SPEAKER: All right, well, we'll get started. Welcome to everyone to Medical Grand Rounds both through the Zoomiverse and here in person. 

Today, we have the pleasure of having Dr. Zach Henry here for Medical Grand Rounds. Dr. Henry started his career in Alabama, where he attended Auburn University for his undergraduate studies and obtained his Doctorate of Medicine at the University of South Alabama. 

He then came to UVA where he completed his residency, fellowship in gastroenterology, and an additional year for transplant hepatology. We were lucky enough to convince him to stay at UVA where he has excelled in numerous domains of academic medicine. 

He's known as one of the best educators able to explain complex cirrhosis, pathophysiology, and still his passion for hepatology for trainees in and out of GI. I can try to list all his educational responsibilities, but that may become a medical grand rounds in itself. 

He currently is the Principal Investigator for several trials and cohort studies and has authored numerous peer reviewed articles, reviews, and book chapters. Clinically, he was one of the founders of the Nash clinic. 

And thanks to aggressive weight loss counseling and interdisciplinary work with Dr. Kirby in endocrinology and Dr. Taylor in cardiology, has improved both cardiovascular and liver outcomes in these patients. We are so privileged to have such a great educator review the management and innovative therapies available for gastric varices. 

So without further ado, here is Dr. Henry. 

ZACHARY HENRY: All right. Thank you for that. And can everybody-- I know everybody in here can hear me. Can you check to make sure that Zoom can hear me? 

So we're using this microphone because if anyone has seen me give a talk before, I like to move around, and I'm very fidgety. So I can't stand behind this thing. 

I appreciate the people here in person, because even though there's a camera, and I know people are listening on Zoom, I'm going to focus on you all, because I can't see them. Our talk today is a little abnormal, I feel like, for medical grand rounds. 

This is somewhat of an esoteric topic. But for our residents and also for our attendings, both on general medicine as well as in our ICU, because of our local expertise, gastric varices are something that we see here actually relatively frequently that in other institutions you're not going to see so much. 

So I do feel like it's an important thing for us to review. And we're going to try to cover a lot, kind of a broad overview about gastric varices. And as I always end up doing in my talks, I will throw in a lot of opinions about evidence based medicine and pitfalls in research that's out there, and try to point out gaps that we can fill in, some of which is work we're already trying to do here at UVA. 

So just for disclosures, I have none. But then also, pretty much every treatment for gastric varices is off label. So it's just a good thing to understand. 

My objectives are first, we're going to do an anatomy review, which I always find fun. Because I feel like it's good to have a picture in your head of what this looks like internally. Because when we start to talk about treatments and classification systems, understanding what things look like is going to be very important. 

We're going to talk about classification schemes. And I'll talk about why that's so important for this particular topic. Then we'll talk about management. And we'll even spend a little bit of time on what we need to do in the future. 

So first, if you leave here with nothing else-- in fact, if you get up right now and you leave or you stop watching on Zoom, this is the only thing I need you to take away from this. Gastric varices are not esophageal varices. 

They are very different. There are some physical connections between them. There are some overlaps in the initial management. But ultimately, these are two very different phenomenon in cirrhosis, and which is why it's so important to classify them correctly and think about their anatomy and physiology when we're talking about management. 

So this is our classic anatomy textbook. Hopefully everybody recognizes Netter. Now, this is the version from when I was in medical school. Because it's the textbook that I have in my office. And I literally just photocopied this, so there may be updated versions. But I'm pretty sure we still look like this internally. So I think it still stands. 

And what I try to do-- this is a vascular image from Netter. Wait a minute. There we go. And so we're focusing on the vessels of the portal system, the left gastric vein going up into the esophagus, the splenic hilum. 

But I've also tried to outline the fundus, cardia, body, and antrum in the stomach to try to show you endoscopically when we're in these different portions of the stomach, when you look on the outside, obviously there's very different vasculature. This is an important concept to understand. 

So here, the cutaway plate in Netter gives you a little bit of a better view of the splenic hilum, so on the right side of the screen. And you can see short gastric veins coming out of the splenic hilum and feeding the greater curve of the fundus and the posterior wall of the fundus. 

And you can also tell these are very separate and very different from the left gastric vein that feeds into the lower part of the esophagus and the lesser curve of the stomach. So you can already kind of tell just from this, vascularly there are already going to be some differences we know between gastric and esophageal varices. 

So classification, so what are the points of classifying something? It's important to think about this as I talk. Because what you're going to find is our classification schemes for gastric varices, while getting better, are still a little wishy-washy. 

So number one, we just need a unified system. As physicians, if we're going to talk about a problem, we all need to be using the same playbook, so when I say something, you need to understand what I'm talking about and vise versa. 

More importantly, using that system, we also need to base prevalence and incidence rates on that. And then at the bottom, the most important for this particular condition is also understanding risk. So what's the risk of bleeding from these? What's the risk of mortality? How do we manage them? 

And classification is very important when you start talking about things like prophylaxis. We need to understand risk to better understand prophylaxis and how to use it. So first, let's just talk about a unifying system, the first part of that. 

So this is probably the most ubiquitous system in gastroenterology for gastric varices. It's the Sarin classification. So you can see it was published in 1992. Yes, we've been using the same system for 28 years. It's still ubiquitous. We're getting better, but it's still ubiquitous. 

And you can also tell, they used gastric varices in association with esophageal. So this O is the O esophageal of Britain, or in this case, India. And so GOV means gastric and esophageal varices at the same time. 

