EUPSA webinar "The surgery of portal hypertension in children: Exrtra hepatic portal vein obstruction and and beyond."

Um, Doctor Sabrina will, uh, be our first, uh, uh, speaker, and, uh, as you can see, I hope you all can see the slides, you talk about, uh, the Mesorex bypass for X-rayathic portal vein obstruction. Doctor Sabrina really doesn't need any introduction. He's, uh, Uh, a world expert, a world leader, and it's really our honor and privilege to have him today and he found time in his very, very busy schedule that we all know is busy, uh, of course in Chicago, but he's a, he's a surgeon that travels around the world, uh, teaching people how to do these complex surgeries. Um, Doctor Superina has, was, is Italian by birth. Uh, Canadian, um, uh, because of course he was raised in, in Canada and surgically also developed his surgical skills in in in Canada, specifically. He was also a staff surgeon for 12 years here at the Hospital for Sick Children in Toronto. Uh, he did a, um, uh, um, transplant surgery fellowship at Oxford University in England and then came back here and established basically and this is what he is known for. Uh, in, in the city, in, uh, uh, in, in Canada I should say, but the one who established the, the liver, uh, transplant sur um transplant surgery program, uh, which is by far one of the busiest, uh, still in North America and I think in fact in the world. Uh, then, uh, 1997. Um, he left the kids to then, uh, uh, uh, just cross the border and go not too far but to Chicago where he's been, uh, uh, until now he's the, in fact, director of the, um, the, the, the division chief of transplantation and advanced hepatobiliary surgery and the surgical director of the transplantation center. Um, he has done, uh, he has contributed, uh, massively with, uh, of course, uh, um, establishing programs, uh, uh, as I said before, educational teaching, uh, the new generations. Uh, of surgeons to do these very complex procedures, but he's also done a lot of research, and this is really, uh, something that, uh, is, is, is phenomenal. I mean you see, uh, papers, seminal papers on portal hypertension, liver tumors, uh, portal hypertensive surgery, congenital portalsystemic shunts. Uh, his name is uh. Always there. He's been a leader in the field and I could go on and on. He's a, he's a fantastic person in the first place and he's always ready to give advice to the young colleagues. So again, without any further ado, we're really fortunate to have you, Rick on the webinar today and I look forward to your presentation. Thank you, Augusto. Uh, it's very nice to be here with friends. I know, I know Augusto for several years. We met in Brazil actually, of all the crazy places, and um Martin, I think we had many enjoyable evenings in Obergoogle, uh listening to you play the piano. Oh yeah, I remember it. In Gaya, we have many good uh dinners in Trieste. And, and, uh, hello to all our friends, uh, all over the world for where you may be. It's my great honor to, to share this, uh, webinar with uh Doctor Lemoine, my colleague now for 5 or 6 years, maybe more. Um, and, uh, so we'll be talking about portal hypertension in children, obviously, and I'll start off by, uh, talking about the Surgery for uh extrahepatic portal vein obstruction, and then uh Carolyn will talk about uh the changing paradigm, I think that we have, are trying to establish for the surgery of portal hypertension from other causes in children. So, um, I'm going to try to advance here, my God, it's like, OK, so I have no disclosures other than that I am from Fiesta and I don't surf. Uh, the aims of this presentation will be to review the current state of the art in uh for the Misorex bypass, um, how it's changed in the last 25 years since it's been uh it basically in use since the early 90s really, but it came into vogue mostly in the mid 90s to late 90s. And uh how the care has evolved from treatment uh to really prophylaxis. And uh then I'm gonna talk a little bit about the end about the measorex registry, which we have been talking about for a long time, but we really think it should be uh something that will be a reality soon. So just for the sake of uh getting our definitions straight. Uh, portal hypertension is, uh, can be measured two ways, either a direct portal vein pressure, uh, which is usually 5 to 10 millimeters of mercury, or more commonly, uh, it's, uh, the gradient between the, uh, the free hepatic vein and the wedged hepatic vein, uh, which should be 1 to 5 millimeters of mercury. Um, the indirect evidence of portal hypertension is, um, Symptoms bleeding from gastroesophageal varices or uh enlarged spleen with a low platelet count. This is called clinically evident portal hypertension, uh, where the portal pressure is assumed to be high because in children it can be quite difficult to measure, unlike adults where it's a routine thing. Um, cavernous transformation of the portal vein. What is it exactly? Some people refer to it as portal vein thrombosis, um, but I think it's either a congenital or uh acquired, but not necessarily by thrombosis. It's not an acute disorder. Some patients are, are sent to us with the diagnosis of cavernous transformation, and they are anticoagulants, but anticoagulations are really not indicated, uh, in this chronic condition. It's associated with umbilical vein catheters. And in our experience, there's a high incidence of congenital heart disease, and there's also a very definite association with hypercoagulable conditions such as factor 5 Leiden mutation or some of the antiphospholipid antibody syndromes. The consequences, of course, are GI bleeding from esophageal or gastric varices and hypersplenism. There's another consequence, which is uh was coined a portal biliopathy by sarin from India, and you can see here the yellow arrows pointing to a dilated bile duct, uh, and this is commonly seen in patients with expatic portal venous obstruction, uh, thought to be perhaps due to stasis in the biliary system from the high pressure varices that surround the bile duct. But I think almost as important and perhaps a greater consequence are the metabolic sequela of portosystemic shunting, which always occurs in patients with portal vein obstruction, and these are chiefly encephalopathy, poor growth, or even more serious are these portal or hepatopulmonary syndromes. So, the surgical treatment that uh I think many of you now are familiar with uh and uh is the uh uh Misorex bypass that was first described as Jean de Ville de Goyer in the early 90s, where uh the internal jugular vein was uh harvested from the neck and uh used as a bridge between the superior mesenteric vein and the intrahepatic portal vein uh accessed through the rec recesses. Um, it was first used as treatment for portal vein thrombosis after liver transplants, but then it became more popular, uh, for basically the treatment of so-called idiopathic portal vein obstruction. Very importantly, for those who may not be familiar, this is not a portalsystemic shunt. Blood is directed back to the liver, not away from the liver, like in, in many cases of portosystemic shunting. It's always a