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Melanie Cole (Host): Welcome. Our topic today in this panel style discussion is the management of complex pancreatitis. Here to tell us about that are my guests Dr. Andrew Gunn, he’s an interventional radiologist, Dr. Ali Ahmed, he’s an interventional gastroenterologist and Dr. Sushanth Reddy, he’s a hepatobiliary and pancreatic surgeon in surgical oncology and they are all at UAB Medicine. Gentlemen, welcome to the show. Dr. Reddy, I would like to start with you. Explain a little bit about pancreatitis. What is acute pancreatitis and can it become chronic?

Sushanth Reddy, MD (Guest): Thank you Melanie. Acute pancreatitis like all the itis’s is inflammation of the pancreas. The pancreas is a large organ located in the back of the upper portion of the abdomen. Unlike the other itis’s like tonsillitis or appendicitis, pancreatitis doesn’t always involve infection and that can be quite confusing to both doctors and patients alike. Acute pancreatitis is when the organ has been damaged by inflammation, but this is reversable. Several episodes of acute pancreatitis can lead to irreversible damage to the pancreas and this is called chronic pancreatitis.

Melanie: That’s an excellent explanation Dr. Reddy, thank you. And Dr. Ahmed speak a little bit about the etiology of acute pancreatitis and is there a hereditary link?

Ali Ahmed, MD (Guest): There are, well thank you for the question. There are many causes of acute pancreatitis. The main risks in the United States are gallstones and alcohol dependence. But genetic factors can also play a role and we will talk a little bit more about the hereditary pancreatitis a little bit later. Drugs, many medications, a common side effect will include pancreatitis and then sometimes it could be a bite of a scorpion, although rare, that can also cause pancreatitis. Most often that is found on textbooks and test questions.

And then iatrogenic which is when a physician does a procedure such as an ERCP or an endoscopic retrograde cholangiopancreatography which can unfortunately have side effect of causing pancreatitis. Now, regardless of the cause of the injury to the pancreas; the mechanism of injury is the same for all cases. There is a disruption of pancreatic enzyme secretion and that’s going to impede the exocytosis of the zymogen granules. These are the parts of the pancreas in the acinar cells that contain the digestive enzymes and if they get activated; this results in autodigestion and it sounds just as horrible as it is. You start digesting yourself. An acinar injury from autodigestion stimulates an inflammatory response and in some cases; this response can be very severe and result in multiorgan failure, sepsis, severe infection and in rare cases death.

To answer your second question about the hereditary link; there are several genes that have been associated with hereditary pancreatitis and some of the common ones are mutations in the serine protease 1 gene known as PRESS1 and that includes for a cationic trypsinogen and this is probably the most common cause of hereditary pancreatitis. Almost up to 80% of cases. Another gene that is associated is known as the serine protease inhibitor Kazal type 1 or SPINK1 and then cystic fibrosis associated with pancreatitis. Cystic fibrosis has many effects on many areas of the body and it can also cause thickening of the secretions from the pancreas and is associated with hereditary pancreatitis. And just to give you an idea, patients that have hereditary pancreatitis often have chronic pancreatitis in the first or second decade of life while those with the more common alcoholic pancreatitis will be diagnosed in their forties and fifties.

Melanie: Dr. Reddy what are some of the symptoms of acute pancreatitis? What’s the clinical presentation?

Dr. Reddy: I always ask my patients if they have had an episode of acute pancreatitis and many of them look at me and they say I don’t know what that is. If I hear that, I usually tell them, you haven’t had acute pancreatitis. Acute pancreatitis is a very memorable event in most people’s lives. People generally tell me that they have abdominal pain. The pain they can have, it can be quite severe. Traditionally, we talk about that pain being either in the epigastrium or the center of the upper portion of the abdomen or in the right side of the abdomen and some cases it can radiate to the back. A lot of folks also get nausea and vomiting. The onset of acute pancreatitis is typically anywhere from hours to at most about a day or so. Most patients will tell you that they were unable to control the pain at home. They had to come into the emergency department and receive pain medication in order to be able to control the pain. As Dr. Ahmed pointed out, people who have acute pancreatitis can actually go into multisystem organ failure and unfortunately that can happen relatively quickly. IV fluid resuscitation is an absolute necessity in the early management of people with pancreatitis.

Melanie: Dr. Reddy, sticking with you for a minute. How important is the early diagnosis as being crucial to improve the outcome prediction? How is it diagnosed?

