All About Intestinal Transplants

Podcast Transcript

Scott Steele: Butts and Guts: a Cleveland Clinic podcast exploring your digestive and surgical health from end to end.

Welcome to another episode of Butts and Guts. I'm your host, Scott Steele, the Chairman of Colorectal Surgery at the Cleveland Clinic here in beautiful Cleveland, Ohio. And today I'm very pleased to have a topic we have not talked about before, and that's all about intestinal transplants. And our guest today I'm very pleased to have on the show, and that's Dr. Anil Vaidya, who is a surgeon and the Director of Cleveland Clinic's Intestinal Transplant Program here at Cleveland Clinic's Digestive Disease and Surgery Institute. Anil, welcome so much to Butts and Guts.

Anil Vaidya: Thank you very much, indeed, Scott for having me on.

Scott Steele: So as longtime listeners know of this show, we always like to start out with a little bit about you. So tell us a little bit about yourself, where you're from, where'd you train and how did it get to the point that you're here at the Cleveland Clinic?

Anil Vaidya: Well, it's been a journey, I must say. I trained at the University of Miami, I did my transplant training there with Andy Tzakis. That's where I got interested in intestinal transplants. My first exposure to intestinal transplants was in the late '90s with Andy. After that, I moved to Oxford University Hospitals, and at Oxford University Hospitals, I set up the intestinal transplant service, which was already there. I mean, in the UK, these high-end services are restricted to very small number centers, and it just needed someone to go there and kind of rejuvenate the whole thing. And so Peter Friend and myself, we took that on and put Oxford back on the map in terms of intestinal transplantation in Europe.

Around 2015-16, I moved to India to take care of my father who was ill. And so set up another intestinal transplant program in India. Very difficult thing to do because of the amount of infections and what have you, and really there's a successful intestinal transplant program there in South India right now. After, which I moved to Cleveland Clinic. Cleveland Clinic was a vetted position to be in. And, when the offer came around, I grabbed onto it.

Scott Steele: Well, we are absolutely super excited to have you here. And it's been fascinating to watch as you continue to grow and develop this program here in Cleveland. And so let's start at a 10,000 foot view level for our listeners out there. And as you know, a lot of our listeners are patients out there or family members. And what is an intestinal transplant? What does that mean? And what type of intestine are you actually transplanting?

Anil Vaidya: So, that's a very interesting question. I do get that a lot of times from my patients and obviously patients have also done a lot of background reading and we're having an access Google and what have you. Interestingly, when you say intestinal transplant, it could mean you're transplanting everything from the stomach onwards down to the colon. So you can transplant the stomach, the pancreatic or duodenal complex. You have the small intestine, as well as the larger intestine for people that have lost the ability permanently of using their intestines for nutritional purposes.

Scott Steele: Can you ever, or have you ever transplanted as a colorectal surgeon, have you ever transplanted the hindgut, [crosstalk 00:03:27] the colon, or rectum?

Anil Vaidya: So again, very interesting question. There are only two groups that have done an animal model, and I've been working with a Brazilian group, so there's a Brazilian group and a Japanese group. And we have done orthotopic as well as heterotopic experiments on seeing whether there is residual sphincteric function on the transplanted rectum. And to our surprise, in the earlier days we were joining the pudendal nerve to see whether there's any function to the rectum. But when we did a heterotopic model on top of the rats belly, the sphincteric function was still there. So it has opened the gates to, perhaps, looking at that carefully in the future.

Scott Steele: So the next obvious question to me is why would somebody need an intestinal transplant? What type of conditions arrive that somebody is saying, "Hey, we're going to refer them to you, to the Cleveland Clinic," to be able to do whatever it is to get their gut function back?