So GOV1, you have esophageal varices. And then in the stomach, you have varices that extend down the lesser curve. GOV2, you have esophageal varices. And then you have some varices in the stomach up in the fundus, so in that little pouch when we do retroflection. 

The I for IGV1 and 2 is just isolated. So it means there's no esophageal varices. But IGV1, we found them in the fundus. Or IGV2, we found them in the body or the antrum. We sometimes will refer to those as distal gastric varices, because they're incredibly rare and a very different phenomenon. 

Most of what we're going to talk about today has to do with what's along the lesser curve and how that relates to what's in the fundus. But this system will probably come up most frequently when y'all, the residents, look at our endoscopic notes. And you see us describing something, most of my colleagues will use this. 

I do something slightly different, but I think I'm the only one. So this is going to be most of what you see. 

This is actually based on a review article that Dr. Sarin wrote in 1989. And I'm telling you this because that's an endoscopic classification system. We look with our eyes during endoscopy, and we tell you what we saw. 

But as I showed you on that anatomy, the underlying blood vessels are a very important part of this. But ironically, this is actually based on multiple studies that Dr. Sarin had read on venography, on actual casting. 

After somebody dies, they can cast their blood vessels and look for connections between esophageal and gastric veins. And based on that, he actually felt like they should be put together. Because he thought he could see connections between the two. 

And so he felt the location was really the only way you could describe these. And he even wrote it. It is difficult and quite arbitrary to grade them according to size. I want you to remember that. You should only use location. 

But in reality, it's an endoscopic classification system based on his knowledge of vasculature at the time. So it might actually kill two birds with one stone. It may give us an endoscopic appearance that I can use as a gastroenterologist and then also better understand what blood vessels are feeding into it, which can help me manage, which we'll see later. 

So it may not all be bad. And this again, is the same picture from before. So anatomically, you can tell GOV1 is going to come down the lesser curve and is very much associated with esophageal varices. 

So remember at the beginning when I said if you take one thing away it's that gastric varices are not esophageal varices, I'm only like 12 slides in, and I'm already going back on that. In this case, gastric varices along the lesser curve if fact are basically esophageal varices. 

Because of this vascular connection, they really are. And so this nomenclature for this is actually pretty good. Where we get confused though is with these two. So these are up here in the fundus. 

But you can tell in the fundus, depending on what part of the fundus it's in, it might have blood vessels coming from the splenic hilum, coming off these short gastric veins. It could have vascularization from this left gastric vein coming around the back into the fundus as well. 

But we won't ever be able to tell that endoscopically. We would have to have some sort of underlying imaging to actually understand that process and understand where those vessels are coming from. And now to make it even more complicated, it can come from both. 

And that drastically affects what we should be doing treatment-wise which is why I'm harping on this so much. And this is why classification is so important so that anatomically, when we say something, we understand what's really going on. And the Sarin classification doesn't fully give us that. 

So again, I'll say it again, last time, I promise. GVs are not EVs. Even though it seems like it on the lesser curve, in general, we have to think of these as separate entities. 

So we have a unified system. But now we need to understand their prevalence. So the whole point of that 1992 study was not actually to introduce that system. In fact, he introduced that nomenclature in 1989 when he wrote his review article. 

But then he quickly realized, if we're going to use this, we now have this unifying system that he was creating at the time, we need to actually define what that means. So in India, he had about 560 patients roughly with portal hypertension. 

And it's important to understand it was very much just portal hypertension. India has a much higher prevalence of extrahepatic portal vein obstruction and portal venopathy, so noncirrhotic causes of portal hypertension. 

Whereas most of what we see in the United States is related to cirrhosis. On one of my EBM asides, this is why it's important to read the fine details about your patient population. Because if I was going to extrapolate this for my patients, which are almost all cirrhotic, I really need to look at the subgroup of patients, which is only about 53% of them, that had cirrhosis. 

So of those 53%-- we'll say roughly it was just over 300 people-- only 17% had a gastric varix at all. But of the 17% that had a gastric varix, 75% of those were GOV1. So remember, the ones going down the lesser curve, so basically an extension so to speak of esophageal varices. 

So the fundal varices, those GOV2 and IGV1, which were most of the rest of them, if you really do the math was really only about 5%. And I say that because this is why it's a rare condition. And this is why somewhat of an esoteric topic for medical grand rounds. 

But again, because we're a tertiary referral center for this problem, it's important to understand when we see this. Because when we see it, we act like we see it all the time. It's incredibly rare. 

Most of the time, we're getting these patients from outside hospitals and clinics, because they're not familiar with it. And one thing to point out, so again, only 17% have cirrhosis. Again, the breakdown. 

The one thing about the fundal GV is that they tend to have more severe bleeding. So massive transfusion requirements compared to esophageal varices. And since this was a population of portal hypertension in general, they actually reported the prevalence of esophageal varices as well. 

And in general, not just in this study, we know that esophageal varices are present in up to 85% of patients with portal hypertension, hemorrhage rates of 10% to 15% per year, and a six week mortality up to 25%. And that's even when we band them and treat them and do all of that for esophageal varices. 

Which brings us to our next point, risk. So we kind of have a unifying system. We have an idea, just an idea, of prevalence. So now, what's the risk of bleeding? 

So as I said before, in Dr. Sarin's study, EVs were more prevalent and more likely to bleed. But GVs, when they bled, were much more severe and actually had a higher rate of mortality, and much more likely to be those fundal GVs. 

Those ones along the lesser curve were much less likely to bleed than the ones in the fundus. But the problem with this study, it was never intended as a risk prediction system. And I'm telling you that because in 28 years, people continue to use Sarin as a classification system and imply risk based upon it. 

