Episode Transcript
[00:00:01] Speaker A: Welcome to Ingest, the podcast series designed for primary care and brought to you by the Primary Care Society for Gastroenterology. My name is Charlie Andrews. I'm a GP with an extended role in gastroenterology and I'm delighted to have Dr. John Leeds with me here on the podcast. Today we're going to be doing a two part series on pancreatic lesions. We're going to start with part one, where we're going to look at benign pancreatic conditions. And then part two will come next where we'll be looking at malignant pancreatic conditions.
So part one today.
John, would you like to introduce yourself to our audience today?
[00:00:37] Speaker B: Yeah, no worries. I'm John Leeds. I'm with the Pancreatic Auxiliary Physicians, endosporist from the Freeman Hospital in Newcastle and also not that long ago gone honorary chair in Pancreatic Ovillary Medicine as well. So finally been recognized for some of the work I've done.
[00:00:53] Speaker A: So you're in a great position to help us with this topic and I'm really looking forward to exploring it with you. We've spoken before and you're a really engaging speaker and it's great to sort of be able to ask you some of the questions as a GP on the front line. It's really helpful to just kind of know about. So let's go. Let's start at the basics really, if we can, John, and just think about what is the pancreas and what is its role in the body?
[00:01:17] Speaker B: Cool. Okay. Pancreas is a gland. It's got a number of functions. In fact, someone put something on Twitter the other day about the pancreas. They'd actually learned what it meant. Do you know what the translation for pancreas is?
[00:01:28] Speaker A: No idea. No.
[00:01:29] Speaker B: Yeah, so it's all flesh, so pan being everything. And creas, as in like creatine or creatinine, you know, very similar. So meaning flesh or muscle, because actually the ancient Greeks thought it was the seat of the stomach and that's what things sat on.
And so it was a very, very long time before people realized there was more stuff in it than just a lump of fat, which is what it kind of looks like when you, when you see it.
But clearly we now know it's got quite a number of roles. So the bit that I'm more interested in is the exocrine part of the pancreas. That's about 98 to 99% of it. There's a whole other specialty that deals with 1% of the pancreas, they're called diabetologists. Well, actually probably GPS more than anybody else, to be honest with you. But yeah, diabetology and endocrinology, they deal with a very small part of the pancreas. The rest of it is part of the digestive system. So most people, if you ask the general public, they've heard of the pancreas because it makes insulin and you get cancers and that tends to kill you. They're about all they know about it. And that's not unreasonable. But there's far much more to it than that. So obviously there's the endocrine part, I'm not going to go into that too much. But obviously insulin, glucagon, octreotide, you know, your sugar balance and a whole bunch of other kind of entero humoral hormones. But the other part of it produces digestive enzymes. And that's really where it's important. And it's about the only part of the GI tract that produces lipase. So we produce amylase in our salivary glands and from various other glands. Proteases come from other places as well. But lipase, I think there's A very, it's like 1% or something produced by the stomach. So tiny, tiny amount from other parts. But without the pancreas, we wouldn't unlock the power of fat. So if you look at, you know, nutrition and what it's actually doing, what we think may have happened and may have, you know, pushed humans into a more advanced stage is the ability to unlock the power of fat. So for each gram, you get nearly twice as much energy out of a, a gram of fat than you do protein or glucose. So if you can do that and also what they turn out to be. So if you think of what lines our cells, it's lots of phospholipids and things, isn't it? Our nerves, maybe our central neural development was based on the fact we could now absorb fat properly. So you can actually grow a big fatty mass in your head, which weirdly likes to consume glucose, but that's how we think it did that. So, yeah, the pancreas job, really, and it's a very elegant way of doing it, produces lipase, but not all the time. So it's very good. It's kind of a. So I've been getting into some degree of, what's the word? Exercise. I've been doing long distance running. I don't like it very much. I'm sure the people do. You know, I'm going to do it for charity. This year, but I wouldn't do it if I wasn't doing it for charity. On the other hand, I've played hockey since I was about 14. Now, that's fart lecking. That's where you stop, start, stop, start, stop, start. And that's much more a pancreas. So you've got the interdigestive phase where it's not doing very much, maybe a little bit of juice coming out, just helping to kind of, they think maybe clean the GI tract along with the acid from the stomach. But then you go and eat and it ramps up to nearly 500% of what it was producing and you get this huge outpouring of enzymes within minutes of starting to eat, probably even when you start to smell the food. So you smell food and your body's like, it's food time. So it starts producing that, but then once it hits the stomach, you get CCK and secreting production, which are two enzymes, so two hormones that. That make your pancreas basically squeeze those enzymes out and then it mixes at the same time as the food coming through to help them digest that food. So one of the things that horribly goes wrong when it doesn't work is fat malabsorption. And that's a lot of the patients you'll see, that's one of the things they deal with. There's other problems they get. But if you've got proper exocrine insufficiency, that's what you're seeing. So, yes, pancreas, little bit of endocrine stuff, obviously, very important endocrine stuff, but major digestive organ and helps us largely to digest fat.
[00:05:23] Speaker A: I think it's really helpful to understand how it works and how it works in health, really, in order to understand what can go wrong. And really helpful overview, really, of what it does. And we're going to come back to fat malabsorption later, so I don't want to ruin the surprise, so we won't jump the gun yet, but we will be coming back to that. But for now, I'd like to talk a bit about when the pancreas goes wrong, as it were, or when things happen. So could you walk us through our current understanding of chronic pancreas and particularly the early signs that primary care clinicians might notice before we start to develop things like the exocrine insufficiency that you're mentioning?