question that I get a lot is how do we know uh if the rec shunt will work or how do we know what the status of the portal vein is inside the liver? And most people rely on imaging such as CT or MR and I want to emphasize that CT or MR is absolutely not useful for demonstrating the intrahepatic portal venous anatomy. Here's a good example on the right of a CT scan where you can see the portalbielopathy, and you can see no obvious intrapatic portal vein. However, I want to emphasize that the intrahepatic portal vein is usually preserved in the majority of cases of portal vein obstruction. The way to determine the patency is to do a retrograde transjugular portal venogram, and for this we rely on our interventional radiology colleagues a great deal. At the same time as getting a beautiful image of the portal vein, which you can see here, uh, they are also able to measure hepatic vein free and wedge pressures and also obtain a liver biopsy. And you can see on the left, this is uh essentially what looks like a normal intrahepatic portal vein. Now, it's not always like that. And uh at the Bovino conference in 2014 or 2015 in Bovino, um, uh, we had a uh a classification was proposed. That broke it down from A, which was uh basically what you see on the left on that portal venogram, where the intrapatic portal vein is preserved, uh, and then it goes downhill from there, B, C, D, and E, where E is a very disorganized system, and everything in between A&E is sort of a partially preserved intrapetic portal vein. Now here there are examples of um on the upper right, what I would call a B and then a C on the lower left and maybe a D. But as everything in life, you know, beauty is in the eye of the beholder. And so the big question mark is, does the anatomy as described by the intropatic by the retrograde portal venous venogram actually correlate with the results, and we have, we have not had a study uh correlating anatomy with the ability to create a successful Msorex bypass. The preoperative assessment is really quite um uh what do I say uh extensive apart from the imaging, and we do get all MR and CT just to get a road map of the intra uh abdominal venous system. Of course, we get the retrograde venogram and then we get a liver biopsy, liver function tests, of course, because it's very important to make sure that you're operating on a liver that has no preexisting liver disease. The coagulation profile is quite uh important in trying to determine what sort of anticoagulation strategies you're going to use after the transplant. And we also do neurodevelopmental testing to test for hepatic encephalopathy, minimal hepatic encephalopathy in children. And a cardiac echo. The neurodevelopmental testing is very important because you'll see in the literature, many people claim that protosystemic shunting in children does not have an effect on neurocognitive testing, but in fact it does. And the problem with those studies is that they do not have any data to support their conclusion. Cardiac echo is done to rule out um portopulmonary syndrome with uh uh pulmonary artery uh hypertension. The operative technique, I'm not gonna spend a lot of time here, but we're surgeons, so we have to show some slides that look like uh we're operating. So the first step is I call it dissect and inspect. So, you have to follow the umbilical ligament into the recesses of Rex, and there on this picture, you can see that there are 3 or 4 nice big branches which are uh surrounded with silk ties. And those will be the conduits to which um the blood is directed with the jugular vein graft from the superior mesenteric vein once the vein is opened. And so and unclamp you can see here the hepatic end of two separate anastomosis. Um, they're not always look exactly the same. Uh, you can see that in one you can't really see the branches, and on the bottom one, you can see a lot of little branches. Um, so, uh, they always quite vary, but those are the steps. Dissect out the rex recessus, inspect the venous branches, and then sew the vein graft first to the liver and then to the vein that is going to bring blood to the liver. There are alternate veins to the uh uh jugular. Many parents are quite concerned about harvesting the jugular vein for uh our operation. So here's a a nice example on a CT scan of a large inferior mesenteric vein, and we're always happy to see that. Um, you can actually see here in this picture that it's actually quite long when you, when you, when you take it out from the pelvis. And we only divide the pelvic end, and this is the, the, the, the proximal end is going into the splenic vein and superior mesenteric vein under the ligament of trites. And so we bring it up over the pancreas, and you only need 4 or 5 centimeters, really, there's not much length needed uh in comparison to what you can take out. It's very important not to twist it, and it takes a bit of practice to get it right, but it's a very, very suitable alternate. Um, I'm going to skip this slide. Now, I got a lot of, uh, there's a lot of debate, and I hear people ask me this all the time. Why is a Mesorex better than a ported systemic shunt for expetic portal vein thrombosis? And in fact, uh, you know, there was actually a paper from Toronto that questioned this, uh, Augusta, I'm sure you're aware of it. You, you weren't on the paper, but, uh, it's based on, I think, uh, some, uh, assumptions that are not really, uh, valid. But, so here's we did a comparison, a comparison of, of, uh, the two methods in, in patients who uh had expatic portal vein thrombosis in approximately 160 patients. This was an older study. And there's no question that the Morex and the potosystemic shunt are both equally effective in controlling GI bleeding, um. What about hypersplenism? Uh, you can see here the preoperative spleen size in the two cohorts of patients were quite similar, and the delta in the spleen size after the, uh, the operation was also quite similar, but the delta in the platelet count was better after the Mesorex, 77,000 as opposed to the porttosystemic shunt, which was only 29,000. And so you can see that there's a modest increase after a splenary renal shunt that is not as good as after a Mesorex bypass. What really stands out though, is the improvement in the liver function. The INR is always abnormal in kids with portal vein thrombosis, and you can see here that preoperative INR is similarly uh prolonged, but in the mesorex bypass patients, the INR goes down towards normal. Whereas in the splenor renal shunt, uh, it goes up or stays the same, so there's a significant difference after the restoration of portal blood flow to the liver, and we think that this is because the liver is able to synthesize factor 5, factor 7, protein C, and protein S better after the Measorex bypass rather than. Uh, after a reported systemic shunt, and you can see here, these are also a study that was done a few years ago that was published in pediatrics, where there's an increase, significant increase in the factor levels after Mesore bypass one year after the surgery. Growth is also something that takes place after um Uh, after Msorex, the