So when we do this, and we see a GOV2 or IGV1, we imply that it has an increased risk of bleeding because of this study. But again, it's an EBM point. If you're going to define risk, you can define it in a cohort. 

But what do you need? Validation. I need to say, OK, I think these are my predictors of risk. And now I'm going to go validate this in a prospective cohort and prove it. And that's very important. 

Because then, I can base treatment modalities, primary prophylaxis on that risk of bleeding, which is essentially what happened with esophageal varices, but didn't happen here. So GVs are not EVs. But to understand them, it helps to understand esophageal varices first. 

Because we see esophageal varices all the time. You will see them everywhere. Anywhere you go, you're going to see esophageal varices. As I said before, they're very prevalent. They like to bleed. We can control them. We can treat them. But you will see them. 

For esophageal varices, we do have risk models. This is from 1988 from Italy. They looked at all these different variables. So on the left, you have endoscopic variables that they kind of defined preemptively and said, we're going to define these and then look at their prevalence. 

And then on the right, you see more biochemical variables, Child-Pugh class, that sort of thing. And so they put it all together. And this is what they found. 

For esophageal varices, if you take size-- small, medium, large-- Child-Pugh class, which is up here, and then the presence of red wales, which can cover a whole host of different little red marks that can pop up in esophageal varices, this is our best risk prediction. 

And it was validated. And we use this. And this is how we know who needs a beta blocker for primary prophylaxis. Or if they can't tolerate a beta blocker, who do we actually need to start banding for primary prophylaxis for their esophageal varices? 

So this is incredibly helpful, but all of those treatment modalities and prophylaxis are based on a good predictive model. Most things in medicine, where we have actual good prophylaxis and treatment data, are based on predictive models. 

So for gastric varices-- that was 1988. Sarin first published his idea in 1989 and later in 1992, published his epidemiologic study of gastric varices and portal hypertension. But in the meantime, and I will say this is behind the scenes, because when I talk about this paper at conferences, pretty much nobody outside of Korea or Japan knows what I'm talking about. 

But in Japan, Dr. Hashizume in 1990 took the same approach that the Italians did with esophageal varices. He took 124 patients with cirrhosis that had gastric varices. You can see just some of the breakdown of who had EVs, cancer, Child-Pugh class breakdown. 

And then he defined a different system. So this thing is the endoscope coming from the GE junction up into the stomach. And we're in retroflexion in this cartoon. So the reason it's a circle is because in theory, that's what you would see through the camera. 

But it's showing you the different parts. It's showing you endoscopically where's the lesser curve? Well, it's behind where the scope comes in. The posterior wall is over here. The fundus is down here, which is also the greater curvature side of the stomach. And then this is the anterior. 

And then instead of looking at size, what he noted was shape might be more important. Because in the stomach, what we frequently see are these nodular or even huge tumorous pools of varices. In the esophagus, we see columns. 

Now, they can be big columns. They can be small columns. They can have high risk marks or not. But they're columns. And they're all the same in everybody, because the vasculature of the esophagus is the same in everybody. So we can treat them the same. 

But in the stomach, you find different things. And you can even find these little serpiginous, swiggly looking varices in the stomach going crossways, up, down, left, right, you name it. So he gave these F1, F2 and F3 denominations. 

So here, you can see the general breakdown. The majority, almost 70% of these right here are in this area, the posterior wall and kind of the greater curve going down into the fundus. And I can tell you anecdotally based on what is referred to us and what we see, that is incredibly accurate. 

It's actually pretty rare that I find lesser curvature GVs. And I want you to remember that, because a lot of future studies on management didn't really delineate between these two things. 

So here's a lesser curve gastric varix. You can see, there's the scope. The fundus is this dip down here. And behind the scope is the lesser curve. That's the posterior wall, so just to the other side. 

That is the greater curvature side of the cardia. And yes, we would say that's F3. That thing is massive. The anterior wall. So in this picture, you kind of miss, the lesser curve is back here behind. And when you rotate kind of towards the right, this is on the anterior wall. 

And then this was a more serpiginous kind of F1. This is what we would consider kind of F2. And this is what we consider F3. You can see there's very clear differences in their size. 

And then there's high risk marks. Now, in that picture at the very beginning where I said GVs are not EVs, I don't know if anybody noticed the picture of the esophageal varices had a nice little platelet plug on it. It looked like a little domed white thing. 

That's where they bled. When we do those scopes, we know they bled. They have that nice little platelet plug. It's very rare that we see an actual platelet plug. And we don't really see red wales, like all those little red, wavy spots and things in the esophagus. 

What we typically see is this. It almost looks like a little divot. And it usually has this little white center to it. That's a high risk mark for a gastric varix. 

So what did this study actually show in regards to bleeding risk? Well, he actually noted that the location, which really didn't make sense because it was kind of 50-50 anterior wall versus the greater curvature had an increased risk of bleeding. 

He also noted that that high risk spot had an increased risk of bleeding. And for some reason, noted originally, he just said F2, so the middle had the increased risk of bleeding. But actually, when he broke it down, it actually progressively goes up between F1, F2, and F3. 

But they're actually a pretty small number of F3 patients in the study. But it was the first hint that as size gets bigger for gastric varices, the risk of bleeding also gets bigger. Well, can anybody see the similarities now? 

GVs are not EVs. But size in a high risk spot, a so-called red mark, seem to be predictive of bleeding. What stinks about this study is he captured Child-Pugh score. He captured labs. It's in his methods. He says he does. 

