Betsy Post 0:05
So welcome everyone to tonight’s DocTalk. Thank you so much for being here to watch this live, and then for those of you that will be watching the playback, thanks so much for your time. I am so excited to bring Dr. Padmanabhan here to talk to us about the optimal management of colorectal liver metastases, the perspectives from a liver surgeon. Dr P has many fans in COLONTOWN, in the hepatic pump group, as well as in the main liver group, really passionate fans of his work and the life saving techniques that he uses at Vanderbilt. So it’s such an honor and a privilege to have him with us tonight. Thank you so much for being here. I’m going to turn it over to you in just a second, but just as a reminder for anyone that’s joined us live, please know that there have been some questions that were submitted in advance. So if you did have some questions that made the cut off to be submitted in advance they were submitted, and then he is going to do his presentation. And then any questions that you have along the way, please put those in the chat. So there’s a chat feature. Please use that to put your questions in the chat, and then at the end, we will save some time to go over the questions that come up throughout the presentation. So you’re all muted. Please put the questions in the chat if you have tech issues, Megan is here. She’s under COLONTOWN cabinet, and then I’m here under my name, Betsy post. So please just ping one of us if you have an issue. I’m going to turn it over to Dr P again. Thank you so much for being here. The floor is yours.

Dr. Padmanabhan 1:41
Great. Good evening, everybody. Thank you Betsy, Thank you Megan and thank you COLONTOWN for the opportunity to speak to you all tonight and to any of my patients who are logged in. Thanks for being here. I am eternally humbled that all of you have put your trust in me to sort of play whatever small role I have in your treatment. It’s truly, truly. To say that I’m humbled is an understatement, and I really appreciate you, know, you guys trusting me. So for those of you that I don’t know a little bit about me, so I’m a I call myself a hepatobiliary surgical oncologist. I practice at the Cancer Center at vanderwald Medical Center. And you know, for those of you that sort of don’t know how you become an HPB surgical oncologist, the path is not a short one. So after four years of undergrad and four years of medical school. I did my general surgery training here at Vanderbilt, and then I went to Memorial Sloan Kettering Cancer Center in New York City for two years, where I trained both in surgical oncology and hepatobiliary surgery. So that’s why I sort of call myself hepatobiliary surgical oncologist. I was fortunate to get recruited back to Nashville, and my family and I have been back here, and I’ve been on faculty for coming up on three years now this summer. So some of you might be wondering what this portrait is. So it’s actually a portrait painted by Peter Paul Ruben, 1618, it’s, it’s on display in the Philadelphia Museum of Art, and it’s actually entitled Prometheus Bound. So for those of you, I was a, I was a classics minor in college, and about the only thing that I remember from my time then is, you know, so Prometheus was a Titan, and he actually steals fire from Zeus and the gods and gifts it to mankind. Zeus, you know, as petty as the Greek gods were, was sort of enraged by this, and he chains Prometheus to the side of a mountain top and sets his golden eagle to sort of feast on his liver during the daytime and during the night time the liver regenerates. And so this sort of happens day in and day out. And it’s just interesting to me that the ancient Greeks, even at their time, had this concept of liver regeneration, you know. And basically, my field is dependent on hypertrophy of the liver after, you know, we remove portions of it. And so I just find this painting fascinating and and so I always have it as my, sort of my first slide, you know. Fast forward 2500 years from the Greeks, you know. And in 1931 a lot of the groundwork for sort of liver hypertrophy after resection was sort of done in early animal studies. And so I just sort of find this concept very fascinating. Real quickly. I don’t have anything to disclose. I have no financial incentives or commercial interests, though, my partners joke that they’re going to start to. Pay me to stop talking about this topic, since it’s all I seem to ever do. I don’t really claim to be an expert in anything. I am very passionate about this. For those of you who know me, this is sort of what I have devoted my life to, in the in the in the in the rest of this talk, I will try to differentiate fact from opinion, because I think that’s very important sometimes in in cancer care, cancer medicine, cancer surgery, a lot of people have a lot of opinions, and usually when there’s a lot of opinions, there’s not a lot of sort of definitive evidence or facts to base the opinion on. So I think it’s important to differentiate that, and I’ll try to do my best to do so. And lastly, I am not, you know, some none of these thoughts are original. Let me put it that way. I stand on the shoulders of giants. You know, I got trained at one of the best cancer centers, I think, in on this side of the Atlantic Ocean. And the faculty there, you know, train me to be who I am today. And you know, the faculty here at Vanderbilt also did the same. So I stand on their shoulders truly. So you can’t know where you got to go without knowing where you came from. So we’ll sort of talk about, you know, colorectal liver metastases really quickly, where, where treatment sort of was, where we are now. And then I’ll sort of talk about some, some future directions, and how we how we sort of plan to hopefully shape the field moving forward. I don’t need to tell this group, so I’ll sort of blitz through this stuff. But you know, we know, we all know that colorectal, colorectal cancer, is the second most common cause of cancer related mortality in this country. And I also don’t need to tell this group you know that it’s highest. Rate of incidence increasing is in younger and younger patients. And the liver is the most common side of metastatic disease, and 50 to 60% of people will develop liver metastases at some point, right? So, and we know that the metastatic disease is what drives the mortality with this, with this disease. And it’s interesting, if you go back to, you know, Memorial Hospital in New York City was called Memorial Hospital back then, in 1948 they were writing about this concept of the inoperability of cancer. George T pack was one of the preeminent surgeons in New York City at that time. And you know, he wrote this in this paper. You know, perhaps the strongest indication for hepatic resection occurs when a very long latent period intervenes between the treatment of the original cancer and the discovery hepatic metastases. And in some sense, that’s still sort of true today, although we are much more aggressive because we have much better treatments to do that. But this is, you know, back in 1948 you know, they were thinking about this problem. And you know, fast forward to the 1990s you know, you look at patients who, sort of, were diagnosed with colorectal liver metastases, this study had 1200 patients in it, and you can see that the patients who were unresectable, or were resectable, but didn’t get resected, did not live very long, and the people who did get resected live much longer, and many of them actually were cured of their disease. So if you look at at the line here, you know it’s about 20% 10 year survival, and this is in 1990 right liver surgery in 1990 or even before 1990 is not what it is today. A lot of it involved moving massive chunks of liver, you know. And the chemotherapy agents that we have today were not even existent or in use at that time. And so that’s pretty, pretty amazing, that that’s, that’s sort of what, what they were able to accomplish. You know, obviously, things have gotten a lot better since 1990 and you know what was a very, very high risk operation of dying just from the operation now is not so high risk. You know, you look at major academic centers like Vanderbilt, you know, Duke Memorial, Sloan Kettering, etc, the mortality after liver surgery is so much lower these days, and that’s why we’re able to sort of do what we do. And a lot of that is because of, you know, we’re able to prevent liver failure, you know. And we use specialized techniques. We were just talking about Alps before, you know, letting the group on, you know. So there’s all sorts of techniques out there that allow us to sort of preserve liver function after liver resection, and it really allows us to be much more aggressive than some of our predecessors were able to be. And you know, we’re able to assess the liver remnant. So you know, for my patients on the call, every time I tell you, I need to make sure that I remove all the tumors, but leave you enough liver behind to survive, right? That’s assessing the liver remnant. What am I going to leave behind, and how? And how am I going to make sure that it’s healthy enough, so that you live? And then, if it’s not healthy enough or big enough, then how do we grow it? Right? And those are the things that we’ve gotten better at. The other thing that we’ve gotten better. That is, you know, we’re better at surgery. And when I say we’re better at surgery, you know, we’ve realized that that less surgery can accomplish the same goal with similar results. And so you can see here, this is published by Peter King and one of my mentors from Memorial Sloan Kettering, that many of you may have heard speak in this forum at others, you know, you look at decade by decade from the 1990s onward, and you know, you can see that the number of major liver resections has gone down each decade, so less than almost a third. Now, if patients get get major liver resections, and you look at the mortality, and it’s gone down from five to 1% and that’s because, you know, you can get the same cancer outcome with removing less liver. And this was a study published at out of MD Anderson. And you know, I don’t want to delve into the weeds of all of this, but if you look at these curves, they’re essentially superimposed. And the two curves, the blue represents, you know, not removing a ton of liver, and the red curve represents removing a ton of liver. And so you can get the same result without removing, you know, massive amounts of liver. And that’s sort of how we’ve especially, I, you know, have continued to practice and trying to remove as little normal liver as possible, which I think is very important, and this is translated into much better outcomes. And you look at this study, also published by my good friend, who was at Duke, you know, so they looked at over 1200 patients who underwent initial liver resection for colorectal liver metastases, 34% estimated 10 year disease specific survival, so meaning 34% of people diagnosed with liver metastases were alive at 10 years. And that’s a that’s a big deal compared to where we were even 10, 15 years ago. And not only that, but people are living longer and people are having improved quality of life. And I don’t think we stress that enough in our surgical and medical communities about quality of life, because yes, you know, we can all sit here and high five where people are living longer, but we need to make sure, and we need to stress that the quality of life is improved, and I think that that’s really important. So who should get an operation in 2024, if you walk into my door, or if you walk into a, you know, any hepatobiliary surgical oncologist store, you know, who gets, who gets an operation? Right? This is a person you know who this is, you know, these are generic CT scans, but, but, you know, this is somebody with one tumor. And I think everybody sort of thinks, Okay, one tumor for sure, they should get get a liver resection. This is another patient that I’ve seen and treated before. You know, these are, you know, several more, but still, you know, very distinct tumors. This, in my opinion, is still, you know, somebody who should get an operation, you know? And then I think the