metabolic profile of these children was studied and published in the Journal of Surgical Research a few years ago, um. Patients with exoppetic portal vein thrombosis have diminished growth. They are usually smaller uh in weight and age and weight, uh, BMI and in height. And you can see that after uh the Mesoic bypass, there's an increase in both the weight Z score as well as the um Uh That is significant, uh, when, uh, you look at it in comparison to the cohort of the protosystemic shunt, um, group. Reversal of encephalopathy. This was a girl who had a splenor renal shunt who was encephalopathic after her operation. We, um, reversed it by doing a Mesorex bypass, and her ammonia levels went from well over 100 down to normal within 2 days after the surgery, and her encephalopathy disappeared. So our total experience is uh now well over 200 patients. There's uh 235 or more. Uh, you can see the average age of diagnosis here on the histogram on the top is approximately 4.8 years, and the age, average age of surgery is 7 years, but we have done children as, as young as 3 months of age, um, so size and age are not a contraindication to do the Mesore bypass. What's interesting here, you will see that there are 12 patients who are asymptomatic, and I will talk a bit about this um in a few more slides. We are lucky to have um radiologists here who have an interest in this, and we are able to calculate the portal vein flow. In the missorex as a function of cardiac output. And you can see here on the Y axis, this is the Mesore bypass flow as a function, I'm sorry, as a function of, of the systemic circulation, and these are individual patients on the X axis, and you can see that the mean restoration of portal blood flow is approximately 18% of the systemic circulation. But it varies anywhere from 5 to 25%, and we think that portal blood to the liver is approximately 20% of cardiac output. So this correlates well with our, our, our physiological knowledge and the results after Mesorex bypass. And what's interesting if you, if you plot missorex bypass flow as a percent of systemic circulation and, and plotted against the platelet count, you can see there's a very tight correlation. And somewhere around 10%, you reached the threshold of 100,000 platelets. Um, so most of these patients have low platelet counts and, um, platelet count is restored towards normal with about a 10% um restoration of, of, of portal blood flow as a percent of systemic blood flow. So in 2006, we published something in pediatric transplantation that was surgical guidelines for the management of ectoppatic portal vein obstruction, and we were very conservative in our recommendations at that time because the experience really was not quite that as extensive as it is now. So usually you reserve the operation for patients who had refractory variceal hemorrhage or severe hypersplenism or had really life threatening symptoms, and we classified the relative. Indications as symptomatic splenomegaly or large varices and poor access to health care or some other form of symptomatology which was not quite as severe. Failure to thrive was one of them, perhaps neurocognitive testing that suggested encephalopathy, but now, um, 20 years later. We are classifying this uh definition of indications for treatment as treatment for symptoms. Prophylaxis with clinically evident portal hypertension, or varices that are there but have not bled. But we also have a group that were pre-primary prophylaxis, and this is of great interest to us. In other words, patients who are completely asymptomatic, who have no physical signs of portal hypertension, uh, whose parents come to us wanting us to correct the defect. So, pre-primary prophylaxis or platelets above 150,000, no endoscopic or imaging evidence of viruses, and a spleen that is really um not, not impressive by physical exam. You can see that if in our total experience, um, most of the patients are symptomatic. Uh, with 155 out of 235, uh, being symptomatic, but we have a large group of patients in whom the operation was done for prophylactic reasons, and we have these eight patients which are of great interest to us, uh, who were operated on in the pre-prophylaxis stage. Now the decision to operate on a well patient can be quite difficult. What criteria must be met? Well, in our cases, the intrapatic portal vein must be near nearly ideal, as in this picture. Uh, there has to be a normal hepatic venous pressure gradient. The jugular veins has to be intact, and there have to be no serious medical contra indications of surgery. And more importantly, the parents must be able to articulate their expectations. In other words, we have to have a high expectation of success, and the parents must also know that this is not necessarily going to change their child's life in the present, but hopefully will improve their life in the future. Now, if you, if you plot platelets uh against the level of symptoms, you can see that the pre-primary, the pre-primary prophylaxis group all have normal platelets. There's only 8 patients, but all of their platelet counts are normal, and that was by design and by definition. But if you look at their preoperative ammonia levels, you can see that the pre pre-primary prophylaxis group have ammonia levels that are actually as high or higher, not significantly higher, but certainly within the same range as the other two groups. And when you do a successful measorex bypass in this pre-prophylactic patients, you can see a decline in pneumonia levels in all patients. There's one that has an asterisk, and that was because it was actually uh the ammonia was level was measured in another patient in another institution, but there's almost a significant decrease in ammonia levels in the pre-prophylactic patients. So we believe that the major impact on operating on pre-prophylactic patients is that we will, we will be improving their hepatic encephalopathy. And to prove that point, now we have an ongoing study, uh, which is uh an NIH toolbox, which is um administered quite easily in the clinic. That measures or assesses neurocognitive testing in children as young as 3 years of age, and we do it before the procedure, 6 months and 1 year after the procedure, and we would hope to have that um. Those results soon. We also have done it in children who have failure to thrive. This is a Mesore, uh, diagram, restoration report of blood flow in someone who was, um, Um, operated on, and you can see here that their Z scores improved from 0.98 in length for age before the surgery to three years afterwards and had gone to a positive number, 0.28. So, overall, sorry, that was my timer. I'm almost done. Um. Of the 237 patients we've operated now for idiopathic portal vein thrombosis, we have an overall patency rate of 70%. In other words, 70% of patients who come to us with exoppatic portal vein thrombosis can have a successful measorex bypass, which is quite a high number. And so now we feel that uh patients will qualify for a prophylaxis or pre-prophylaxis if they have acceptable intrapatic portal vein anatomy, uh uh a good sinusoidal wedge pressure with an acceptable liver