But he didn't report it. And he didn't include it in any of his models. So this is purely endoscopic, which is great. Because if it's in the middle and you know nothing about the patient, in theory, you could use something like this without having to know all that other data. 

But in a perfect world, based on what we saw for esophageal varices, it would be nice to see if any of those biochemical markers actually have an effect. 

So seven years later, this is a study out of Korea where they looked at a lot of patients, so 1,400, which is a little bit misleading. Because at the end of their study, they actually only had about 150 patients with GVs. 

Because what they were specifically trying to find is what's the risk of bleeding for fundal GVs. And a fair amount of the gastric varices patients they noted actually were lesser curvature. And so they kind of excluded them. 

But based on Sarin's study, epidemiology, we think fundal gastric varices bleed more frequently and are more severe. So that's what we want to focus on. But they also did a good job in this study of taking Hashizume's criteria and looking at size and high risk marks. But they also looked at biochemical data and Child-Pugh class. 

Overall, they didn't think bleeding incidence between the different types of fundal varices, i.e. whether esophageal varices are present or not, really mattered. The bleeding risk was actually the same in both groups, which is important. Because why? GVs are not EVs. 

So regardless of EVs, fundal gastric varices seem to have the same incidence of bleeding. The cumulative risk is there, one, three, and five years. And then they looked. 

Let's look at size. Let's look at child status. And let's look at red spots. They looked at like 30 other things. But just like with esophageal varices, the things that stuck out were those three components. 

And instead of using Hashizume's criteria of F1, F2, and F3, they actually went down and measured. And when you say measured, when we measure things through an endoscope, we usually just open something like biopsy forceps that we know are x millimeters wide. And we're actually using that to kind of estimate size, which is exactly what they did. 

And they kind of dichotomized 5 millimeters and less is small. Kind of 5 to 15 or 20 millimeters is medium. But if you have something that's bigger than 20 millimeters, that's large. 

And this also looks very similar. But this is for gastric varices. And they found the same sort of risk factors appeared to be indicative of bleeding risk for gastric varices in the fundus. 

So this is kind of the first study that's a good reference of [INAUDIBLE] gastric viruses. It's only 130 something patients total though. And again, what do you need for this? You need validation, which unfortunately never came. 

Some other studies that tried to identify long-term bleeding risk, but are all very different. So in fact-- let's see, this 2007 study is actually just a therapeutic study that was looking at acute bleeding in the hospital. So there's no long term follow up for them. 

This was a very small study, not very many patients. And this was actually a prophylaxis study. So they were all fundal by design. Whereas these had lesser curve, fundal varices, and even distal varices. 

So I'm bringing this up because overall what we've found is over 30 plus years of looking at these things, we're still stuck with case series, severe heterogeneity, and no validation. So while I have lots of theories-- anecdotally, I think I know what's right, nobody's yet proven that. 

So which system is right? The one on the left is the one that everybody uses. The one there kind of in the middle and to the right seems to be one of the better ones for actually predicting risk of bleeding. High risk marks are important. 

And the short story is we'll probably need all of that. So what we really need, instead of saying GOV1-- because we don't think esophageal varices matter. But what we should say is lesser curve. 

The lesser curvature gastric varices are probably associated more with that left gastric vein, probably tend to react more like esophageal varices. And we could probably treat them that way. Versus those top two, the fundal varices, we know have a higher risk of bleeding even though they're less prevalent than the lesser curvature varices, and probably need to be their own category as well. 

But again, the presence of the esophageal varices doesn't matter. So instead of saying GOV2 or IGV1, we should just say fundal varices. 

And then distal varices, distal gastric varices, IGV2, like I said, incredibly rare. In all of those studies, we're talking about maybe two or three patients. And so we just call them distal, i.e. they're below the fundus. 

And most of the time, those are going to be related to things like blood clots or chronic pancreatitis, things like that. Less related to cirrhosis and what we normally see with classic portal hypertension. 

But regardless of what we say endoscopically, we need to include an assessment of size and of high risk marks. Because even though we don't have great validation, we at least have two studies that suggests that those things are added to risk of bleeding. 

So this is my classification system. This is honestly what most people are trying to shift towards in the United States now. It's what most people in Asia already use as they're more familiar with Hashizume. 

And so hopefully we have a better descriptive system like this in the future for endoscopic classification. But we can't do endoscopic alone. Vascular classification is important, as I said before. 

So esophageal varices are easy. Look at this. Pressure, the squiggly line, is portal pressure finding its way back up here. You get this little plexus of veins in the bottom of the esophagus. They're the size of shoestrings. They can't handle that kind of pressure, so they swell up. 

It's a column. It fills from the bottom to the top. And there it is. It's coming from the bottom, distal in the camera, up towards me. The esophagus has the azygos and hemiazygos system higher up. 

So when you get higher up, actually these things drain into a very low pressure systemic circulation. So really, it's this zone that we worry about bleeding. And this is the zone that we treat and we band. 

But as I said before, it's always the same. Esophageal varices are the same. That column is the same in everybody. Whether you have a portal vein thrombosis, cirrhosis, whatever, that's what they look like. And so we can treat them the same. 

Gastric varices are a puddle. They're not a column. And you can have multiple routes of inflow, so pressure off the short gastric, the splenic vein, coming off the left gastric vein feeding into these. 

And then you can have outflow through a systemic shunt into the left renal vein, directly into the vena cava. I've actually seen these things drain straight up into the chest and actually empty into the pericardium. 

That's all important stuff to know. So at least for the people in the room, raise your hand if you've ever heard of our Glue procedure. Wow. Only four of you. OK, well, we're going to talk about that. 

