Autologous Islet Cell Transplant With Dr. Vavara Kirchner

Dr. Varvara Kirchner, an associate professor in the Division of Abdominal Transplantation, explains autologous islet cell transplant. In addition to the procedure, its benefits, and its ideal candidates, she and host, Rachel Baker, also discuss the history of the procedure, Dr. Kirchner's mentors, and her future plans for the program.

Rachel Baker: [00:00:00] Welcome to Scrubcast, where we discuss the latest advancements coming out of Stanford University's Department of Surgery. I'm your host, Rachel Baker. Today, we're speaking with Dr. Varya Kirchner. Welcome to the show, Dr. Kirchner. Thank you very much. Dr. Kirchner is an associate professor in the Division of Abdominal Transplantation.

Why did you choose to specialize in transplant?

Dr. Vavara Kirchner: Well, it's a very good question and very related to this particular podcast. In medical school, I always wanted to do hematology, oncology, and then I thought of surgery. And then during my surgical rotation, my first case that I was scrubbed in, I met my first mentor.

in my life. And it was Dr. David Sutherland, uh, who was doing total pancreatic ectomyeloid transplant. That was my first case. I loved working with him. I really found this procedure very cool. I found the patient population cool [00:01:00] and I just fell in love with surgery. And since he was a transplanter, I said, I'm going to go into transplant.

I love it.

Rachel Baker: Well, so that is the impetus for me inviting you on the show today. Um, your new chief. Dr. Mark Melcher recently invited me to observe a new procedure that we're doing here at Stanford called the autologous islet cell transplant. Islet for everyone out there is spelled I S L E T like the tropical island, not E Y E like the fabric.

Dr. Kirchner, can you tell everyone what an islet cell is and why they're important?

Dr. Vavara Kirchner: So ILADS is actually a combination of cells and this is in a majority of it is endocrine cells that produce certain hormones. We know it because of the insulin and the beta cells in the islet produce insulin. However, there are other cells that produce, for example, glucagon, the hormone that counteracts the action of the insulin [00:02:00] and responds only when the sugars are low in the body.

Insulin obviously increases in the body when there is a very high levels of sugar. And U. Usually patients who are diabetic and have a very high sugar levels, there's not sufficient insulin, so they have to take the ex uh uh, external or insulin.

Rachel Baker: Got it. But in this particular instance, we're talking about removing an organ and rather than replacing it with an organ from somebody else, we're removing the patient's unhappy pancreas.

Then we're extracting its islet cells and then we're re implanting them back, just the cells, not the pancreas, into the same patient.

Dr. Vavara Kirchner: Correct. There are two types of islet transplantation. There is one that's called ALO, where you actually transplant islets from pancreas from a different donor, from a donor to the patient who is [00:03:00] diabetic.

That's a different indication. So this is auto islet transplant. And we do it for patients who have chronic pancreatitis. or acute recurrent pancreatitis. And if anybody is familiar with this, it's a disease that's really signified by very severe pain and that pain for people who have chronic pancreatitis, that pain never goes away.

Unfortunately, it affects the quality of life. Some of them cannot. call the job because they have to constantly go into the hospital or be at home because they're just not capable of controlling their pain. A number of those patients require quite a bit of pain medications in order to manage the pain.

And unfortunately, pancreatitis, it's In addition to causing pain, it causes also burnout of that gland of the pancreas and the subsequent complications are malabsorption because pancreas also produces [00:04:00] digestive enzymes as well as development of diabetes. because you burn out those islets eventually, but when the gland is very inflamed, it can make patients very sick and cause inflammatory reaction and organ failure throughout the body.

And, uh, some patients end up in ICU on dialysis and multi organ failure. It's a disease that has a wide range of presentations, but this particular patient population. has a problem with pain and if this pain is not controlled with medical or endoscopic management, this is when the surgery is considered.

Rachel Baker: Well, so you're re implanting the patient's own cells in the auto Right. Does that mean there's no risk of rejection? 