biopsy. But more importantly, um, those, those conditions outlined in yellow were things that we discussed at the time of the vena conference in 2015, which I don't think no longer apply. Um, in other words, I, I don't think we can exclude patients who have an intrinsic prothrombotic state cause many of them do. We've operated on patients well below the weight of 8 kg, and we have certainly done, uh, these operations in patients who have, um, Pulmonary hypertension. In fact, it's mandatory that we do that. Otherwise, you will need a liver transplant. But I think what's most important here is number 2. In order to do these operations, you have a, to have an institution and a team that is really uh uh experienced in doing these operations uh before you can take on patients who have uh minimal symptoms and expect to have a successful outcome. So institutional competence is something that I think is quite important, and that's not just the surgeon, it includes the hepatologist, interventional radiologist, and the ICU. So in conclusion, I, I want to say that uh I hope that I've convinced you that the Mesouric bypass is preferable to purported systemic shunts for the treatment of this disease. If you have to, uh, distal sin or renal and meso cable shunt can provide acceptable palliations. And that the Morre uh provides relief from not only the life-threatening symptoms of portal hypertension, but it corrects the physiological functions of the liver, including restoration of coagulation factor synthesis, and reversal of encephalopathy. Um, we have done patients from all over the United States and from many different countries on the left. Um, Nobody from Italy yet, but uh there's always hope. Um, and we invite you to join, uh, an international registry, which uh we will, uh, People can write to me if they wish to join this registry, um, and it's really a simple database that will be sent out to anyone who is participating who wishes to participate in terms of getting an idea of the international uh volume of patients who have had the measurex bypass. And some simple follow-up data. Um, it'll be quite exciting to have an international group to that that can join together to do research and to get an idea of what the activity is out in the world. So thank you, Merci grazie, gracias. We'll see you in Istanbul, hopefully um in June. Thank you very much. Thank you very much, Rick. That was, uh, an awesome talk. Uh, by the way, it's not Istanbul, it's Izmir. So it's, uh, Turkey. Oh yes, I'm sorry. My, my, my slide is correct, but I slipped. I just wanted to make sure nobody books a flight to Istanbul. I think there's good connection to Izmir, however. So, um, yeah, I have a bunch of questions already, but the tradition of this webinar is that we listen to the second speaker first and then do it like a joint. Um, so I have the privilege to introduce the second speaker of this afternoon's session, which is Professor Caroline Lemoin. Uh, she's a pediatric transplant surgeon, also and hepatobiliary surgeon, got a degree in biochemistry from the University of Montreal, studied medicine at that university and did her residency at the de Sherbrooke. Um, this was followed by the, uh, Pediatric Surgery Fellowship in Montreal and two other fellowships at Northwestern University in pediatric transplant and hepatobiliary surgery and abdominal transplant. And finally, uh, 3 years ago, she received a Master in Science and Clinical Investigation. Currently, since the last 6 years, she is assistant professor of surgery at Northwestern and um a pediatric transplant and hepatobiliary surgeon at the hospital where Ricardo Saarina is working, and she's, in fact, the surgical director of the pediatric kidney transplantation Program at that hospital. Uh, Caroline has a, a lot of honors, which Please, Caroline, forgive me that I do not list completely, but um you're a very active surgeon scientist, uh, publishing a lot of interesting papers, especially which are clinically relevant uh to a lot of us and in the field of hepatobiliary and transplant surgery. Um, her research is supported by two major grants, uh, from the Lore C Children's Hospital. Um, and she's co-PI of the NIH, two grant that Rick mentioned on metabolic sequela of, um, horsystemic shunting, and another grant on the nutritional, uh, evaluation of children with apatic portal vein obstruction and deficit undergoing Msore bypass. So, Professor Lewan, it's a great honor and pleasure for us to have you with us this afternoon, and, um, we are looking forward to your talk. Thank you, Martin. I will uh share my slides. Perfect. All right. So, um, I want to echo, uh, Doctor Supina's mention on inviting me to be part of this webinar. I really appreciate it. We're both sitting in the same room, so I'm actually talking through, through doctor's computer, Doctor Sabrina's computer. Otherwise, there would be some weird echo and it would probably take a while to fix this, but, um, All right, let's try this. Uh, Should be working now. All right. So, Doctor Suprina covered uh very well the extrahepatic portal vein obstruction, and I will be focusing on what is not extrahepatic uh portal vein obstruction. So I have no disclosures either. So, uh, I will be covering briefly the causes of portal hypertension that are hepatic or post-hepatic and then focus on the interventional options and why at our institution, in our experience, we favor portalsystemic, uh, surgical portalsystemic shunting for those children, specifically the distal splenorenal shunt. I'll focus on our experience also and, uh, on specific populations that, uh, We shunt so the biliotresia cystic fibrosis and the congenital hepatic fibrosis. So, uh, I don't, I won't repeat everything about portal hypertension, it's diagnosis or what makes, um, uh, the specifics of it, but just to review the causes. So again, focused previously on the prehepatic causes for which the measorex bypass, as Doctor Suprina, I think really made clear is the measorex bypass is really the best intervention for that, uh, population when at all possible. Now, for patients that have liver disease, uh, the Meteoric bypass is not an option because as you're gonna bring blood flow to the liver, the high pressure inside the liver are gonna make it impossible for the shunt to flow. So therefore, you have to look at the portal systemstemic shunts for that subpopulation. Now, there are some important things to, to think about, which is if you have liver disease, it has to be compensated liver disease for protosystemic shunting to make sense. Obviously, if you have decompensated cirrhosis, then that would not be um a good intervention. So, when we think about the options for managing a patient with liver disease and portal hypertension, well, first, if some of our uh gastroenterologist colleagues maybe join or people at their institution, maybe the gastroenterologist will recommend ongoing banding for varices, um, either before they bled or after bleeding. But as there's research that's ongoing looking at the neurological effects maybe of repeated general anesthetic, uh, those are the, the options I have listed here