Melanie Cole, MS (Host): Welcome to the podcast series from the specialists at Penn Medicine. I'm Melanie Cole, and we have a panel for you today with Dr. Ty Dunn. She's the Surgical Director of Kidney and Pancreas Transplantation at Penn Medicine and a Professor of Surgery at the Hospital of the University of Pennsylvania. And Louise Berry, she's the Nurse Coordinator and Program Manager at the Total Pancreatectomy Islet Auto transplant Program at Penn Medicine, and they're here to highlight total pancreatectomy islet auto transplant. Before we begin, I'd like to mention that the specialists of the Total Pancreatectomy Eyelet Auto Transplant Program at Penn Medicine can be reached at T P I A T, Penn Medicine .upenn ,or by calling the program's dedicated referral line at 215-662-3304.

Thank you both for being with us today. This is a really interesting topic, and Dr. Dunn, I'd like you to start by telling us a little bit about chronic pancreatitis, why somebody might need a total pancreatectomy islet auto transplant. Tell us a little bit about the scope of the issue we're discussing here today.

Ty B. Dunn, MD, MS: Thanks for having us. Patients that develop inflammation in the pancreas, we call that pancreatitis, can sometimes go on to have pancreatitis problems that over time can become very difficult to manage and essentially turn into a chronic condition of pain.

Sometimes patients will have what's called acute relapsing pancreatitis, where they'll have unpredictable attacks of pancreatitis that are so severe that they can land in the hospital and even in the intensive care unit. So pancreatitis is a very serious condition. It doesn't affect very many people. But when it happens, there are treatments for it. Many of those treatments work. But what we're talking about today is a treatment option for patients that have not been successful with other more traditional and commonly practiced treatment options.

Host: Well, thank you for that, Dr. Dunn. Then tell us about how in the last decade, total pancreatectomy with islet cell transplantation has emerged as a promising treatment for the refractory pain of chronic pancreatitis. Tell us how it's made the prospect more acceptable to patients and clinicians.

Ty B. Dunn, MD, MS: I think it's really important to understand a little bit of surgical history here where for decades and decades, removing the entire pancreas was very problematic because we did not have good therapies for diabetes care. The pancreas is a gland. It makes insulin, which is how our blood sugar is controlled. It also secretes digestive juices. So, removing the whole gland creates immediate brittle diabetes. And so when people have pancreatic problems, usually the operations that are offered are limited to either the head of the pancreas being removed, that's called a Whipple procedure or a Distal Pancreatectomy where the body and tail of the pancreas are removed to treat conditions that are primarily localized, either in the head or the tail of the pancreas.

And part of the reason to do that is to leave enough islet tissue behind so that patients don't become diabetic. The problem is that some patients have the whole organ involved in their disease process, and one of those lesser operations is not going to cure them of the pain from the disease. And so removing the whole pancreas is really the way to remove the source of the pain.

Host: Well then I'd like you to speak about patient selection. How must physicians balance several considerations in determining which patients are optimal candidates for this, and can you offer some recommendations for that patient selection as that determination can often be challenging for clinicians?

Ty B. Dunn, MD, MS: So patient selection is a fairly complex endeavor. That's why we have a multidisciplinary team. It's comprised of physicians in various specialties that are related to the pancreas or related disciplines. So gastroenterology, motility, radiologists, surgeons, diabetologists, social workers, nutritionists, and team members that specialize in the treatment of pain; who all can contribute toward the review of the patient's case, what they've experienced, what testing they've had, what procedures they may have undergone, what medical treatments they've been under, and to assess the response to those treatments. Also to assess the patient's ability to follow a very complicated medical regimen because when the pancreas is removed, the patient then relies on taking oral medication to help with digestion. Those are called pancreatic enzymes.

And then also to follow a treatment regimen for insulin to treat any blood sugar abnormalities. And so patients are heavily counseled. They need to accept the fact that they could become diabetic for the rest of their life or have a very high lifetime incidence of diabetes as a result of the procedure, depending upon how many islets we are able to recover.

It's important to know that patients with cancer are typically not candidates for this procedure because the procedure includes not only removing the pancreas, but processing the pancreas to extract the islet cells to give them back to the patient. So you can imagine we would not give back any potentially cancerous cells, so that's why cancer patients are not candidates for this procedure.

Host: Dr. Dunn, sticking with you for a moment, as pain is subjective, as is quality of life, and we've already spoken. You just told us about patient selection and how this is really indicated only in those for whom the postoperative sequela cannot further diminish their quality of life. How effective is it for remediation of pain? What is the quality of life afterwards as far as pain management?