ultimate thing is, this is a, this is a patient that I took care of when I was a fellow in New York, you know. But even this patient got several operations, you know. And I think that we really shouldn’t be thinking about, you know, tumor number, tumor size, you know, some of the things that we historically have looked at. But rather, we need to think about, how is the cancer behaving? How are we testing it? And, you know, figuring out who is going to benefit from an operation. So I think, you know, there are degrees of respectability. You know, there’s people whose disease are is resectable up front, there’s people who need to have two stage liver sections, and there are people who are not resectable, you know, up front, but we try to get them to resection. And, you know, I think each of those require a very, very trained eye, by, you know, a trained eye of a liver surgeon who understands the disease process, who understands the disease biology, and ultimately does whatever they can to get these patients to a liver resection, because we know they do better. So what do we do in the modern era, right? What do we do in 2024 right? So chemotherapy, for sure, plays a role, you know, and so does surgery. And I think that one of the issues you know, that we see on my side of the things you know, especially here in Nashville, is a lot of times, you know, patients coming from from rural areas or areas that don’t have, you know, specialized liver surgeons sort of available, sort of get put into this chemotherapy only pathway. And, you know, I am by no what means saying that chemotherapy should not be done. I think that it has a very, very important role, but I think that it’s really. Important, and you’ll hear me say this a lot. You know, getting the opinion of a liver surgeon early in the disease process, early in the diagnosis, is really, really important, because it helps, basically provide a roadmap for how the treatment is going to progress, with the ultimate goal of getting to an operation, you know, and then chemotherapy has a big role in that, but it shouldn’t be the only thing, in my opinion, and that, you know, just, and I use the word opinion there, because, in my opinion, all patients should try to get to a resection if possible, when they’re talking about liver metastases from from colon cancer or rectal cancer. We know that chemotherapy can be toxic, right? So those are, that’s when you have your when you have your meetings with the medical oncologist, and they’re checking your blood work every couple weeks. They’re looking for toxicity. They’re talking to you about toxicity, and they make their decision to, you know, hold doses, dose, reduce, etc, based off of those toxicities, you know, and I’m not going to belabor this point, but these are some of the things that happen. But if you notice, you know, all of these things result, all of these drugs, which are sort of the mainstays of the chemotherapy that we use, are directly toxic to the liver. So we have to be really careful with how much chemotherapy we give before we do liver surgery, because if you give too much, it really increases the risk of liver failure, and it really increases the risk of having a bad outcome after liver surgery. And we know that, you know, it’s associated with not only liver failure after liver resection, but also complication after liver resection. So that’s why it’s really important to involve a liver surgeon early, so that we only give as much chemo as needed before we can get to an operation, you know. And this is sort of hitting those points again, you know, the more chemotherapy people get before liver surgery, the higher the risk of complication and liver failure is, you know. And I’m not going to belabor the points on this slide you guys can read, but, but, but, you know, the more chemo you get, the riskier the operation is. And so again, trying to minimize how much chemotherapy you get before a liver operation is extremely, extremely important. And I put these on not that I know what any of these things look like under the microscope. I rely on my pathology colleagues for that, but, but really, this is what I see, right? So on the left, that’s a completely normal liver. On the right, you know, we’ll see blue livers like this because of all the chemotherapy that’s been given. And in the middle is sort of a fatty liver from chemotherapy. And those things can be really, really challenging to deal with in the operating room. Not, not deal breakers, not, not, you know, we can’t do this at all, but it definitely just increases the risk of a complication, you know. And my ultimate goal is to get you through your liver operation with minimal risk of complication. So when somebody comes into my clinic, I break it down by, you know, is this something that I can remove up front in one setting? Is it something that can be removed but may need two settings, or is it something that can’t be removed and I need to get some response so that I can get to an operation, right? So initially resectable disease, meaning I can remove it up front. Okay? This is a really busy slide. All I want you to focus on is, is that when we tested whether chemotherapy should be given after removing liver tumors or liver metastases from colorectal cancer. None of the studies that we have shown have ever demonstrated sort of a five year overall survival benefit. Okay, it’s a mind blowing concept that often gets glossed over, but when you have tumors in the liver that can be removed. Giving chemotherapy after, systemic chemotherapy after removing the liver has never been shown to provide a survival benefit. It’s mind blowing, you know? And then you even go to chemotherapy before and after. So some people are like, okay, maybe it doesn’t work after, but maybe it will work if we give some before and some after. And again, this is for tumors that are removable up front, even then, you can see that the five year survival benefit is not there and it’s mind blowing. And we don’t truly understand in the cancer world why that is, but we have to be really, really selective of who gets chemo upfront, because it seems like it may not be helping, and so I usually reserve, you know, chemotherapy for detectable disease, for patients whose tumors are big, and if we can get a little bit of response. It’s we can do less liver surgery. Right? In my mind, I want to take out as little normal liver as possible. And if I can get a little bit of shrinkage here, getting the tumor to move away from this blood vessel here, or this bile duct there, and I think that if I get that couple millimeters, it will spare, you know, a bigger liver resection, and we can do a smaller liver resection, then I think it makes sense. But again, I have to in the back of my mind, I always have to think about the fact that, right, we’re not improving survival with this, and we are definitely increasing the risk of complication. So again, we try to do some chemotherapy if we have to. I love to do it without it if we don’t need it, but if we have to, trying to do just enough to get response without causing too much toxicity in the liver. I’m a big, I’m a big the office fan. And oftentimes when I think about, you know, chemotherapy and colorectal liver metastases and all the data out there, none of it ever seems to make any sense. You know, like, in your mind, it’s like, well, chemotherapy should work for this. I don’t understand why it doesn’t, and I think it I think it does work. I’m not saying it doesn’t work. I think it does work, but I think we have to be really, really selective in who we use it in for people that have disease that’s resectable up front, people like this, where you know the tumors are so widespread you can’t remove anything up front. I mean, obviously I think chemotherapy up first. Here is the right answer. Okay, we need to get these things under control. We need to get them to start responding. We need to get them to shrink. We need to make sure that, you know, the disease is not sort of growing gangbusters. And we lose, we lose control, you know. And so in the last decade, you know, 2014 to 2020, or so, we studied this to figure out what chemotherapy, you know, we should do, and we should use, you know, and so, you know, most of you are probably familiar with FOLOFOX Avastin FOLOXIRI plus Avastin, FOLFIRI plus Avastin, and that’s typically what we use based off of this, excuse me, this first study here, the tribe study, right? That’s pretty much first line for anybody who comes in, unresectable. Upfront, colorectal liver metastases. Now, there are unique scenarios where we may use, you know, full Fox plus panitumumab or an EGFR inhibitor. Those are very unique. Most people were talking about full Fox hearing Avastin, okay? And it’s a really, really good regimen, okay? And if you’re able to be healthy enough and strong enough and well enough to get all three full Fox hearing Avastin, the response rates are really, really high. They’re really good, but at the cost of complications, diarrhea, issues, with neuropathy, I’m sure anybody who’s gotten Oxaliplatin on this (inaudible). You don’t need me to tell you what the neuropathy is and how that, how that can affect your your day to day well being. And so I think, you know, we have to be really, really careful, because, again, we get really, really good response rates at the cost of complication, you know, and then in the unique scenarios where we can use panetumab, again, the response rates are unbelievably higher compared to not using it. But we have to be really careful, because in some studies, if you’re doing a liver resection and you get some of these drugs before liver resection, it can actually increase your risk of dying from the operation. So all of these things are going on in my head, in our heads, in terms of trying to find the right cocktail, trying to find the right treatment for you. It’s really personalized medicine at its finest, even though it does, you know, it’s the same 2-3-4, drugs that we’re using, trying to find the right ones, and for how long, is really, really important. And so, you know, again, we typically reserve FOLFOXIRI and Avastin if you are really, really healthy, really, really strong. Otherwise, we typically will do FOLFOX and Avastin, or FOLFIRI and Avastin at the expense of higher toxicity. And you know, the unfortunate thing, though, is that the systemic chemotherapy alone rarely allows for conversion to resection. Okay, and so again, I put, I put, I put this here because I just sort of want to summarize chemotherapy helps. We don’t really know who truly benefits. If you have upfront resectable disease, if you have upfront unresectable disease, it might help convert to resectable disease, but you know you have to be really, really careful about toxicity, and then you know the risk of developing complications after liver surgery and involving the liver surgeon early, if it’s one thing you take away from this, involving a liver surgeon early in this process. Process is extremely helpful, because it helps us plan which chemo to use, how much of it to use. What are the goals of chemotherapy? Right? What are we trying to shrink? What are we trying to sort of move away from major blood vessels? What operation are we trying to plan for and potentially avoid if we’re talking about a major liver resection. So I cannot stress that enough, get a liver surgeon to look at your case early. Is it’s extremely important. And again, it just, you know, I love this Michael Scott look, because every time I look at these studies and just it just baffles me that we can’t, we can’t, in a scientific way, show you know, who actually benefits from what. But obviously, you know, chemotherapy has a role here. I’m not trying to say that it doesn’t. Where do the liver surgeons fit in, right? So, so moving on to sort of what we do and what I do, right? So colorectal liver metastases, yes, they have spread beyond the colon to the liver, but it’s a regional problem, right? The liver can be treated regionally, if it’s just there, you know. And surgeons are really, really good at dealing with regional problems, you know. So in 1994 or so, Nancy Kemmeny and, you know, Humon Fong