are more a single intervention, one general anesthetic as opposed to many repeated ones. So, obviously, this talk is going to be on portalsystemic shunts, so what could be the benefits of it? So the, the complications that are technical from it should be low, and there's a possibility that it could maybe delay the need for a liver transplantation in well-selected patients. However, shunting can lead to complications that we've already presented, so hepatic encephalopathy, liver masses, hepatopulmonary syndrome, which are not insignificant complications. So, um, other institutions may be looking rather at tips for patients with underlying liver disease. It's not a surgery per se, although you get radiation and maybe a long time under general anesthetic. Um, most of the literature is in teenagers rather than small children, and we know that the rate of complications in smaller children will be higher, and this is mostly from case series really. But, uh, you will again get those um complications of portalsystemic shunting, hepatic encephalopathy, the nodules, uh, possible thrombosis of the tips, hepatopulmonary syndrome, such as, uh, so that actually in most institutions, including ours, this is used as a bridge to liver transplantation. So we do not routinely perform TIPS. It's really the exception that we'll get the TIPS at our institution. Um, other teams might say, well, if you have liver disease and portal hypertension, might as well transplant the child. You will cure the portal hypertension, and you will treat the underlying liver disease. But it is a very major surgical intervention with um possible life-threatening complications um and independent of that, it will subject the patient to lifelong immunosuppression and complications of immunosuppression, so this is not a small uh ordeal. And also there is scarcity of resource, right? Are there enough livers for the entire people on the waiting list? And the answer is no, there is still mortality on waiting lists, especially in the United States. So, so for a child that has decompensated cirrhosis, absolutely, that patient should get a liver transplantation. But for patients that have preserved liver synthetic function, then we think that Other interventions should be offered to those patients so that the livers, the organs can go to the patient that absolutely need it and therefore portal systemic shunting comes into play. Uh, when you look at protosystemic shunts, surgical ones, that is, there are two main classifications, the selective and non-selective shunts. So the selective shunts is the, um, distal splenorenal shunt, the Warren shunt. Uh, versus the non-selective ones that include proximal splenorenal shunting, portal cable, measle cable, clapworthy, and again, those compared to the tips that I, uh, previously discussed. Both are very good at treating portal hypertension. Um, the GI bleeding, uh, will be improved and the hypersplenism. However, the main difference and the arrows kind of point to it, the selective shunt is only a selective portion of the mesenteric venous, uh, splektic circulation will be derived away from the liver into the systemic circulation. So therefore, there is still some blood that will go to the liver. Mind you, the liver being a high resistance organ because of the intra uh hepatic pressure. Um, it's not gonna get normal portal venous flow, but it will still get some as opposed to the. Non-selective one, sorry, where the blood flow will go away from the liver and then lead to um worsening complications of protosystemic shunting, so hepatic encephalopathy nodules, which um is less in our experience in the selective shunts. So I'll just take Little sip of water. And let's keep going. So, before you do a portalsystemic shunt, however, there are some very important preoperative considerations, and those are the tests that we perform, um, because obviously, if you detect, uh, a condition that becomes a contraindication to portalsystemic shunting, again, this patient should be referred for liver transplantation instead. So the first thing obviously is liver synthetic function tests. You should have preserved synthetic function in order to consider a portalsystemic shunt. So nearly normal INR, normal bilirubin. And the albumin. If for any of those reasons, the tests are so abnormal, then refer for liver transplantation. As we see the patient in clinic, all patients get a 02 saturation measurement, um, as low saturation can be associated with hepatopulmonary syndrome, which again would be a contraindication to shunting. All patients get an echocardiogram to look for both, uh, mostly for pulmonary hypertension, but for patients with a low saturation, we also add a bubble echo to evaluate for hepatopulmonary syndrome. We obviously get cross-sectional imaging for two reasons. One is, again, a roadmap. So see what vessels are available, make sure that the splenic vein is available before performing a splenorenal shunt, and making sure there are no liver masses, uh, which again could be exacerbated with protosystemic shunting postoperatively. Last but not least, hepatic encephalopathy, like Doctor Stuparina mentioned, is very difficult to really identify in patients. A stage 4 patient that's comatose is obviously very obvious. But patients that have really minimal hepatic encephalopathy, change in their sleep-wake cycle, um, patients with ADHD, um, patients that may be irritable, uh, especially small children, it's difficult to determine if it's encephalopathy or if it's just normal development. Um, and I think both surgeons and hepatologists still struggle in making a clear diagnosis preoperatively. Um, there are, uh, ongoing studies like we have here with, um, toolboxes that can be administered in clinic in less than an hour, which might be the next best thing in evaluating those patients, uh, to determine, uh, if they are candidates for shunting or not. So, uh, looking at our experience, and I will solely talk about the distal splenorenal shunt because this is the vast majority of portal systemic shunts that we perform. Uh, uh, we've also done measal cable shunts, uh, but again, this is, uh, a minority of patients. So for our patients in the last 25 years that have received the distal splenorenal shunt, so 131 patients, you can see that it's pretty well divided between patients that have a history of liver disease or uh extrahepatic vein obstruction or patients with uh normal um liver disease, liver, I'm sorry, after liver transplantation but who are not candidates for a measorex bypass. So I'm focusing solely on those with underlying uh parenchymal liver disease. As you can see in the pie chart, the majority of patients referred to us are the patients with congenital lymphatic fibrosis, um, autosomal recessive, uh, polycystic kidney disease, Joubert's syndrome. Biliary atresia and cystic fibrosis then compose the other two groups that we see frequently. And in the other group, uh, you have patients with autoimmune hepatitis, PFIC, PSC, alpha-1 antitrypsin deficiency, uh, and veno occlusive disease after chemotherapy administration. Uh, that present us with portal hypertension. Um, so, Just