Ty B. Dunn, MD, MS: So pain management is, as you said, it's a highly individualized situation to assess someone's pain and the response to a treatment to pain. Sometimes when patients have this condition, they have been on daily narcotic therapy for many, many years. What we've learned by studying these patients is that when they're on narcotics for too many years, it may be more difficult to remove their pain because of what's called central sensitization, which is a phenomenon where the nervous system had this pathway activated so many times, it's almost like a phantom pain can happen.

So you can remove the pancreas, but they will still have this pain kind of syndrome. So what we want to do is identify patients that are not responding to therapy, and when it's clear that really there's not anything else that can be done, we really want to secure the islets from the pancreas.

So that we don't lose islets along the way waiting, because the pancreas does get replaced with scar tissue over time and we don't want to wait too long because that does diminish the pain resolution for the procedure. And it also can be associated with loss of islet mass, which makes the islet auto transplant part of the procedure less effective.

Host: Louise, what should a patient expect once he or she is referred to Penn for TPIAT? Tell us a little bit about what it's like for them as they're going through this process.

1. Louise Berry, EN, BSC:. When patients are referred here, and I would like to make the point, they do not necessarily have to be referred by a physician. Patients can self-refer themselves, and I make a point of calling all the patients myself. I like to get their story from them before I even look at their medical records because that sometimes throws a very different perspective on the person you're getting.

We collect all their medical records. This has got a lot easier in the date of electronic medical records and pushing imaging. And then what I do is I'll review all the information, and then as Dr. Dunn mentioned, we have a multidisciplinary team. We look at all the medical records and decide does the patient need any additional testing?

And if they do, we'll schedule that into our team evaluation and then we've already mentioned all the people they may see, and then once we've had seen a patient in an evaluation and it'll take a couple of days depending on whether the patient's out of town or whether they're local, then we'll present them to this multidisciplinary routine.

And then the decision will be made not necessarily to proceed immediately to surgery, but what the best treatment for that patient is at that particular time. That said, it may be proceeding to a total pancreatectomy and auto transplant, and if so, then I continue to work with the patient scheduling surgery, doing all the planning for surgery and then we take care of our patients long term. They kind of get stuck with me because I'm with them from the first phone call to the whatever long term follow up we do, which would be for life if the patient wishes that.

Host: Louise, tell us a little bit about the follow up period. What are the options for patients who become insulin dependent, or for whom insulin dependence wanes over time, as you are the person from start to finish? How do you work with those patients? Because primary care providers want to be able to counsel their patients on what to expect at this time. How do you do that? And tell us what to expect there.

1. Louise Berry, EN, BSC: So if patient's undergoing an islet auto transplant, simplistically, 30% of them will come off insulin. They will not be a diabetic. About a third of those will be kind of a once-a-day dose of insulin and then a third of them may become as the traditional diabetic taking long-term and short-term insulin.

Today things have changed radically. There are so many options for diabetics with insulin pumps and continuous glucose monitors. In the immediate post-operative period, they'll be followed by an endocrinologist at Penn Medicine. If they are local, they can stay with us. Otherwise we will send them back to an endocrinologist who can basically treat them like a regular diabetic with some special provisions.

But we will follow these patients if they wish to be followed here. Since I first started doing this, the options for treatments have broadened extraordinarily. I mean, it's not like in the old days where people were brittle diabetics and they had to test their urine for their blood sugars. Now it's instantaneous with all these continuous glucose. So I think trading pain for the possibility of diabetes is something people just consider.

Host: Dr. Dunn, as we've said, as this is made on a case by case basis; are there some guidelines for defining a severe quality of life impairment?

Ty B. Dunn, MD, MS: Acute relapsing or chronic pain pancreatitis can be incredibly debilitating for patients and it can interfere with their life because pain can impact all of their spheres. It can impact their ability to maintain social relationships. People cannot go out to eat sometimes because they'll have pain flares.

We've seen patients that don't go on vacations cause they're afraid they'll end up in a hospital, in a remote area. And, they're dealing with this ongoing seemingly non-solvable problem sometime for years and years. When patients have pain when they eat, sometimes they become malnourished because they don't eat enough.

When we look at outcomes after total pancreatectomy and islet auto transplant, there's really several spheres that I think about when I meet with patients, which I also consider during their evaluation. I look at their pancreatic function. Are they already requiring enzyme supplements to be able to digest their food because their pancreas is already that scarred and not functioning properly?

What is their nutritional status? Are they going to make it through surgery appropriately nourished? You know, are they going to heal properly? So then we do a endocrine assessment, and that means we determine whether there's a normal amount of islets, insulin producing reserves. So do they have normal glucose control and capacity for that?

