The expanding role of TIPS beyond refractory ascites and variceal bleeding

Episode Transcript

Recorded live from the Cook booth at SIR and featuring leading experts in the field of interventional radiology discussing a wide range of IR related topics, this is the Cook@ SIR Podcast Series.

Welcome, portal hypertension enthusiasts. I am your host, Steven Sauk, and I am presenting to you live at the Cook booth in Nashville, Tennessee. Today, we’re diving deep—deeper, perhaps, than portal venous access—into a procedure that’s been bending the rules of liver care for decades. TIPS, today, talk. Sure, you’ve heard of refractory ascites, variceal bleeds, but what about TIPS for mesenteric ischemia, Budd-Chiari, hepatorenal syndrome? That’s right, this once narrowly focused procedure has grown up, gone global in many of its applications. We’ve brought together a panel of seasoned interventional radiologists, Nassir Rostambeigi and Siobhan Flanagan, who have seen it all, from high-stakes decision-making to unexpected curveballs in the IR suite. They’ll be sharing their most compelling cases, discussing what makes or breaks a good candidate, and offer a peek into the future of this ever-evolving procedure. So grab your lead, check your flow rates, make sure your pressures are all set up, and let’s explore about how far TIPS can really take us. So, thank you, Nassir, Siobhan, for joining us together.

Thanks for having us.

Thank you.

Maybe in the beginning we could talk first a little bit about yourselves. If you could just explain, where are you coming from and how long you’ve been in practice.

I can go first. This is Nassir Rostambeigi. I graduated from the University of Minnesota in 2018, and I’ve been around the block for about seven years now doing interventional radiology. I’ve been in Mallinckrodt Institute of Radiology, Washington University in St. Louis since 2019, and it’s been exciting years.

I’m Siobhan Flanagan. Nassir and I go back quite a ways. I’ve been in practice for, it’ll be 12 years in July. I practice at the University of Minnesota, and we have a long history of a lot of innovation including, portal interventions and TIPS, and I’m just excited to be here to talk about all this today.

Absolutely.

Wonderful. I’m Steve Sauk from the Mallinckrodt Institute of Radiology as well. Nassir and I work together every day. I see him every day, and I get to see him again in this booth.

Excited.

And it’s certainly an honor to serve you as your chief, as well, and hope that we can have some good fun today, you guys. So, I would love to know a little bit more about your guys’ practice. How is your practice set up? How does your group receive referrals for what we’re going to call the nonconventional TIPS? Maybe, Siobhan, if you don’t mind going first.

Yeah. So, we’re an academic health center, but we are part of a large hospital system called Fairview Health Services, and I would say most of our complex referrals are coming from outside, but we get a decent number of our referrals at our institution, as it’s a transplant center. And, as you guys know, the word’s getting out on all of these. There’s the typical indication for TIPS, but also the atypical indication for TIPS, so it’s a combination of outside referrals that are local, but also we see a lot of referrals coming from North and South Dakota in our neck of the woods.

That’s pretty large of a catchment area, I imagine. How far of a city have you seen a patient?

We’ve seen patients actually come as far as rural Montana. Everybody look at a map and look at population density. It gets a little sparse from Minnesota going west. It is a large geographic area, but it’s, of course, not as populated as Greater Chicago area, for example.

Yeah, I remember we did a case from Texas, actually, when I was a fellow at Minnesota. So definitely.

Word gets around, Siobhan. Your practice is very famous.

I don’t know about that, but you know what? If you start driving west—or, excuse me, east—from out west, you’re going to hit us in Minnesota. It’s a good stopping point on a car drive.

How about yourself, Nassir? Tell us a little bit about that.

For us—as you know; we work together—we have also a large catchment area, plus a lot of internal referrals from very complex situations, from oncology patients, from complex patients, from hepatology, from inpatient services, as well as from outside from around Missouri, from Kentucky, from Tennessee, from Arkansas even. And, as you know better, we have to have a lot of different licenses for our practice to be able to really service those, all the catchment areas around the St. Louis area.

So you have an Arkansas license, as well, in addition to the—

Not that one.

… Illinois and Missouri one? Or maybe we need to have all 50 states, at some point—

Maybe.

… given the way things are going.

That’s right.

That’s great. So, how often—or I guess how seldom—or tell me a little bit about the frequency of what we’re calling the nonconventional TIPS, and for our listeners, that we’re calling nonconventional TIPS, those TIPS procedures not performed for refractory ascites or variceal bleeds or related to cirrhotics. Tell us a little bit about your volume and your frequency and a little bit about your experience.

Yeah, for us, it’s growing, Steve. Maybe five to seven years ago, it was less than 5% of our referrals, and it’s probably in the range of 15% and maybe even up to 20% for us, at this point. And that makes sense, because there’s a large audience listening to us talk, and there’s a lot of very capable providers out in the community placing TIPS for standard reasons, but the university practice tends to get these unusual referrals for the non-classic indication.

That is much more frequent than what you would expect in the general population, so clearly, your referral base understands your potentials and what you guys can offer to—

Yeah, I think so.

Yeah. Congratulations. Your reputation precedes you, I guess. Nassir, how about you?

Indeed, indeed. That’s really amazing. As we all know, these are really niche areas, very rare areas, but as the word gets out, more and more of these we see every day, especially from complex situations such as oncology patients or non-cirrhotic portal hypertension patients. And the patients who have, as you’ve seen, Steve, the portal occlusion cases, these are all rare cases that they were even not really within our radars. But now more and more, we are seeing it every day—not every day, but much more frequently than before.

