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Polymerizing Agents For AVM Treatment: Is It Curative Alone And How Often Is Surgery Required
Polymerizing Agents For AVM Treatment: Is It Curative Alone And How Often Is Surgery Required
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Treating Complex AVM Cases With Multiple Embolic Agents
Treating Complex AVM Cases With Multiple Embolic Agents
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Ethylene Vinyl Alcohol Copolymer In The Treatment Of AVMs: Long-Term Results And Histology
Ethylene Vinyl Alcohol Copolymer In The Treatment Of AVMs: Long-Term Results And Histology
abdominalabnormalamputationangiogramarterialarteriesavmscalfcomponentconsistscopolymerdecreaseddilateddirectdistaldmsoembolicembolizationembolizationsethylenefemoralfollowgraftHigh flow AVMimageimaginginjectionintercostalintramuscularLiquid embolization systemmalformationMedtronicminimalmramultipleonyxpainpatientpatientsphaseportionsprofundaradiationskintranscathetertreatmentultrasoundunderwentvascularveinvenousvinyl
Long-Term Histologic Evaluation Of Resected AVMs In Head And Neck Post-Onyx Embolization
Long-Term Histologic Evaluation Of Resected AVMs In Head And Neck Post-Onyx Embolization
avmsdosedosimetersembolizationendothelialgiantheadhistologicinflammatoryinterstitialLiquid embolization systemlymphaticMedtronicminimalneckonyxradiationrecanalizationresectskinvenousvesselvesselsvialswallwalled
Ethanol Curative Endovascular Treatment Of Hand & Foot AVMs
Ethanol Curative Endovascular Treatment Of Hand & Foot AVMs
avmsbleedingclinicalcuredilatedembolizationethanolfavorfoothandhealinginjectinjectionligationmanifestationsmicronecrosisnidusoutflowpulsatilerefluxswellingtreattreatmentulcerulcersvascularvein
Transcript

- Hi, I'm going to talk about the use of Onyx and glue versus alcohol. I have no disclosures. So in our little group of vascular malformations people, just like in your family, everybody has their sort of designated job, or role. My job is to stand up here and bash Onyx.

So that's what I'm going to do, sort of. I don't really feel as strongly about how horrible I think Onyx is as you're going to see me present in the two presentations I have left, but we'll go for it that way anyway.

So these were the questions I was supposed to answer. Is it curative alone, and how often is surgery required? I added the third question, because I think that's, probably the most important part of it is, can you use it to control symptoms? So you need to know that I come from

a vascular malformation center that was created by some prominent, aggressive ENT surgeons. So pretty much everything at my institution goes to surgery, unless it somehow skipped their, (laughs) their hands in the mix. So it took me a long time to go way back to find

some Onyx cases that did not end up getting surgerized. Because I don't use Onyx for AVMs very much anymore, at all, so, you're going to see what I found. And of course this isn't working, so, we'll replay this, this is a girl which elbow pain,

and she has a large hand AVM, which is what we spend a fair amount of time working on, but the hand ended up getting operated on. The elbow did not. So I'm going to show you the elbow. (laughs) And this is back in the late 2000s, like maybe 2008 or so.

So there's a microcatheter in our tiny branch where we're going to put our polymerizing agent in to fill up the distal portion of the AVM. And this is what it looked like eight years later. Because she came back, she had multiple embolizations

of her hand, and then surgery of her hand, and we did a couple of spots on her elbow and then she came back six or eight years later, complaining again of elbow pain. So what you see, I think, on the left is the old. Sorry, I'm going to try and do this without blinding anybody.

On the left is the old and the right is the new, and they're in a little different projection. So this is this cast that you see right here that's embolized. And what I think you see now, is this vessel coming straight off the brachial, is now

re-canalizing and sort of filling all the stuff on the back end. So I think the parent vessel on this late image looks occluded, but I think you're still back filling into that AVM network. Could we chase all this down

and re-embolize it with Onyx or glue? Certainly, I think you could. And then, this is the same elbow a little different picture. We also embolized this part of the AVM here, and you can sort of see there's a little nubbin

of a cast agent down here, and now I think you can see this start to back fill. You can see it better in the videos, but 'cause I'm a Mac person they're not playing very well. So this back fills into this a little bit. So, did it control her symptoms?

Absolutely. Is it curative? I would say, based on this, no, but, we'll see. Maybe there will be some more data later that'll show us that it is. This is our final glue cast on this,

or I mean Onyx cast on this girl's elbow, from I think 2012-ish, 2014-ish, was the last time we put anything in her hand. So this is a different patient, also late 2000s, a painful right shoulder AVM. And this, I think, is what made us feel really good

about Onyx in the beginning, is you get your little tiny microcatheter out there and it looks like you're going to put that Onyx right in the nidus. You're going to push from there and get it through, maybe it'll catch on the venous side.

So we did this over, and over, and over again, about every three to six months for about two years in this girl. And her pain got some better, and then she disappeared for a few years, didn't want us to mess with her anymore.

And I think what you notice over time in her is that what looked like a little, sort of, fine pattern where you thought you could see the niduses changing into this more lobular, see down here, it's starting to look more venous dilated, which it didn't really have that appearance

at the beginning, on the first runs of all these images? This is her some more. Her some more. And this is our microcatheter, this is just a still shot of the run, but shows that this,

that this vessel is occluded, except, behind all this Onyx you can see this little tiny wisp of something coming right there. And then this is now four years after that previous picture. And now she definitely has this

sort of venous, aneurysmal, type picture in the AVM. And this is why I think it's a pain in the rear

- So, my talk now, is about treating with multiple agents and I think there is a lot of consensus here. We have multiple agents out there, you normally use liquid agents, and you combine it with some mechanical thing for flow modulation.

So you can use coils or plugs, but you never use something like particles. That's not really, in any way, worth while. And, I knew what my role is here. My role is I'm always here as a counter-part to all these alcohol things, and we will discuss it later.