[00:05:59] Speaker B: Yeah, I think it's a really difficult one because often there's a lot of. What's the word? Reserve in the pancreas. Is there are in many organs which we recognize. You don't suddenly get heart failure. Your heart's got down to a certain level before it stops working. And the pancreas is the same. You can lose, you know, people have operations and don't develop some of these problems, you know, so you can lose quite a lot of pancreatic, functional pancreatic parenchyma before you actually get organ dysfunction. And so the symptoms unfortunately in early disease are often very absent or in fact very mild and usually get mistaken is the wrong word. But get put down to other stuff. So yeah, a good example of the things you might get is a bit of dyspepsia, a bit of IBSE times, kind of functional bloating. That kind of stuff's not uncommon. Sometimes a bit of change in bowel habit. That's normally when you're getting more of the extra grind insufficiency and usually if you haven't got to that. So when you get extra insufficiency because you can't absorb fat, you tend to lose weight. So before then your weight doesn't seem to change very much. There's not often a lot that points you in that direction.
I guess the quality of the pain is sometimes what I'd look at. So, you know, epigastric discomfort is pretty common. I'm sure you see patients with that on a daily basis, Most of which is probably gastric, you know, or acid related or what happened have you gets better with ppi. Brilliant. And in fact you might even get some improvement in PPI with the pancreas because you're actually alkalinizing the duodenum and making the enzymes that are there work better anyway. So, you know, PPI is sometimes what we use. But if the pain is more central, goes through to the back, you have to think pancreas is very far. It's about as far in you as you start coming out through your back. So it's very retroperitoneal. And often the pains. If you talk about patients with acute pancreatitis, which is a bit more obvious, they often feel like been absolutely speared through. So the pancreatic pain can very much feel like it goes through to the back. Sometimes they say it's better if they lean forward. I've never quite understood why that would be the case, but that's what they say. Um, so yeah, it's often quite vague, often quite upper intestinal, very easy to kind of mix with. Or could it be your gallbladder, could it be your stomach? Could it Be acid, You know, could it be functional? I think it's very hard to spot. And I think until you get really major signs, it can be very difficult to spot. And so we've struggled to find early symptoms and early disease for a very long time.
[00:08:24] Speaker A: It sounds like it is quite a challenge to sort of make that diagnosis. And I just wonder, are there any patient groups or things that we should be looking at and being more suspicious of chronic pancreatitis than others? Is there anything else that we can use to kind of guide us a little bit?
[00:08:42] Speaker B: I mean, there's certain risk factors, we know, that increase your risk of pancreatic disease.
People often go to alcohol. Of course, that's common. But if you, you can almost make an argument that alcohol isn't that as important as you might think. There's many, many people who drink far too much alcohol, who never get liver disease, heart disease, pancreatic disease, whatever. So it's quite a small percentage. Of course, if they're a heavy drinker and they're talking about these things, well, maybe that's something to think about. Smoking is actually probably more important.
And certainly for chronic pancreatitis, you get much more benefit from stopping smoking than stopping drinking. Although very commonly what they've done is by the time they've developed it, they stop drinking but carry on smoking quite heavily. And that can be very difficult to manage. But so smokers. So alcohol, smoking, family history is important. And it's a group that really don't like being asked about their alcohol input because, you know, it's normally not the issue. So that if someone's got a family history of pancreatic diseases, got to think about it in, in that group, maybe.
And again, you get into the rare stuff. We'll cover this later. But some of the autoimmune things are related and, and I guess, you know, I've done some work in the past looking at things like celiac disease. So there are some underlying other conditions that increase your risk of getting a pancreas problem, if you follow me. So celiacs get a bit more. They don't so much get chronic pancreatitis, they get pancreatic insufficiency, but, but so do some other groups. So, you know, people. Assisted fibrosis, it's usually quite obvious.
But I guess I try and think of the other groups who would would be important though. And I guess there are some people, things like dyslipidemia, there's been a bit of interest lately. And so we've heard of fatty liver Disease, or mazalde, as I think it's now called, there is a fatty pancreas. So if you've got metabolic syndrome, then there's certainly an increased risk because you've got more fat in your pancreas. We think similarly to the liver, what you need is less of a hit to then cause chronic inflammation and scarring.
And I guess the other group would be to think about people with diabetes already because again, there was a study many years ago where they looked at 2,000 people with diabetes and found that they thought they were type ones and type twos, but 10% of them turned out to be what called type 3C. So pancreatic diabetes, did that make a difference? Probably not in all of them, but it will have done in some. So, you know, they're the kind of group. So people with, what's the word, things like alcohol and smoking history would be important, family history would be important.
Other autoimmune diseases and a history of diabetes just makes me think sometimes, you know, is it. They've got. So the most common cause of diabetes is that you've got diabetes. It's, you know, either you've got type two and you need to work on your risk factors, or you've got type one and you're unlucky. But there are a group of people who actually, maybe they've got type 3C and you don't notice that because you manage it as a glucose problem. You don't. We know that if you scan everyone's pancreas with new diabetes, you don't find much pancreas problems, but some of them, you need to think. So I think if you've got weight loss or something else, I would look at it there. But that's not so much early disease as you were suggesting.
[00:11:54] Speaker A: Okay, and what's the role of investigation? So blood tests. So we've got blood tests like amylase, lipase, do they have a role in diagnosis and monitoring? And also I was just going to ask a bit about imaging as well. So, you know, if we are in primary care and, you know, we got someone with difficult pain, we're just not quite sure what's going on. And, you know, some things are maybe flagging up. Maybe there's some family history, maybe there's some risk factors and we're beginning to think maybe we should consider pancreatic issues here. How can we take that forward?
[00:12:26] Speaker B: Yeah, I think so. The diagnosis of actual chronic pancreatitis is often multifaceted. It's symptom based, it's you know, you have to do endocrine and exocrine function testing but imaging is also a really important part of that and none of these things are 100%. So I've got plenty of people with actual chronic pancreatitis, they don't have diabetes, at least they don't start with. I've got some people who've got pancreatic insufficiency but don't actually have chronic pancreatitis. They're not the same thing. I've got some people with chronic pancreatitis who don't have exocrine insufficiency. So there's no one thing that fits. And I've got a bunch of patients who've got clearly chronic pancreatitis on their CT scan, but zero symptoms from that whatsoever. You think, what's that about?