Dr. Reddy: I will start Melanie with your second question which is how it is diagnosed. To have a clinical suspicion of pancreatitis is really, really important. Patients are diagnosed with acute pancreatitis if they carry either a classic symptom such as abdominal pain, nausea or vomiting combined with an elevation in biochemical markers specifically serum amylase or lipase and or a radiographic finding. In other words, a CT scan or MRI that shows evidence of pancreatic inflammation.

Early diagnosis is critical in the management of pancreatitis. I tell our students and residents to think of the pancreas as a gigantic sponge in the back of the abdomen. And just like the sponge in your kitchen, the pancreas can soak up so much liquid. The result of that is that patients can become acutely dehydrated very, very quickly. The first step in managing somebody with acute pancreatitis is to resuscitate them with IV fluids as quickly as possible. It’s not unusual to have to give anywhere from five to ten pounds worth of IV fluid within the first twelve hours after someone comes to the emergency room with acute pancreatitis, just to try to keep them hydrated enough to avoid multisystem organ failure. The most important factor when it comes to treating patients with pancreatitis is diagnosis and early fluid resuscitation.

Melanie: Wow, that’s great information Dr. Reddy. So, Dr. Ahmed, what are some of the possible complications from acute pancreatitis? As Dr. Reddy has pointed out, and you mentioned earlier about multisystem organ failure and the need to really hydrate heavily. Speak about some of the other complications that might arise if this is not treated quickly.

Dr. Ahmed: Yes, so the acute pancreatitis can have many complications and they include infection of the pancreas, pancreatic necrosis, and that can lead to the infection and sepsis that we have talked about, that Dr. Reddy mentioned. People can get recurrent attacks of acute pancreatitis so if you think one attack is bad, they can have more attacks, more frequently. They can have chronic pancreatitis where there is actually damage to the pancreas and is not able to perform its function in assisting in management of protein digestion, carbohydrate metabolism and in management and resulting in a lot of complications from that. Patients can get pseudocyst formation where fluid develops outside of the pancreas and that can result in blockage of the digestive tract with resulting nausea, vomiting and inability to eat. They may get bleeding and complications from bleeding and life-threatening bleeding. And the complication is also death. And I would say the other thing is in this new era with concern about pain medications; people may develop chronic pain and then dependence on pain medications.

Melanie: And Dr. Gunn to you now, what are some of the current issues in medical or surgical management? Speak about nutritional or pain meds, antibiotics, surgery. How is the management of complex pancreatitis treated?

Andrew Gunn, MD (Guest): Well I think what we have heard so far is the biggest problem with pancreatitis is the fact that there could be such a diversity of clinical presentations. Patients can present with abdominal pain, in the acute phase, they can present much later in the chronic phase. Patients can present without symptoms of infection. They can present with symptoms of infection. They can present without vascular complications, with vascular complications, without pseudocysts, with pseudocysts and so as far as medical and surgical management; the diversity of options depending on how that patient presents; can pose a problem for a physician who is trying to manage a patient with pancreatitis on their own. And that’s really the important part of having a multidisciplinary approach to pancreatitis because you can really bring in the expertise of a variety of physicians especially the surgical oncologist, or surgeons who could potentially remove part of an infected pancreas or part of a dead pancreas, but especially the combination of having an endoscopist like Dr. Ahmed or a skilled interventional radiologist because when there become infected collections in there, they need to be drained out and whether that’s drained endoscopically where the fluid goes back into the gastrointestinal tract or whether that’s a percutaneous image-guided drain placed by interventional radiology where we drain that fluid outside; those discussions are really best had in a multidisciplinary approach. And so, some of the current research in this area is really looking at what are the best ways to manage this drainage. Is it dual drainage, both endoscopic and interventional radiology, the size of the drains we put in, the size of the stents that we put in, what’s the appropriate timing of that and all of those things are active areas of research which is really exciting time for us at UAB with our pancreatobiliary disease institute.

Dr. Reddy: I would like to add for years surgery was thought to be the primary mainstay for treatment of pancreatitis and what we have learned the last fifteen to twenty years is that surgery probably should be reserved for those patients whom the other interventions that Dr. Gunn mentioned were not effective. And we have moved more toward a minimally invasive approach to treating patients with pancreatitis. The situation where we have to actually remove large portions of dead pancreas is a very rare event nowadays. And that’s a good thing for most of these patients.

Melanie: Dr. Ahmed let’s talk about diet now because I think that this is a big issue with someone who may have recurring flare ups of pancreatitis. What kind of diet is recommended to avoid these flare ups and why are some foods triggers at some point and sometimes they are not.