When you guys are getting these referrals, what type of physicians are the ones who are actually sending the patients to you? Are they hepatologists, hematologists, PCPs? Tell me a little bit about that, a little bit more about your referral bases.

Yeah, for us, the majority of them are coming from hepatologists. Patients eventually get to that specialist within their care. Occasionally, a hematologist who notices, “Well, I’ve got a patient with chronic mesenteric thrombosis who’s having some issues and could use your help.” But, by and large, I would say hepatology.

I would agree with that. Yeah, hepatology as the main leader for these patients. A lot of those patients can be funneled from the oncology service, for example, but then, hepatology is the one who is actually contacting us, since they’re on board and they are more familiar with our services from previous patients.

That’s fantastic. Again, word seems to be getting around. It sounds like more of our audience, not only within the hepatology world, but outside of hepatology, is aware of some of the interventions that can be offered in a safe and high-quality fashion, it seems. So this may transition us into three sections—and for our listeners, so we understand what we’re hoping to address, we’re going to be talking about acute mesenteric venous ischemia/Budd-Chiari, chronic mesenteric venous ischemia encephalopathy, and portal hypertension and malignancy, hepatorenal and hepatopulmonary syndromes, and these kind of categories. Perhaps we can start talking about acute mesenteric venous ischemia and Budd-Chiari first, as kind of an interesting topic, especially as we’re seeing a lot more of patients post-COVID with hypercoagulable disorders. What do you guys think? Shall we talk?

Yeah.

Let’s do it.

Well said. Yeah, let’s do it. Very fascinating area these days, like you said, Steve. So, Siobhan, the timeliness of the acute mesenteric ischemia varies quite a bit from more acute phases towards more and more chronic phases. Where do you see them in your practice, and how do you work with the referrals, and which referrals are you working with mostly to get the best outcomes?

I would say most of our referrals come from outside, and in general, these cases have advanced quite a bit, and it makes sense, just from a pathophysiologic standpoint. You know, these patients who had developed acute ischemia from a venous thrombosis, maybe they start with a localized occlusion. It’s indolent, very slow onset of abdominal pain, but as they progress, clearly something’s going on, and maybe that’s a number of days before they’re finally going to an outside hospital to get evaluated. And once they hit the door there, we think about it.

Venous thrombosis is a cause of mesenteric ischemia. It’s a very small fraction of all comers with mesenteric ischemia—obviously, the arterial thrombosis is more common—and those arterial patients, it’s almost like a switch gets flipped. They have an interruption of flow, and their symptoms come on really quickly, whereas the venous folks, it’s more indolent, so they’ve got this vague abdominal pain, and it’s really—often, they’re not getting seriously addressed with imaging. They’ve got abdominal symptoms, they’re just out of proportion to the clinical exam. That finally prompts an imaging study, and then they’re found to have thrombosis.

The vast majority of these patients, like all of us know, they’re anticoagulated first. But those patients, if they’re not recovering, then they’re sent to us. And they’re typically coming from outside hospitals to us. It’s pretty rare that mesenteric thrombosis finds its way initially in our hospital. And I think it’s, again, just the nature of our hospital system. We’re a transplant center—you know, organ transplant, bone marrow transplant. Most patients out in the community want to go to a community site. They don’t just hop in their car and drive downtown to the university, so there’s some delay there.

What kind of anticoagulation do you see these patients being initially treated with, especially if they’re coming from multiple hospital systems that you may or may not have much influence in terms of medical management first?

I think, by and large, hospitals are just heparinizing patients, seeing how they’re doing. If you understand mesenteric thrombosis, the last thing you want to happen to the patient is them to develop bowel ischemia. So I think most community hospitals are really good about getting surgery involved once the diagnosis is made: “Hey, is there any concern for bowel ischemia here?”—whether it be on imaging or combination of imaging and a clinical exam that would lead them to maybe do a laparotomy, explore resect bowel at first. So, keeping that in mind and knowing that patients might progress on anticoagulation, they’re usually doing a short-acting agent, and heparin is what I see the most.

You bring up an interesting topic about surgery first. Some may talk about acute mesenteric ischemia being like the phlegmasia of our legs, and I’ve seen multiple practices, and I don’t see a consensus. Someone who has maybe an elevated lactate, some angry bowel, a surgeon comes to you, “Should I operate first, or should we revascularize first?” I don’t know if you guys have any kind of opinions about this. Obviously, there’s not much data, so we’re kind of flying off the cuff a little bit over here, but I would love to know a little bit about if you’ve ever had these conversations with surgeons before.

Yeah, plenty of times.

You both are looking at each other like you both talked to the same surgeon.

Yeah. It’s like deja vu, for sure.

Oh, really? Oh, interesting.

I don’t know, Nassir, you’ll give your opinion, but from my perspective, if you don’t obviously have ischemia, if I can prevent the ischemia from happening, that’s my job. So if patients aren’t turning around on heparin, listen, they get started on anticoagulation, they have all their team members involved that they need. There’s the hospitalists, maybe the gastroenterologist, surgery, us. Hematology is really important too. They need to work them up for hypercoagulable disorder, make sure that they don’t need to be on anticoagulation for a lifetime. Maybe there’s a better agent for them. But at any rate, our job is to prevent the ischemia if they’re not turning around.