So nothing Quite matches up 100%. So it's often putting those bits of jigsaw together. So for me the, often the first go to test is a CT scan. So TC pancreas or CT abdomen, CT pancreas, whichever you are able to access.
And then there can be various different features. A barn door. Chronic pancreatitis is really obvious. So you know you've got a withered, horrible looking gland with lots of calcium throughout the gland with, you know, calcification in the duct. Fine, get that. That's fairly straightforward. What if you don't have that? What if it's just a little bit atrophic?
Well, how do you interpret that? You know, if they're 20 and it's, it's small, well that's fine. If they're 19, it's small, well that's probably normal for their age. So there's a whole bunch of other factors that fit in there. Is the duct abnormal? Is there other things about the pancreas that makes you wonder, are they cysts? I think we come to CIS later, the bane of our lives. But yeah, imaging is really useful. The other thing that can be really handy is if it's completely normal, and I suggest this is the other way to look at it. If the CT is completely normal, chances are it isn't chronic pancreatitis, that's not entirely fair. There are some very minimal change versions of this and we end up doing things like endoscopic ultrasound. That's in a minority of these patients to be sure about that. But yeah, if you've got a very normal, chunky, healthy looking pancreas in someone who's got epigastric pain, probably not their pancreas that's causing that. Blood tests aren't particularly helpful. So amylase lipase are usually good for diagnosing acute pancreatitis. They have to go up, you know, two to three times the upper limit, normal. What I do find this on the chronics is actually their, if you do their baseline in between attacks or if they're well at the time, it's often low. And the idea being that you need some parenchyma to actually put that one out there. So if you've lost some pancreas and it's low, that can be suggestive, but again, not diagnostic.
So again, there's no one kind of do this test and you'll find out what it's all about. And the other one we sometimes get sent in is people do a fecal elastase. And again, this is not always available in primary care. Some do it, some don't, but it's very commonly falsely positive. So if you've got a very liquid sample that you can get a low level and it's not exocrine insufficiency, it's, I don't know, some of the cause of diarrhea that's just giving you a liquid, you know, and diluted sample. And we end up then going down the line of oh, it's your pancreas, your pancreas. And then, you know, doesn't really turn out to be that. And it can be quite hard to unpick that because again, you've probably seen this. Patients think a test means that that's definitely the answer.
And understanding things about, you know, pre procedural or pre test probability versus what you get from the answer makes quite a big difference to isn't very. Most tests aren't binary at all. You know, they, they give you a spectrum idea.
So yeah, you could, you could do a bunch of those things and you still might be left with thinking, I'm not sure this is the pancreas in that, you know, you get some with a lowish but kind of okay fetal elastase. They've got symptoms that fit. They may or may not be a diabetic. We've done a CT scan. The pancreas is probably not as big or whatever you expect it to be, but I think they've done CT scans in diabetes cohorts before and some of them is small. So in type ones, I think insulin is trophic. And so if you don't have insulin, you get a bit of a shrunken pancreas. It's more of a secondary effect than the fact that they've got an underlying pancreas problem and a similar thing in people with type 2. So none of these things will be absolutely definite or say, yes, that's it, it's definitely chronic pancreatitis.
So you have to kind of put it all together and it can be very difficult.
[00:16:41] Speaker A: And I'm guessing that that's where specialists like you come in, John, that we'd refer and you'd be able to help sort of pull that apart in more detail.
[00:16:50] Speaker B: We would certainly try. So, yeah, we get people referred in with, you know, say, upper abdominal pain and something kind of suggesting, could this possibly be from the pancreas? And so, yeah, we'll try and put those things together. You go into. So I try and take a good history, get an idea if it's pain, where that's coming from, but also risk factors. They don't all have to have any obvious ones.
And then look at imaging and exocrine and endocrine testing and then kind of see what. What fits together there. So sometimes it's really obvious, you know, sometimes it can be really tricky. And I've got several people who, you know, and then you try a few things to see what happens. They've got a few where you're not sure. So you might try them on some enzymes, for example, and see if they get any advantage from that. So. And again, that's sometimes a good way of trying to spot those who have got a false positive elastase. So if you've actually got true pancreatic insufficiency, you will almost certainly get better from taking enzymes because it works and it works very quickly. They should find out very fast because it's basically every meal. So if you have that with every meal, things will dry up and you'll get better, you'll gain weight very quickly. If they kind of come back, you know, three months down the line and say, well, I took it, but I'm not so sure. I'm never convinced that that's what it was.
If they've still got raging diarrhea despite, you know, good example, a good amount of enzymes, I'm looking elsewhere, I'm thinking, is this some, like, bile salt malabsorption? Is it ibd? Have we actually excluded some of the usual causes of diarrhea, for example? So, yeah, you know, they're the kind of ways to think about it. Yeah.
[00:18:29] Speaker A: I've got two more questions about diagnosis that have just been on my mind. And the first one is, what's the role of Ultrasound. Because we do ultrasounds a lot. You know, can that be helpful? And the second one is, how do people generally end up at your clinics? Actually, that'd be really helpful to know kind of what. How do they end up with you, you know?
[00:18:46] Speaker B: Yeah, that's a good question. So ultrasound, yeah, for pancreas is really not that great. If it spots something, fine. You know, it's actually quite a powerful test. So if it says yes, the pancreas looks abnormal and there's calcifications through it and blah, blah thing. This is chronic pancreatitis, great.
But, yeah, I don't know if you get the same. But very often when we're doing an ultrasound in someone, even as an inpatient, you know, the things like the distal bile ducts in the pancreas are, you know, obscured by bowel gas. That's what you tend to find. And so, yeah, it's not as useful as you might think. If you think something's wrong with the pancreas, it depends whether you're looking for duct or the parenchyma. I mean, you often end up doing a bit of both. But CT or an MRI scan is much more useful. A CT scan probably easiest to get hold of and the. The quickest to understand and is easily interpretable by most radiologists.