In short, we inject glue into these things, literal super glue. If glue embolizes, and your outflow is going up to your pericardium or towards any of your vessels in your chest, it's probably a bad thing. 

Understanding that before we stick glue in there is actually a very important thing that gets overlooked in literally every study done with glue injection. Because people overlook the vascular classification, because they assumed like esophageal varices, these things must all be the same. But they're not. 

So in 1988-- this was a really neat study-- they just stuck catheters in people's portal system, patients with portal hypertension. Some had esophageal varices. Some had gastric varices. Some had both. And they just watched. 

They measured pressures. They watched blood flow. So they injected dye, and they saw where it went. Did it go up through the varix? Did it go to the liver? Did it go to the spleen? Where is blood flowing in this whole portal system? 

And they identified kind of three routes, so to speak. So a right-sided route, meaning that normally, as it should, you have high pressure in the portal vein, but blood is still flowing this way. And those patients tend to have big esophageal varices. 

Versus the left side where you can get blood flow almost steel going backwards to the splenic vein and up through a gastric varix. That's what they saw here. And then these people in the middle that have a little bit of both. 

The interesting thing was what they found in the patients who had gastric varices-- so large gastric varices with no esophageal varices-- is that most of them actually had this left-sided circulation. 

So if I was to draw an invisible line kind of right down the middle of this patient, this is the left-sided circulation. And this is the right-sided circulation. The esophageal varices are much more likely to have this what we would call normal right-sided circulation. 

I bring this up because we frequently talk about this. When we're talking to you guys, to interventional radiology about how blood is flowing in these things, we use this dichotomy of left and right-sided circulation because of some of these findings. 

They found that in those patients with gastric varices that have left-sided circulation, the portal pressure's much lower. So an esophageal varices-- now, this is-- we're used to millimeters of mercury. So this is a little different than what you're used to. Gastric varices, it's much lower. 

And then again, they found that also in these patients, if we go one more, most of them had flow with at least a little bit of steel through the gastric varix or the entirety of this SMV and splenic vein going through the gastric varix. 

And this is why this phenomenon comes up of left-sided circulation. So man, there's a lot of arrows on here. What I tried to show is that if you have mesenteric veins, you actually get steel of blood flow back into the splenic system through the gastric varix and then out this systemic shunt. 

And so this, once it forms, is totally segregated from the portal system now. It's basically its own circulation. So that's why this is an important thing to define. 

So this is a Japanese classification system from 2003. They were doing a bunch of BRTOs. They noticed variations in inflow and outflow. And they created this. 

Here at UVA, one of our formal interventional radiologists, Dr. Saad and Dr. Caldwell, who all of you know, created our own vascular system. So the Saad-Caldwell classification system, which kind of combines those two things and is a way for us to understand and use a unifying theory of both the inflow and the outflow, whether or not there's a shunt or not, of these systems. 

Now, these things are used differently in different places in the world. So as I said before, when you have classifications, you need a unifying theory. We're not unified yet. But they're very similar. And people are going in the right direction thinking about the vasculature. 

So treatment, you guys are the ones in the ICU at 3:00 in the morning when these people come in bleeding. But how do they come in bleeding? They're just vomiting blood, right? And hopefully you already know they have cirrhosis, or you have an idea that it's portal hypertensive. 

So you got to do the basics. So in this big algorithm of things to do, you've got to start with what you know. What do we do for everybody? Modest transfusion strategy. Don't go crazy giving them FFP. Don't give it at all. 

Don't go crazy giving them red blood cells. Some of the MICU attendings and I differ on this. That fast transfusion protocol can be dangerous in these folks, because we can ramp them up and take them from a hemoglobin of nine before their bleed to hemoglobin of 12 after. And all we're really doing is pumping their system back up to have yet another bleed. 

So you want to be modest. You're shooting for a hemoglobin of seven to eight. You want a vasoactive medication. So unfortunately, the FDA still hasn't approved this. So we still only have octreotide, which of course is on shortage right now. 

Avoid volume expansion. And then, when the patient is stable, because we've got to be able to see what we're doing, we do need some kind of endoscopic evaluation. And that's because it's important to differentiate between initial hemostasis. 

So I go in. I look, the so-called surgical peak-and-shriek. And I look in there, and I see this bloody fundus and this huge gastric varix. I can do something to stop immediate bleeding. But ultimately, that's not our definitive therapy. That doesn't mean we're done. It just means I've temporized it until we can get more information. 

OK, so temporizing, sclerotherapy. This is actually-- you see sclerotherapy used for lots of different things. But traditionally, this is an ethanol-based sclerosant. It causes pretty severe ulcers and has really high rates of early rebleeding. 

So pretty much across the board for any variceal bleeding, this is kind of shunned and not really used. That being said, if you're here in the middle of the night, maybe not necessarily you guys, but my colleagues, you got to use what you have available. And if that's what you have available, that's fine. 

And endoscopic clip, it's been reported. So you see this. You scream. And then you do this. And it stopped. And we're all happy again. 

But what do you notice behind the clip? Oop. Where am I? There we go. This thing is still pretty engorged, right? That's why this is a temporizing solution. Because that clip may stay on for weeks. 

But another hole is going to pop up somewhere real quick. So that means we've got to figure out what's going on underneath this, i.e. imaging, understand the vasculature, and then decide what our best management is going to be. 

The Blakemore is still used. In fact, unfortunately, we had to use it a few weeks back for a patient. Ideally, all we really need is this thing. But we don't have this tube. We have this tube. 

So all I'll say is don't inflate the esophageal balloon ever. It doesn't help. This is the only balloon we need down here. Most of us place this endoscopically now. 