Yeah, exactly. Optimization, optimization, optimization. If we can do that ahead of time, that’s the best. And then, if you really are moving towards it being more ischemia, then if we are really catching the patient in kind of the penumbra zone, if we kind of use a stroke as an analogy, so then that will be a good time to catch the patient and perhaps do some sort of intervention and save them from a very big surgery which could have a lot of morbidities for the patients.

Interesting. So, in other words, these conversations with the surgeons can go either way. If someone’s kind of on the brink in what you’re calling the penumbra zone or kind of the purgatory moment, it’s not a completely obvious perfed dead-bowel situation, but it’s not the completely normal bowel situation, either. Is it safe to say that it seems like the conversations can go either way, whether the patient should go to the operating room first? Does that impact a little bit about how you actually perform the procedure if you are going to revascularize? Because, if you are going to use TPA, a patient just got operated on, is that something that changes your algorithm in terms of treatment? Sorry, we’re jumping the gun in terms of how you’re treating these patients, but I’m curious to know if that factors in.

I think that’s led to the current focus on revascularizing, trying to prevent ischemia, because you’re right. Listen, if you’ve got a diffuse thrombosis and they progressed a necrotic bowel, they get a resection. If you’re trying to salvage other segments of bowel, you need to clear out that clot, and chances are, you’re going to need to use lytics, so it’s great to obviously not be doing that after a bowel resection, if you can help it.

Yeah, if you can help it. Exactly. Which is the big, big question, how much we can do, so definitely, it can go both ways, like, Steve, you said. It’s definitely, we don’t have a clinical trial on this, we don’t have a clear line yet, so it will be a lot of discussions with the surgeon and both ways can go.

What approach do you guys have when you have a patient in this purgatory kind of threat and bowel situation? How do you actually approach the clot? Transjugularly, percutaneous? Tell me a little bit about why. Does it depend on how much clot burden there is? I mean, if it’s just one little goombah in the main portal vein, versus the entire splenic system being completely thrombosed, tell me a little bit about your approaches.

Yeah. That’s a great question, Steve. And, for me, I look at three things in these cases. One, do they have a history of cirrhosis leading into this, where you know they’re going to need a TIPS at the end of this? Kind of on that same spectrum, do they have anything that looks like a chronic-appearing portal venous occlusion? That really complicates your treatment, makes it a bit more complex, and obviously, a TIPS is really going to be needed in those two circumstances. And then, the extent of the clot. If you’ve got a pretty central complete occlusion, you can approach that—in a patient, let’s say without cirrhosis, healthy-looking enteropathic portal venous system, could you potentially just approach that from a transhepatic approach? Possibly. I think, more commonly, we’re doing the TIPS approach just because it’s a lower bleeding risk, in my opinion, in my experience. And you don’t have to leave a TIPS in at the end of it, and I know we’re going to get down to talking about that here, but a TIPS approach for lytics is, in my opinion, way more comfortable to me than a transhepatic approach for laying some lytic.

Let’s talk about that. To TIPS or not to TIPS, that is the question. There is a lot of discussion and literature from all over the world as far as leaving that stent behind or not. Can you flesh that out a little bit more, Siobhan, about when you come in to perform thrombectomy lysis or clear out the clot in some form or another, when do you decide to put in this TIPS—or tell me a little about, maybe, when you haven’t decided to put in a TIPS, perhaps, if that seems to be a little bit less common of a practice.

It really boils down to how things are looking at the end. What does the outflow look like? Is there a well? If they had portal vein clot at all, is the system looking open, receptive to blood flow? When the flow is not looking good, that’s when I pull the trigger and place the TIPS.

Yeah, I would agree with that, totally. Those situations, first of all, when we have a large clot burden, definitely a transjugular approach would be my go-to, also, because of the lower risk of bleeding. We don’t want to be in a situation that we are fighting the clot and we have to use the lytics and we have a big {inaudible} percutaneously, and definitely, that would be something to have very safe as a transjugular approach. And then, the flow at the end would dictate us what to do at the end in terms of placing the TIPS or not, so that we have a good patency of the stent.

So when you guys finish, you cleared out 100% of the clot, as you always do, I’m sure, you inject, and you see the beautiful portal tree and the SMV and the splenic vein, if that’s also involved, and it just lights up the liver. You see the parenchymal stain, and you see some draining veins. You just pull out, take everything out.

You can add a pressure to that, Steve, to feel really comfortable. But if they don’t have that history of cirrhosis, liver disease, and things are looking great, I’ve done okay not leaving a TIPS in those circumstances.

Which is rare.

It’s pretty rare.

Understandably, you are posing a very good question, which is a very difficult question. It’s very rare. We rarely run into a situation that is acute, it’s not chronic, there is no cavernoma, there is no cirrhosis, there is no issues like JAK2 mutation that cause a whole bunch of different occlusions. So there you go. It’s a very, very, very selective population of patients that we’ll leave out like that.

We should be giving your guys’ number at the end of this podcast, for all of us who have that question in our head at the end of the procedure, and ask for a consult from you guys, because that is something all of us, I think, are debating every time we get into these situations.

Exactly, exactly. And moving on to the next niche indication: Budd-Chiari patients, Siobhan. In what spectrum of disease you would usually see them in your practice? They can be early or advanced. When do you see them, usually, and how do you decide? Do all of them need TIPS? How do you decide between which technique would you use and whether to TIPS them or DIPS them? How do you decide?