Now, how do we get to my clinic? Well, that's a good question. So I work in a big tertiary center where we get sent people from all over, but they come to us, you know, from. There's quite. There's more pancreatic disease around than there ever was. Maybe we're getting better at spotting it, but there is some epidemiology that I think is rising.
And even in the cancers, that's changing. So upper GI is going down, pancreatic biliary is going up. So there's. There's some. It probably just changes over time, you know, so there are. There are more patients coming through.
I mean, I get patients referred to me from all over the Northeast, so they get picked up in other hospitals. And if you've got someone locally is happy to look after pancreatic biliary stuff, then great, do that.
I often get referred people who've had that and aren't better or they've got some troublesome other issue or particularly for what we do, someone who might need an intervention. So we do a fair bit of advanced EUs and the RCP. And again, even in our region, most of the pancreatic capillary stuff, like all the pancreatic stuff will be Done largely at the Freeman because it's lower volume than, you know, most of the other general. So ERCP is usually for stones, sometimes for stenting tumours. Pancreatic stuff's really, really quite unusual.
So we do what would be considered a lot of it amongst a few of us. So we do do a lot of it and do it well, or that's the hope. It's still very tricky. Plus also we integrate well with our surgical team. So even today I was at the regional pancreatitis meeting, so it's about acute pancreatitis, but so the northeast of England's got about 4 million people in the, in its catchment, so patients get admitted all around our region and we have a meeting set up for if someone's got serious acute pancreatitis. We review their imaging locally at the Freeman and then decide, you know, what's the best treatment or help. Help to manage the team. A lot of which can be done in the, in the place where they are. There's a lot of stuff that we do that isn't. Doesn't need specialist intervention, but if they need, you know, interventional radiology or interventional endoscopy, we then transfer the patient for that because most of the rest of the stuff is pretty, pretty standard. So. But to get into my clinic. Yeah, well, I'll see anyone you like, really. But my, my preference, you know, I don't really do IBD anymore. I've got colleagues who do lots of that. But, yeah, I see people with pancreatic capillary problems or advanced endoscopy problems. And, I mean, our system kind of triages those to the people like me who do that. And. Yes, but it's for a lot of people who've got issues where they may need an ERS or an ERCP or. I see a lot of patients with chronic pancreatitis who I just managed medically, so a lot of them don't need an intervention from an endoscope or a surgeon.
And I guess we're a bit of a new thing. So other regions won't have people like us necessarily. So a lot of these would be under surgery because that's classically where pancreatic problems went.
But if you look at benign and malignant pancreatic disease, 20% of them get an operation at best. So most of the rest of it is not an operation. And so if you're a surgeon, why would you want to do not an operation? Which is what I think a lot of them doing. So I've Had a lot of them fed into our clinics from the surgeons who said, while I was following this guy up, I don't need to operate on him. So I look after them, I manage their. So help to try and manage, in a way, their diabetes. I'm not a diabetes specialist, but I try to certainly their exocrine function and remembering to do things like DEXA scans. So, you know, there's loads of guidelines on doing that in liver disease, ibd, celiac disease, and yet the incidence of osteopenia and osteoporosis is up to 40% in chronic pancreatitis. And we don't routinely do this. So I do, and we do that and we find it all the time. So spotting that. And we know from the NICE guidelines that reduces. Well, it improves quality of life and beyond that, it stops people dying of a fractured naked femur. So it's a good thing to spot.
But we also help them with things like their.
I talk to them about if they've got alcohol issues or if it's smoking, what they can do about that, some of the other modifiable risk factors. So in the autoimmune guys, we've got various of them on various agents to try and get under control.
Some may or may not need an intervention, like I say.
But what we found is there's a bit of a lost tribe of patients. I think people find them. Yeah, the one that some people think of a heart sink, thinking, I don't know what to do with these guys, what do I do with them? I don't know. So I take an interest and actually do stuff with them. If you engage with them, it's amazing how far you can get.
So I've had several who've managed to come entirely off the thing that was setting it off. They've got a lot better for doing. So they've maybe had a stent as well. We've got their enzymes optimized. Or the other important thing from the diabetes perspective. And this is much more of a primary care thing. I'm sure you're aware of the continuous glucose monitoring devices. That's not just for type ones, it's actually type 3C as well. So it's for people who are insulin deficient. And so anyone who's had a total pancreatectomy, chronic pancreatitis, you know, absolutely mangled pancreas, whatever it might be. They are also entitled, I think, to cgm. I don't think they're entitled for closed loop. I'm sure they'll Work that in. But they're certainly entitled to CGM and it's made a massive difference. So some of them get diabetes related issues like gastroparesis for example. And so if you get the sugars flattened out for them, that makes that a lot better. So you often find you can manage all these different medical things together. Pain is very difficult. Pain in pancreatitis is one of these things that you could spend all day talking about that we tried to say try to avoid opiates. It's very hard to do that. They're often on them by the time I get to see them. I quite like pregabalin for these guys. I think opiates 1 don't work, 2 they get a bit addicted to it and they turn to it every time there's a bit of pain. Whereas actually I think it's more nerve based pain. So low dose amitriptyline, things like pregabalin I think could be really nice. Gabapentin is not as good. I think pregabalin's a bit better yet less side effects. He probably had experience with that in other areas. But often treat it as a chronic nerve type pain and they do well sometimes get them off to see the pain teams and what have you.
So yeah, there's a lot of not operation stuff to do to these guys.
I seem to have gained a reputation for doing that with these guys. I quite enjoy it. I'm much rather seeing these patients than other people I've got no idea what to do with. At least I know where I'm starting.
[00:26:02] Speaker A: That's amazing. That's such a helpful. Just run through of those, of those different options. And I've certainly seen patients where pain is a real issue and so just getting some advice around kind of treating it sort of in a neuropathic way as it were. And in primary care we're pretty good at that. And yes, so that's really helpful advice. Yeah, you mentioned about that 20% needing some form of surgery or surgical intervention. What sort of surgical interventions do they consider for this?