If you're there in the middle of the night, and you have a patient that has a history of gastric varices, and you're absolutely convinced they're bleeding, and it's not stopping, you've got to do something, you can try to place one of these blindly. 

I've attempted four of those in my life, including as a fellow and an attending. And I've only had success once. These patients are intubated. When you have an intubated patient and what is essentially an incredibly lax, floppy, slippery tube, it is very difficult to get it down. 

So don't feel bad if you can't get it in. The best success is when we do it endoscopically after doing an initial evaluation. 

These are case reports of other various and sundry items we have in endoscopy. We don't actually have these two things. They're actually not really worthwhile even talking about, because there's no real need for them. 

Hemospray, I'm not going to go into any talks about right now. But basically, it's a powder that we just, poof, cover. And it can stop bleeding. 

It's been used a little bit, or written about a little bit in esophageal varices. Not so much gastric varices. But again, when you're there in the middle of the night, and you're on the hot seat, you've got to use what you have to temporize bleeding and stop it until you can definitively manage it. 

So is the initial therapy ever definitive? Well, yeah. Remember, lesser curve varices, what could I do to those that are definitive? See that. I can band them, right? 

I mean, they're basically esophageal varices. If I go down and I see esophageal varices extending into the stomach, I can just start banding in the stomach, and then work my way back up in the esophagus. And potentially, I have now completed both my temporizing and definitive therapy. 

In most of those patients, I still want to look at vascular imaging to make sure I'm not missing something, whether it's a clot or a shunt that's unexpected for a lesser curve gastric varix. Because otherwise, I'm just assuming my bands are right. 

And what if I'm wrong? What if it goes, it drains in a completely different place? My band's going to fall off. And it's just going to start bleeding again. 

And that's because for fundal varices, band ligation is not super effective for long term. In fact, the rebleeding rates are up to 60%. 

So we do this. This is our definitive therapy. So this is what we deal with here. But this is pretty close to what it really is. And that's not a joke. This is superglue. It's cyanoacrylate. They've been around forever. 

It's pretty much the same thing. But it's like the dermabond we put right on the paracentesis site, except that it's faster. And we'll talk about that. 

So there's over 50 studies. And in fact, I counted this yesterday. I think we're up to 69 in the last 30 plus years since about 1986 that have evaluated cyanoacrylate injection for gastric variceal management. 69 studies. 

So how is this not the definitive therapy, right? Guess how many of those are randomized control trials. Anybody? Six. Most of these are case series and case reports. Why? 

This is a rare condition. This is a really hard thing to do a randomized control trial for. It would probably take 10 years to do an adequate randomized control trial at one center. And that's what most of these are, single center studies. 

So there's a ton of heterogeneity. They're almost all case series. They use different agents. So butyl is what we use. Octyl is dermabond, more carbons in it. So it doesn't polymerize as fast. 

Now, there's even EUS guided coils with injecting cyanoacrylate. None of these things have been effectively compared. And we don't even know what the right volume is. 

Most studies inject small volumes. I can tell you in my experience here, Dr. Caldwell and I inject much higher volumes than most people do when we do this procedure. We don't really have any different or worsening side effects in most other places that have reported it. 

So what's right? The short answer is I don't know. And the agent does matter. So the agents we use-- and this is how we test them. So that's a slide with our drops of blood on it. 

So we put a drop of blood. We put a drop of glue. And we literally just time, because you can actually watch it polyermize on the surface. The butyl versions that we use polymerize generally around four to six seconds. 

Dermabond's going to take a little bit longer, maybe 25 seconds. And when you add plant-based oils, so like lipiodols and things or like what radiologists use, so if I inject that, I can do an X-ray. And then I can see where I inject it on an X-ray, which is important. 

Because I mentioned embolisation, right? So if I did that, and I was worried somebody had an embolisation after my procedure through one of those shunts that I didn't image beforehand, that's how I could find it. 

And that is, in fact, in old studies, why they did it was so that they could actually see where they embolized, because they didn't do imaging beforehand to see if there was shunting. However, the irony of this is that doubles the polymerization time. 

It actually increases your risk of embolisation. I need that glue to clot quickly so it stays in place. I don't want it to run out of the varix. I want it to sit right there and shut down what is in the wall of the stomach. Does that makes sense? 

OK, so it definitely matters what agent you use. That being said-- and there's only like two studies with the dermabond agent-- most studies show initial hemostasis over 90%. And then rebleeding rates vary depending on follow up, usually out to a year. 

You saw that one study from Kim, even without treatment showed a 16% risk of just initial bleed at one year. After treatment, rebleeding rates where somewhere between 15% and 25% on average. Some were a little bit lower. Some were a little bit higher. But that seems to be pretty average at one year. 

Of our six randomized control trials, so four of them compared band ligation to glue. One compared glue to glue. And then one compared glue to an alcohol-based sclerosant. 

They all used different populations. Some of them included the lesser curved gastric varices as opposed to just banding them. None of them assessed underlying vasculature. So we have no idea if they really had shunts or not. 

And we know that in other vascular studies, up to 85% of patients with fundal varices do have shunts. But like I said, they could be all over the place. It can be a gastrorenal shunt. It can go to the chest. It can go right into the vena cava. None of these tell you that. 

And so based on all that heterogeneity, even with this nice Cochrane review-- and this actually has a wonderful explanation of these limitations. Cochrane reviews are very long. But this is a one worth reading. We still don't have a good idea, right? 