and Les Bloomgard and Bill Jernigan and all these people thought, you know, why not add regional chemotherapy to liver resection? And if you don’t know those names, those are the sort of the people who were at the very, very forefront of HAI chemotherapy at MSK in the late 90s and early 2000s you know. So my pump patients don’t need to, you know, have a reminder, but this is what it looks like. And if you’ve if you’ve not seen it, this is what we do, you know, we put the pump in and the abdominal wall and, you know, feed the catheter to the artery that goes to the liver, and it pumps the high dose chemotherapy into the liver, treating the liver tumors. You know, this is sort of what it looks like when we, when we do the operation. Now, I’m going to warn you, my next slide actually has intraoperative pictures, so if that stuff sort of grosses you out, maybe just look away for a little bit. But this is sort of what it looks like, you know, in the real world, where we, where we put the catheter into the artery and and, you know, you can see the blue dye. I don’t know if you can see my mouse here, but you can see the blue dye in the liver. That’s how we check to make sure that the liver sort of is getting what we wanted to get, you know. So why do we use this? Well, you know, the liver has a dual blood supply, you know, he has an artery and a vein. And we, you know, we know that the normal liver gets most of its blood supply from the venous system. And tumors, especially colorectal liver tumors, derive their blood supply from the hepatic artery, you know. And so we can give chemo directly into the hepatic artery. And this is, you know, from 1951 right? Not new. You give, you give stuff in the artery and it goes to tumors, you can sort of see the liver tumor here, and you see the dye going into the arteries, and the tumor lights up. So what do we use? We use a drug called fudr. You know, it’s a it’s a drug that is similar to five fu but, and it’s not new, but what it allows us to do, and my, you know, my patients on the call hear this all the time, it allows us to give a concentration of drug that’s 400 times strong to the liver. And the reason for that is, is that the liver metabolizes it all, and you know, so none of it gets out into your systemic circulation. And we’re able to sort of blast these tumors with really, really high doses of chemo, you know. And you go back to the original studies from the 1970s and you can see, when you give the chemo in the hepatic artery, the tumor gets much more drug than if you give it in the portal vein, you know. Again, it’s not new. This is sort of the original 1962 this is how they used to do it, you know, thankfully, it looks a lot better and cleaner. Now, you know, these are the, these are the these are the studies that they show. These are the X rays. This is, this is the, for those of you who’ve had the the pump study down in nuclear medicine and the big donut that you sit under, this is what they used to do in the 1960s so, obviously not new. But you know, when do we use it? So we use it after liver resection to treat micro metastatic disease in the liver, meaning disease that we can’t see, that may still be hiding in the liver, after liver surgery that we want to treat. And then we also use it to sort of in a neoadjuvant, or what we call conversion, where we want to convert somebody who may not be resectable yet to resection, because, again, I showed you those initial studies, right? If we can resect the tumors, you’re going to live longer, and increases your chance of cure. And so that’s sort of, those are the ones that we sort of put this in, you know, and we’ve referenced Nancy. And Humon Fong and Les Blumgard, you know, these are the people who who were on this initial study published in the New England Journal of Medicine, you know. And not to belabor the points here, but you know, we compared liver section with pump chemotherapy versus systemic chemotherapy after liver resection, you know. And again, this is sort of looking at, you know, we had a wide range of patients with a wide number of tumors in the study. So it’s a good, broad representation of, you know, who we treat in this in this fashion. And this is sort of just pointing out, you know, we did a lot of big liver surgery back then, right tri segment techniques and lobec, to me, those are big liver operations that we try to avoid at all possible costs these days, if possible. And you can see here that the patients who got the pump, they hai P, they did better, right? They had better two year overall survival. They had better median overall survival. Their recurrence in the liver was much improved with the pump versus not having the pump, you know, and their progression everywhere was better with the pump versus not having the pump. And this study, you know, published in 1999 in the New England Journal of MSS. I mean, this is the seminal study that Nancy Kemmeny published. And she just for those of you don’t know, she just recently retired, though she may be still giving talks on COLONTOWN, I’m not sure you know. And then long term follow up. I mean, you don’t need a magnifying glass to look at this and say, like the patients who got the pump did a lot better than the patients who didn’t get the pump right. This is sort of why we do this, because I think it really gives you all the best chance of having the best possible outcome after a liver operation, you know, these things were sort of shown in the long term, you know. And you can still see that your progression everywhere was better with the pump, the yellow line, and then the liver progression was, was, was much less with the pump compared to without the pump, right? So this is why we do this, and obviously there’s evidence for it, and I use this line in my clinic all the time. You know, it’s the only adjuvant chemotherapy, meaning chemotherapy after liver resection, that has been shown to demonstrate an overall survival benefit, a progression free survival benefit, and a hepatic progression free survival benefit. So really, you know, we should be doing this much more than you know most centers are doing, in my opinion. Okay, again, that’s an opinion, not a fact. Biggest argument that people have with the hepatic artery infusion pump is that, you know, those studies were 20, 30, years ago, and chemotherapy has come much further along since then. And that’s true. There’s no question that we’ve developed new chemotherapy agents, better chemotherapy agents, and we really have not, sort of tested it head to head in the modern era. You know, we’ve had some retrospective studies, meaning, you know, patients who we go back and look, but we’ve never tested it sort of in a prospective head to head setting, you know. And this study is out of the Netherlands and memorial sloane Kettering, you know. And again, the yellow line is pump patients, and the blue line is no without the pump. And you can see that patients with the pump did better. And you know, here, yellow line higher than the blue line means they did better, and they live longer, right? Almost 20 months longer. And you know, the issue with the study is, is, it’s the they use this fancy technique called propensity score matching, and it’s like this really advanced, complex statistical thing, you know, but you got to be really, really careful when you do this, because, you know, I can make anybody look the same, right, if I use these, if I use these characteristics, right, and try to find, you know, two people who would, who would potentially be the same to study and look at, and they’re wealthy and famous. I mean, you get two very, very different kinds of people, right? For those of you that don’t know Ozzy Osbourne on the right, and hopefully everybody knows the person on the left. So you have to be careful with these kind of studies and how you interpret them. And I bring that up, you know, for that reason, because, you know, sometimes you get a lot of people that say, Oh, well, you know, in this study, we compared pump patients with without, pump patients with moderate chemotherapy, and the pump patients did better, and that’s true, but I have to stress that it’s never really been tested head to head. You know, again, a lot of the studies this one was done in 2006 so that was a long time ago, but, you know, it was the only study that demonstrated better quality of life in patients who got pump chemo versus systemic chemotherapy. And as I said, that’s really, really, really important. We see you every two weeks. We pump you full of this stuff, you know. We do these operations, you know, but we need to make sure that your quality of life is good and not enough of the. Studies that we do these days take that into account. And I think, you know, we’re making a push to start including that in our studies these days. It’s really, really important, in my opinion, that we need to take that into effect, you know, and then, and then, you know, when we talk about conversion therapy, for for using the pump, you know, comparing it to modern chemo. Yes, patients who actually were converted to resection did better than than those that didn’t. Furthering, you know, trying to get to liver resection is key. But I think this is the slide that you know that I that struck me the most. And this is the one why I, you know, offer the pump. You know, as much as I do in these scenarios, right? People who got the pump, who had unresectable disease, 52% of people converted to resection. Okay, that’s over half that. That’s sort of unheard of when you’re talking about systemic chemotherapy. Nothing has ever been shown to be that high. Most of the systemic chemotherapy trials or studies that you’re looking at, we’re talking about converting to resection, 1520, 25% when you talk about the pump, 52% okay, and I’m not going to name them, but I know that there’s some patients on the call who we’ve we’ve used this to convert them to resection. And this is why, because it really gets them to where they need to be. And, you know, even, even if we can’t get you to resection, right, you know, you can still get really, really good responses with this, with this pump. And so I’m a big believer of it. Obviously, I, you know, I come from a long heritage of pump believers in New York City, but I truly believe that in the right patients in the right setting for the right reasons, it can really, really be helpful. You know, I showed you this scan, you know. So, these are patients that I took care of in fellowship. This was a 38 year old, a man who who presented after, you know, his son. He was playing soccer with his son. He got hit in the belly, and he had pain, you know. And he had really, really high CEA, you know, his liver was not happy. He got some systemic chemotherapy. He got really, really, you know, bad side effects from it, you know, but he did get some response. We, we, this is what happened after the systemic chemotherapy, you know. We put a pump in, we were able to get him to a liver resection, got his primary tumor out, and he was no evidence of disease for three years. At three years and that I left New York City, so I haven’t had a chance to follow up, but he made it to three years with no evidence that his disease, which is pretty amazing considering where, where he started. This is another patient that I saw when I rotated with Nancy Kemmenyat her clinic. And, you know, presented in 2008 37 year old, you know, had a lot of liver tumors, right? You can see all the liver tumors here. Got treated with pump and systemic chemotherapy for six months, got a portal vein embolization, got two stage right? Hepatectomy, and, you know, 2008 was when she was diagnosed, and she’s NED in 2019. Okay, so this really, really does happen. It’s not a myth, it’s not a it’s not a story, it’s not something that we’re feeding. It really, really does happen. The the biggest issue is, is that we just don’t know, you know, who these people, these remarkable stories, are going to be, right? But they they definitely are there. They definitely happen. And I think that, you know, it happens more frequently in patients who are treated with the pump. Okay, so what? What are my take home points here?