to look at all those 66 patients and how the splenorenal shunt has been effective in treating them. So you can see that there was a significant improvement in their platelet count. And also in their spleen size after the distal splenor shunt. Most patients that were referred to us had a history of GI bleeding. And only a minority of them uh have GI bleeding afterwards, and actually most of those patients had, um, either a stricture that was diagnosed or another reason why uh the shunt was not performing as well as it should have. Importantly, this is their liver synthetic function before and after the shunt, so you can see there's no change in the INR albumin. Uh, the direct bilirubin did increase, but only by 0.2, so it still remains in. Uh, overall normal range. And also when we think, think about the repercussions of protosystemic shunt, again, hepatic encephalopathy is extremely difficult to evaluate. Um, if it's occurring or not, and the only really measure that we have is the ammonia measurement, um, which is not a perfect and not the most reliable way to see if there is underlying hepatic encephalopathy or not, but you can see that did not change significantly as patients are often shunting beforehand anyways, um, from their portal hypertension. The incidence of complications is low, uh, thrombosis or stricture from the shunt requiring intervention. The recurrent GI bleeding. Um, the masses, hepatopulmonary syndrome, and you can see that down the road, about 10% of patients will ultimately require a liver transplant. On average, 5 years after um they're shunt, so at least you have bought them some years with their native liver before having to undergo a transplant. So now looking at those three specific populations. First biliary atresia. You can see that 11 patients have been referred to us. You can see that they have preserved synthetic function, and it was about half and half in patients that were referred to shunting for hypersplenism or history of bleeding, but that those who were referred for bleeding, uh, received their shunt at a younger age. Looking at results, uh, again, significant improvement in the platelet count, nearly significant improvement in, um, spleen size, and no recurrence of bleeding after shunting. Without any negative impact on the liver synthetic function, um, as previously described. No shown strictural thrombosis. One patient who developed hepatopulmonary syndrome that ultimately was um transplanted. No mortality, and you can see that about half of the patients are alive with their native liver. Uh, 5 patients were transplanted, but as you can see, the median time to transplant was 10 years, so the one who had the shortest time is the one who developed hepatopulmonary syndrome, and that makes sense. But you've gained 10 years with their native liver, avoiding the transplant, avoiding the immunosuppression, and the possible complications of transplantation. And 2 of those patients were transplanted as adults. Looking at cystic fibrosis, 10 patients with preserved synthetic function, most of them referred for hypersplenism, only 2 with bleeding. Significant improvement in spleen size and uh almost significant improvement in platelet count, no recurrence of bleeding, and again, preserved liver synthetic function. No, uh, technical complications or uh other development of portalsystemic complications. However, one patient died, uh, about a year after her shunt. She had the worst, uh, Function, lung function before her shunt and for that specific population, it's important to say that they all have obviously pulmonary function tests preoperatively, um, and they usually have a good, uh, preserved lung function, otherwise they would be referred for a lung liver transplant probably or at least a lung transplant, but this patient was actually not a lung transplant candidate because her pulmonary reserve was so bad. So the only option really for treating her was the deposplenorenal shunt. So the patient survived, only 1 patient was transplanted with a median follow-up of 5.5 years, and this patient was transplanted as a teenager. Last, looking at the congenital hepatic fibrosis, so the majority of our patients, 26, half and half referred for hypersplenism or bleeding. Significant improvement in platelets, spleen size, uh, and two recurrence of bleeding postoperatively, so a minority, uh, associated with a stricture post, uh, shunt. And uh you can see that the one thing in their liver synthetic function is that the bilirubin increased but still uh remained relatively low. One patient uh strictured, like I mentioned, one had thrombosis that was in the very early experience of uh our uh program in the late 90s. And, uh, the vast majority is alive with their native liver. Only 3 patients were transplanted and not because of progression of liver disease, uh, but for example, 1 had a recurrent cholangitis or had other interventions, um, or, um. That were unrelated to their liver synthetic function. So in conclusion, looking at the distal splenorenal shunt for patients with compensated liver disease, and that's a very important point to remember. It effectively treats hypersplenism. Uh, reducing spleen size and also, um, almost nearly, uh, in all patients, uh, preventing recurrence of GI bleeding postoperatively. It preserves liver synthetic function and allows uh prolonged survival in the majority of patients with their native liver. And, uh, either prevents the need for a liver transplantation, at least as a child, or increases the time to liver transplantation, and again, they can therefore be alive more years with their native liver. However, complications may arise and therefore those patients need to be followed at least yearly to look for the development of pulmonary hypertension or hepatopulmonary syndrome, liver masses, or hepatic encephalopathy. So in conclusion, liver transplantation is not always necessary to manage portal hypertension. In our experience actually, for patients with stable chronic liver disease, uh, it is rarely needed. Uh, however, uh, it's important to refer patients to centers that have both expertise in hepatobiliary vascular surgery and transplantation in order to, um, help those patients get the best intervention for their condition, which may be transplantation, but in many other instances, uh, maybe a, a portalsystemic shunt. Thank you. Thanks, thanks a lot. This was a great talk, 222 great talks and uh an incredible amount of experience and uh and a number of patients, so. Um, we'll go through the chat. there's quite a number of questions, uh, starting off with Dr. Haider Ali Canrias. He's asking how, how I would like to ask for the opinion of the panelists about using vein grafts from tissue bank in case of patients with inaccessible internal jugular vein. I think you're both muted. Hi, uh, thanks for that question. Um, So the history of tissue banked vein grafts is not a good one, at least not in the liver transplant world, uh, there's a high incidence of thrombosis, so we prefer not to use them. Um. There's nothing better than an autologous vein graft. Uh, we have used, uh, vein grafts