Dr. Vavara Kirchner: Absolutely right. So we take the pancreas out of the patient to pretty much get rid of that pain. Right. But then they become really diabetic. So this is when we digest the pancreas and it's an [00:05:00] enzymatic.

as well as the mechanical digestion of the organ that takes about four to six hours, and then we infuse the islets back into the patient, and that's an auto transplant. So, in theory, there's no immune response because they're patient's own cells. There are some exceptions to that. First of all, some of the inflammatory reaction when we infuse those islets have similar pathways as some of the rejection, but it's minimal compared to actually infusing islets from someone else.

So, this reaction called immediate inflammatory reaction to the islets and they can be destroyed. Again, we have a methods of controlling it or decreasing the injury to those islets. And the other very, very rare event is when patients have actually antibodies to their own pancreas and islets. And then that actually over time can still destroy the islets.

that were infused. But majority of patients do not have a severe reaction to infusion of their own islets. 

Rachel Baker: I mean, this just sounds kind of unbelievable. We're pretty sure it works. I mean, how did you learn to do this?

Dr. Vavara Kirchner: Yeah. So, it depends. I mean, that's a good question. It works. And in fact, so, Dr. Sutherland is the one who actually invented the procedure in 1970s.

And so you learned from the originator. I learned from originator. They initially, the idea was developing this procedure is actually to develop minimally invasive treatments for patients with diabetes and transplantation of islets from donors. But in order to understand better the procedure and islet biology, they eliminated.

the allo, the immune, the immune response portion of it by using patient's own eyelids in the setting of chronic pancreatitis. So it definitely works and the eyelids actually go [00:07:00] into the portal system and they get seated usually in the liver. and they find their own home in the liver. So the success of the, this particular part of the procedure, which is the insulin independence and good glycemic control will depend on amount of islets that are being infused, the size of the islets, so the more islets the better.

And at, at the higher levels, which is about 5, 000 kilogram, uh, roughly 70 percent of patients will be insulin free at three, at three years. So it's definitely works.

Rachel Baker: Wow. So, and then you brought this procedure to Stanford. Tell me about that. This cannot be an easy process.

Dr. Vavara Kirchner: Before even I came to Stanford, uh, Stanford was planning on developing this program, so there is a huge team actually.

of professionals, multidisciplinary professionals from research and [00:08:00] clinical fields. They've been working on the program. I joined this team when I came to Stanford and I was lucky that Stanford already had so many resources. So in the collaboration with multiple physicians, uh, including Walter Park, Brendan Visser, uh, Marina Bessina, uh, Vita Kaur, Alex Vesidius.

We were able to perform this procedure, but you have to also know that all the supporting members of our team, including Naoko, who is one of our nurse practitioners, as well as our research team in the diabetes center, who've been very helpful. So I think the main point is that it takes the whole village.

It's not one person's kind of invention or achievement. And I'm very thankful for our amazing team. And Sung Kim, who actually is leading the Diabetes Research Center at Stanford and was really interested in developing this procedure to further understanding of [00:09:00] islet transplantation.

Rachel Baker: Fantastic. Last question on this topic.

For any patients or referring physicians listening to the podcast, who is a candidate for autologous islet cell transplant? What does your ideal patient look like? Because I know you mentioned this earlier about the burnout, so I imagine that Your pancreas can't be too sick. Is that right?

Dr. Vavara Kirchner: Yeah, you're absolutely right.

So it's patients who Have acute recurrent or chronic pancreatitis Who failed medical management as well as endoscopic management such as the ERCP who capable of managing complex lifestyle after the operation because remember they have to still monitor their sugars because not everyone's going to be completely insulin free.

Sometimes early on they require additional nutritional supplementation and since a number of those patients have [00:10:00] history of pain it's also lots of work to actually weaning off the pain medications. Of course, yeah, that's been hard. Yeah. And in terms of the islet functional status, you don't necessarily have to be non diabetic.