Dr. Padmanabhan 38:50
One size fits all strategy should not apply to anybody anymore. I think it’s really, really important to be really thoughtful about, how are we going to plan this treatment strategy with the ultimate goal of getting to a liver resection? Okay? And it’s really, really, really important to involve a liver surgical oncologist or compatibility or surgical oncologist, whatever you want to call it. really, really important to get that person involved early and then plan the roles of systemic chemotherapy and pump chemotherapy in that plan to get you to a liver section. Those are sort of how, what I think the important take take home points are here. I’d be remiss without you know, giving props to my team so many of you know these people. Dr Siagmore Dr Agarwal, were the two medical oncologists who started this program here at Vanderbilt with me. Sarah is our amazing pharmacist who helps us with the dosing, has helped us develop all the treatment plans and helped us sort of. Try to make this as seamless and as smooth as possible for our patients here, we’ve thankfully recruited several other medical oncologists here, Dr Humon, Dr Gibson, Dr Koloff, to help us with this. We have a lot of people in the infusion clinic help us, help train all the nurses, and we have a lot of people in the or as well who you know behind the scenes make this program, make this program grow. So I cannot This is not a one man show or one person show, and that’s really true anywhere at any of the institutions that do this, you know, yeah, the surgeon definitely plays a role, but, but we can’t do this alone. This is a team sport, and getting the right people on the team, I think, is really, really important. So with that, I’m gonna stop sharing my slides and because I can’t see you guys, unfortunately, if I share and I’m happy to answer questions those that have any.