Do we think they've got a retrievable islet mass that we can hope that they have a good response from a post pancreatectomy diabetes perspective? Some patients don't even know, and they present for their evaluation and they're a borderline or early diabetic. And so we know we're not going to get as many islets.

And so, you know, if someone's already diabetic and already requiring insulin, then we know that the islet auto transplant portion of this procedure is not really an option for them because you're not going to be able to retrieve islets enough to impact their post-surgical diabetes, which all patients have.

Remember the minute you take the pancreas out, they are a hundred percent dependent on insulin. The islet auto transplant part of the procedure is where we return the islets to the patient. It takes several months for those islets to develop their own little microvascular environment and what we term engraft into the patient.

We infuse them into the liver. So we're kind of just relocating the islets from the pancreas that we remove, into the patient's liver. So there's no immunosuppression, right? It's an auto-transplant. They're getting the islets back to themselves. The islets will start to function gradually over time.

And when we see evidence of that, in working with our transplant endocrinologist, we will start to decrease their insulin support and then let the patient come off insulin if they're able to. Some patients can take even a year to come off of insulin. There's so many things going on in the early time.

It's a big procedure. It's very impactful and it is a very long recovery. And people have to learn to manage diabetes and sometimes learn to manage the enzymatic replacement that they have to take. So there's a lot of learning to do even early after surgery when a patient might be otherwise really impacted by their post-op pain and recovery.

Once all of that is going on, then we start to focus on weaning pain medication and our specialists in pain management help the patient with that and construct a weaning regimen so that they can completely get off narcotics. And that is the best thing for the patient because the narcotics affect motility and bowel function is very important to not having additional abdominal issues. So really focusing on that hard work of coming off pain medication is an important aspect of recovery during those first few months, and that first year.

Host: Such an exciting time in your field. These are real advancements in medicine. I'd like to give you each a chance for a final thought here. Louise, I'd like you to speak to providers about some important criteria that can help improve the odds of a successful outcome for this. What would you like them to know as they counsel their patients, whether their patients have been a previous diabetic or not? What do you tell these people every single day?

1. Louise Berry, EN, BSC: Oh, stay in contact with your providers. That is a single most important thing. If I would say stay in contact with the center that did your surgery, because especially your nurse coordinator has probably all the answers to most of the common questions that come up. And if they call back to the surgery center, we can probably. If they drop out of sight and don't stay in contact, there's nothing we can do to help them. Here at Penn, I think what we do, we send the primary care physicians a letter after surgery with just the basic ABC of the procedure that the patient has and what we expect and possible complications. If they stay in contact with us, we can triage most things.

Ty B. Dunn, MD, MS: I'd like to build on what Louise just said. That was so important. Louise, thanks for bringing that up. I think it's really important as we embark on this really life-changing opportunity for the patient that might benefit from total pancreatectomy and islet transplant; I will personally call their referring gastroenterologist, their primary care doctor and their pain medication doctor, to really understand from their perspective how it's been to work with their patient.

Because we're going to be all in this together and we've got to have good, clean communication. Then I call the patient's care team, their local home care team once the patient's ready to transition back to their home community, which is generally about a month after surgery. So they do need to stay close by our medical center for frequent visits and a lot of adjustments and things that need to be done.

But once they transition back to their home center, then their home care team will carry on the treatment plan, whether it's pain medication weaning, optimizing their diabetes care. This is an operation for pain. The goal of the operation is to solve the patient's pain.

Now, some patients will pick up diabetes along the way. Sometimes it's problematic diabetes. But when we've surveyed those patients, patients will tell us about 96% of the time that they would rather have diabetes than have stayed with their pain problem. So really the whole point here is to address the pain and so people can move on with their life and work and be productive and care for their children and have their social activities.

I mean, there's just so much to life that resolves around being able to navigate, people that can have social events, people that can eat normally. It's hard to have a job if you're having pain attacks in the middle of your job. So many of these patients have lost a lot along the way, in their journey with pain.

And so being able to have a good support system is really key. All of our patients require a support person to be with them during their evaluation and as part of their aftercare, because no person can do this alone. It's very, very persistent and hard work for them.

3304. Louise Berry, EN, BSC: I totally agree with that. That is a very important point that they have to have an adequate care system. The people that come in with a strong family support system are the people that tend to do better. And providers can reach us two ways. We have an email, which is tpiat@pennmedicine.upenn. And we also have a dedicated referral line, which is 215-662-3304. And I monitor both of those. And I usually try to get back, respond to emails and call back within 24 hours.

Host: Thank you both so much for such a fascinating episode and what comprehensive work you're doing for patients at Penn Medicine. Thank you again for joining us. And that concludes this episode from the Specialists at Penn Medicine. I'm Melanie Cole. Thanks so much for joining us today.