from, uh, deceased donors that are, that have not been used during the transplant. And, uh, I think the experience in that, and I, I, I've only done it once, but that, uh, vein underwent chronic rejection because the patient was not on immunosuppressive medication. Um, and I think, uh, that has been the experience of, of another person who, um, I spoke to. Um, so the answer is we have not used it, uh, because we are worried about the higher incidence of thrombosis. OK, OK, then there's a question from an anonymous. No, I just want to say it is a problem when you have an inaccessible internal jugular vein. There's no question about it. And so in those cases, we try to use the uh inferior mesenteric vein, as I sort of alluded to briefly in my talk, and we've also used Gore-Tex graphs with some success. Right. Then there's an uh question from an anonymous delegate post Morra as these patients are thrombocytopenic, do you still anticoagulate with heparin? Obviously, uh, thrombocytopenia is a contraindication to heparin. And then the question, the second question also goes into the anticoagulatory, um, field on discharge, which anticoagulation do you discharge with warfarin? Or any newer agents like revo, Rexiban, and ixaban. And what is your target level and so on? Can you comment on that? Sure, um, so, uh, one thing we've learned is that you can clot very well with platelets of 20,000, so we don't let thrombocytopenia, uh, make us nervous about bleeding. In fact, the night before surgery, we give them, uh, clopidogrel, um, which is an antiplatelet agent, so And then during the surgery, we give heparin, full heparin dose to anticoagulate them. So during the surgery, we have both an antiplatelet agent as well as heparin, uh, full anticoagulation. After the surgery, uh, we will, uh, give low dose heparin until the patient can start eating again, and when they start eating again, we stop the heparin and restart the clopidogrel. In patients who have a defined hypercoagulable condition, say they have a factor 5 Leiden mutation, or even worse if they have a homozygous factor 5 Leiden mutation, then we anticoagulate them for 6 months with usually uh So we say it it was low molecular weight heparin like Lovenox. We have not used some of those other agents that you that you mentioned, um, which there's no reason, it's just a matter of, of habit, um. I'm, I'm sure that we could use those too, but in most cases it's only necessary to use an antiplatelet agent for post-op. OK, thanks. The next question from Doctor Amit Gupta asks, what is your preference in non-cirrhotic portal fibrosis? I'm sorry. You're taking. So for non-cirrhotic portal hypertension, um, and, and that can be difficult sometimes to diagnose. So some patients are referred to us to do the venogram, and the intrahepatic portal vein looks good. They usually would have a normal extrahepatic portal vein, but sometimes it's not that simple to, to differentiate. And, but in general, if we know ahead of time that it's really non-cirrhotic plural hypertension, then we'll go ahead with the, the distal splenronal shunt. Uh, we've had Less than a handful of patients, maybe 3 or 4 that I can think of that were maybe not that clear ahead of time. The biopsy was not really diagnostic either. We went ahead and did a measorex bypass on them, and then the mesorex bypass was, the flow never worked out. The, the spleen didn't improve inside, the platelets either. We troubleshooted, making sure there was no stricture of any anastomosis of our shunt, and ultimately repeated venograms really showed that intrahepatic pruning. Of the veins that's associated with um non-cirrhotic portal hypertension. And, and those kids sometimes need to be converted to a distal splenorrenal shunt. So, so we consider those as patients with intrinsic liver disease and therefore we opt for portalsystemic shunts and not the sorex bypass the main problem. OK, next question is, um, how often do you monitor with ultrasound on discharge? And if I may add that, you mentioned that your, um, your patency rate is around 70%. So you may also comment on when do they close, if they stenose or close, and what is the, is there a critical time and how do you monitor that? Yeah, no, I think, thanks for bringing that up. So I just want to clarify that 70%. The 70% is not the patency rate. The 70% was the percentage of patients who come to us with expatic portal vein obstruction in whom we can successfully do a Measorex bypass. Um, Of the patients who, who do get a Mesoic bypass, I would say, you know, 95% of them remain patent. Um, so it's just a matter of Of, uh, of, uh, basically assessing the patients who can be successfully bypassed or not, and I think this is where the preoperative venogram comes into question. If they have a very good preoperative venogram, there's almost 100% chance of success, and those patients will stay patent for, you know, for forever. Uh, I followed the patients for 10 years, and then I finally, uh, feel badly that I keep bringing them back for nothing because they're basically normal patients. Um, the 30% in whom we cannot do a Mesorex bypass because, and it's usually because of the poor quality of the portal vein inside the liver. There's nothing we can do about that, and those patients get a splenor renal shunt, you know, Carolyn didn't talk about those patients because they're not in that intrinsic liver group, um. You were you saying the uh uh warfarin? What was the second part of your question, Martin, or the second person? The follow up with ultrasound. Oh, ultrasound. Yeah, we do a lot, a lot of ultrasounds. We keep our radiologists very busy. Um, we use, you know, we do 1 or 2 ultrasounds during the first week while they're here, and then we bring them back every 3 months with ultrasound. If there's a problem. For the first year. For, yeah, for the first year. If there's a problem with any suspected stenosis or some problem with the shunt, we will get an MR and we get an MR, uh, fortunately, we have very good access to MR and we always get an MR at one year. And that data that I presented in terms of calculation of portal blood flow as a percent of systemic flow comes from our MR data. And so we get, everybody gets an MRI at one year. And if we suspect that there's a problem during the uh somewhere in the postoperative period, we will get an MR. And I didn't talk about our interventional radiology, but. Of the patients who have marginal intrapatic portal veins. Some of them need to have strictureplasties done. There's about a 15 to 20% incidence of strictureplasty, so we didn't have time to get into all of that. But, um, needless to say, the radiologists are, are very uh close colleagues in all of this. So the next question is for Dr. Suri and from Dr. Rustam Yilishev, I think from Uzbekistan, and he's asking, how do you manage children with widespread thrombosis of the portal venous system. Hi, Risdom. Good to hear from you. Um, Yeah, it's a big problem, um. What we've done, I mean, it depends on how widespread. So if the intrapatic portal vein is patent, but the extrapatic portal venous system is uh has widespread