We have, and I just want to make one point here. You have to use this thing, this Onyx, or Squid, or PHIL- or whatever it is. You have to actively inject it, and you have to know the technique, and you have to do it like pressure cooker or plug and push technique, otherwise it won't work.

Otherwise, you will make things worse. So, just show me some failed cases where you used the plug and push techniques. Don't show me cases where you did it wrongly. Of course, that doesn't prove anything. Um, and I think, well you know all of this about

the plug and push technique, here, and I want to go too much into the details. I just want to show you two examples here, and this ght-sided, it's a dominantly venous thing,

it's something that we really like to treat because we'll cure it. There is definitely, regardless with which technique you do, you occlude the vein- you will cure the patient. But, the patient was totally Asymptomatic at the time. So I decided, we wait, he's asymptomatic.

Even if it's something we can do, you mustn't do everything. And, that's interesting because this was 2007, and this is how it looked like in April this year. So, 11 year later, you can see a huge... oh we'll have to go back because it's interesting. You see it, the same patient, after 11 years,

and this is something that is speaking for your hypothesis. That, is an acquired thing, because he's quite old. He's like 40ish/50ish this patient. And he is for us, for an AVM patient, it's brutally old. I mean, I'm really thinking about 'should I treat him?'. (Audience laughs)

Yeah, you know, and this is after 11 years, the sort of venous flow-related aneurysm, it really dilated, and it not only dilated, the venous outflow dilated as well. And, this is how it looked like, here at the perineum pod. You can see, he developed some draining veins

under pressure here at the perineum. So, this is something you have to treat now. I think we all agree, and, my topic here is to do it in the mixture, you can see of course, this is a predominantly venous AVM. Here is the one venous outflow, and the other venous outflow

is up there, it's fed by multiple feeders from the right iliac and of course, at this stage, even from the left internal iliac artery. This is one venous drainage, and this is the other venous drainage. First of all, you occlude the venous drainage.

Because, I don't want to fill this giant aneurysm with coils. You could've done it, and it would be obviously successful. So this is an occlusion of the distal part, with coils, and the proximal venous outflow occluded with an Amplatzer Vascular plug, and this is retrograde

transvenously injection of the venous pouch. So, there was almost no outflow, but there was a little bit left. So, you have to go for it, because otherwise, it will be recanalized. So then, I injected from the transarterial,

so, this is why I have to call about mixed agents. So, we put in an AVP, we put in plugs. And this is some, in this case, squid, in into the venous pouch, and that's at the end.

That's the result in one session. First, block the venous outflow, and then push enough material in that it clots, and its done. So, you don't need to use any ethanol in these cases. You could just do it, just with coils,

but you'd need hundreds. I prefer to do it with some coils, or a plug into the venous outflow. Then I'd push some Onyx into the venous cast, it thrombosis, and it's done, and it's very safe. This is another mixed method,

this is really a failed Onyx case. And, I call this a failed Onyx case, because its really properly done. It's not just some arteries filled with Onyx, but you see some residual like capillary shunts there. And, if you have this small vessel type, or type 4 AVM,

you can never cure it with Onyx alone. Or, I'm not even doing it. This is an ethanol case, you can just kill it, and with this 50/50 mixture, this is very helpful. And, what I do in these, formally type three b, with (mumbles).

I treat them with the safest way I know, with a polymerizing agent, and at the end, if it's necessary, you have these (undistinguishable), you add some ethanol injections, I call that finishing, and then it's done as well. So, at the end, and this is the most important slide here.

We do have different agents, and sometimes we have to mix them. And, ethanol is not everything. A type one, direct connection, whatever classification system you use, a type one, a direct connection,

you can use any mechanical things, and you will cure it. A dominant venous outflow thing, you have to occlude the venous side, and you have to occlude it as close to the arteriovenous connections, or whatever you call it, as you can, and you will be successful.

And, from my point of view, I never use ethanol in these cases, because I think it's dangerous. But anyway, you have to occlude the veins, and in the type three ones, you have to use ethanol in some cases, I call that finishing, before I've done something safer.

And, maybe, we have something more like the MEK1 Inhibitors, that's really something I hope that will be helpful for all of us. And, of course, if you use the wrong technique, and if you use Onyx like glue, you will make things worse. Thanks for your attention.

(Audience claps) - [Audience member One] I just wanted to make one comment, when you talk about ethanol, using it as finishing, I would sort of, think that more as the start of the case. In that, you're doing all of these other things, which I do too, to shut down flow.

What you are doing is occupying space within the venous side of things, what you are doing it basically maximizing the concentration of ethanol to where at's the definitive part of the therapy, and that everything you're doing

up to that point... Like, I mean, granted some of them you're curing without it. But, I mean, when you're giving that ethanol then, I've had a number of cases where you're sort of filling that type two- B Nitus or type three situation, what you then are actually enveloping that with the ethanol,

it's actually going to where it's exactly meant to go, and that's the critical manoeuvre. - (Lecturer) That would be true, if the only cases where it was successful were with a mixture. - [Audience Member] Mhm. - But this is for just for maybe 30% of the patients.

- Well, I guess what I'm trying to say is if, that up to that point on those cases though, it seems that the ethanol is the thing that's probably finishing the job. I mean, help me out here Wayne. (Laughter)

- [Wayne] We will have that discussion later. We will have that discussion later. - [Audience Member two] (mumbling) Can't we stick to a specification lets say (mumbles), not because I like it so much, but type two b, three a, three b, if we throw in some other specifications then

we can (mumbles). - [Audience Member One] But then, I just have to say, please publish it. Because you can't look up everywhere, there is no publication, so if you publish it I could use it.

- I'm going to talk about the use ethylene vinyl alcohol copolymer in the treatment of high-flow arteriovenous malformations. I'm going to describe our long-term results and some of our histology. I have no financial disclosures. The DMSO, the Onyx liquid embolic system,

as you know consists of ethylene vinyl alcohol copolymer suspended in DMSO solvent and mixed with tantalum powder. The polymer will precipitate upon contact with aqueous solutions, such as blood. The study population I'm going to describe consists of 38 patients with high-flow AVMs.