Dr. Ahmed: Well I think this is an excellent question and it brings straight from my patients to your question. A patient will tell me heh, I ate this last week and I was fine, and I ate it three months ago and I was sick or vice versa and it has almost no rhyme or reason and this speaks to Dr. Gunn’s point we don’t fully understand all the intricacies in the cause of pancreatitis. And that’s why there are a lot of variables that are unanswered. So, we have to sort of look at it in a focused approach and use some of the evidence that’s in the medical literature. So, a couple of things looking at acute pancreatitis and nutrition, we do know that early feeding is better than late feeding especially with the risk of infection that Dr. Reddy talked about. And we have also found that early feeding through the digestive tract is probably better than feeding through the vein or TPN or trans-parenteral nutrition. So, any time we can give enteral or feeding through either a tube going through the mouth, gastro-oral feeding or through the nose a nasogastric feeding, that’s going to be preferred. And studies have also shown that whether that tube gets past the pancreas for jejunal feeding versus in the stomach, it’s probably okay and in some cases if there is a blockage you obviously want to get beyond the blockage. But that addresses sort of nutrition in the early stage.

In terms of a diet for patients, people have studied low fat diet, high fat diet, controlling carbohydrates, protein rich diets and unfortunately, there is no real recommendation. For along time, we thought a low-fat diet would be appropriate for our patients, but recent data seems to show no evidence and the gastroenterologic pancreas work study group has actually recommended a healthy diet. So, we will follow a balanced diet and hope that that will help. And then I think outside of food, we also want to modify reversible risk factors. Tobacco, smoking use as we know increases complications, risk and susceptibility for pancreatitis through mechanisms that aren’t fully understood and then stopping alcohol. So, if those things we can control and have people on a healthy diet, that should help them long-term without giving them specific food recommendations.

Melanie: Dr. Ahmed, I’m sticking with you for a minute because I would like to ask you about vitamins or supplements and the risk for chronic malabsorption as you were mentioning about various tube feeding, what is the issue as far as absorbing the nutrients that they are going to need and what do you recommend as far as vitamins and supplements and even enzymes?

Dr. Ahmed: Yeah, that’s a very good point and I think as people progress to chronic pancreatitis; enzyme supplementation plays an important role and that becomes part of their regimen. And often helps with pain management and symptom control. Patients that have problems with absorption are going to have problems with absorbing vitamins and they are going to have vitamin deficiencies and it will be important for the physician to be looking out for that and sometimes they will have to check for vitamin deficiencies and do supplementation. People have looked at probiotics which is a hot topic but studies have not shown a benefit of probiotics in patients who have either acute or chronic pancreatitis. So, I think we come back to looking at managing pain, giving them enzyme supplementation when they have to, especially those patients that have enzyme insufficiency and then work on giving patients vitamin supplementation when they need it.

Melanie: Dr. Gunn what types of care are involved? Does this require the management of several aspects of care? You mentioned a little bit before the multidisciplinary approach. Speak about that a little bit in more detail.

Dr. Gunn: Yeah, I really do think it requires a multidisciplinary approach because as you can see, there is medical management for pancreatitis, there’s minimally invasive endoscopic management for pancreatitis, there’s minimally invasive percutaneous management for pancreatitis and then at the far end of the spectrum, there’s surgical management for pancreatitis. And so, all of these different specialties have a role to play and just kind of depending on where the patient presents in that spectrum and what their symptoms are; it’s worth a healthy discussion from a group of specialists to be able to decide what’s best for the patient. Here at UAB, we have recently started a pancreatobiliary disease center which involves surgeons, radiation oncologists, medical oncologists, gastroenterologists, interventional radiologists and radiologists and we have actually really seen even in the first few months that we have been doing this, great success in treating patients with very difficult pancreatic necrosis and chronic pancreatitis, being able to transition them away from drains and kind of back into normal lifestyles. So, I would say that a multidisciplinary approach is crucial.

Melanie: Gentlemen, I’m going to give you all each a last word. So, Dr. Reddy I’d like to start with you. Can acute pancreatitis be prevented and where do you see this whole multidisciplinary approach and treatment modalities and where do you see this going in the next five years?

Dr. Reddy: That’s a good question. Can acute pancreatitis be truly prevented? And as Dr. Ahmed pointed out, there are several modifiable things that we can do to try to minimize the risk of acute pancreatitis. The first and most important thing is stopping risks such as smoking or even alcohol abuse. I tell my patients that those that quit drinking will likely decrease their risk of pancreatitis, but it won’t turn to zero. The second most common cause of acute pancreatitis in the United States is gallstone related disease. And for patients who have gallstones; their gallbladder should be removed when it is safe after the acute pancreatitis flare has ceased. That could probably give you your best chance of avoiding another flare of pancreatitis for gallstone related disease.