You know, the patient always decides for us. Right? And I would say it’s very similar to the acute mesenteric thrombosis scenario. These are referrals from outside. And what would be the ideal? Well, we would capture them when you just have a hepatic vein problem. These are patients with a kind of primary internal issue, usually some prothrombotic condition that leads them to occlude things. But I haven’t had a single hepatic vein case in my practice at the university. They’re all patients who have progressed to the point where the hepatic veins are occluded.

And that becomes a complex question in my mind, When’s it okay just to intervene on the hepatic vein itself and count on that to be enough, even a single hepatic vein being enough outflow for the patient’s condition? But the decision is typically made for me. We have patients who are just too advanced, their hepatic veins are gone. Or maybe you just have a little bit of central hepatic vein left to place a TIPS. So we’re more often TIPSing them or DIPSing them in our practice.

I have yet to see a hepatic vein-only intervention. I’ve only been in practice for, now, 11 years. Have you guys ever seen anything like that, where someone just went ahead and pulled the clot out—

No.

… of a hepatic vein and said, “We’re done?”

No. You know, the literature tells us that that’s possible in patients who present just with the isolated hepatic vein issue, but in our practice, in a university setting, we don’t see it.

Yeah, yeah. And it goes back to, also, the etiology. Because the etiology is there, being prothrombotic syndrome or compression, the recurrence therefore will be high if you just address the hepatic vein and come out. So that probably goes to the fact that it’s going to be very high recurrence; therefore, we don’t usually see that to be just a solo hepatic vein intervention.

Can I ask you guys, then, if you get a referral with someone with Budd-Chiari, these are going to be not very old people, right? These are going to be very young patients. And say that it’s someone even younger than 21, and say I’m now the father of this patient and you’re telling me that my daughter or that my son needs to have a TIPS. How do you counsel not just the patient, but also the parents, in terms of a TIPS? Because most parents are going to be then looking online, saying, “Wow, these are all for cirrhotics, and there’s this whole risk of encephalopathy, liver failure, and all these other things.” I’m curious to know if you’ve ever needed to have that type of conversation, not just with the patient but with the parents as well, which is not something that we typically do when we get a usual TIPS, conventional TIPS consult on someone who’s cirrhotic, because these people are older than 21. Have you ever had kind of a pediatric conversation before in your practice?

I’ve had pediatric conversations, but not related to Budd-Chiari. Our paradigm is swinging a bit in the pediatric realm, and we’re trying to reopen occluded portal—extrahepatic portal vein occlusions, and sometimes those occlusions are complex. We always give the reopening a try, and sometimes it fails. Those complex occlusions that go from main portal into central, right, and left, those are really the hard ones to keep open. And maybe the occlusion is even more extensive than that. Usually we know that ahead of time, but sometimes you don’t and you have to make a decision, well, do you want to try to see if this is just going to work without a TIPS? But honestly, the pediatric conversation is not that difficult, because the alternative for them oftentimes is a surgical shunt, like a splenorenal shunt, and that puts them at risk for encephalopathy as well, and what they have in their corner is, if you have preserved synthetic function, that, by and large, encephalopathy can be medically managed. Not ideal, but that’s usually the conversation I have.

Yeah. One thing to add, also, is that we are fortunate to be in multidisciplinary teams, so that usually helps these kind of conversations, because usually, these patients are coming from outside. They have kind of an initial workup done, and since these are pediatric populations, there is a transplant surgeon, and there is a pediatric hepatologist on board, and there is a lot of teams on board that we are working together. That’s kind of fortunate because that makes the conversations more effective, because patients are already coming to us with some sort of idea. For example, pediatric patients that I have worked on, they are really complex patients. But it was very funny, a story, that I had a patient that I did TIPS on his brother, and a year later, the other brother came to me for the TIPS just because they had a congenital disorder that would lead to this condition of them. And then, it was kind of easy, at that point, because they already had the experience. Just speaking to the fact that having the team and multidisciplinary discussions are really helpful in these scenarios.

That’s very interesting. It’s almost like a two-for-one. You must have already understood the anatomy, then. I imagine their portal vein anatomy was relatively simple and—

Actually quite different. These were two spectrum of biliary atresia patients: one of them kind of almost normal patient, the other patient full of bilomas and full of cysts in the liver. Very interesting in terms of appearance, completely two different spectrum. And we were able to use the transabdominal ultrasound TIPS for the one who had large bilomas and cysts, very successful, which ended up having a transplant a year later.

Well, the acute mesenteric ischemia Budd-Chiari, we’re going to shift topics a little bit here. You know, Steve, the acute mesenteric ischemia venous thrombosis conundrum is interesting to manage, but I don’t know what you see in your practice, but I often see those patients that didn’t require an intervention by us early on, they come back in the chronic phase. So I’d love to hear from you. Tell me about a case you performed a TIPS on a patient related to chronic mesenteric venous ischemia, just from the standpoint, you know, how did you get involved, and what was really the reason for the referral, and what led you to place the TIPS?

Sure, totally. It’s almost like when we see someone with post-thrombotic syndrome and we’re like, “Should we have intervened when the patient had a DVT earlier?” and now we see someone with leg ulcers and all sorts of venous hypertension leg issues. I could tell you about a case—or two cases that basically are the same thing. The patient was billed to me as preoperative TIPS. And the story in—both of these patients both had postprandial pain, and a surgeon from an outside hospital worked these patients up and said, “This sounds like biliary colic.” You eat, 30 seconds later, you have severe pain, and when you stop eating, the pain goes away. And you eat again, repeat, same thing. And the surgeon said, “Let’s go ahead and operate. Let’s do a lap chole.”