Their demographics are shown here. The mean age of the patients was about 28.9 years with a range of less than a year to 67 years. 16 of these patients had been previously treated with other embolic or sclerosing agents before Onyx. All patients were symptomatic at time of treatment,

all underwent MRI MRA prior to treatment, and ultrasound was performed as needed pre-treatment to assess legion visibility during treatment. We used Onyx 18 and or Onyx 34. The Onyx was delivered by subselective arterial or venous microcatheter techniques.

It was also delivered by a direct injection with ultrasound and fluoroscopic guidance with either tourniquet or manual compression. In any patients that went to operation, histologic examination of tissue explants was obtained. The distribution of the AVMs is shown here.

There was a preponderance in the lower extremity but they were distributed throughout the body excluding the head. The delivery routes, 24 patients received the Onyx via transcatheter delivery, five received direct injection under image guidance and in nine,

a combination of transcatheter and direct injection techniques were used. Our technical success rate was 97%. We were able to get the Onyx to where we wanted to get it. Our clinical success rate was 89%. This was defined as decreased pain

at the six to eight week follow up visit. Unfortunately, not in all patients was the pain response persistent. Four of our patients with diffused AVMs went on to eventual amputation. Our mean follow up in this population was 56 months

with a range of one to 348 months. Our mean follow up following their last Onyx injection was 26 months with a range of one to 124 months. One patient in this group was lost to follow up. Complications occurred in four patients. We had two patients who developed skin ulceration,

one of which required a skin graft and this graft did yield. One person presented to us with a pre-existing radiation burn and his radiation burn got worse during our treatment period but it has subsequently healed but required hyperbaric treatment.

In one newborn patient on Onyx filament from a high-flow AVM in the liver migrated through patent doctospinosis as a strand persisting in the right atrium. I'll just show you two selected cases. This person presented at age 17 following rib trauma,

he was diagnosed with a high-flow AVM. He underwent a series of 19 embolizations beginning in 1983 with a variety of agents being used including alcohol. His first Onyx treatment was in 2013 at age 50 and he underwent a total of five Onyx treatments.

This MRA, oops, sorry, shows the component in the abdominal wall and this other image shows the plural component. The MRA angiogram shows multiple dilated intercostal arteries and recall, these have been treated previously.

The venous phase of the MRA shows this large venous conglomeration down here in the right lower abdominal wall. This is his final Onyx embolization and you can see with direct injection, we have been able to fill the interstices

of this large venous conglomerate. On the arteriogram you can see that we have Onyx in multiple intercostal arteries and we have a coil here to treat the aneurism. We sometimes use the Onyx in conjunction with coils. Here is his final MRA taken two years ago.

You can see we still have that plural component, we've been somewhat reluctant to go deep into that, but the venous component along the lateral abdominal wall has resolved and we can see that we still have some intercostals that are slightly enlarged but the overall number of intercostal arteries

is significantly decreased. Our second patient is a patient who presented at age four with a left calf mass, limp, and pain. He underwent surgical resection of the left medial gastrocnemius muscle, and pathology diagnosis at that time

was an intramuscular hemangioma. He did well for five years but then at age eleven, his symptoms recurred and he was referred to us for work up. His baseline MRA shows a large hypervascular complex malformation in the distal fi. It extends across the joint and we see it

in the proximal calf in the mid calf. The cross-sectional imaging on the MR shows the extensive intramuscular involvement of this legion. This is in the thigh and here we are down in the calf. Our initial angiogram on him showed several components.

This portion was supplied by the profunda femoral artery. We have another component of the malformation supplied by distal branches of the SFA and here in the calf we can see some of the trifurcation, and down in the mid calf. He underwent his first embolization in 2005

and we used embospheres and alcohol. We had minimal response with the alcohol. Over the next year he underwent a series of nine embolizations with Onyx. And here is his final MRA. His problem was significant pain and difficulty ambulating.

You can see on the arterial phase of this time resolved image that we have significantly decreased the arterial in flow of the malformation, however on the venous phase of the MRA, you can see that we still have these aneurysmally dilated veins draining into

the deep femoral vein of the thigh. This is the cross sectional imaging post Onyx embolization just before amputation and you can see, there has been a reduction in the intramuscular involvement but we still have dilated venous channels which we saw on the earlier study.

He underwent amputation in 2008 and you can see that the residual Onyx is there in profunda distribution. His histology is shown here. In some portions of the malformation, we had this abnormal area with multiple small abnormal vascular spaces,

which looked quote more hemangiomatous in type even though we don't prefer to use that word. And here on the trichrome stain, you can see that we have these small abnormal vascular channels. In other portions of the malformation however

we had the more typical appearance of a high-flow AVM with these very thick walled abnormal arterial structures where it's difficult to distinguish where the artery is and where the vein is. Here we have the intraarterial Onyx, producing a cast in the vessel.

On a higher power image, you can see that there are some giant cells interspersed around the Onyx, however this particular case had more giant cells than we typically see in our other specimens. There are some limitations to the use of Onyx.

The first and biggest problem is getting it to flow distally into the nidus. And in order to accomplish that, what we do is we dilute our Onyx 18 with additional DMSO to make it more runny and to make it easier for it to traverse distally.

We agree that the radiopacity of the Onyx can sometimes obscure the anatomy on subsequent treatments however we can usually get around that using oblique injections and using an embo roadmap. The advantages of Onyx are it's a permanent embolic agent. It's associated with minimal post procedure pain

and minimal skin changes. In our experience, Onyx is a safe, durable agent for the treatment of high-flow AVMs. It's associated with minimal post procedure pain, has a low complication rate. It's an effective palliative therapy for large lesions

and it a useful presurgical adjunct. Thank you.

[Mollie Meek] We are going to talk about our histology of head and neck AVMs after Onyx embolization. Like I said previously, we were in love with Onyx at the end of the 2000's. So we used lots and lots of Onyx, and then the patients generally went for resection.