In terms of things that I’m looking forward to in the next ten years or five years; it really comes down to things that Dr. Gunn has been pointing out this entire conversation. The idea that we can have multiple people working together to each bring their own expertise into a complex disease allows us to stop working in boxes and treat the patient from a true multidisciplinary approach. If I were a patient with a complex disease, I would love to know that I have got four or five doctors working together to try to treat me than having each person come in and give their single opinion and try to do things in a sequential manner instead of in a much more coordinated manner. That’s the thing that I’m looking forward to most is seeing the things that people are going to come up with from interventional radiology, from advanced endoscopy, showing me the different ways we can treat things without having to resort to much more invasive approaches that we have been doing in the last five, ten or fifteen years.

Melanie: Dr. Gunn your take on all of this, because it really is a fascinating interview when I have all three of you that work on different aspects of pancreatitis. So, from your vantage point, what would you like to see happen in the next five years and what would you like other providers to take away from this segment?

Dr. Gunn: Well first, I think what I’d like other providers to take away from this segment is that if you have a patient with pancreatitis and you feel like the support system around you isn’t sufficient to have a true multidisciplinary approach to that pancreatitis patient to feel free to send them over to us and so at least we can evaluate it in our multidisciplinary conference and we can – the patient isn’t necessarily going to stay at UAB; but that patient is going to be evaluated and we can send recommendations back to help physicians that are out in the community along and so that’s always our goal is to help all the patients in this region with this disease process to a more normal and healthy lifestyle.

As far as things that I see happening in the next five or ten years; I really think looking at some of the things that Dr. Ahmed was talking about as far as molecular markers, or genetic markers or some of these modifiable risk factors. If we can improve on some of those things to prevent pancreatitis from happening, I think would be some of the things that would be most advantageous looking forward into the next five years or so.

Melanie: And Dr. Ahmed, to you now. Promising new therapies and as you are an interventional gastroenterologist, where nutrition and all of these therapies are involved; what do you see happening in the next five to ten years and as a summary and a wrap up, tell other physicians what you would like them to know about pancreatitis and when it’s important that they refer.

Dr. Ahmed: Well I think pancreatitis has been around for centuries and in the last 100 years, I think we have had trouble advancing our knowledge of the disease process, partly because what happens in the animal model cannot be replicated in the human model. And part of it is just learning more about it. and like Dr. Gunn and Dr. Reddy have mentioned, I’m very excited about this interdisciplinary approach where we have different guys or different disciplines that work normally separately are now working together to solve complex patient care. Pancreatitis often involves lengthy hospital stay, huge cost to the health system, and a lot of time and by working together; we may become more efficient on how we approach these patients and hopefully result in better outcomes.

Looking forward, I think there are going to be advances in how we look at the pancreas. I mean I think from both the percutaneous approach and the endoscopic approach, there are new devices and tools that will look – will be a camera known as pancreatoscopy where we will be inside of the pancreas duct and have better tools to manage complex lesions within the pancreas that may down the road lead to chronic pancreatitis. So, perhaps we will be able to better identify which patients will develop chronic pancreatitis and maybe we will be able to have molecular or genetic therapies for people with genetic deficiencies to prevent them from progressing from acute to chronic pancreatitis and maybe even reverse their disease process.

For physicians out there, I think it’s very important to understand that these patients may get sick very quickly and as Dr. Reddy pointed out earlier in this talk; he had mentioned how early fluid and volume resuscitation is going to be very important to get patients better and if they are not getting better in a day or two; I think it’s very important to call quickly and get help from an institution that may have more resources because even though surgery is not often used and going forward, people may not be as equipped to handle the surgical procedures; knowing who can will be important and at the end of the road, surgery still remains an option for a small segment of patients.

Melanie: Thank you so much gentlemen for coming on with us today in this panel discussion and sharing your expertise on pancreatitis and letting other providers know the important red flags and the treatment options available and even the important information on prevention and promising new therapies. Thank you again for joining us. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST. That’s 1-800-822-6478. You’re listening to UAB Med Cast. For more information on resources available at UAB Medicine you can go to www.uabmedicine.org/physician, that’s www.uabmedicine.org/physician. This is Melanie Cole. Thanks so much for listening.