[00:26:29] Speaker B: Yeah, so it kind of depends on where they're at, so. And also a bit on what group they're in. So our centers are a big pancreatic ability operative center as well. We're a transplant center. But we also, we have Steve White who is one of the guys who has done most of the islet cell transplant work here in the uk.
So the role of surgery in these patients, some of it is about drainage. So the idea about pain is that the duct is kind of packed full and tight. And so if you can open the duct up and release that ductal hypertension, you get improvements in pain. I think you have to work out whether you think it's a plumbing problem or is it a wiring problem. If it's a plumbing problem, then drainage procedures work very, very nicely. If it's a wiring problem, that's where the gabapentin and progabalin and ST comes in. Now, trying to work that out is sometimes very difficult, but the imaging can help. So if you've got a big duct with lots of stones in it and it looks like it's under tension, there's a stricture, say, in the head. They're the ones who. And they've got pain. They're the ones who are meant to get some improvement with an intervention, whether it's endoscopic or surgical, because you're decompressing the pancreas. And you can imagine how, just on a technical basis that means, well, there's less pressure, that means the pain's better.
The thing they used to do is a pusto procedure or lateral pancreaticojejinosomy. So they basically fill it, the pancreas, from kind of tail to neck, open it out and bring up a loop of judging them and just basically everything. When they take all the stones out and drain it that way, we quite often do ERCPs where we basically stick a stent in. The problem is you then have to keep coming back and forwards. If you've got a stricture, you can't always get that fully open, so it's a bit more tricky. But there's a role for things like total pancreatectomy. So in some patients, you remove the entire pancreas. And in some of those, if they're not yet diabetic, that's the ones that you then consider for islet cell auto transplantation. So quite a different group of patients. A good example for that would be people with things like genetic causes of pancreatitis. So they've got an underlying genetic condition. So there's various mutations. The most stark one is the cationic trypsinogen gene 1, which is PRSS1. You may have. You probably have one of them in your practice. They're that rare. But if you have one, you probably have the rest of the family. That's the. So you see a lot of these guys, but what they get is they get horrible calcific pancreatitis with pain often from their teens. And by the time they're in the 20s, they've got lots of trouble. So the total pancreatitary removes the pancreas. Naive, the chronic inflammatory condition, it's never going to get better. This is a condition where the trypsinogen gene is faulty and basically switches on too early. So rather than opening the trypsinogen, sorry, the trypsin enzyme kind of coming out in the duodenum, it starts in the pancreas. So they're basically autolyzing themselves the whole time. So you've removed the underlying cause, but in doing so you've also removed all their really healthy beta cells and what have you. So suddenly you've made them diabetic. So if we remove anyone's pancreas, pretty much it's like 99.9 become diabetic. I think there's a few people who never did. We don't understand why. But what you can do, I say you can do what our surgeons can do. In those cases, they can then basically extract the islet cells from the, the pancreas, purify that and then inject it in the portal vein into the left lobe of liver and basically create a nice little islet cell patch in your liver. And it means that you maintain your beta cell function. So they either don't need insulin or need a very small amount of insulin as compared to having zero pancreas whatsoever. So that's, that's auto is cell transplantation. They do that sometimes as well. For people who've, say, had acute pancreatic injury, you know, a classic one is going over the handlebars of a bike and you basically hit your pancreas right in the middle, split it in half and, you know, you can remove it or you can put back the beta cells.
So, you know, they do that. But the other, the other types are, it depends on where the disease is. So in some patients, mostly it's in the head. So some will get what's called a fray procedure or fray burger, where they kind of core out the head of pancreas, remove all the inflammatory tissue, and again bring up a bit of bout and to drain that. There's a number of different chronic pancreatitis operations, but they're mainly about drainage and removing inflammatory tissue. In fact, sometimes a Whipple is a really good thing too. If someone's got a big inflammatory mass in the head of the pancreas, it's causing duodenal, biliary and pancreatic obstruction. Well, Whipples will sort that out because it takes out the entire head of the pancreas and they re plumb. Everything works very well. But that's a huge operation, as I'm sure you appreciate. In fact, none of these are particularly small, so we have to choose the patients correctly. And the other thing we find is some of them have wiped out as they've been having episodes of pain and inflammation, they sometimes wipe out blood vessels. So portal vein thrombosis, splenic vein thrombosis, leads to varices. As soon as you've got a load of varices around there, the surgeons run a mile because they're going to open you up and then go, ah, yes, we'll cut into a varix and that'll end everyone's day very badly. So they just don't even go in. There's no point. So they often. They're the ones who, if they need intervention, very often then becomes endoscopic, because we can avoid. We go nowhere near those blood vessels. We're literally going up tubes that already exist.
So, yeah, and there's newer things that we can do down the scope in a select group of patients. But, yeah, most of it's about kind of damage control. A lot of what we're doing in clinic is trying to prevent further damage. The pancreas is unforgiving, unlike the liver, the liver will grow back, the liver will regenerate in the vast majority of people. Once you've scarred up your pancreas, you've pretty much lost it. It's not coming back. It's about not going any further down that line. So a lot of what we do is trying to prevent that from happening. Get drainage to improve pain if necessary. Also sometimes improves their exocrine function.
And sometimes that's endoscopic, sometimes that's surgical hope. That all makes some form of sense.
[00:32:15] Speaker A: Sounds like there's so many very clever things going on with surgery and with management of pancreatitis. It's really fascinating to go through some of those different options with you. Actually, we're going to move on from chronic pancreatitis and you've already touched on this already, so apologies if we cover the same ground, but I wanted to look at pancreatic exocrine insufficiency, because, as you said, it's not always linked with chronic pancreatitis. So what I wanted to look at was sort of what symptoms should prompt us to test for this, because we see a lot of patients with things like diarrhea. You know what can prompt us to test for this? How do we test for it? You mentioned about the faecal elastase. Can you just go into that a bit more? And then how is it managed?
[00:32:56] Speaker B: Great. Yeah. Pei. Wow. Huge subject.