Sometimes immediately, and sometimes years after the embolization. We are not as in love with Onyx anymore, and our hospital was certainly not in love with us using Onyx the way we were using it in the past, because it was super expensive,

and they weren't getting reimbursed for the multiple vials we were using. I had no disclosures. If I have time, I'll talk to you about radiation dose. The most important part is the pathological response. This is a slide of a typical AVM.

You see the thick walled arterial portion of the vascular channels and the thinner walled venous portion. This is just a higher magnification. I am not a pathologist. So when we did our scoring of our specimens,

we scored some acute and inflammatory changes, some chronic inflammatory changes, and then the amount of recanalization that we saw. What we found is that recanalization was extremely common. We saw it in 13 of our 18 specimens,

and the specimens that had minimal inflammatory changes had minimal recanalization. That's the take home message. This is a specimen with Onyx in cast material in the vessels. Trying not to blind our moderators like I did earlier.

This is a really pretty picture of the vessel wall, the Onyx material, and a brand new vessel in the middle of this old vessel. This is what just sort of a scout image of what their faces looked like.

One of, a sample. This is like a longitudinal slice of a vessel. So this is vessel wall on one side, vessel wall on the other side, Onyx material, and then new vessel formation

and interstitial tissue stuff in the middle of that old, big vessel. These are just some pictures. Another example of Onyx with vessels inside the Onyx. We saw a fair amount of giant cell formation, which you can kind of see these clusters

of multi nucleated things, are the giant cells. They come in and clean up the Onyx material. These are just more Onyx specimens. Here's a nice picture of giant cell. We also counted vessel wall necrosis in our tabulations.

And you can see this Onyx material is in the endothelial cells, and it kills the endothelial cells. So we did see some vessel wall necrosis. So the short story is there's no definitive time for the recanalization,

but we think it takes about a year for you to really see nicely formed vessels in the Onyx. And in our experience in the head and neck, it was common. It may be different in other locations, because obviously your head and neck

has different lymphatic ratios and inflammatory things, and there's all kinds of differences between the head and neck, and say your arm or your leg. The second part of this is your radiation dose,

which has been touched on a little bit. The plug and push technique, part of why I don't like it, and why I don't like using Onyx, is it's just slow. You have to wait, and wait.

And it takes a lot of x-ray penetration, because your computer is going to try to up your dose because you've got the black Onyx in the x-ray beam, if that makes any sense. Your machine's going to try to help you, and it amps up your dose

really quickly if you're not careful. And for our head and neck patients, obviously we're doing AP and lateral views. This is our equipment. We put dots, radiation dosimeters on peoples' heads

and one in their oropharynx before our treatments, and we did calculations of a sequence of patients. You can see the ages of the patients in the group, and the number of the patients. This was just for a short time period we did this.

This is the important part, that the AVMs have a much higher skin entrance dose than the venous malfs. Part of that is we don't put on in venous mals. Sometimes I will put glue in a venous mal if a surgeon wants to resect it

because they like the way it comes out when you do that. But otherwise I generally just use alcohol in venous mals. And then these were on X AVMs at this point in time when we collected this data. Some alcohol.

This is a reminder about the dosimetry. And this was the number of sessions, embolization sessions versus the skin entrance dose. And just some more pictures of yeah. So Onyx is not permanent in my histologic experience.

Watch out for wound healing issues and recanalization, and watch out for skin burns. That's it. Thanks.

- This my presentation about ethanol curative treatment about hand and foot AVMs. Now, yes AVM treatment, it were a challenge. But in foot and hand AVMs are much more challenge, where it's very limited. So, because in foot and hand one limited area,

some abnormal vascular architecture were clotted to normal vascular architecture, some types are difficult to identification of NIDUS. So when some ambulant agent should be

reflux to arteries, will cost and we are supposed necrosis. About some patients, will comprise as our study group, 12 in hands

five in foot, they're a puncture with a man approach, as known is in our favor to treat men. Whence the outflow

(mumbles) were denoted, requires different force. The clinical manifestations part, ulcer is the most common, then pain,

then pulsatile swelling, red plaque, some dilated outflow vein. Here is into some, yeah, into some leave a hole,

in a ring, in the middle and in the past and where can be a wound. But also it were common in the bleeding vein

out of our source. This was serious (mumbles) and the vessels bleeding also. This is in their index finger, in the little finger also. But in the (mumbles)

These were leaks ditched of AVM in the foot, we found several networks in the treated veins replaced one by one. Yes, were little of surface, and surface bleeding occurred.

This is AVM in the foot, ulcer also, in the middle here. And here in the foot, AVM. But the swelling pain makes this girl on the foot,

starts to keep this gesture, starts to keep like upward everyday with several pain. Indications of Embolization for ulcer, pain and some

dilated that overflow veins. The goal of treatment it's actually evaluating their symptoms, especially referred to ulcer, especially pain. The how to,

how to evaluate the treatment is successful or not, it's for healing of ulcer, recovery of dilated DOV and vanished pulsations, and no enhanced mass in CT.

It's actually according to these they trying to evaluate. Key points of successful embolization about I think, yes ethanol was selected (mumbles)

And sometimes the NIDUS surely located in the NIDUS, in the same operation. When the outflow vein it did not require release, aiming to alleviating,

improve clinical symptoms. Sometimes you will get ligation of distal end on foot, on hand. Sometimes we use, 18 G needle,

that are punctured all the way, then induce the micro chester to everywhere, I usually release the quails of micro chester, we can get

everywhere we want. Up to quails of collision, as it points the injection ethanol. Sometimes we have serious bleeding here serious bleeding, but here in NIDUS

ulcer also. But this ulcer here on the foot, there are puncture, but I think x type two, this is NIDUS, this is (mumbles)

Usually about one cure is rare, about three cases, but 11 cases get improved symptoms, include about ulcers healing. Such as this, more serious ulcer

and certain bleeding, but one year later, we confirmed ulcer's healing and fibrosis happened. Yes, ulcers healing, up to that,

we received ulcer, ulcer healing begin. These before treatment, before actual treatment, (mumbles) within (mumbles) structure of treated vein,

about half year later, the ulcer's healing. This is before treatment, when we found outflow vein here, after treatment, outflow totally gone.