They worked them up with the ultrasound and said, “There’s a pretty normal-looking healthy gallbladder with some stones in it. Let’s go in and operate.” They open laparoscopically. They see a flurry of varices, a flurry, and they say, “Nope, time to abort. This is a bloody mess.” And the patient then gets worked up further to show that there is chronic venous ischemia, chronic venous occlusion of the portal vein, mesenteric veins, and referred to a tertiary center, usually a hepatologist, to then say, “How do we clear this patient for surgery later?” And then, the hepatologist or hematologist who gets the referral for this occlusion sends the patient to IR and they’re asking for an opinion to say, “Well, how do we get this patient optimized for biliary colic surgery?”

You see the patient, you get the history, and you’re like, “Yeah, it could be biliary colic, but why couldn’t this very well be related to your mesenteric venous occlusion?”—meaning every time you eat, it’s not the bile ducts that are screaming, causing you pain, or the gallbladder, but it’s your intestines because they can’t outflow, they can’t drain their blood, and you develop chronic mesenteric venous ischemia. And so, interestingly, when I talk to these patients, I say, “Look, I want to get you your surgery. That’s why you’re here. I know that’s the plan. Let’s go ahead and perform PVR-TIPS, do whatever necessary to restore flow from intestinal veins through a TIPS into the heart.” They say, “I’m all for it and I can’t wait to get my surgery done, because I’m losing weight, I’m feeling really bad,” yada yada. Okay. We perform procedure, you see them in follow-up. They’re like, “I don’t have pain anymore.”

Problem solved.

And they’re like, “When do I get the surgery?” And I said, “Wait, hold on, hold on. I’m not sure you need the surgery, sir. It sounds like this diagnosis of chronic mesenteric venous ischemia was perhaps not thought about, and while we were performing this to optimize you for a surgery, I think we’ve just obviated it and you no longer need it,” and they’re like, “Well, if I don’t think I need it, maybe I don’t need to see the surgeon, I guess.” “Well, go back to the surgeon, definitely get their opinion, as well. But if you’re feeling well, let’s just watch you, and let’s just make sure your symptoms don’t come back.” And both times, these patients, two, three years later, they’re doing just fine.

That’s fantastic.

Yeah. Great outcome on that one, Steve, but I have a question for you. Number one, how do you manage expectations with these patients preoperatively? Because I’ve had patients with chronic mesenteric ischemia, and they’re a mess—and I’ve got more questions kind of on the technical side about how you handle that—but how do you speak to them in terms of, “Hey, this is going to solve your abdominal pain. Will it not? Will it? What’s the chances that it will?”

Yeah, that’s a hard question. It’s so hard to tell them, “This will cure you.” I mean, it’s hard for me to say that for a lot of things, even if someone has a diverticular abscess and I put a drain in, I’m never—it’s hard to even say, “Your pain’s going to get better after we put this in.” No, sometimes the pain gets worse when you put in these drains. And their expectations is such that we say, “We’re here to improve flow. We are going to get some symptom improvement, but there’s not enough data to tell—I couldn’t give you an exact number that this many people feel better, this many people feel better by this much.”

And their expectation is such that they know they’ve got a very complicated problem. They also know that if they don’t do anything, there are going to be consequences. I discuss then the other risks, such as encephalopathy and so forth, and these non-cirrhotics—knock on wood, Siobhan, like you mentioned, I haven’t had a serious hepatic encephalopathy situation with these non-cirrhotics—and so, I do explain that there is a risk of that and that we got to have you on lactulose and we got to have you have all sorts of fun bowel movements with that. But they have so far not needed that.

And I think—I don’t know how you feel about this—but when there’s the possibility of solving pain, preventing future problems like GI bleeding from their occlusion, it hasn’t been too hard to help patients understand that it’s a good idea to go ahead with it.

Yeah. With also the risk of the procedure itself, which we know that PVR-TIPS is not like something, you brush your teeth and you get a PVR-TIPS and you go home and pick up some milk on the way. These are involved, and maybe—

For sure.

… this is something in general that I tell patients, is that there’s the X factor. I tell them that. There is an X factor about these procedures that the unexpected can occur. One patient I did a PVR-TIPS on, he had hemobilia and it lasted for a couple of days. His bilirubin shot up to 32 after the PVR-TIPS. Everyone thought this was liver failure, but he was a non-cirrhotic, so I said, “No, that doesn’t make any sense.” He was hospitalized for a week, had an ERCP, cleared out the clots, and eventually the clots in the bile ducts disappeared and his bilirubin came back down. But, I mean, this is not described in the literature. We don’t know that there’s going to be biliary obstruction from hemobilia. I call that the X factor.

Yeah, absolutely. Talking about all of these details definitely matters, and setting the expectations in a reasonable place is very important. Moving in the same theme as we’re talking about encephalopathy and the risk of encephalopathy, in a patient who has a large gastrorenal shunt, isn’t that backwards to create a TIPS in them? Isn’t that going to be actually increasing the risk of encephalopathy? How do you feel about that?

That is the question all hepatologists say, when you see someone with a large gastrorenal shunt and you’re maybe treating varices or something else and you put in a TIPS and they’re like, “Wait, wait, TIPS equals encephalopathy. Gastrorenal shunt equals encephalopathy. Aren’t you just going to double the risk of encephalopathy in these situations?”