Betsy Post 41:12
okay, so I’m going to go back to the beginning of the chat and ask some of the questions that are here. Or did you want me to try to take some of the ones that I did get that I sent you an email yesterday too.

Dr. Padmanabhan 41:30
Yeah, Betsy, you do it however you want, I’m happy to, I’m happy to answer any of these. I can stay on for as long as people want. But truly, I really don’t, really don’t mind at all.

Betsy Post 41:40
perfect. Well, one that is actually coming up quite a bit in the liver groups in COLONTOWN is, can we ask him about disappearing disappearing mets due to chemo, and what happens to those if they can’t be resected because they’re gone? So there, this has been coming up a lot lately, and patients have a lot of questions about that. Are they really gone or not gone?

Dr. Padmanabhan 42:06
It’s a it’s a really, really challenging question that we struggle to deal with. In fact, a lot of what I a lot of the research that I’m participating in now sort of focusing on, what do we do about that? How can we find them? How can we detect them? I think people approach it differently. My approach, you know, and the thing that I do, pretty much the night before every operation that I do, is I pull up the very, very first CT scan or MRI before that patient started any treatment. That is the most important. And I tell the residents and fellows that rotate with me the most important scan is the very first scan, because that tells me where all the tumors were, and if any of them disappear, I can still tell where they were based off of that initial skin and so what my approach is, is I try to look for them. And yes, oftentimes I don’t actually see the tumor, but I can sort of figure out where in the liver the tumor was, based off of its relation to other critical structures like blood vessels and bile ducts. So in the operating room, I will actually use an ultrasound and have the CT scan right up in front of me, and I will say, Okay, this tumor was this many centimeters away from this, this many centimeters away from that. Let me find it with the ultrasound. Okay, here’s that structure. Here’s this many centimeters away, here’s this many centimeters away. And I’ll look at that area, and oftentimes I’ll actually see something there. And if I do, I think this will probably answer some of the other questions. That’s where I really utilize ablation, because if it’s that small, ablation is an excellent technique that spares a lot of normal liver, but still treats these tumors extremely effectively. So I spend a lot of time looking for these tumors, looking for where they were, and then treating those areas with ablation and other ablative techniques. Now, some of my patients know that sometimes these tumors, I can’t ablate because they’re too close to critical structures. I think one of the one of the questions that that was asked was the role of irreversible electroporation or ire I think that is a really, really nice technology that allows you to ablate things that are near critical structures a little bit more safely than ablation. Unfortunately, not all centers, like my center doesn’t have ire so I can’t use that. So in that scenario, I tend to use sort of radiation techniques if need. It sort of external radiation. I think another, another question that was brought up was histo trip See, I’m sure all of you have heard about that at this point. I think that histo trip see, is it’s a very, very exciting technology. I think that it’s really, really new and in its infancy, and has not been rigorously or appropriately tested to bring it out into prime time yet. I know that there are a lot of centers out there that have them and are doing the appropriate studies that need to be done to make sure that it’s safe, to make sure that it works, to make sure it does what it claims to do. And I think that that’s great. There are some really big limitations with histo trip. See, mainly the right side of the liver, where it’s covered by the rib cage, you can’t treat as well with histo trip. See, I think in the future, my hope is, is that that company works on intraoperative way to do histo trip. See, that’s down in the road, but hopefully I knocked out some of the questions there. Bottom line, I don’t think those tumors ever truly disappear. I have seen them truly disappear with pump chemotherapy. I have not have them ever truly disappear with systemic chemotherapy. So I try to go looking for them if I can.

Betsy Post 46:20
Thank you. One other question was about diets. So on a scale of one to 10, separately or collectively, how important do you find dietary intake, even a radical diet change, like veganism to help combat cancer recurrence?

Dr. Padmanabhan 46:39
Yeah, that’s a question that I get a lot. Actually, I don’t have any great evidence to say one is better than the other, or one diet is better than another diet. I think this is where, sort of what works for you, right? Like you guys are going through a lot in this treatment process. Your body is going through a lot. It’s going through a lot of changes. And I think the important thing is to eat healthily, you know. And that’s just the standard, you know, don’t eat, you know, the stuff that your mom didn’t want you to eat when you were a kid because your teeth would fall out. Right? Don’t eat that in excess, everything in moderation, and I am not aware of any evidence that suggests that veganism, vegetarianism, or any other diet, is better than another diet. Now, one thing that I get asked a lot is is like, do I need to quit sugar? And the answer to that question is, is universally No, you don’t need to quit sugar. Cancer does use sugar to grow, but it is irrespective of your dietary sugar intake, right it? It hijacks your cells to use the sugar that’s already there. And so you eating sugar, or you not eating sugar is not going to change anything. So if you want that brownie, I love brownies, go ahead and eat that brownie.

Betsy Post 48:02
I’m going to quote you, “eat the brownie”. I love it. Do you see any advances or anything down the road, anything with the HAI pump method of fighting metastatic colorectal cancer, or any brand new technologies that aren’t really being talked about too much, that you see promise in Yeah,

Dr. Padmanabhan 48:27
that’s a great question. I think that the next big thing that we need to figure out is how to get our immune system to attack metastatic colon cancer once it’s metastasized to the liver. Colorectal Cancer once it metastasized to the liver, right? All the studies right now for microsatellite stable which is like 99% of the cancer that spreads to the liver, immunotherapy does not work, and I think it the way that we need to move forward as a medical field, as a surgical field, is figuring out how to get our immune system to sort of get primed in the liver to start, to start tackling these tumors. I think the pump has a unique ability to provide sort of direct access to the liver while bypassing the rest of the body to do that we are, you know, we and others are looking at ways to sort of supercharge the immune system, to sort of seek out and attack these tumors in the liver. We are nowhere near where we need to be, but I think that is where the field needs to go. Even there, even the early studies that have shown promise for tumors that have spread to everywhere else but the liver, where immunotherapy seems to help in those situations, for for reasons that we don’t truly understand, the tumors in the liver don’t respond as well. So we need to figure out how to make that happen. I think the pump could be used as a tool, because it’s a gateway to the liver and bypassing the rest of the body. But we’re not there yet, and we definitely need a lot more progress in that, in that, in that arena.

Betsy Post 50:12
Great. One more question before I go to some of the live questions, it’s interesting. You sort of talked about this, but I do want to ask it outright. So you as a liver surgeon, working with your medical oncologist, you have a patient that perhaps has just one or two mets. How do you make the decision on ablation, IRE, resection? How do you make a decision on those patients with very minimal disease?