So, classically, what you get is changing bowel habits. So if you're. If you aren't producing, and it's basically you're. You're not producing enough digestive enzyme to manage the fat that's coming through in your diet, and once you're down to a certain level, you know, that means that what happens is you get fat malabsorption. So the classic symptoms people describe steatorrhea. Now, most patients actually can't describe that to you very well. They haven't looked or they don't care, or they haven't worked out what that means.
There's a couple of things in the history to try and work that out. So some people say, yeah, I can see fat globules in the stool might. Well, you've looked very closely to find that. You can imagine if you've got a very fatty stool, it takes several flushes to get rid of. So actually it's the number of flushes that sometimes gives you that. That. So if someone's saying, yeah, I have to go four or five times at least, like a sheen on the top of the. It floats, it won't go down very easily. I was thinking, well, there's, there's. There's some fat in there, isn't there?
Or possibly that's what's going on.
And then, you know, sometimes they have abdominal pain, sometimes they don't. So it depends on the underlying cause. And I've come. Come to that in a bit. But the other thing that's meant to be quite classic, if you're not absorbing fat, you should lose weight.
So someone who's got, you know, someone's going 10, 15 times a day and they're not losing weight, got to think that that's probably not pei. Doesn't mean it definitely isn't. But why, why wouldn't you be losing weight? So if you ever meet someone who's got proper pei, they are literally losing weight in front of you. That's why when you give them enzymes, they get. They get better quickly and they gain weight and you think, yes, we've got this right.
So most patients will describe some form of diarrhea, and in fact, you don't have to go that many times a day. But, you know, normally some form of diarrhea. Often difficult to get to go down the toilet. Sometimes they might see fat in it. They may have some upper Abdominal pain. They often actually have lower abdominal pain, very IBS Y sounding, because actually that fat's gone through, entered the colon, the bugs have gone, whoa, what's all this stuff? And then fermented a load of it. So they get gassy, they get bloating. And so that's. You can see why PEI gets classically thought of as IBS or functional type symptoms, because that's exactly what they've described. Some of it's colonic distension. I did one of the studies looking at that. We looked at 300 and something patients with diary predominant irritable bowel, and 6% of them had PEI when we actually investigated them. So, you know, the problem with, with ibs, for example, is it's based on symptoms. There's no, oh, your IBS blood test is positive, well done. You've got ibs. No, it's based on a set of symptoms and a bunch of other things around that that you kind of think, yeah, this sounds more like IBS than something else. And a few exclusion things. So these days everyone does a celiac test and if they're young, fecal CAB protectin or whatever it might be. So if they're negative and it sounds functional, you'll get told it's functional. But P.E.I. is one of the things that sometimes behaves that way.
So they're the kind of symptoms, weight loss, as I've mentioned, testing. Well, the problem is we used to have about 10 different tests for looking for retrograde insufficiency, and they've pretty much all gone, except for faecalastase, which is a bit of a shame. It's a nice easy test to do. Although again, in that study I mentioned, I think we screened 400 odd people. And these are people turning up to secondary care with diarrhea. And about 20% of them didn't do the stool test. So you've come with a diarrhea problem, we've asked you to do a stool sample and you haven't done it. That tells you a lot.
So, yeah, and it's not a great test. The problem with it is is its false positive rate is reasonably high. So all it's measuring is the protein level in the stool of this enzyme elastase, which accounts for about 6% of your pancreatic output. It's pretty much unaltered as it goes through your gut. So what you're measuring, the rectum, is what you measure in the duodenum. So it's meant to be very, very similar. What you do find is if You've got very, very watery diarrhea that you just get a very diluted sample. So you get a low level. That doesn't mean you've got pei, it just means it's a low level.
So in some patients we will certainly repeat that and see if it changes.
I mean, very often the lab says the sample was too liquid. Can you do it on a solid sample? Like no, that's the problem we're doing on a liquid sample. There are ways around trying to get them to do it differently. They can do something called.
What's the name of that procedure they do lyophilization where they basically remove the water from the stool. So they basically have to bake it. I bet that's a lovely day in the lab. Baking stool today, you know. But it means they get a solid pellet or they can spin and get a solid pellet. And so you've got to measure it on the solid part. So that's the trick. There used to be all kinds of different breath tests and there is a fatty breath test and there's a carbon 14 breath test. And it used to be something called the pancreal oral test, which some people may remember.
They even used to be more direct tests where you could put a tube in the dude and give some more secreting and then actually measure what came out of the pancreas. As you imagine, that's pretty invasive. Takes about four hours. No one's doing that. I think there's some odd labs in Germany still doing that for, you know, that's meant to be the gold standard.
So we're left with elastase. And so you kind of have to put those things together with symptoms, what the elastase shows, what's the imaging show. But yes, so we do get patients who have P.E.I. who don't have chronic pancreatitis. Could example celiac disease. So again, we looked at a bunch of new celiac patients.
In fact the ones it was those who had ongoing diarrhea despite a gluten free diet. About 30% of them are PEI. And the reason we think for that was your CCK and secreting comes from your duodenum. Well, and then their duodenum is all atrophy, doesn't it? Because they've got celiac disease. So they've lost that enterohumal response. And so their pancreas is sitting there waiting for a signal. Their duodenum is just not giving them one. And it takes a long time before those enzymes. Sorry. The gluten free diet means that the villi go back to normal and so it takes a while before that signal normalized. So we treated some of those with enzymes. They got a lot better. Long term though a lot of them came off it because actually improved on their gluten free diet. They didn't need it anymore. And the other group of people is those who've had pancreatic surgery. You know, remove some pancreas. Ain't going to work as well. You don't have chronic pancreatitis. So they're good data for those and the surgeon should be telling them to be on enzymes and usually they've sorted that out. But there's some data in some diabetes patients that get P.E.I. never quite so sure about that.
People with cystic fibrosis usually have a degree of PI but that's usually managed from a very early age and spotted very obviously.
So yeah, there's probably a few other groups knocking around out there.