There was another case. It was a cirrhotic who had chronic occlusion of the portal vein, and he was referred for variceal bleeding, and, yeah, large gastrorenal shunt, chronically occluded main portal vein, but he was hospitalized three times over six months for encephalopathy, as well. So he was bleeding, he was encephalopathic, he was going to the ER pretty much every month for one of those two. And when we met on the clinic, in his lucid moments, when we talked about his hospitalizations and how much encephalopathy medications he was taking, he was on lactulose, rifaximin, Linzess, and MiraLAX. So he was on four laxatives, and he was compliant, and yet he was still coming into the hospital. I said, “Well, I’m going to perform an embolization of the varices, but if I just do that, I’m going to pressurize your system. You’re going to blow a varic somewhere else, or you can develop ascites or something else, a thrombocytopenia,” and so, I said, “I’m going to put in a TIPS.” The hepatologist is like, “Whoa, whoa, wait a minute, hold on. This guy has been admitted every other month for encephalopathy and then for variceal bleeding in the in-between months. Why would we consider doing this?” I said, “Well, essentially, we’re trading a big shunt, an 18-millimeter shunt in this gastrorenal shunt, and we’re going to embolize that and trade it out for a 10-millimeter shunt. So think about having an 18-millimeter TIPS and I’m actually going to reduce it to a 10-millimeter TIPS or an 8-millimeter TIPS.”

And then when you start going over the anatomy with the hepatologist, they’re like, “Okay.” I mean, they’re still a bit hesitant because the word TIPS equals encephalopathy for a lot of them. But in so doing, after performing said procedure, the next day and for months ahead, he was like, “I am so clear in the brain. I’m so lucid. I can’t believe how much better my life is.” And so, I thought that was kind of an extra side effect of performing these procedures.

Well, kind of parlaying into the whole encephalopathy conversation, Steve, what kind of role or involvement does your team have in managing or preventing encephalopathy in your TIPS patients?

Good question. We have the clinic at APA, as well as our attendings are actively involved in prescribing medicines before and after the TIPS as needed. A recent paper talked about using rifaximin two weeks prior to a TIPS significantly reduces the risk of encephalopathy in these cirrhotics. Afterwards, we are going to set up appointments with these patients one month, three months, six months after the TIPS, and thereon with our PA, really looking out for this encephalopathy risk, because I feel like, especially given our large catchment area in St. Louis, there’s a lot of patients who are at home, hours away from downtown where we’re working, who are developing brain fog, lethargy, insomnia, and no one’s really checking in on them. And so, the longitudinal care model that we all now believe is the most important thing of IRs all across the globe, this is how we’re going to improve our patient care. So, in short, the IRs are the one who performs the procedure. We’re the ones responsible for the encephalopathy.

Okay. And let’s say, Steve, the day of the TIPS, this patient’s not requiring medications yet. Do you guys have prescriptions ready for them to fill if they’re at home, in the middle of nowhere, to help them get started on treatment? What’s the instruction to the patient?

Good question. So, my practice before I joined Wash U was to already prescribe lactulose, rifaximin before the patient goes home. Now, over at Wash U, because we also have a strong partnership with the hepatology team, closer follow-up is probably the better way to go rather than just to prescribe medicines that the patient may or may not need. So, in short, whenever I have a high suspicion that someone can be encephalopathic, I do prescribe lactulose as a rescue medicine to bring at home so they have their big jar of lactulose waiting and ensure that they have someone at home with them, living with them. Now, they can’t live alone. They have to have someone checking in on them for at least a week every day, making sure that they’re not becoming encephalopathic, with the rescue lactulose at the very bare minimum.

Okay. We could talk forever about all these topics.

Exactly.

I know. Nassir, you have a very interesting practice down in St. Louis, and of significant interest is approaching patients with malignant visceral vein compressions or obstructions. In the past, people thought cancer diagnosis, no matter where it’s located, palliative, but that’s changed a lot. Can you talk to us about your approach with these patients and how you consider a TIPS in the setting of their malignancy?

Yeah, yet another exciting topic, really in the last decade especially. We see a lot of series of papers on this topic, and like you said, it’s really intriguing. Always, we were thinking about patients who have malignancies, we are not going to do TIPS on them. And then, if we want to think about, we can categorize these few studies on two group of population of patients. Some of them have, for example, HCC, and they are perhaps within Milan criteria, and then, a TIPS is being done for them. And another group of patients, they have more advanced disease portal vein thrombosis in the setting of malignancy, and yet they are still doing the TIPS for them. And there is actually even a recent meta-analysis and systematic review on them. Almost all of these studies are from China, which is interesting, and they also even looked at doing the TIPS and then starting to do the treatments such as TACE for these HCC lesions in the liver.

What we can learn from this is that, first of all, we need data. We need a good longitudinal study and perhaps even a clinical trial. I don’t know how randomization is feasible in this setting, but we definitely need more data, maybe, perhaps, registries. And the other thing is that, interestingly, these patients do not get seeding of the tumor. Those kind of well-known or well-thought-of complications of this usually doesn’t happen and it’s not seen. One thing that we do see is that the patency of the TIPS is much lower in these patients, which is more towards the spectrum of patients who have portal vein thrombosis in the setting of malignancy and their patency can be compromised because of that.

