Jordan Winter, MD, PhD, Professor of Surgery at University Hospitals, Cleveland Medical Center and Sidemen Cancer Center, Chief of Surgical Oncology, Pancreatic Surgeon, talks about a drug that brings cholesterol levels to such a low point they are able to prevent some heart diseases.
Can you tell me about pancreatitis in kids? I didn’t even know that could exist.
WINTER: Pancreatitis is a rare disease in children because the most common causes are gallstone disease, which occurs in adults, or alcohol consumption, another adult affliction. When it occurs in kids, it’s generally related to a hereditary predisposition and an inherited disease.
Does it resemble adult pancreatitis?
WINTER: It does resemble adult pancreatitis in symptomatology. The most important symptom is pain, but also problems with eating and nausea. There can also be other associated symptoms that are rarer like bleeding or obstruction.
Before this transplant, how would you treat a child with pancreatitis?
WINTER: You treat them supportively or asymptomatically, meaning you’re trying to address symptoms as they develop. A patient who is having pain might get pain medicines, whereas somebody that’s developing fluid collections related to pancreatitis may get a drain placed to treat the fluid collection. So, it’s really symptom by symptom, hospital admission by hospital admission. There’s no definitive intervention. Sometimes patients may develop strictures due to the inflammation in the ducts in their pancreas, and those can be treated by putting stents across those strictures. That’s usually only temporary and doesn’t resolve without some definitive surgical intervention.
But now there’s a new treatment?
WINTER: There is a treatment that is rarely done that we think is very effective, and that is removing part or all the pancreas. If you take out the disease, the patient is often cured, which is exciting to be able to restore a quality of life to somebody that’s been living in pain for so long.
Do you need a pancreas to live?
WINTER: Your pancreas is not essential for life. It’s an important organ and has a purpose. The two main purposes can be managed with supplemental medicines. So, those functions can be replaced pharmacologically.
What are those functions?
WINTER: It has an endocrine function. It produces important hormones that are particularly important for regulating glucose levels. The pancreas makes insulin and if you don’t have any insulin, you become diabetic and require insulin to regulate that. We all have seen diabetics manage their blood sugars by taking their blood sugars and then treating with shots of insulin as needed. The second function is an exocrine function. Endo- is internal and exo- refers to external and our GI tract. It interfaces with the environment, so the exocrine function is digestive. The pancreas secretes digestive enzymes, into the GI tract to help us digest our food.
Let’s talk about Lilah. Did you take out almost all of her pancreas?
WINTER: Lilah has a hereditary predisposition to pancreatitis. It’s a genetic defect referred to as PRSS-1, and it’s an enzyme that’s important in digestion. It’s not supposed to be activated until the protein enters the GI tract, but in people with this abnormality, it becomes activated in the pancreas itself and can start digesting the patient’s own pancreas. She’s had symptomatic pancreatitis for many years and was debilitated by it. The pancreas kind of looks like a tadpole in the center of your abdomen with a head, neck, body, and tail. Her whole gland was affected by this, but the part that was causing her the most symptoms was in the body and the tail. She had a variant of chronic pancreatitis referred to as calcification pancreatitis, or calcified stones that are a byproduct of all the inflammation over years throughout her pancreas. There was so much inflammation due to the recurrent relapsing episodes that at one time in the past year, her entire abdomen was filled with pancreatic fluid that required drains. So, all of that intensifies the scar tissue and the inflammatory response of the body around the pancreas.
Did you then do something else with Lilah?
WINTER: Yes. What is a really innovative option for patients with pancreatitis is the auto islet transfusion, auto meaning your own. We were able to give her islet cells which make insulin back to her.
Where do you take them from?
WINTER: In her case, we didn’t remove the whole pancreas. That certainly was an option, but we removed about 65 or 70 percent of her pancreas, the part that really was the most involved. The rest of her pancreas we’ll surveill very closely during her lifetime. We took away the most diseased part, and rather than send it to the pathologist for evaluation and then discard some of it, we took all of that tissue and sent it to the lab. The lab goes through a process where they extract the islet cells. The islet cells make insulin and comprise five percent of all the cells in the pancreas. They homogenize, meaning break down and digest the removed pancreas, that is, the pancreas that we deliver to them, both mechanical digestion and also enzymatic chemical digestion. They’re able to separate the islet cells from the other cells. Ultimately, they aggregate all of those cells in a bag and that bag is transported back to the OR where the next day we take Lilah back to the operating room and infuse the islet cells directly into her liver. In that case, her liver becomes her new endocrine organ, or insulin producing organ.