But this case, it didn't occur on my center, in other hospitals. After treatment of necrosis here, the fingers were analyses, this index finger and vein,

cause the pressure are good, with injection ethanol, but in this part, we refract to the arteries, but in this operation, injection ethanol,

it will cause disasters. But this complication has nothing to do with ethanol itself, but related to doctor experience. In this operation, it's not in tradition for ethanol injection,

but you inject it. Complications are saying for expected for necrosis (mumbles) Why would I use inject ethanol to arteries, inject ethanol to tissues.

Sometimes post-treatment swelling can cause little little slide necrosis. So conclusions I think, the embolization for foot and hand is a challenge. We don't treat the patient,

don't treat a patient with no symptoms, no treatment for symptoms. I think the goal of treatment AVM in hand and foot, it's actually alleviating or improve clinical symptoms.

But pre-enhanced CT, intraosseous, and if outflow vein is denoted, quail with (mumbles). Ethanol is the most popular agent in my center.

I think ethanol use cure and treatment may be portable. Thank you

- The proposition is polymerizing agents can and do cure AVMs and are now the agents of choice, ethanol is too dangerous. When I saw what Wayne had asked me to talk about, I immediately called him. And I said there are two words in this proposition

which are giving me some trouble. The first word is dangerous. In IR we do dangerous every day, especially in July. And with respect to cure in IR, mostly we just try to fix things.

Nonetheless, there are proper uses of ethanol. There are, however, some risks to the use of ethanol in medicine. First off, ethanol is a sclerosing agent and it is toxic to tissue. It denatures the proteins

of the endothelium, activates the coagulation system and produces blood clots. While we are trying to do that, when we're trying to control an AVM, it does also generate acetaldehyde and reactive oxygen species

which damage healthy tissue. It can result in endotoxin leakage, inflammatory cytokine release, and modification of signal transduction in the cell membrane and when we deliver alcohol, unless we dilute it with contrast,

we really cannot see where it goes. There are some other issues with ethanol. The first is that it's known to impair wound healing. If ulcers occur with ethanol use, they are difficult to heal. If you place skin grafts on these lesions,

they typically fail. And if you use ethanol in an area of prior surgical scar, there is a high risk of skin injury. In addition, the use of ethanol is associated with pain, it's a painful procedure.

If you deliver ethanol in proximity to a nerve, you will develop nerve injury and if you have sciatic nerve injury, that can be devastating which can take months if it all to heal. The other issue relates to the dosing

and the volume of ethanol that's delivered. If you deliver high doses of ethanol at one sitting, you can get systemic effects. Now, a slightly tipsy patient post-embolization is not necessarily a big problem, however, if the patient develops hemoglobinuria,

that can be significant. If you use low volumes of ethanol with each treatment, it requires multiple treatments. You can also get cardiopulmonary problems with ethanol. The ethanol can induce arrhythmias, it can induce bronchiospasm,

it can precipitate pulmonary emboli because of the sludge that migrates up to the lungs and you can get cardiovascular collapse with the use of ethanol. Fortunately that is rare. Other polymers such as the cyanoacrylates

or liquid embolics and their viscosity can be altered. The downside in our experience with the cyanoacrylates is that they're difficult to control, they tend to spatter.

And our long-term experience with the cyanoacrylate shows that it is not permanent and it does degrade. The ethanol vinyl alcohol copolymer or Onyx behaves as a filler. It induces a mild inflammatory reaction.

It's associated with minimal pain post-procedure and skin injury is infrequent and it is in our experience a permanent agent. There may be difficulty getting it to travel deep into the nidus and that can be a big problem,

if you just deliver the Onyx in just a push away, it will not go very far and you will leave your nidus untreated which can lead to recanalization. So, we dilute our Onyx 18 with DMSO

which makes it more easier to spread out into the distal portion of the malformation. It is somewhat harder to see when it is diluted. We also use a glue roadmap. This will reduce our radiation dose

and we don't deliver the Onyx the way the neuro-interventionalists do, we tend to deliver it much faster than the neuro people do. And if you have obscuration of your vessels by prior Onyx placement, the glue roadmap can help.

When we use Onyx without operative resection, it is an off label use. But nonetheless, when used, it does facilitate operative resection and you just have to remind your surgeons to use a bipolar bovie otherwise you will get sparking.

With respect to cure. I think cure, when we talk about it, it really depends upon our definition of cure. Polymer occlusion will result in relief of AVM symptoms. And it can cure some lesions.

Whether we are able to remove all shunting in large lesions I think is doubtful, but nonetheless, Onyx copolymer is associated with lower morbidity than alcohol. And when we look at ethanol versus polymers, the ethanol is a one-generation agent.

Whereas if we look at polymers, if we consider cyanoacrylate as a first generation and Onyx as a second generation, and squid maybe as a third, the future is pretty much unlimited for us because you can prepare polymers which will contain drugs

or other agents. So, I think the choice is you have to determine whether you want to use ethanol, or whether you want to use a polymer. Thank you.

- Thanks a lot for again for inviting me because you know, (laughs) I'm in very hostile territory, (audience laughs) but, I will tell you the truth now, (audience laughs) and being in hostile territory and telling the truth can

be totally different things and I, I'm also never in any way, you know I'm totally scientific type, I will never be polemic, like you are. (audience laughs) Okay, so let's start with the truth, start with the truth, I show you two typical cases, this is a typical ethanol case

here with couple of, it was successful, at least in losing it's toes, and I'll show you another example again, a foot AVM, this is one session, one session, in fact its 14 vials of squid in this case, and it's done. so, this is not statistic, but I always

see, and I've seen it today in a couple of talks, Onyx used as glue. And that doesn't work, you have, if you start to treat a patient, you have to really treat him and it's not something you inject, and that it's gone, you have to fill all the AV shunts, you have to fill the whole lesion.

