessels and his condition resolved within a month it's something he'd been living with for several years so fairly dramatic outcome

for this patient uncommonly I say we see maybe one of these patients a year but it's actually known - how to treat it and how to work it up it's very critical

well switch gears and start talking about Kyllo societies histology the

etiology of Callao societies historically used to be malignancy in tuberculosis first described in the 1600s in a two-year-old who had a tuberculous peritoneal disease more recently now we see it due to aggressive

surgery whether it's renal resections for kidney cancer lymph node resections etc it can also be due to cancer the incidence is climbing rapidly this is just a graph of the incidence at different hospitals from 1930s and 1980s

I can I don't have the data for the 2000s this was a graph that I actually generated from based on several studies just to show you how profound the leak can be in these patients well looking at what we do with

maduk college societies fairly similar to what we do elsewhere we map it out we have three major Studies on that right now and a lot of smaller studies so the total nineteen manuscripts ninety six patients and in those eighty two

patients had to report whether or not they saw a leak they saw a leak in 60 of those eighty two patients and when we saw a leak we were able to cure 70 of them just by doing than paying geography and eighty eight percent when we were

able to actually embolize it so again going from in ninety percent mortality at one year if you have caused societies due to cancer or forty percent for any other cause to cure with the simple procedures is pretty amazing just to

kind of show you an example this was 55 year old gentleman who had removal of his left kidney they found a seven centimeter renal cell carcinoma incidentally while he was being worked up for a kidney stone it had been six

months of constant Kyllo societies and loss of 63 pounds before he saw me here's a lymph angiogram showing fairly typical anatomy until you see this little leak and you see the surgical clips there where his kidney was and all

of the hollow pile spilling around and surrounding his spleen I'm doing this and then we did an embolization right around that area he sent me an email two months ago just before I left the University of Michigan thanking me for

changing his life and saving his life another example this gentleman had had major debulking surgery for for testicular cancer he also has had prior bone metastasis with a hip replacement there and you see a bilateral leaks he

see multiple drains they couldn't control his fluid and we embolize all of these small leaks around his pelvis and also fixed him as well and just she see all the focal areas of leak throughout this was a three year old who'd had a

Wilms tumor resection we're mapping them out and you see the area of leak in the center there and was able to fix this child as well discharged and continued on his merry way cured protein losing

interrupting something else getting back

to a paddock with angiography something that we're starting to look at the group at University of Pennsylvania has a publication out on this as well I looked at the liver lymphatics certainly the livers where we produce a

lot of protein it goes through the lymphatics to be returned to the circulation in patients who have heart failure they tend to have increased lymphatic flow in the liver and they think that protein lost in enteropathy

protein losing a property happens when the liver lymphatic leaks into the intestines just some images from their article you see them looking at the hepatic lymphatics there and once they had a needle in the hepatic lymphatics

they actually put her scope in and they injected blue dye and as a proof-of-concept they saw the blue dye leaking into the intestine so now that they see that the blue dye leaking the intestine they say well we can embolize

that they embolize it with some glue and that's what it looked like at the end and then the algorithm levels and all these patients return to near normal so a new a new frontier and lymphatic intervention so just to summarize

lymphatic imaging the current status you know we have very effective non-invasive as well as in vases imaging in the peripheral and central lymphatics we certainly need to this allows for improved diagnosis and once we have

these diagnostic capabilities we were able to come up with these novel treatments for these diseases that were previously untreatable we still don't have good ways to consistently visualize the paddocks invasively and then and

non-invasively it would be great to be able to see that hepatic and intestine lymphatics cuz that's 80% of lymphatic flow so if we can find a way to image these under mr it could be a game-changer for a lot of diseases in

terms of lymphatic interventions Calla thorax interventions greater than 90% effective technical knowledge you know when I was a trainee was really centered to just a few major medical centers now it's defusing out to more places we've

certainly shown as a proof of concept the plastic bronchitis lymphatic flow disorders cattle societies and protein losing enteropathy are all treatable and we're getting emerging experience so don't be surprised if you start to see

more requests for this more patients at your centers these are uncommon disorders that's not to say that you still won't see them every once in a while the role of lymphatics in pathophysiology is still being studied

particularly in terms of heart failure transplant as well as in different cancers in the spread one of the cool stuff that we're looking at right now is actually sampling different lymphatic fluid in different areas of the body

trying to see how the different cancers may spread and/or possibilities in immunology immuno oncology thank you guys and just something I noticed a couple weeks ago in jeopardy clear body lymph continuing white blood cells body

fluid and you guys know what is limp that's your answer so thank you saying thank you to the avir committee and it's been a pleasure [Applause]