Is that enough to keep her off of insulin?
WINTER: We hope so, but there’s no guarantee. Patients who undergo this operation really need to feel comfortable with the possibility that they’ll be trading their pain for diabetes. That’s something that’s very manageable. In patients who are afflicted with this disease, it’s a pretty obvious tradeoff that makes sense to them. But in about a third of the patients who get the islet transfusion, they’re able to actually be off of insulin completely.
Is it immediate or does that take a month, a year?
WINTER: It’s not immediate. It can take up to six months for the islet cells to find their new home and to adjust and start functioning optimally. About a third of the patients have partial insulin function or production, which really makes management of their diabetes much better.
Do these islet cells replicate themselves or do you have just so many that you work with your whole life?
WINTER: That’s a great question and I’m not sure if we know the answer to that. Their replication abilities are likely very minimal, but it is possible that there are some stem cells that are also part of that cocktail and seed the liver. So, I suspect there is some islet cell generation over time. The exact quantification of that is something that’s very hard to do. We hope in the future technologic innovations will allow this to actually be something that realistically can happen, where we can regenerate those islet cells not only in the patient’s body, but in the lab in a petri dish and infuse many more islets of the patient’s own islets into their body.
Is this something you could do for anybody with pancreatitis? Even when you don’t take out the pancreas, would you be able to use these cells?
WINTER: This procedure is specific to those who we remove their pancreas because it is an auto islet transplantation, meaning we’re taking their own islet cells in the transplant. In order to do that, we must remove the pancreas. However, in the transplant world, there is an option of an allogenic islet transplantation. You’re taking islets from somebody else. And in this case, it’s typically a cadaver. In those patients who receive somebody else’s islets, they have to be on long term immunosuppression to suppress the rejection of those islets. In the case of Lilah, or other people getting auto islet transplantation, no immunosuppression is needed because it’s your own cells.
What’s the prognosis for Lyla’s future?
WINTER: I think the prognosis is excellent. She’s pain free right now, which is really a gift not just to her, but to everybody who’s ever taken care of her. It’s extremely gratifying to see. My expectation is that she will continue with that level of quality of life. In her case, she does have some remnant pancreas that is still diseased, and we have to watch it very closely. It certainly is possible that that part of her pancreas can also act up, in which case we have the option to remove that and infuse those islets, too. But one thing that’s a nice prognostic reality for Lyla is that she inherited this from her father, who had the same exact operation, 65 percent of his pancreas removed as a child, and over the last 40 plus years, he hasn’t had any new flare ups in his residual head. I hope that Lyla has the same success.
Is this just standard procedure now for people who get their pancreas removed?
WINTER: Total pancreatectomy with auto islet transfusion is not yet standard procedure. There are only a couple handfuls of institutions around the country that are doing this regularly. The barriers to it are that you need a facility and the technical expertise to extract the islets and prepare them. However, in our case, we partnered with a company that is doing this called Koligo, and that enables institutions like us who formerly did not have the clean-cell expertise and extraction infrastructure in place to prepare these cells to do this very easily. It is something that many institutions have the technical expertise in terms of doing the pancreatectomy or the resection. The islet transfusion is something that is still a very specialty, niche option. There are, to my knowledge, three or four institutions in our state that are currently doing this. We’re the first ones, as we understand, to perform this operation in a child.
Is there any risk to transplantation of these islet cells?
WINTER: The most immediate risk in the early post-operative period is that the portal vein could clot. What that means is the main vein, which provides the majority of the blood flow to the liver, could develop a clot immediately after the procedure because we infuse the islets into that vein. That vein then branches in the liver and the islets then seed various areas within the liver organ. But when you’re infusing a large number of cells, that risk is possible. It’s about one percent and we have not seen that to date.
What would happen with the clot there? Is there a risk?
WINTER: When a portal vein clots that could cause significant liver injury and the greatest risk is liver failure. Even if the portal vein clots, there are interventions we can do to break up the clot. We can do that surgically. We can do that through minimally invasive interventional radiology procedures. Or sometimes we just place the patient on a blood thinner and the patient does well. The majority of the times when there is a clot as a result of this, patients do fine. And again, it’s a very rare complication. Other than that, the complication risks are fairly minimal.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
KATELYN MCCARTHY
KATELYN.MCCARTHY@UHHOSPITALS.ORG
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