And if you don't do it, of course you see a lot of failed on ex-patients and if its used improperly, and that's the only thing I, I wouldn't say I agree with you, I would say I'm thinking in the same direction, yeah, that's if you use Onyx in the wrong way, you have a very good chance to make thing worse.

So, its a technical thing, and if people start to use Onyx, and they inject something, and then its something like putting in some coils, that's not worthwhile, it makes no sense to include some arterial feeders, we know this since, I think more than 20 years, it's like making a surgical ligation of the feeding

artery, it's totally senseless. You have to completely occlude the area of the arteriovenous shunting, apart from the predominantly venous one, where you can just occlude the venous outflow, by whichever thing you use, and the area of arteriovenous shunting is always bigger than you see it in a normal DSA,

because the blood does the same as the contrast medium does, it flows along the route of the least flow resistance. And so, at the end, if you want to be sure that you have to completely occluded the AVM, you will end up with a cast which is much bigger than what you see at the beginning of a DSA, yep, it was agreed, see.

- [Audience Member] You know I'm shaking my head as you talk. - Yeah, yeah, your getting tired. (laughs) Here we go, So, and this is only the really scientific slide in my talk, because when people die when you inject ethanol

in vascular malformation treatment, its something, its banal, all of us have seen it many times, but there was a scientific question, why do people die on the table if you inject ethanol in AVM treatment on vascular malformation treatment? And there's one scientific publication here, because we

all thought do they die because of complete vasoconstriction in the pulmonary arterial system, or is it, are they dying due to the thrombi? That, you know ethanol, it uses small slatch or big thrombi and they go to the pulmonary circulation and they die. So, is it the vasospasm, induced by ethanol, or is it the

thrombi induced by ethanol, that they die is clear. So, there was a very nice publication out there in 2012, was presented in Malibu, at the IFSA meeting, it was about four patients, which three of them died, two were just after injecting of between five and 12 milliliters of ethanol, one was a direct puncture pelvic AVM, and it was caused,

that this was nicely stated there, it was caused by multiple small peripheral emboli. So it's not vasospasm that kills the people, it's the thrombus, and I think this was a very very worthwhile contribution to all our knowledge and really thank you Bob for this paper, thank you

very much, now we know why they died. I haven't, unfortunately I can't contribute to this discussion with Onyx because there wasn't any patient dying on the table during my embolization's and I've done now, we're preparing the paper of 160 AVM patients with I don't know, 400 sessions and well maybe if we wait

40 years more, 50% will have died but, (audience laughs) from natural cause, so I can tell you again this is the truth, we will talk about the truth here, and this is, ethanol can be worthwhile even in AVM's, I don't deny that and maybe it will have its place for a couple of more years

before we do Onyx and MEK1-Inhibitors, so there is for couple of more years, this is a role for ethanol, but it's somewhere deep down there, and this is a slide I show for the third time now just for you Wayne, please and I show it because you should start to publish your classification.

I didn't use it because there is no paper there, please publish it then I will always classify according to your classification. - [Audience Member Cheers] - Thank you for your attention, thank you for giving me the chance to talk about the truth here in this seminary

and please don't do anything stupid with ethanol.

- I am not Walter's enemy. I can tell you that. I am against the motion. (man laughing) I will stick to the truth, to the facts. I don't like polemic, like you. I don't like to play, let's say games

of undermining what my opponent is saying. I'm just showing what I believe in because it is the truth, okay? (quiet laughter) I have nothing to disclose. Let's stick to the definition of 'cure.'

We all know that 'cure' means 'at least one year follow-up, angiographic follow-up after the, so-called, final angiography, that shows that malformation is gone.' Call it whatever you want.

Technical success, obliterated, trombosed, concluded, ablated, gone. Then at least one year follow-up on that. Angiographic to prove it's gone. The rest is just a scale on how you can evaluate the results.

Angiographically and clinically. The only way, for me, to speak to the truth is to find in a material where there is a chance to compare.

Hat to hat. Both type of treatments. Polymerizing versus alcohol. And, the only way to find such a place is to go to Wayne's place, because he's also constantly called

talking about salvaging this and salvaging that. I am very critical about what Wayne does. You can be assured about that. He's had 16 patients, I dig out there, and polymerizing agents they were failed.

Definitely, failed. Actually, they were salvaged, by Wayne. And, I'll show that to you. These are the patients. This is the time to which they've been treated. The usual type of distribution.

Young patients. All of them extensive. There is no, for a lack of an effort. There is no, for a lack of knowing how to use

the polymer. Onyx. How we can tell that, most of those is Onyx, some of them are glue. Or a combination. The median number of sessions

with this polymerizing agent is 8.5. Range from one to thirty. The other radiologists, the other experts, besides my honorable opponent, Doctor, Professor Wolgemuth,

they also know how to use Onyx. I can assure that. Sixteen patients, all symptomatic. They are all decompensated, showing three, four tier symptomatically. They have high cardiac output,

they have required repeated, repeated blood transfusions, infections, ulcers, disarticulation. To have disarticulation of vascular malformation means, oh, horrible bleeding, infected. There is no doubt,

they are symptomatic. Couple of examples. This is a young woman, extensive AVM in the foot, type four. Been treated five times with Onyx. And they know what they've done.

They've treated well. Yet, worsening symptoms, wheelchair bound, infected ulcer. Seventy-one session. Now, pay attention. Seventy-one sessions of ethanol/coils embolization. And, this woman is now running with her friends

after her amputation of couple of necrotic toes. Not because of the alcohol. Because of the malformation. Angiographically, not cured. Example of that. Okay.

This is malformation. This is not something in a tiny, little bitty thing. It's a malformation, no question about that. Before treatment. And, this is after treatment. We can all agree that,

this is not completely cured. It is a grade three it is 80 to 99 percent still left. But, clinically, she's running. She continues to be treated. Another example.