Small amount of insulin dependence is still okay because the goal of this procedure, not necessarily to make everybody diabetes free, but what you're trying to avoid is to have a severe diabetes. with hypoglycemic inawareness and severe complications. So, even if patients end up on a little, small amount of insulin, but with no pain and well controlled sugars, I believe this is a success, because you can't believe how many patients go back to work and go back to school and able to get their life back.

Rachel Baker: That definitely sounds like a win to me. We'll put information about how to contact your clinic in the description. I'd like to move now to our final set of questions that we ask each of our guests. First up, who is a surgeon you admire

Dr. Vavara Kirchner: and why? I was thinking about this question. I have three. I have to say that.

The first one, obviously the person who created this operation and who really inspired me to go into surgery, to go into transplant. He was not only fantastic clinician, he was a fantastic researcher, obviously, because he developed all this from the lab. to to clinical practice and also most amazing, uh, generous individual who shared his knowledge and always welcomed everyone.

Um, Dr David Sutherland and my second most admired surgeon is my mentor from residency and fellowship. Dr Timothy through it. He really inspired me to become a liver transplant surgeon. So again, I think he knew how to develop young individuals, [00:12:00] both clinically, academically and really knew how to find a common language with everyone, everybody.

And this was absolutely amazing. And the last one is the Professor Sang Woon Lee with whom I trained in South Korea and living donor liver transplantation. He is also innovator. He performed the first living donor liver transplant in South Korea and developed the largest center there, which performed over 400 living donors a year.

Uh, and again, um, extremely talented individual, but very generous, very kind, always help keeps his doors open for every single individual who wants to come and learn from him. And, you know, there is no, none of these guys have egos and is just despite their achievements. And it's just, I, these are the people you want to actually portray and be like.

So these are the three people that I, surgeons, I admire.

Rachel Baker: Second question is. What is the best advice you have received in 10 words or less?

Dr. Vavara Kirchner: It's funny because my mentor, Dr. Timothy Pruitt, always would tell this to me when I get super upset. And recently, I heard it again from my very good friend and mentor, Dr.

Jill Helms. Don't throw away baby with, uh, with the water, with the dirty water. So I think it's really true. I mean, sometimes you throw away very good things just because you're trying to get rid of something that's not as, not as pleasant. So I think that's, uh, probably teaches you about the patience and about thinking actually the issues and things globally and try to see the best things and preserve the best things. 

Rachel Baker: What bath water were you trying to throw away here? 

Dr. Vavara Kirchner: Oh, just, you know, some passionate discussions [00:14:00] during the grant submissions time.

Rachel Baker: I totally sympathize. Well, we are about out of time, but I wanted to ask you one last question.

Now that you have this program underway and off to a great start, what is next on the timeline for Dr. Varia Kirchner?

Dr. Vavara Kirchner: Well, I think that now we perform the first two adult, uh, TPATs. We're working on developing our pediatric total pancreatic ectomyotoilet program because of, although, um, One thing I probably didn't mention that the pancreatitis there has always been a stigmata that it's caused by, you know, um, over excessive alcohol use.

But the reality is that now that we have a better testing, we realize that a lot of those patients actually have underlying genetic, uh, genetics that, uh, contributes to the pancreatitis or other conditions. So, [00:15:00] and it's not only adults who can, uh, in fact, from the more recent data, up to 60, 70 percent of patients that we evaluate have genetic predisposition.

So, um, it's not only adults who can have this, uh, disease, it's also kids. And kids sometimes, even at the age of one or two, and nobody can diagnose and think of that, how uncomfortable they are. So the youngest, I think that we... TPIT that we performed at my former institution was at the age of three years old.

So it's definitely rare, uh, to do it, uh, to perform surgery in such young, uh, patients, but you just, you have to be cognizant that children suffer the same way as adults do.

Rachel Baker: Definitely. Well, I look forward to seeing it come to LPCH. Thank you so much for coming on the show today.

Dr. Vavara Kirchner: Thank you very much for having me. It was really fun.