thrombosis, we have sometimes used larger viruses. Uh, to function as the inflow. Uh, the coronary vein sometimes can function as the inflow. Sometimes we've used large general branches, uh, as the, uh, for the inflow. So there's usually some vein that's open, um, that can function as the inflow into the Mesorex bypass. If there's really nothing, then of course you can't really do a shunt, uh, or you can't do anything really, um. And in those cases, what we have done is if they are obviously bleeding and have a life threatening hemorrhage, we will do a segura operation on them with the the esophageal and gastric devascularization. Uh, we do the modified segura, which is Uh, sparing the spleen. We tried to do a spleen preserving Segura operation, not like the classic gua where they took the spleen out. Then there's another question of another or maybe a colleague as well. Hello, uh, doctor. My son was born with genital heart defect, uh, which was corrected surgically at birth. It was a transposition of the great vessels, VSD ASD at one year old. He was diagnosed with a portalcavaoma, portal hypertension and esophageal varices. And at that time, they were told that he was not a candidate for miserection. Is there any chance, that is the question now, then this will change in the future? We are now waiting until the shunt will be done, but I was hoping that as he grows, Misare will be possible. What do you think? He's now 2 years old. So, uh, if you remember, I, in, in the early part of the presentation, I said something about 25% of our patients have congenital heart disease. In fact, the very first measorex I did was a kid who had um tetrology of flow. So, depending on how bad this Child's heart is. I mean, if he has very high elevated central venous pressures and the intrapatic portal pressure is high, and, and, uh, it, it's possible that the gradient, um, there has to be a favorable gradient for the flow to for to go forward into the liver. So I would have to say that in order to answer that question properly, we would have to know what the. The uh central venous pressure is, what the prehepatic vein pressure is and what the wedged pressure is. Some patients do develop fibrosis with uh chronic heart disease, and it may be possible, it may be not possible to, to do it, but um we would have to know that kind of information or to answer that question. I think in absolute terms, it should be possible. We have operated on many patients with congenital heart disease, uh, successfully with the Mesore bypass. So I'm, I'm not sure what the reason for, uh, whoever said it's, it's not possible to do it now. Do you want to comment on the likelihood of success in older children versus younger children? Cause I think that's part of the question also, hoping that as he grows, he's a candidate. Yeah, I don't know what the, what the, what the reason for that is. Um, we didn't get into that in terms of this whole business about waiting till the child is older is not really something that I believe in, um, for patients, yeah, I think part of that was because you, people thought that the veins were larger and that it was easier technically to do the bypass, but, uh, in fact, now with, you know, we do liver transplants on small babies, size is not an issue really. But thank you for for that clar was 3 months old you mentioned. Yes, 3 months old. Two twins actually, one, and they were both born premature, so. Another question from Dr. Amit Gupta seems like a a case like a vignette. 11 year old boy, type 1 diabetes, diabetes mellitus, massive epitospernomegaly, pancytopenia, hypersplenism, portal hypertension, non visualization of middle and left hepatic veins, and attenuated right hepatic vein, dilated portosystemic collaterals. Is there a question there? I think, what, what's your next step in management? I, I, I. I think, uh, the first question is what's the reason for the portal hypertension, right? So, it looks like the hepatic veins may be obstructed. Difficult to know why with the information we have so far. Um, like I mentioned, we've had at least 3 or 4 patients with veno occlusive disease after chemotherapy, um, and that's the reason it's like a budchiari setting where they more of a chronic one than an acute one obviously where they end up needing. They end up getting uh portalsystemic shunt. But uh we've had patients with diabetes, um, but they've had, they have other kind of liver disease, so I would wonder if there was a liver biopsy that was done, maybe to help in diagnosing, uh, what the underlying liver problem is. Uh, if the non-visualization of the veins is based on what kind of imaging? Is it cross-sectional imaging? Is it ultrasound? Maybe a venogram would be good to see, uh, what's going on because Diabetes in itself is not a contraindication for a measorex bypass, but obviously if you have post hepatic obstruction of the hepatic veins, then a measoric bypass would probably not flow. Um, I think a venogram with, uh, pressure measurement to see what the, the parenchymal pressure is would be helpful in confirming that he is not a measorex bypass candidate. And that therefore, uh, maybe a spleen shunt would be a better option. Obviously, making sure that the uh splenic vein is also patent, so I just saw that I think it's on ultrasound, I guess USG is that what the acronym stands for? Maybe the same, yeah. So if it's only been an ultrasound, I think you need cross-sectional imaging like a CT scan or an MRI, um, then probably a venogram with pressure measurement and better evaluation of the hepatic veins, a liver biopsy that could be done transjugular at the same time by the radiology team to better understand the cause of liver disease and but it seems like it's, this is really true that he would be looking at a total systemic shunt like a distal spironal shrunk, for example. It's asking interventional radiology. Um, so this is the team for us. Uh, it's a team of radiologists that does the, um, the venograms for us. So there are specialized radiologists that do intervention, so they will do the pressure measurement and the liver biopsy. They would be the same also in certain institutions. All right, I see no more questions in the chat. So as we are over the hour already, I think I can, uh, close this, uh, session. Thank you very much. I think we heard two really awesome talks, speakers in the field. Really enjoyed it. Um, and we were, uh, in the meanwhile, I think around 100 delegates watching this. Um, it was great fun. This video will be edited and put on the YouTube channel, uh, YSA YouTube channel next week. And I bet a lot of people will, will, uh, listen to that at a later time. Um, again, thank you very much from my side. Thank you also to Gaya for setting this up. Um, I know you guys are all busy, and uh we really appreciate that you took your time to To share your knowledge with us. Thank you very much. It was great. It's great to see everybody virtually. Bye-bye. Ciaos a person he needs me. Bye. Bye bye. Diechvog von Neum Lieben ist wiglichber Einrogensweitereffenfernander Verlieben sighund Werden Eitz. 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