One year old girl with bleeding malformation from the lip. Admittedly only one Onyx being used because we didn't know what to do. Luckily, the little girl was close by so she came to Wayne and after,

it's intravenous predominant lesion. It's a type two lesion. Only after a six month treatment sessions, cured. This is before start of ethanol treatment. No question there is recurrence. We can not close that only by pushing

polymerizing agents somewhere in something called 'nidus.' But if you ablate the cells, ablate the nidus. You achieve cure.

And it's cured in one year angiographic follow-up. This is time and time and again. I will show these examples. This is the outcome. The outcome tells you six cured angiographically. Eight considerably improved, they improved.

None of them is failed in this. All failed polymerizing agent treatment. Then we can move on. Complication because that's where talking about how dangerous. Alcohol is very dangerous,

but so is knife in operating room. Take a knife and stab it somewhere in some artery, or in a pressurized vein, you'll have all this blood in your face and a shoot of blood doesn't taste very good in your mouth. So it's dangerous.

But, if you use it carefully, that's what you achieve, as a result. Where do we stand with these patients? Ongoing treatment, five. Cured, five, by summation.

One still waiting for a follow-up on angiographic follow-up. Improved on watchful observation is two. Lost to follow-up because schizophrenia. Lost to follow-up because of unknown reason, after two years of follow-up.

He's been doing well throughout these two years. One clinical failure. I will tell you that Wayne have, he's seen this person. Not clinical failure. Yeah, it's clinic.

By definition, is clinical failure. Angiographically, improved. Clinically, improved. The little boy was wheelchair bound, didn't want to continue with that and, therefore, went for amputation.

So it's a clinical failure. One. To summarize that, I highlight on this, venous predominant lesions. These are the ones these create.

Type four. (man speaking off screen) Tough. Couple of examples. Striking examples. This is venous predominant lesion, IIA.

I'm sorry. IIIa, IIIb being treated. Sorry. Can we go back to that? Any way I can go back on that?

This IIIa, IIIb, there's has been five. That's moves forward. Five surgery, Onyx, anything thrown in. Extensive malformation. Shoulder, arm, a no-flow into the lower arm

because of the. And it's moving forward. I'm sorry for that. But it was cured. And there was a follow-up, too. I believe there was something.

Twenty, 15, 17 months follow-up. So we have the next patient. Thirty-two year old female treated with glue in the past.

Twenty procedure including all vessels. Everything that can not be, could be embolized, was emolized. Ended up with the worsening and this is the typical example a IIIa malformation, typical example.

This was way back in the past. This is how Wayne has developed that. It took him, I heard, nine hours and another 100 coils, but he cured that.

- [Male] 298. - Two hundred ninety-eight. This is the follow-up, you know. Eighteen months later. To summarize on that. Nothing to do with my feelings for Wayne.

Nothing to do with Walter being my enemy. (quiet laughter) No, it's just a fact, a truth. Polymerizing agents, by definition, do not cure AVMs. Do not cure.

Sometimes, when used properly, still worsen the patient's symptoms. Ethanol cures AVM. Provided that you do that with precision and skills. How you acquire precision and skills? Ask the surgeons around here.

How do they lift up this face? How Max can lift out, you know, big time metastasis sections in liver? How do you do that? With skills.

How do you acquire skills? Learn. Thank you.

- Alright, that's our beautiful city by our inland freshwater ocean. I'm against the proposal because, in my opinion, ONYX and the polymerizing agents don't do what they're supposed to do, which is cure. You know, we could talk about this, but in preparation for this, I looked at the

relatively sparse, but available, literature on ONYX, and the fact of the matter is, repeatedly when one looks at what is in the literature, ONYX does not cure with a few exceptions. For example, this is the curative exception. This is a mandibular AVMs, three of them cured

at one year angiographic followup. Now, I consider cure a very simple metric: is it gone at one year followup angiography or imaging? And this meets that criteria, but again, we know that mandibular AVMs, as Dr. Fannis has so nicely shown, this is a bone cyst, essentially,

fill it with anything, it'll get cured. All venous predominant legions, three A. So, yes, cure is possible in isolated circumstances. I think Walter has acknowledged that. But, all the other data, including Dr. Loglos' own data, is that there is no angiographic

followup, short clinical followup. Other papers, Embolization of peripheral high-flow AVMs by Kilani et. al, surgical excision in nine out of 19. Right, that's not the same thing, but it is one aspect of doing it, and there's no angiographic followup. And we see this again and again and again.

Very short clinical followup. So paper after paper refused to tell us that we don't really know what the behavior of ONYX is, as defined by the very simple metric of cure. Although complete, in this paper for example, although complete angiographic exclusion of the nidus

is obtained in a minority, 36 percent, of cases, there's no angiographic followup, so the exclusion is presumably based on immediate post-embolization angiography. In other words, ONYX looks good, acts bad. Other embolization agents in this paper also used,

probably some of them ethanol, which actually got the job done. And then finally, another paper with zero clinical or angiographic followup. So the answer is obvious: ONYX, while it is used copiously by some of the participants in this debate, does not cure,

and I, as my Chinese friends said, think ONYX is garbage. I don't think it works. Few examples of that, here's a young woman, a patient of Dr. Yakes, who, 12 years old, extensive facial maxillary scalp AVM, nine ONYX embolizations, left blind in the right eye

with persistent massive oral and nasal hemorrhage, and after appropriate embolizations, patient was stabilized clinically, and the ONYX was resected. She's stable now, not cured, but she's actually had an excellent clinical result. And you can see that's what it looks like.

Now that's hideous, that's not going to work. And it also, I think, points out what Dr. Walgramuth has actually admitted to, which is it's very difficult to see through this stuff. Radiation dose is increased, and identifying what to do and where to go is a real challenge.