So if I were an oncologist taking care of a patient, Nassir, and for X, Y, and Z reasons, there is a good reason to perform a TIPS, whether it be variceal bleed, but there’s tumor in the vein or really close to the vein or possibly invading the vein, I’m Dr. Country Doc Oncologist. Wait, aren’t you going to just release the cells into the lungs?

I am. And definitely, like I said, above all, we need data. We need more safety data. But all of these population of patients that are published out there, they didn’t have any sort of seedings, let’s say {inaudible} for example, as the result. And, obviously, these patients are in the spectrum of patients that are having less survival compared with our normal population that we do the TIPS every day, so they may not get to that point, but this has not been reported, and it’s very interesting.

The other thing is that, so, obviously, a lot of patient selection goes here. First of all, what’s the life expectancy? What are we achieving in terms of tumoral control? How much oncologic help we can do and we can have in our disposal for this patient? So those kinds of things definitely need multidisciplinary discussions in terms of what options do we have for this patient. But interestingly and surprisingly, we do see more and more publications saying that perhaps it’s safe.

Can you describe an example, perhaps, for our listeners, of a case or two, or however many, of a patient that had a malignancy related to portal hypertension that you treated, if you don’t mind?

Absolutely.

What was the indication? How did you meet the patient? How was this patient referred? All of that.

This patient was an interesting admission to the hospital for GI bleed. And out of nowhere, this patient was diagnosed in our hospital with the pancreatic cancer. This was just the first diagnosis, and the patient presented with GI bleed. And on cross-sectional imaging, we found out that the main portal vein is occluded. These are ectopic varices from a cavernoma, essentially, that are bleeding in the duodenum. And at that point, patient really has advanced cancer, but, at the same time, everything else in terms of—patient was almost, like, working, and the quality of life, and patient was having a normal life like two months before that. So we wanted to make sure that we can do as much as possible for the patient. This patient, actually, we performed a percutaneous access, we recanalized the portal vein and did really well. With that advanced pancreatic cancer, he was alive for the next eight months and no complications. And the patency was also there without any GI bleeding. And definitely, the patient selection was going there in terms of discussing with oncology,

It’s interesting to see—these oncology cases are really interesting to me, and I think we’re going to be seeing more and more of them in our institution. You bring up good points of, you know, the length of life matters—how long is the survival?—but the quality of life is really important, too. That was one message that I really learned during my fellowship years, honestly: Listen, people might be terminal, to some degree, but what can you do to improve that quality of life?

Indeed.

I think these are really interesting cases just for that reason. But you made a comment about these cases you’re seeing, that maybe there’s a higher rate of rethrombosis in these cases. And why do you think that is?

And that’s a very interesting question. I think it has to do with the pathophysiology of disease. So we have inflammatory markers going on in the portal vein. We have the actual compression from the tumor going on. Perhaps patient had history of radiation in that area, and that can change the anatomy and also the tumor itself. So, obviously, we are not doing any sort of treatment at that point when we are creating a TIPS or we’re canalizing the portal vein. So all of those processes can be a risk factor to reduce the patency, as opposed to just without any portal vein thrombosis.

Oh, actually—

I know we’re—

…. can I ask, in your practice, Siobhan, also, what kinds of oncology patients are you seeing, since I obviously kind of share the same practice as Nassir?

Yeah, they’re mainly pancreatic cancer patients who have severe compression. Usually, it’s closer to the mesenteric splenic confluence, so sometimes those can be treated just with stenting.

What symptoms are they having, if you don’t mind me asking?

It’s usually GI bleeding, rarely ascites.

And so, is the reasoning you guys, that, “Hey, we know that we’re going to pass from pancreatic cancer, however many months down the line. We’re just trying to prevent a catastrophic bleed”?

For us, that’s usually the answer.

Yeah, that’s usually the answer.

Do you have any other symptoms with these patients? Do they have pain? I mean—

The pain’s a tricky thing, because they have pain directly related to the malignancy, so the promise can’t be pain relief in those patients, but we’re trying to spare another catastrophic GI bleed.

TIPS or not to TIPS?

It’s a great question.

Great question. So that case, for example—

Shakespeare is going to really love this podcast,

… had a good—so non-cirrhotic patient and had a good flow at the completion of the procedure when we recanalized the portal vein, and obviously, everything was at the porta hepatis just from the compression from the cancer. And we were able to achieve a patency for that patient without issues. In other spectrum of patients, if they have some level of cirrhosis or the flow is not good or there are insinuating masses within the liver, perhaps those patients need a TIPS creation.

Very nice. Let’s switch gears. We have a little less than 10 minutes, I think, here. We see a little bit more of an indication of the TIPS in patients with renal impairment, lung issues, hepatorenal syndrome, hepatopulmonary syndrome, but isn’t it contradictory and contraindicated if someone has, perhaps, really severe hepatorenal syndrome and their MELD calculation, MELD 3.0—so all forms of MELD or whatever favorite scoring system you want to use to offer a pretest probability of liver failure. These patients are going to have high MELDs, and they have hepatorenal syndrome, so I get a consult: hepatorenal syndrome, but MELD is 22, but it’s maybe driven just by the creatinine. Tell me a little bit about, how do you reconcile that, Nassir? Are you saying, “It doesn’t matter, it’s just creatinine?” Tell me a little bit about how you choose to treat these patients.