Management. Well once you've identified and you're happy, that's what it is. It's with enzyme replacement. So there's no role, I mean zero role for a low fat diet. So some people say oh yeah, just don't eat fat really. So you know, that's vitamins A, D, E and K down the drain plus a really good source of energy. Plus you know, our fat and cholesterol is the source of most of our decent hormones. You need fat. You know, I know we're told these days not to eat much fat and you know, I'm someone who's worked very hard to do so. But, but, but to be honest with you, we still need some fat in the diet. It's essential. There are things we need so no, they need to be able to try and eat as normal a diet as possible.
And what you're doing is giving them pancreatic enzyme replacement therapy or PERT as we call it to try and normalize or at least significantly improve their mild digestion and malabsorption.
And it doesn't quite do it the same way. As I said earlier, your pancreas has got this lovely kind of really eloquent, sophisticated way of measuring how much you need and when to stop and what have you. We go take these capsules with a meal. You know, it's not quite the same thing but there are things you can do to try and improve that. So it isn't just take them all through at once or in fact we often start with.
So there's various, well there's issues. We're getting enzymes at the Moment. I don't know if you guys have come across the same thing. You may have done the main company that produces them, there's been issues with distribution, should be hopefully sorted by 2026, they say.
But there's only another couple of companies that make any of these. And the problem is they've got such a small market share that it's like asking your corner shop to take over from Sainsbury's. You know, if the other one's out, they got nothing. You know, their stores went in seconds. It's like the toilet roll crisis in Covid. You know, basically no one can find any. But anyway, if you can get it, what you're meant to start off with is about 75,000 units per main meal and about 25,000 to 50 with each snack. The important thing is, I think often those numbers seem horrific. You're like, we're talking about 75,000 years or something like, wow, that's huge. And we should have called it 25s and 75s and what have you. But no, that's what it is, actually. Your pancreas in health will produce something like half a million units of lipids in a meal without even trying hard, if not more than that. So, you know, 75,000 really is very small amount of that. And that's the starting dose. So if that hasn't made them quite better enough, it can go up. And I tend to get to about 150,000 per meal before I think, do they need something else? Because sometimes people just eat, eat different meals. I'll usually send them to a dietitian and the same way they do with their insulin and things like the Daphne courses. So they look at how much glucose they think is in their meal and think, or carbohydrates and go, well, I'll need this amount of insulin. You can do the same thing with fat and your enzymes. So if you're having, you know, ham sandwich, you might need 50, 000, what have you. If you're going to go and have fish and chips or a big curry or, you know, Toby carvery, Sunday lunch or something, you might need 10. You know, it depends on where you're going. So if you can educate your patients to kind of go for roughly 10 grams of fat, you need about 10,000 units of lipase then. And that's what the number is on those, those things is the amount of lipase. If they've also got amylases and proteases in there, they don't mention that. But it's Got that amount of lipase in it, then you can usually try and help them to get an idea. So when you eat this amount, take this amount of the enzyme. When you take this amount, only take that amount. And if you have a snack, you might need one or two. But the important thing is also to spread it out through the meal. So don't just take it all at once. So I tend to tell patients, take the first one as they're starting. If they're on four, for example, they say one at the beginning, two in the middle, one at the end of the meal, and then it's spread throughout their entire food, spread throughout the entire meal and actually helps to digest things as they go along. And again, dietetic help can really help with that. In some patients, it's not quite enough. And again, we talked about PPI earlier on. So these enzymes are very acid sensitive. So the other thing that the pancreas produces, and we all forget this, is bicarbonate. Imagine you've gone through the stomach pH2 to 3 and then you get into the duodenum. All that lovely acidic stuff goes into your duodenum. That's why you get horrible ulcers. In some patients, something's got to neutralize that and it's the pancreas. Pancreas chucks out a load of bicarbon. Again, chronic patients don't do that.
And the enzymes in a very acid environment just don't work. So in some patients, if it isn't enough, we add in a ppi. Some people do that routinely. I don't really have a huge problem with that. It's just another tablet. And I kind of think, really, if you don't need this, I'm not that first. A lot of people seem to be on PPI these days anyway, but that's something you can also add in. So, yeah, it's about trying to get sufficient enough enzymes into their diet with them and if they're able. So some people can't do that. You know, modification depending on what they're eating. It depends on how motivated they are. So if they're not, then you kind of. It's fine to overestimate how much they need. This stuff is protein. One of the company guys didn't like it. So it's not really even a drug. If you went home and ate a whole box of this stuff, nothing bad would happen. It's just a load of protein. You'll digest it. I'm not suggesting anybody does that, obviously, but if you, you know, if you thought they needed 75 and you give them a hundred thousand, nothing bad will happen. You know, they can actually have quite a lot. There was old, old history of some of these patients developing some weird inflammatory problems in the colon. That was a very old preparation and only in cystic fibrosis children. And that doesn't seem to occur anymore. So in adults particularly, you know, usually we've underdosed people with P.E.I. for a long time. So aim on the side of giving them a bit more than you think they need. You'll do well for doing so and you'll get much better control of their fat malabsorption symptoms and that they'll feel better, you know, they'll gain weight. You can adjust it as they go on. As often we start on 75, 000, you know, as I say, with meals and about 25 to 50 with snacks. And then see how they go. And if they need more, they need more. Very rarely go. I can't think of going down in anyone for that matter. I've tended to go up and be, be brave with that. There's no, no harm you can do. This isn't anti. Hypertensive. They're not going to get hypotensive or it's not insulin. You know, there's, you can, you can err on the side of too much without too much trouble.
[00:45:57] Speaker A: That's really helpful to just think about that because we are a bit scared of big, big numbers. They are quite big numbers. But actually maybe we shouldn't be surprised. We should be, you know, really trying to optimize that treatment. I'm assuming that success equals weight gain equals control of diarrhea. That's kind of what we're looking for, I'm assuming.