Anil Vaidya: The indications of intestinal transplants are divided into whether it's a pediatric patient or it's an adult patient. So with a pediatric group of patients, the most common indication is necrotizing enterocolitis. That is you're at birth, as you know, they have intense necrosis of their colons and they have the whole colon's out. And they have repeated resections after that leading to what's called a shortcut. Their gut's not enough for them to feed, so they need exogenous sources of nutrition. So that, is best one of the biggest causes of pediatric age patients coming towards transplantation. There are other congenital malformations, anomalies that lead to the loss of guts, that's in the pediatric patients. In the adult patients, it's a bit of a different cohorts of people. The majority reasons are for ischemic gut where the blood supply to the intestine has been blocked off by a clot, an embolus that originates from the heart or from the lower limbs, and has a paradoxical way of getting into the blood supply of the intestine.

So ischemic gut is perhaps the number one reason for adults having to come to an intestinal transplant service. What's got to be understood is that it's not like liver transplant and liver failure. You see, if someone's got acute liver failure it needs to be transplanted very quickly. Whereas when you have acute clot in your intestine, you lost your intestine. The patients need to be stabilized first before we can think about an intestinal transplant. So there is a window, about three to four months. It's an extensive surgery, take out all the gut that's not got blood supply, take it out, stabilize the patient, get the patient on to what's called TPN, exogenous nutrition, and wait for all the inflammation to settle down before you evaluate these people for a bowel transplant. So that's the number one thing that's ischemic gut, but there are other indications since we've gotten better at what we do and our outcomes have got better, the indications have increased.

And you know, the other major indication that we look at right now is a fallout from Crohn's disease. With Crohn's disease, there could be multiple resections done to take out structured components or inflamed components leading up to short guts. In fact, at Oxford, we wrote a paper and it's published in JAMA Surgery about a scoring system on which physicians who are looking at patients long-term with Crohn's should be starting to think about transplant as an option, which we would develop that scoring system that give us a certain amount of points for every landmark or metric that the patient comes across.

So, ischemic gut, inflammatory bowel disease, and now slowly getting into the tumors in the abdominal cavity, like your desmoids. Very slow growing tumors that in case the blood supply to the intestine, and sometimes cuts off that blood supply to the intestine, the last, but not the least indication is something that we buy in yet again in Oxford is for slow growing low grade pseudomyxomas that are appendicular in origin, but not as [inaudible 00:08:15] for patients who failed conventional therapy with pseudomyxoma and the conventional therapy is resecting all the jelly-like material, taking the colon out and have something called HIPEC therapy.

That's the first conventional therapy they should go through. If they fail that, then we have a way of giving them an option to get rehabilitated.

Scott Steele: And I encourage all of our listeners out there to look back in our back episodes, and there was an episode with Dr. Michael Valente talking about cytoreductive surgery in HIPEC. So, how common are these intestinal transplants? Is this something that, I mean, inflammatory bowel disease is surely a pretty common type thing and ischemia. So how common is the need for intestinal transplant or even an evaluation for intestinal transplant?

Anil Vaidya: So the way to address that is to look at intestinal failure. And what is the prevalent intestinal failure? And intestinal failure is divided into three parts: it's type one, type two, and type three. Type one happens if your patient's in the hospital, comes for an extended procedure, and the abdomen has got a bit of ileus and needs some TPN to go through that period when the bowel is returning function and just a standby for that is for less than 30 days, that is type one. Now, some patients might migrate and do what's called a type two intestinal failure, where they need that exogenous TPN for perhaps about a year, but after the year they stabilize and as surgeons, we can take care of what's happening in their belly, like fistulas and what have you, and take care of that surgical problem.

And they come off TPN. Some of the people from type two may slide into type three. Now, type three is irreversible intestinal failure. There's nothing that you can do surgically to get the intestines longer, to be able to absorb nutrients. And these people will be permanently on TPN. Most of them do well on TPN. It is about 10 to 12% of this population in type three intestinal failure that might not do well on TPN, i.e. they might have line infections repeatedly, they might have fungal infections, they might have liver failure from the TPN. These are the patients that we're looking for.