Dr. Padmanabhan 50:39
I think that most people, myself included, if you can remove the tumors without having to sacrifice a lot of normal liver, that’s that’s usually the best way to go. I think that ablation techniques definitely have a role in the upfront setting, especially if you’re talking about maybe one or two really, really small tumors that are really, really deep. The problem you know that I have with with ablation up front is when you when we do it percutaneously or through the skin, the ablation zones end up being really, really right. In my mind, the purpose of ablation is to try to minimize damaged liver, right, or removing too much liver. And when you have these massive ablation zones, you’re really sort of, you know, killing normal liver cells that, you know, we want to try to preserve, right? Because we’re playing the long game here, right? We want to make sure that you have enough liver, you know, I would love for me to remove, remove tumors, and the liver tumors never come back, and everybody’s cured and everybody’s happy, right? But realistically, that’s not what happens in the majority of cases, right? We need to play the long game. We need to make sure that we leave enough liver behind so that if it were to come back, God forbid, we have options, right? That’s how I every time that I look at anybody, anybody’s scan, anybody’s story, anybody’s, you know, what they come in and present with, I’m trying to play the long game. And I worry that sometimes when we do these percutaneous ablation techniques, we end up damaging too much liver and and sort of hinder our ability down the down the road. So I try to, you know, if we can remove them and remove them with minimal liver resections, I think that’s the way to go. Ablation has a role, but I think we just have to be really, really careful as a field, not to ablate too big of a zone and really spare the normal liver, because the normal liver is key. Hopefully I answered the question.

Betsy Post 52:57
Yes. Thank you. Let’s see. Is there any data around mortality rates for individuals who were able to have early resection versus patients who have had several rounds of chemo in order to get to the point of resection?

Dr. Padmanabhan 53:17
Great question. We don’t have any, any when you say mortality rates, I’m assuming you mean sort of survival from the cancer long term, and not mortality from the operation itself. I think that that we don’t have a great we don’t have any great evidence to suggest one is better or worse than the other, if it’s a small number of cycles of chemotherapy. Now we do know that as the number of cycles of chemotherapy before liver surgery increases your risk of having complication or liver failure or even dying from the liver resection increases exponentially. So in that sense, your mortality is higher if you get too much chemo before your liver resection. But as I said, I think that you know, for if you have a small number of tumors in the liver, usually less than four is pretty reasonable cut off that most people use, and they are all upfront, removable. The best data that we have says that they should be removed and that you don’t need to have chemo upfront. And so that’s sort of where most, most liver surgeons sort of practice that way. There are unique scenarios, as I suggested, where if you can shrink a little bit and spare a bigger liver resection, then it makes sense. But there’s no data to suggest that you know mortality is or survival is worse in patients who get a few rounds of chemotherapy before their liver section.

Betsy Post 54:50
And I think you answered this one, but I just want to hit this point home, because it comes up quite a bit for new folks in the liver groups. So for some of. With just one or two liver mets, would going to a surgeon before any chemo be a good idea?

Dr. Padmanabhan 55:06
Yeah, yes, absolutely. Because, again, it’s, it’s, it’s all about planning the treatment. And oftentimes, if you have one or two liver mets, you may not need systemic chemo right away, right? And again, we’re trying to play the long game. Every time you get exposed to systemic chemotherapy, it’s giving the chance for the cancer cells to become resistant, right? And if you don’t need it, then why give the cancer cells the opportunity to get resistant to that therapy? Why not save that therapy for if and when you may need it down the road when you have more tumors or tumors elsewhere? That’s sort of my thought process for people who have a small number of liver metastases. And again, it’s never a bad idea to get evaluated by a liver surgeon early, and sometimes that means before seeing a medical oncologist. And that’s okay.

Betsy Post 56:09
Thank you. We have a patient who had a question. She had a solitary liver met five weeks after LAR surgery in 2021 it was ablated, had chemo. So far, all the CT scans have been clear. She did have some lung nodules, but she hasn’t had an MRI Since 2023, and since you know it’s there’s a lot of talk that MRI is the best imaging for the liver. Should she be getting regular liver MRIs in addition to the CT scans?

Dr. Padmanabhan 56:43
So, you know, that’s an interesting question. Yes, I think in general, MRI is more sensitive at picking up these liver tumors than CT scan, especially if you have pre existing fatty liver disease or chemotherapy associated fatty liver disease, I don’t think that getting regular MRIs is necessary. I think that especially if you were able to see the tumors in the first place on your CT scan. Now, there are some people where you just never see the tumors on the CT scan, and you only see them on an MRI. And so I think in those patients, it makes sense, but I don’t advocate getting surveillance MRIs of the liver, sort of just for everybody. I think there are unique situations where where that’s important. We have other ways of detecting, you know, cancer recurrence, in addition to CT scan, so tumor markers, and then, more recently, circulating tumor DNA, you know. So I think that it’s a, it’s a, it’s a combination approach of how we do these surveillance, imaging and and I don’t think that doing an MRI every time is going to be helpful, especially if you can see them in the first place.

Betsy Post 58:06
Thank you. Now, while you were doing your presentation, talking about the toxicity, a couple patients said, is the liver toxicity reversible after chemo is done?

Dr. Padmanabhan 58:17
sometimes and sometimes it is not. And I can tell you, it’s the worst feeling in the world as a liver surgeon, when somebody comes into my clinic and, you know, they got started on, you know, the three or four drug regimen, you know, because they’re they’re young and healthy, and they can tolerate it, you know, and then they develop irreversible liver injury, because then, especially when those tumors were removable, because it I can’t, I can’t safely do liver surgery. When the liver is is permanently damaged. It’s not common, you know, it’s not, it’s not like it happens all the time, I think the incidence is very is still it’s quite low where it’s irreversible, sometimes, most of the time, it is to some degree reversible. But again, I don’t know why you take that chance, especially if you have a small number of tumors that can be removed. I think that, again, getting the liver surgeon involved early can help prevent those scenarios. And, you know, and then, and then, and then making a plan, right? That liver surgeon should be working with the medical oncologist and having a plan right, and making sure that we do the right thing. First, very important.

Betsy Post 59:45
Thank you. So for a patient that has had lung mets in the past, and then liver mets, is there any evidence or studies on the benefit of chemo post liver resection? So for those patients that had had lung metastases in the past also.

Dr. Padmanabhan 1:00:03
I just want to make sure I get it so the lung metastases came first, and then the liver metastases. Is that the question?

Betsy Post 1:00:10
Are there studies on the benefit of chemo, post liver resection for patients who have also had lung mets?

Dr. Padmanabhan 1:00:16
I see, I see. So, yeah, I think that. I think that if you have existing disease outside of the liver, but we’re still going to go after the liver disease, there should be a plan to somehow manage the lung Mets. That plan can involve chemo, but usually, if we’re talking about doing liver surgery in the setting of lung metastases, we’re usually going to be treating the lung metastases with some form of local therapy as well, whether that’s microwave ablation, cryo ablation, radiation therapy, you know, we want to, we want to, we want to do the liver surgery, you know, with a plan to be able to treat the lung disease as well, at least that’s sort of our approach here at Vanderbilt. And so that may involve some chemotherapy to allow for sort of liver surgery, you know, healing time and planning for the lung stuff. But we don’t want to, we don’t want to do again. We don’t want to do too much chemotherapy for too long. And I think that if you have a small number of lung metastases, and we’re going to go after the liver first, doing the liver first, you know, maybe doing a little bit of chemotherapy between and then doing some form of local therapy to the lung would be how we sort of go about doing it here. And so, has that been sort of officially studied? No, it has not. It’s sort of, you know, think this is the best

Betsy Post 1:01:50
Have you seen any research on high fructose corn syrup and the liver?