Yeah, it’s fascinating just because of the fact that how beautifully the TIPS and the pathophysiology of hepatorenal syndrome and liver disease goes together. So if you think about this, this is, first of all, very niche area—very, very rare situation—and it’s evolving. We see clinical trials are still going on on this matter. There is a Liver-HERO clinical trial going on now in Germany that is comparing—head-to-head, one-to-one randomized trial comparing TIPS with terlipressin, which is a vasoactive medication. And the whole point is to try to show survival benefit, if we do the TIPS for these patients, with the idea that when we create the TIPS and the portal hypertension is relieved, this arterial underfilling can be relieved and therefore, this functional issue that we are going on and we are seeing in the kidney is going to go away and the creatinine clearance will improve.

So now, kind of stepping back on how to choose these patients for TIPS creation, you’re absolutely right, these patients are going to have high MELDs. Confirmed trial also showed it that these patients have high MELDs. Some of them have very high bilirubin levels, too. So those are obviously kind of will be very bad spectrum of a disease that we may not be able to TIPS them, but if the patient has a better bilirubin levels below five, if the creatinine is below five, usually those are the patients that we can optimize.

Again, kind of going back to our previous discussion of optimization of different scenarios, this is also if the patient can get terlipressin, albumin for volume expansion, and then we can help the kidney improve the creatinine clearance to some extent such that the patient becomes the TIPS candidate. Those are really sweet spots that even the clinical trial that I mentioned is trying to do that: optimize the patients, bring them to a more favorable MELD, then TIPS them, and then we’ll see if that trial actually shows survival benefit for these patients.

And I’ve got a piggyback question. I know we’re almost out of time here, but, just for the audience here, because I imagine this is a question, do you look at patients with chronic hepatorenal, versus acute hepatorenal, any differently?

Yeah, and we can go on on this. This is a very interesting question. So, historically, we had that Hep Type 1 and Type 2, and now, as you said, you are moving on to AKI and CKD, hepatorenal AKI, hepatorenal CKD. And usually, we see these patients more acute, like these are inpatient who have acute deterioration of their renal function and we’re trying to optimize them so that we can perform TIPS on them. Those patients who are more on the CKD spectrum, they perhaps have other comorbidities, and that’s why they are more on the CKD spectrum that perhaps they get more—because for ruling out these patients, we have to make sure that they don’t have any chronic kidney disease, they don’t have any hematuria or proteinuria or any other medications causing this. So I would say more spectrum of the patients that we see are going to be the AKI patients and they have more acute settings.

It’s so funny, the TIPS procedure really kind of started around the 1980s, and it was performed for patients on death’s door. These were the patients that, practically, you could clip their toenail and they would end up passing because they’re so sick. And now here we are, talking a lot more about the indication of the TIPS basically on an elective basis, right, not just the refractory ascites, but you’re talking about Type 2 hepatorenal syndrome, we’re talking about chronic symptoms, pancreatic cancer. I’m just smiling because of how different the TIPS looks like versus back in the 1980s.

Amazing.

Yeah, and it’ll be interesting to know what are the conversations 10 years from now, because I feel like things are changing. They’ve been changing quite a bit over the last four to five years probably. This has been a great conversation, you guys. Very exciting discussion. We’ve gone from, like you’ve said, Steve, something that was just placed mainly in an emergent situation or just for people who bleed. Later on, we got down to it with helping people with ascites. But now, there are all these great other indications to consider, patients that might be helped with TIPS placement. Can you two think of anything else that’s coming down the pipe at your institution for other unusual indications for TIPS placement?

Malignancy is one. Pancreatic cancer, GI cancers, the life expectancy is improving a little bit when they are locally advanced or metastatic. But with new therapies, I think these cancer patients are going to live longer, and so palliation becomes even that much more important. And so, performing and studying at what point can someone metastasize through the liver, to me, is actually very interesting. If someone’s going to live 12 months with their pancreatic cancer, is it really safe to perform this procedure or not? Should we be doing it or not? So that’s my thought. It would be a question to have.

With the immunotherapy on the horizon of treating cancer, more life expectancy, then here we go. We can have more opportunities to help these patients when they have more life expectancy. Looks like it that, yeah, malignant patients with portal hypertension will be really a big topic.

Yeah, and at our institution, we’re recognizing preoperative indications for relieving portal hypertension. I think most of what we see are patients who have cirrhosis, have hernias that need repair. That’s probably the biggest pre-op indication we’re seeing, but very interesting. It’ll be great to see what comes next for us. Any last-minute thoughts, you guys, on advice to IRs about how can you improve referrals for this? What advice do you have on team building for these patients?

I would say engaging and being engaged with discussions with the other providers is the key. And having a good conversation with them before and after the patients are being served or being intervened upon is very important. Even if those patients are not getting intervention from us, still having the conversations with them, being engaged with them, having scientific discussions with them—these are, I think, the key elements that the visibility will be there so that whenever a patient’s help needed, we can be there.

My mantra to the trainees is, Own the disease. Do a procedure if necessary. Own portal hypertension, own the medicines, own the pathology, learn the language that hepatology speaks, and then everything else will follow. And, of course, when doing so, you’re naturally going to not only see the patient before, during consultation, during procedure, but for the rest of their lives afterwards. And so, this day and age, more important than any other thing that we do in IR is to set up a clinic and see these patients forever. Once you see them, you’re never going to stop seeing them.

Great points. And it’s a great opportunity to work with all these other providers, these specialists that really need to be taking care of these patients, as well. Well, great session, you guys. I know we can go on probably forever on this topic, but it’s been a pleasure talking about it.

It’s been fun.

Thank you.

It’s been great.

It was awesome.

Thank you.