So in terms of numbers, overall number the incidents is 19, one-nine per million as type one intestinal failure. Then we're looking at half of that. So we're looking at about eight or nine per million at type two. And again, 50% of that into type three. So we're looking at about three or four per million in type three and 10 to 12% of that may qualify for intestinal transplant. So, in a country like the United States with 350 million people, we're talking about in the hundreds, not in the thousands.

Scott Steele: That's a very interesting thing. So, on our podcasts, we like to do a segment that's called Truth or Myth. So truth or myth, to you: intestinal transplants are more common in adults than children. Truth or Myth?

Anil Vaidya: Truth.

Scott Steele: Can you go into a little bit more depth on that, so is it just because of the stage they're at in life or just the disease process that affect them, tend to be a little bit more?

Anil Vaidya: You're absolutely right, the disease process is more of a varied disease process. So that cohort of people are more, so they could be more ischemic guts, more inflammatory bowel disease, there's more tumors. Whereas in the pediatric segment, you're looking at a very narrow window of kids that have necrotizing enterocolitis and the incidence is very low, kids that are born with congenital abnormalities, like gastroschisis that could go wrong. So that denominator is quite small, but if you compare the number of kids that have that problem, and then the amount of transplant done for that, there's again, a huge difference between the numbers. So the transplants have very small in terms of the denominator there.

Scott Steele: You touched base on this a little bit, but Truth or Myth: when intestines don't function properly, they can be repaired and transplants are not needed.

Anil Vaidya: I would say that is false. That's a myth. The patients that come to us, as I said, are part of type 3, irreversible intestinal failure. So, all bridges have got to be burned before they come to us. It is not something that I would try to do with a person with type two intestinal failure, where there is something that I can repair. That is the going to be the first port of call. Let us repair something that we know how to repair, and after repairing, there's got to be an algorithm saying, "After I have repaired what your problems are, you are going to come off exogenous feeding modalities or TPN".

Now, in type 2, as I said, 50% would go on to type 3. Is there a way of identification of who are those people who may not benefit from trying to repair their guts, and you jump the queue and say, "Well, actually, even if I repair your gut, there's a very good chance you're not going to come off TPN". And these are the people that we need to be able to talk to them and counsel, and they would benefit from having a chat with a transplant surgeon, which is exactly why we came up with a scoring system for Crohn's disease. And it gives the surgeon taking care of that patient, or the physician, a little heads up and a little metric to see is this going to work, or should I be calling the transplant surgeon sooner rather than later?

Scott Steele: So surgery in general can be a little bit scary and intestinal transplant surgery sometimes can even raise the eyebrows even further. So, let's talk a little bit about the patient journey. So first, how does a patient get involved or in touch with Cleveland Clinic's Intestinal Transplant Program? And, when they are in touch, what can a patient or their family expect as they navigate that preoperative and postoperative journey?

Anil Vaidya: So that's a very good question, in terms of what is the referral practice, or how can a patient get in touch with the department of intestinal transplant? Well, clearly the Cleveland Clinic is well represented on the internet, and there's a website that they can easily click on and get an appointment scheduled. However, it's quite a mammoth task to think that, "Oh my God, I need an intestinal transplant". The level of insight that you have to have to say, "I'm going to call that website on my own". And you say, "I want an intestinal transplant," is practically not going to happen. So essentially, it's going to be a referral practice from gastroenterologists, fellow colleagues as surgeons, with having the knowledge that perhaps there is something more that we can offer this patient in terms of rehabilitation, in terms of transplant. And therefore that would be the majority of the referral practice.

And for patients who are on TPN, they have a reversible intestinal failure and are facing problems with the TPN, with the lines, with the liver function, they themselves could perhaps encourage their primary physicians to make that referral. And, but again, that needs, as we all do we believe in our doctors and you say, "Okay, if the doctor's not yet said that I perhaps don't need it," and there's always that I'm on TPN and I'm good, until a point comes when I'm on TPN, I was good, but now I'm frequently going in and out of the hospital for line infections, or I become a bit yellow. Those are the alarming signs, which usually trigger a referral to the transplant service.