Dr. Padmanabhan 1:01:56
Ooh, I have not. And admittedly, I have not gone looking for that. So I don’t think that I’m I can answer that any sort of knowledge.

Betsy Post 1:02:07
No problem. Um, when should one do a PET scan after colon and liver resection? What if the pet caught one lesion? Ultrasound caught us, caught seven lesions? Which one would be considered accurate?

Dr. Padmanabhan 1:02:22
Yeah. I don’t usually use PET scan after liver surgery. The reason for that is, is because PET scans pick up areas of cells that are using a lot of sugar. Okay, whenever you have an operation, your body is healing, and whenever you’re healing, those parts of your body that are healing are using a lot of sugar. So the PET scan will light up, and it’s only lighting up because you know you’re you’re healing, your body is in an inflammatory state, and it’s rapidly dividing and using a lot of sugar to heal your operation. And so I rarely will use a PET scan after a liver surgery or even a colon surgery, for that matter, for very, very, very unique scenarios. That’s sort of our approach here, my approach here. So I don’t, I don’t know. I think an ultrasound is sort of the best of those two modalities. The better, the better modality. But if there was any concern about a lesion in the liver, I mean, you’re going to be getting a CT or an MRI, okay, if you come to see me, because, without fail, those are better than ultrasound or pet every time.

Betsy Post 1:03:50
Thank you. This one is I’m very interested in as well. We have a lot of patients that seem to be on supplements. In your experience, do you see any effects of supplements on the liver? I’d just love to hear your opinion just generally on supplements, and what your take is on that for patients with liver meds. Yeah,

Dr. Padmanabhan 1:04:12
I am not an expert in supplements. I do think that some of them certainly have a role. I do think that some of them can cause significant liver injury, and so you have to be really careful. What I tell my patients is that if you want to take them, make sure you keep a list and you run each and every single one of them by your medical oncologist, because that medical oncologist will then run it by the pharmacists, and then the pharmacists go into all their databases and like they compare each one and see which one could interact with whatever chemotherapy that you’re getting. You don’t want to have any issues with liver toxicity, because the supplement is interacting with therapy agents. So if you want to do it, I think you need to be really, really smart about it. And. The list, be honest with that list, and run it by your medical oncologist, so that they can run it by the pharmacy people, because they’ll be able to find the ones with known interactions. They’ll be they’ll be able to tell you which ones those are. And I would recommend not doing that while you’re getting treatment, because the last thing that you want is to have an interaction that then prevents your liver from being able to get you know a therapy that we know is helpful.

Betsy Post 1:05:26
Thank you. So for a patient that is trying to get to resection who has used hai systemic chemo including Cetuximab, what if any recommendations would you make to minimize potential complications from surgery.

Dr. Padmanabhan 1:05:43
Yeah, there’s not going to be a lot that you as a patient are going to be able to do. I think again, the key is trying to get the fewest number of chemotherapy cycles before to get to where you need to get to. You know, there are some interesting stuff that’s coming out of some of the cancer centers in the Northeast about trying to reverse chemotherapy induced liver injury. Nothing has been has sort of been approved in the FDA yet to be able to get there. I think the important thing is exercise, eating a good, healthy diet, making sure you’re not losing a lot of weight while you’re getting all this treatment and staying physically active. You know, your doctor may sort of talk to you about fatty liver disease. Sometimes we will sort of change your diet before liver surgery to try to reduce the amount of fatty liver disease before we get you to the operation. But again, I think the most important things are staying physically fit and making sure that you’re eating a good, well balanced diet, so that you’re not losing a lot of weight. Those are the two things that are within a patient’s control to minimize post operative complications.

Betsy Post 1:07:01
Thank you. I’m really interested in this one too. It comes up a lot. How does a patient select a good liver surgeon? I have one in mind, but I’m not sure exactly what to look for.

Dr. Padmanabhan 1:07:13
Great question. I think you want to look at where they trained, and I think you want to ask them how much they do, how much liver surgery do they do? You really, and that goes for any surgery, right? Like, you don’t want to go get your colon or your rectal surgery from somebody that does one or two a year. You don’t you don’t want to go to a liver surgeon who does one or two a year. And you should ask, you know, I have people ask me, how many of these do you do? How many? How many, how many liver operations do you do? How many have you done? And then the other thing is, you know, I promise, I promise. Betsy didn’t pay me to say this, but, but I tell all my patients to get on COLONTOWN, because who knows better than you? You know, I always tell my patients, you know, this idiot can talk to you about all sorts of things, but I probably haven’t had all those things happen to me, but you all are sort of the community that I on and, you know, and get that information from and you know, you can ask all the patients that I that all my patients who are on here. I tell every single one of them you should get on COLONTOWN If you’re not on it, because it’s one thing for you to hear what I’m going to do from me, but it’s another thing to hear from somebody that’s actively undergoing it, or has undergone it, and I think that that opinion is actually more important. So.

Betsy Post 1:08:50
Gosh, I just love it, and I didn’t pay you to say,

Dr. Padmanabhan 1:08:55
No, you didn’t pay me.

Betsy Post 1:08:56
What would you suggest patient advocates and nonprofits like COLONTOWN, for example, do to help spread this important surgical point of view.

Dr. Padmanabhan 1:09:09
I think just continue to talk to each other, you know. And really, really, really, look, I think, you know, one of the things that we’re doing here is this really trying to figure out, how can we get, how can we get what we do out to the people who need it? Because there are a lot of people that aren’t on Facebook, that aren’t on Twitter, that aren’t on all these, you know, groups that we can’t get this message to. I think, I think really just continuing what you all are doing, you know, holding events, community, getting the word out there, I think, is really, really important, you know, I think what I’ve come to learn over the years is, is that, you know, doctors, doctors sort of get really entrenched in sort of the way they do things. You know, they’re in their. Small community and and, you know? And I’m calling other people out without calling me out, you know, we really rely on, on on, I think we really should rely on patients to sort of help us figure out where we need to improve. And I’ll give you an example I didn’t even know what histo trip, see, was, I hadn’t heard of it. I had not come across any of it, any of it in the in the journals and things that I read. And there was one clinic, like, in end of January or February, right? I think I had like, four people come in, and they asked me, Do you do I do histo trip? See, I’m like, I don’t even know what that is, but what did I do? And I go look it up. I, you know, read about it, I learn about it. And, you know, and I wouldn’t have done that if a patient didn’t ask me, you know. So, so I think, I think, you know, keep challenging us, keep forcing us to sort of, because you guys are all over it, right? Like you read all the stuff. You know, I’m, I’m standing in an operating room for 12 hours a day usually, right? I’m not, I’m not like out there looking at this stuff all the time, you know. So, so challenge us, you know, keep, keep forcing us to get better. I think that’s really important.