Another such example, I think, suffice it to say a picture is worth a thousand words is this illustrative case of an extensive pelvic AVM, treated with what appeared to be gallons of ONYX, with very little benefit, and an enlarging ulcer. This was later treated by direct alcohol injection

with cure and improvement resolution of that ulcer. So, in summary, it's real simple, folks. There's no evidence in the literature that polymerizing agents have cured AVMs with an exception of a few venous predominant legions. And as I said, you could probably put Jello

in the outflow of those things and it'd work. My own personal experience is repeatedly had ONYX failures, and importantly, many patients are worsened by this treatment, and actually, their subsequent curative treatments are hampered. Thanks very much.

- I've made this agent comparison chart, just sort of summarizing the areas where I think that Onyx is better as compared to ethanol. I think things to come, oops, sorry, I got to go back. I think the items to be commented on are one, that there's less skin necrosis with the polymers.

It's a less painful procedure, and the Onyx, in our experience, is durable. But in the treatment of any type of AVM, you have to get your agent into the nidus of the malformation. If you don't do that,

then you're just doing a proximal occlusion. And we know from the surgical literature that that does not work. They will simply, the angiogenic stimulus, whatever triggers it, will continue. And that gets me to another point.

I really don't think that we really know what stimulates these malformations to grow. We think it may have something to do with a resistance in the flow, but we have some pelvic AVMs who have been stable for 30 years.

We're not touching them, and we have no intention of touching them, whereas we have children who will present with an AVM at age four and then by age seven, they are unable to ambulate. So in any event, I think that

polymers represent the future. And I just want to quote from this old movie, The Graduate. "Plastics," thank you.

- Now we all have seen one thing. We have to treat AVM's according to their classification angio anatomy. If you have something like, direct arterial venous communications, like pulmonary HHT patients, like the rare patients with inborn arterial venous fistulas,

you will never use ethanol. That's my opinion. That's an opinion. But I think most of us will agree on that. Will you? - [Audience] Yes.

- I think many of us will agree. So would you just do it for a HHT pulmonary patient, you would inject ethanol? - [Audience] No. - So, okay. And the direct arterial venous communications inborn,

they are very rare and they can be beautifully treated with plugs and whatever. These are one part on the AVM patients. Second part is predominantly venous outflow. However you say it's 2B, 3A or whatever. It's a dominant venous outflow

and you can cure them and I say cure, even in my paper there is imaging of follow up, but it's not in the abstract bar. (smiling) So you just, - (laughing)

- So you just occlude the venous outflow, as close to the nidus as you can. So I don't need ethanol for that. I don't need to take the risk for my patient. And so that leaves the type 4 small vessel AVM's. They are, even in my opinion,

not treatable with a polymerizing agent. There is a real place for ethanol. And then you you go to these difficult, more net-like, type 3 or whatever, AVM's, then my opinion is, I do it as long as possible,

with a safe agent. Like pushing in tons of onyx. And if there is something left over, or if there comes something in follow up, because we all need follow up for these patients, then you can finish it with ethanol.

That's my statement. Thank you.

- I think it's unfair to have Wayne here with all his expertise and knowledge and throwing all these combative comments, vulgar attack, et cetera. But the bottom line is all these types, no matter how you define them, they are mixed.

They are mixed, they are not, with the exception for HDT. You have Type 1 in a midst of Type 2. You have Type 2A and then 3B, type something. I don't even know what they are, except that you say venous predominance, yes. Can be multiple venous predominance, yes.

Then you can have Type 4, these are the major groups. But to have a filler that occupies a space, can be Onyx, it's fine. It doesn't cure. You have to do something to these cells. You have to compress them.

You have to ablate them. You have to take them out. And a filler doesn't do that. The filler recolonizes on top of that, as you've put it already, from Molly. Recolonizes.

You can use it as a filler, but the cure, the ablation, has to be something that's powerful. Like a knife, even worse than knife, burn injuries, burn it to the bottom. That's how you achieve a cure. If you don't believe me, just look at ...

Can you play us that clip that was rotating constantly as Walter was talking, here, how Onyx is wonderful? This is the girl that you show on the pictures from Bob. Can you look at that? It's a ton of extras placed into the veins,

arteries, everywhere. She continues to bleed. On top of that, it's horrendous, how to treat it. Wayne managed to stop and control the bleeding, but this is an example.

This is the most scary sample of what Onyx cannot do. So back to the motion. Polymerizing Onyx can cure, and it's the material of choice to use? The answer is no. Alcohol is dangerous, personally,

I say yah, very dangerous, if you drive and you don't know how to use it. But so is everything else. But if you know, you can cure them. Thanks.

- My rebuttal is short and sweet. I think that those of us who have seen both agents, seen it in a fair comparison, understand that while ethanol has an appearance of difficulty to use, have come to the conclusion that it is actually safe. It has to be applied in the right spot. If it is such it will absolutely cure

and in it's very, very safe fashion. I think Walter mentioned the four deaths that I referred to. I agree, tragic, terrible, but we learn. Haven't had any deaths since, because I understand now the mistake I made and how to use ethanol.

I think the same thing is true. Max will tell you that there were enumerable deaths during the development of transplanting these difficult operations. No longer, all controlled, it's all because of learning. Thanks.

- Alright-ey, hands put up. Who is for Onyx? Put your arms up. - [Male Audience Member] Who supports the Onyx Motion? - Onyx Motion, that's correct. He should've gone to law school. Who supports the alcohol motion?

Who supports the motion in the ocean? Alright, thank you I think we covered a lot of territory today. We want to have theses things and we are so glad that everybody came. I think this is Tony's first time,

Walter's first time here, Loronze and we really learned a lot today. I'm really glad Pletio Rossi was here because without him and his development of selective catheterization, I mean where would we be

sticking needles in every artery like that, trying to do angiograms, much less advanced sheaths or anything else. Pletio was wonderful having him here, one of my hero's. Anybody like to say anything?

Anybody got any questions or anything? - [Female Audience Member] The HHT scientific meeting's in June in Puerto Rico if you want some more good-- - Do they have electricity there yet? - [Female Audience Member] I hope so, I knew it looked nice before.

- Oh, okay, okay. Alright, well thank ya'll so much and we'll see you next year. (Clapping)

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