And once they've gotten that transplant service, what we do is we have a first meeting, that's just to get to know each other. It's nothing, no big words used just to get used to each other and get comfortable with each other. We would be looking at what is the kind of support that the patient has, who comes to that meeting, what are the questions being asked, what is the level of indulgence of the people with the patient? So, that would be our first thought process.

Then we'd arrange a second meeting. We'll give them a lot of material to read, give them links that they can go in and have their own look and see what they're getting into. And then the second meeting, this is when we tell them exactly what the procedure means, what is the recovery period and what have you. And intestinal transplants have come a long way in terms of what that recovery period should look like, how easy can we make it for patients to actually take care of themselves and have ownership of their health and try to let them know that we're always there to help them, but essentially they're having a transplant to get better, get back to life, to get back to doing what they were doing before. And that is what we tried to push across. That dependence on the healthcare system has to calm down, and they have a transplant they have to get on with life.

Scott Steele: So how early in the game, you, as the director of this program, would you like to be notified about these patients? I'm now a provider out there listening and think, "God, I got a patient, but I don't think they're quite there yet". Do you want to be contacted earlier rather than later, or what stage, or when they're in the hospital and they just had a massive resection and they're on life support, where we're in that process and that unfortunate potential consequences, do you want to be notified?

Anil Vaidya: So I would be delighted to be involved earlier because the later you put this off, patients come in at later stages, either they've lost line access, they've had problems with their liver, their enzymes going up. My back's against the wall at that point because I have to do things in rapid sequence, trying to get them on the list and what have you, and the understanding that this transplant is a journey. And that doesn't really percolate through, it doesn't give them time to think. So, I'd rather be involved earlier, know that they are there, do not reach out, reach out only when the current physician has made a referral, but have a little database where my coordinators can be keeping a watch on them. And we can discuss them on a monthly meeting with a primary physician to see how they're doing, what have you.

So that would be an ideal situation. That usually doesn't happen though, especially with ischemic gut, it's a catastrophic event for the patient and they are in the ICU with a lot of irons tropes and there's a 50-50 chance of making it through. And of course, at that point, I would be delighted to begin to be involved. But I'll still be one step behind because I need to see patients' recovering and showing signs of recovery. And as I said, it's not something that jump in, and I need to transplant them right away, which used to happen in the old days, but no longer. For trauma, in the old days, they would be put on the waiting list right away after a trauma and having intestinal transplant, we found out the level of inflammation in the body is so high that, you'd have a worse immunological reaction to that transplant.

Scott Steele: So when patients make it through a successful transplant, two questions: one, can they resume normal function as well as normal eating habits after that? And second, do they have to be on lifelong medication for that transplant?

Anil Vaidya: So to answer the first question. Yes, that is exactly why they're having the transplant. And that is the goal to be off TPN and to have your transplant intestine do all your nutrition and electrolyte balance work for you. So, that is the goal, and that is where we consider it to be a success. Lifelong immunosuppression is quid pro quo, it comes with the whole transplant. What's interesting is that over the years we've understood this lifelong immunosuppression or drugs thing has actually drastically come down. In the early days we were thinking, "Intestines, my God, such a big graft, we're going to need a lot more immunosuppression". And we've learned our lesson that the last 20 years we've come now down to a single drug. In my practice, I am totally against steroids, I do not use steroids in the long run. It's only one drug, and that too, that drug is given once a day. So, that is the quid pro quo for getting back to your autonomy of eating.

Scott Steele: So what's on the horizon as far as additional research or innovations in the intestinal transplant? And specifically as we talk about improving quality of life post-transplant, it sounds like that's a major win in terms of just being on one medication, I can tell you that, but what else is on the horizon in this field?