So we do what we know. In our experience, it works pretty well. So we have comparison to TIPS. We have a case series here of just-- this is from the late 90s and early 2000s of Dr. Caldwell doing it. 

More recently, we published this just last year, long term follow up. And again, we're kind of in that same range, that 15% to 25% one year rebleeding rate. But a lot of that probably relies on follow up as well. 

So summary of endoscopic therapy, anything you can do in the acute setting to stop bleeding is OK. Ideally, we don't want to use alcohol-based sclerosants. But again, if someone is bleeding to death, you've got to do what you can do. 

I would favor using a balloon, whether it's the Blakemore or different kind of balloon. It's highly effective. It gives you time to get imaging or to go downstairs, pull up glue, and come right back and actually do a glue procedure at the bedside, depending on where you are in the world. 

But regardless, you need some initial temporizing therapy. Definitive therapy endoscopically is kind of all over the place. I think everybody would agree-- or I know everybody agrees, because I've been to these meetings-- cyanoacrylate is probably the best therapy. 

It's definitely better than banding. But what formulation? Should you mix it with anything? How much? How often? All of those things are still up for debate. 

So we have endovascular therapies. So TIPS. So I think most people know what a TIPS is. We just put a stent in the liver, kind of completing the hepatic vein to the portal system. And it reduces the pressure. 

For esophageal varices, that's great. The pressure's here. This is not that far away. So when I drop the pressure here, the pressure in here drops, and they go away. 

But we already went through this. With gastric varices, we have this left-sided circulation. It 85% of those patients with fundal varices have a shunt, then how is a TIPS going to help? 

If a TIPS drops the pressure on the right side, but all of my blood is just churning over here like this, it may not do anything. And so sure enough, what we found-- so we know the portal pressures are different. 

But we've also found in studies of TIPS for gastric varices, up to 50% will rebleed. And most of them already have a portal pressure less-- or HVPG less than 12 to begin with even at the time of bleeding. 

Which, again, argues that left-sided circulation has its own pressure system that we're missing in these studies, and we're missing by doing TIPS without doing anything else. So generally, TIPS might help temporize. Because it will cause an acute shift in portal pressures. 

But if you're going to do it, you probably actually have to go through the TIPS, find the GV, and directly embolize it as well. Or you're going to have pretty high rebleeding rates. 

So what about BRTO? We talk about BRTO all the time. At UVA, we're really fortunate from a gastric varices standpoint. One of the reasons that we have such a high referral base for this is not necessarily just because of Dr. Caldwell's experience, but because of our interventional radiologists. 

We literally have just about every technology you could think of to treat gastric varices here at UVA. And more importantly, we have the expertise to do it. So BRTO is essentially going backwards. 

So instead of going through the liver, we actually go up through the femoral vein, go into the renal vein and find that shunt, and then go backwards into the varix. 80% to 85% of these have a shunt. 

They may not all-- they might not all be catheter-- catheterizable, something like that. We may not be able to get to all of them. But a fair amount of them are going to have a shunt where BRTO is appropriate. 

Since BRTO was first done in the early 90s, there have been like five different technical variations. So now we have BRTO, BATO, PARTO, CARTO, you name it. And it's all just they're using slightly different materials. But it's the same theory that they're going intravascularly, closing down a shunt, and obliterating the varix with a chemical agent. 

So it's not a temporizing therapy. This is the thing we do imaging for and we plan for. This is not something where somebody comes in bleeding, and you call IR, and you say, oh, they need a BRTO right now. 

Mostly because you don't even know if they have a shunt. Or if they do, you don't even know where it's going or how they would access it. So we always need to do endoscopy first to figure this out. But it is a definitive therapy. And we just have to remember the anatomy. 

This is why we need imaging. This is why we need to understand what kind of shunts they have. And you can see there, A, B, C, and D, all various kinds of shunts. 

So 77% to 97% success at stopping active bleeding. 77 is the lowest number I've ever seen. It's from many years ago. If you look in the last say 15 to 20 years, this number is almost always over 90, and mostly over 95%. It's a highly effective therapy. 

It also has pretty low rebleeding rates of like 3% to 5%. The problem with a lot of these studies, similar to my glue studies that I mentioned, is heterogeneity. In fact, in this meta analysis of 1,000 patients, 1,000 patients got BRTO, like 900 weren't actively bleeding. 

It was done prophylactically based on Hashizume's study, which as I said, wasn't validated in the first place. So really it was we see a shunt, we see varix. We're just going to treat it and see if we prevent bleeding. 

And yeah, it works. But the question is whether or not it needed to happen in the first place. And it doesn't really help us understand fully active bleeding. And more importantly, we don't have any direct comparisons between BRTO or cyanoacrylate. 

We have retrospective cases series, which is what we have published. But we don't actually have a randomized control trial to look at the two interventions and document in someone with a shunt, which is actually the best therapy. 

All that to say, can't really make a great recommendation on that. It's a multidisciplinary discussion. We have to have it with interventional radiology and with you all, because how the patient's doing, their comorbid conditions, those all play a role in this. 

If they have huge esophageal varices, I may not want to do a BRTO. Because if I close down that shunt, where's that blood flow going to go? I rerouted it. They went from left-sided back to right-sided. But that means all that excess blood flow has to go somewhere. 

So they're going to get worsening esophageal varices. They're going to get worsening ascites. So I have to take all of that stuff into account when I'm making these kind of decisions. So what do you do? 

Endoscopic therapy has to happen first. We got to look. We got to place a Blakemore, a clip, ethanolamine, a band, something to get it to stop. And then we have to do imaging. But really, there's just not a lot of randomized data to tell you this is definitively the best thing to do, no matter what I think. And of course, I always think I'm right. But I may not be. 