Betsy Post 1:11:12
Q2, people were asking, how much damage does the pump chemo do to the liver to complicate future resections. Yeah,

Dr. Padmanabhan 1:11:22
it’s not free, for sure. I think the biggest thing that we worry about with pump chemotherapy is not direct liver toxicity, but it’s bile duct toxicity. And any of my patients tell you that that’s what I’m that’s what I’m concerned about, right? So the pump chemotherapy does a really, really good job of treating the liver tumors, but it also does really, really good job if we’re not careful, to sort of injure the bile ducts. Now, thankfully, if the bile ducts get injured, we usually have ways to treat it and fix it, and that involves, you know, stents and, you know, endoscopies and things like that, but, but But you have to be really careful. And sometimes we’re really careful, and it still happens, you know, you sit there, you monitor the liver tests and the in the blood work every two weeks, and you put the steroids in the pump and all that stuff, and you do all the things that are right. And sometimes it happens anyway, right? But I think that’s the thing that we worry about, is the biliary toxicity, you know. And I think that’s where the experience comes into play, you know, really, really understanding the nuance of what the liver tests are doing, what the what the Alkaline phosphatase is doing, and understanding how to dose reduce, how to hold the doses at the right time. And I think that’s where the experience comes into play.

Betsy Post 1:12:41
And I think I’m down to the last two questions here, and they’re very similar. So one person’s asking if I’m no evidence of disease based on my latest MRI, but I’ve had to resect two, respectable two ablated tumors in the past. What do you think about getting hai as a preventative measure even though I’m Ned now, or should I wait until more tumors pop up?

Dr. Padmanabhan 1:13:04
I think you wait, because we don’t know if you will benefit, based off of the studies that that we have, in the studies where the pump showed benefit, the pump was started within two to four weeks after liver resection, so I don’t, I can’t, I can’t tell you if it would work or not for you, and therefore, if I don’t know, then I shouldn’t be experimenting at you, just sort of willy nilly, in my opinion. I think it’s an interesting question, and one that I’ve thought about a lot, but we don’t have a good answer from a rigorously, you know, performed study to be able to answer it.

Betsy Post 1:13:53
And I think that answers the other one, because the other one is basically when the the Mets are no longer visible, and scans and blood work, you know? I mean, I guess you’re saying I can’t treat what I can’t see,

Dr. Padmanabhan 1:14:05
you know. So I in those scenarios, I usually say, let’s wait, you know? And if something comes back, and it’s a liver, we can cross that bridge when we get there.

Betsy Post 1:14:16
There’s one more that I actually have, one too. What percentage of resection plus pump patients. Do you do robotically or laparoscopically? And how do you decide that versus open? Yeah,

Dr. Padmanabhan 1:14:28
laparoscopic zero. I don’t do any laparoscopic liver surgery. That’s there. There are few people, I would say in the world that do that and do it really well. I am not one of them. I do do, I do do robotic liver resections. We did our first robotic pump in at our program a few months back. I think that it’s sort of, it’s sort of robotic surgery takes longer, okay, especially with the liver, because you’re. Limited by angles that the robot can get to certain places in the liver. And so I think it becomes a law of sort of diminishing returns, right? Like if you’re in the operating room for 14, 16, 18, 20, hours to do it robotically, there are risks associated with being in the operating room and under general anesthesia for that long. And so I’m very selective in who I do robotic liver resections and robotic pumps in and I think a lot of it depends on whether or not you’ve had open surgery before. So is there going to be a lot of scar tissue that I’m going to have to sit there and cut through robotically that’s going to increase your operative time, increase your risk of having a general anesthesia associated complication? If you have a lot of tumors that we’re trying to remove that can increase operating room time, it can change, you know, and you can’t with the robot, you can’t really utilize ablation techniques as well, because it’s the technologies just don’t mesh yet. So if I have to do ablation, and a lot of ablation. Usually I’ll do that open if I’m just putting a pump in and nothing else. Often, I have switched my practice at this point to doing it robotically, so that’s sort of how I decide with that.

Betsy Post 1:16:17
So my question has to do with Dr Kemmeny was pretty specific about her protocol she had, and I may mispronounce it, so just I apologize in advance, but she did put her patients prophylactically on protonics and Ursodiol. That was just standard for her. And what I’m seeing with the new pump programs that are opening up. It’s not consistent. Do you have an opinion on that?

Dr. Padmanabhan 1:16:44
We definitely do. Protonics, the literature is pretty good. Ursodiol is a little bit of a wishy, washy thing. In my opinion, I usually will reserve it for when people have symptoms of biliary issues. I don’t, because people don’t. It’s not a great drug to take. It has just doesn’t. People don’t like it very much. But to my patients out there that are on it, I’m sorry that I’m doing that to you, but, but, but, but, yeah, I don’t, I don’t do it. We don’t do it routinely, the Ursodiol, we definitely do the PPI, the protonic. So the omeprazole, for sure. So, okay, there’s no, there’s no, I love Dr Kemmeny. I still have to call her Dr, Kemmeny. I love her. You know, she certainly has the most experience in the world. But the there’s no, there’s no real good evidence for the for the Ursodiol. So.

Betsy Post 1:17:41
it’s okay to have a different opinion. It’s okay. And one last one that I see, did you want to talk anything about? We’ve talked a lot about ablation. How do you make the decision between something like SBRT for a small met versus ablation?

Dr. Padmanabhan 1:17:59
Yeah. I mean, I think if I can get to it safely, I will try to ablate it, microwave, ablated. Here we, you know, SBRT. I typically will reserve for tumors, for for reasons, you know, whatever reason that I cannot get to to do an ablation, or if, you know, people have had a biliary issue and they had to have a stent or something like that. You can’t really ablate people after they get stented. Microwave ablate, I should say. And the reason for that is because you’re a very, very high risk of developing liver abscesses. And so in those scenarios, I will tend to use radiation if I need to sort of treat smaller tumors when they have, when they have had some sort of bile duct intervention, stent, ERCP, etc,

Betsy Post 1:18:52
Well, I know you have done such an amazing time this evening, and you have been so generous of your time away from your family, you know, resting, relaxing, eating some brownies. So hopefully you can see your patients up there. I don’t know if you can see them, but they’re waving at you. They sing your praise. In COLONTOWN, and we just really appreciate you being here tonight, being so generous with your time and your information, answering everyone’s questions and being so patient. So I just want to thank you on behalf of all of your patients and everyone in COLONTOWN that gets to benefit from this.

Dr. Padmanabhan 1:18:59
Thank you for the opportunity. I do want to end with one last thing so Mike Lidsky, who is sort of a few years senior to me, at Duke University, is opening, has opened a very, very important clinical trial involving the pump, and it is going to be the first trial that’s going to compare the pump to the modern systemic chemotherapy in patients who have unresectable liver metastases, okay, really, really important trial, and I think that this community would be really, really helpful in sort of getting patients with that disease to be evaluated for a pump on that trial. Really, really important, really, really important study that we need to do, and we need to accomplish as a group, and this is where I think we as doctors and surgeons can work with the community and the patients and and I think it’s really, really important that we we do that. So I wanted to mention that Linsky has put a lot of hard work. I know Betsy. Betsy knows Mike, and he’s put a lot of hard work into that, and we’re going to open that trial here. And I know a lot of other centers are as well. I think really, really important to do that.

Betsy Post 1:21:31
Yes, thank you so much. And I we had a great talk on that from Dr Lidsky, and I’m really excited to hear about when that you know, when it’s opened and recruiting, that’ll be great. And lots of thank yous for you in the chat. And Kenzie says, Thank you, Dr P for doing this and taking the best care of my Sissy and my sweet friends. So lots of love for you in the chat also. So thanks again for being here, and thank you to all the patients and caregivers for being here as well, and all of your attention and your great questions. So have a great night, everyone.

Dr. Padmanabhan 1:22:04
Bye, thank you. Bye.