Anil Vaidya: So I think the majority of strides have been made in giving patients their own control of their health in terms of they become their own masters of what's going on with their intestine and the way we've done that, and that's again the binary work we did in Oxford, is transplanting a piece of skin from the same donor.

We transplant the skin either on the forearm and re-vascularize it, we joined the blood vessels, so it's not a split skin graft, it's different from a split skin graft. It's a whole vascular composite allograft from the same donor. And we put it on the forearm where they can see it, or we insert it into the abdominal incision where no one can see it, only they can see it. Now, what does that do? That has got some amazing immunology attached to it, once you connect blood vessels. What that piece of skin does is, it protects the intestine by a mechanism called innate immunity. That means if I'm the recipient of that skin graft and the intestine, whenever my immune temperature's gone up, guess what? I'm going to be attacking that skin first. And it'll show up as a rash.

It's a visual canvas. I alert the doctor, send a picture, come in, get a biopsy, grade it and treat it. If I don't treat that, within the next 10 to 15 days, I will have rejection in my intestine. So what has happened now is we've bought ourselves time and therefore there is a dynamic window into the immune system, through that skin graft.

And we've published, we've written a lot about it, and it's gaining popularity, slowly. We're trying to implement that at the Cleveland Clinic. We've gone through the IRB and trying to get all the regulatory tick boxes and be able to make this as a add on procedure done at the same time, but it is a useful procedure because then you have remote patient led immune monitoring. You don't have to come to the hospital. If your flap is good, brush your teeth and flap is good, all is good. You do not have to be keeping on coming to the hospital. So, that's the quality of life changes there. Not only a once a day medication, but also you've got this window here. Suddenly, you are in control, you know what's going on. And that makes it very endearing for our patients.

Scott Steele: That is incredible, fantastic stuff. And so for listeners of this podcast, you know we like to get to know our guests a little bit better. So we'd like to end up with some quick hitters. And so, to get to know you a little bit better, Anil, what's your favorite food?

Anil Vaidya: Thai food.

Scott Steele: What is your favorite sport?

Anil Vaidya: Cricket.

Scott Steele: I knew you were going to say that. I just knew you were going to say that. What is the last nonmedical book that you've read?

Anil Vaidya: Oh, Zero to One by Peter Thiel.

Scott Steele: And finally, you've been all around the world. Tell us something that you like about being here in Cleveland.

Anil Vaidya: Cleveland's got this fantastic, during the summer, ability, you just drive maybe less than 10, 12 minutes out, and you're in beautiful nature. It's just unbelievable. We just love that, especially you're going out with the kids and they love nature, they love walking. It's just the Metroparks have been a delight.

Scott Steele: That's fantastic. So give us a final take home message to our listeners about this Intestinal Transplant program.

Anil Vaidya: So intestinal transplant is there as a support act for patients who have type three intestinal failure. We are there to be able to give them one more option to what they currently have, and intestinal transplantation has gotten better and better over the years. Our success rates have gotten better than what they were perhaps 10 years ago. If you think that lung transplantation is here to stay, and is something that is a normal procedure that we do, intestinal transplantation has done better than that by closing the gap to liver transplant in terms of outcomes and the amount of innovation that's come through, we've created a situation where patients are in control of their transplant grafts.

Scott Steele: That is absolutely exhilarating stuff. And so, if you or someone you know is interested in learning more about Cleveland Clinic's Transplant Center, please visit clevelandclinic.org/transplant. That's clevelandclinic.org/transplant. You can also call the Transplant Center at 216.444.2394. That's 216.444.2394. Finally, please remember, and you've heard me say this multiple times, in times like these it's important for you and your family to continue to receive medical care and rest assured here at the Cleveland Clinic, we are absolutely taking all of the necessary precautions to sterilize our facilities and protect our caregivers and patients like you. So, Anil, thanks for joining us on Butts and Guts.

Anil Vaidya: Thank you very much. It's been an absolute pleasure. Thank you very much, indeed.

Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts and Guts.