So expert opinion is all we got. And I say that because Dr. Caldwell and I are on a lot of these papers. So it's a little biased to say expert opinion when we're calling ourselves the experts. So I understand if you take this with a grain of salt. 

But over the years, this has gone to this has gone to this, which is hopefully finally going to be published next month. We'll see. And you can see this is based on a lot of things. 

So this is based on the endoscopic appearance. Are they lesser curve or cardiofundal GVs? Which when we say cardiofundal, we really just mean fundal. But then after we do all of our acute management, now we have vascular classifications. 

And then based on the vascular classification, within this endoscopic category, we have treatment options and follow up. It's incredibly complex. It's a theory. I might think it's right. But it's up to me and others in the field to prove it, because we just don't know. 

So endoscopically, we can use this. Vascularly, we can use this. And that's what I think is best. But it has to be multidisciplinary. So two minutes, prophylaxis. 

Ideally we want to prevent rebleeding. So with esophageal varices, we keep banding them. We bring them back in one to four weeks, we band them again. But what do you guys discharge them on as well? beta blockers. 

Beta blockers, Propranolol, Nadolol, Carvedilol, that helps us reduce portal pressure. So why wouldn't we do it for gastric varices if they bleed? They decrease blood flow in general to the splanchnic vasculature. And if I have less blood, I have less pressure. If I have less blood in general, even if it's left-sided circulation, it should make a difference. 

And this study, though, suggests beta blockers don't. So in one of the only secondary prophylaxis studies, this group just for fundal varices compared beta blockers to glue injection. 

Well, glue injection, if you do it every three to four weeks actually works pretty well. I mean, this is out to like 2 and 1/2 years. beta blockers, after about a year, for whatever reason tend to fall off and not be super effective. Probably because of this, isolated circulation not really affected by drops in portal pressure. We know that from the TIPS studies too. 

A more recent study, so from just a couple of years ago, looked at following these people up and actually randomized them and had a pretty good-- I think was 120 patients, about 60 in each group, to getting glued repeatedly every three to four weeks. Or just like we would do for esophageal varices, doing the endoscopic treatment plus a beta blocker, in this case, Carvedilol, and actually showed no difference. 

So here, this is-- the side just says, prevention of recurrent gastric variceal bleeding. There's a lot of words over there. But you can see, even though it kind of looks like group B here, which has Carvedilol, does a little bit better than group A. It's not statistically significant. 

And really, in that first year, it's really not that much different. OK, so based on this, there doesn't seem to be strong evidence, right now at least, for us adding beta blockers. But can y'all guess what this study is missing? 

What are all the endoscopic studies missing? Vascular imaging. We have no idea who has a shunt, who doesn't have a shunt. That could actually play a pretty big role. 

What if the people without a shunt do respond well to beta blockers? Maybe that's a group we should use them in. But we don't know that data, because people don't do both. We have endoscopic studies. We have vascular studies. We don't have both. 

So-- oh, yeah. These aren't significant risk factors in their study. Which I just found-- I mean, we knew Carvedilol wasn't. That was their primary outcome. But even presenting with acute variceal bleeding as opposed to having subacute bleeding didn't appear to make a difference. 

So secondary prophylaxis, beta blockers don't seem to add much. Post-BRTO, beta blockers might help prevent esophageal varices from bleeding. Because I just said pressure is going to go back to the liver. So that might be OK. 

But after endoscopic therapy, we don't really know if there's any room for that. We'll skip that one. So the take home points, don't ever include esophageal and gastric varices in the same system. 

People can have both. I'm not denying that. And people can have lesser curve gastric varices that we probably do end up managing like esophageal varices. But I want you guys to leave here understanding that they are very different. And the underlying vasculature is wildly different and very much affects how we can manage these things. 

You should always have cross-sectional imaging. Emergent endoscopic therapy can be all kinds of different modalities depending on what you have. But no matter what we do initially, we have to have a definitive therapy after that to prevent rebleeding later on. 

We want to have a unified classification scheme, so endoscopic, vasculature. But more importantly, we know we need to do more. So this is something I've been working on for the last two years of trying to unify North America into creating a database for gastric varices for this exact reason. 

It's still ongoing. So I don't have any preliminary data for you. But this is our goal is that within the next two to three years, we can be the center that kind of defines gastric varices in North America. 

All right, I went over. I apologize. The residents know I always go over. If there are any questions, I'm happy to stick around and answer them. I will be here as long as I need to be. But I understand you guys have to get back to work. 

SPEAKER: Yeah, so if we have a couple of questions, you can either use the microphone in the center. 

So Dr. Henry, I have a question for you. So if there's an isolated circulation possibly with gastric varices, if they get transplanted, and theoretically, portal hypertension is gone, do those gastric varices still stick around? 

ZACHARY HENRY: Yeah, so that's an excellent question. So sometimes after transplant, because now you have a low pressure system with the liver, the superior mesenteric vein will start to flow back into the portal vein. And it'll start to steal flow back from the splenic vein. And then it can just shut down. 

In some cases, the gastric varix in the wall of the stomach may go away because the pressure goes down. But you may be left with an ongoing shunt. So even though it goes through a gastric varix, that shunt between those short gastric veins and the splenic hilum or the splenic vein itself may still be maintained with that left renal vein. 

So you may always have that what's called splenorenal shunt, even though the varix may go away. 

SPEAKER: Great, well, thank you so much, Dr. Henry. 

ZACHARY HENRY: Absolutely. 

[APPLAUSE]