I was going to ask just because in my practice as a GPU extended rollout, you know, people come to me and ask questions. You know, sometimes I'll try and. Well, I'll try and give as sensible an answer as I can, but sometimes I can.
Pancreatic side of things generally not my strong point. But I recently had one of the GPS come up to me and say, I found someone with pancreatic insufficiency. Do I need to arrange some imaging? What's your answer to that?
[00:46:43] Speaker B: Yeah, really good question. Actually, we wrote a paper on this because the answer is not as clear as you might think. The answer is probably yes.
It might depend a bit on the patient.
We got asked to write a paper on what to do with the patient with the lower last days. Someone's done the last days of Part of whatever else, and it's low. So what do you do?
So it covers all the stuff around. Well, could it be false positive, which would be a bunch of those.
But if it isn't, well, what is it? So pei, so isolated PEI is actually relatively uncommon. You think, why would that be? Your pancreas stop working.
What's made that happen? So our suggestion was really to go and look for other causes. So primary P.E.I. is really unusual. It's usually secondary to things like chronic pancreatitis or surgery or something like celiac disease, whatever it might be. So we suggested, first, exclude things like celiac disease, look at risk factors for pancreatic problems and imaging their pancreas, I think be quite useful, because even if it's normal, well, fab.
But there'll be some patients who will present with pancreatic cancers, for example, who might just present with pei, or basically, weight loss. And PEI symptoms, it depends where it is in the pancreas. If it's not in the head, they may not get jaundice. So what they might just get is malabsorptive symptoms to start with. And if you thought that might be pancreatic, you're almost certainly going to want to do a CT scan. So I think it does. You know, for most people, you know, if they're 20, it's very unlikely to be that. If they're 50, then, or 70, then you've got to think, well, something worrying. But then in that group of patients, anyone over 50 who's got weight loss ends up with a CT scan, usually these days anyway, and I think that's not unreasonable. We find all kinds of reason for that. In fact, I commonly get a bunch of patients with pancreatic problems presenting by the colorectal pathway. So they come to us to change about habit and weight loss. And of course, everyone goes, all right, cool, we'll do your fit test. It may or may not be positive. And they end up with the colonoscopy, which is normal. And then they go, well, they've got weight loss. We'll do a ct. And they go, oh, the pancreas, look, that's funny. And they've got no pain from whatever's causing their pancreatic problem. Not on chronic pancreatitis, actually. They've literally just presented with pei.
You put them on enzymes and they feel fantastic. I like those patients. They get better very quickly. You give them enzymes, they stop losing weight, their diarrhea goes away, and they think you're amazing. Like, well, I didn't actually make the diagnosis someone else did. And my job is then to make sure that they, you know, are nutritionally replete and follow them up for often the rest of their life. Yeah, so they come in weird ways. So colorectal pathway is a really interesting group to go looking at because we know what percentage of those actually have colorectal cancer. It's like 3%. So what the other 97% of people turning out to be got to be something.
So, yeah, there's a bunch of me turn up as other stuff similarly, in the way that I think we identified that celiac can do all kinds of different stuff. There's a bunch of conditions out there like that that just mimic other things. And, you know, basically if you, if you manage to somehow hamper your absorptive ability of your small intestine or pancreas, you'll get quite stark symptoms. And of course, everyone thinks colon to start with, and that's not unreasonable. It's common. But they're the. They're the ones to go looking for.
[00:49:57] Speaker A: Okay.
Really useful discussions about some really big topics. And what I want to sort of end this part of the. Of the podcast on is thinking about imaging and autoimmune pancreatitis. So got a couple of questions. So, pancreatic cysts are sometimes seen on imaging that we order for unrelated reasons, and then the GP will get that back and panic and think, what am I meant to do with that?
Hopefully they've got some guidance on the report, but, you know, it can be quite hard to know what to do. I suspect that you get quite a lot of advice and guidance around this sort of thing, but I'm not sure. But what sort of advice and guidance could you offer to primary care clinicians about this? So if they do get a report back that says something found in the pancreas.
[00:50:42] Speaker B: Yeah.
[00:50:43] Speaker A: Where do we go next?
[00:50:44] Speaker B: Sure. So we. We get obviously loads of these and they are probably very similar to the concept of things like lung nodules, adrenal nodules. I'm sure there's a few of the blips and stuff, but the incidental Lima. So, yeah, the common one we get them from are someone's in the CT of the abdomen for some reason. So urology, vascular, general surgery, doesn't matter. It. It isn't what they were looking at. And then someone comes, oh, there's a blob in the pancreas. What do we do?
If they're confident it's cyst. So if it's a mass. So again, it could be an early mass, it could be even a neuroendocrine tumor. We'll come to that another time maybe. But if it's a cyst, the vast majority are utterly benign. And so people get really worried about these. And yet actually I tend to take them straight off the pathway to see them in clinic and see and they're commonly in, in older people. So the, the main concept for pancreatic cysts is some of them will become malignant, a bit like colonic polyps. So it's the colonic polyp of the pancreas. It's probably the best way to think about it. There's lots and lots of time before those things will turn into cancer. So unless it says on the CT I can see a cyst, there's a lump inside it, or the duct is dilated, or there's some other worrying feature. If it's just a cyst, and that's almost always what it is, then you've got a lot of time to try and work out what to do. The most important bit is actually how fit is the patient, because the only treatment for these so far is surgery. So there's some look at the idea of doing things like radio frequency ablation via us, and that's a very small number of people. So the only curative thing we have is surgery. So if this is in a very elderly person, it's in the head of the pancreas. You're talking about a Whipple's procedure and that's never going to happen. Maybe the answer is you don't need to do anything. They're going to grow old and die of something else long before a 10 millimeter cyst will cause a problem. It was in the tail. Well, it's still not a nothing operation. But a distal pancreatectomy is a lot less of an operation than a Whipple's. So you may go a bit older with that. The main features that worry is if it's more than 3cm, if it's got any nodule lump or something inside it. So, you know, if it's a cyst, you can imagine what you've got is a epithelial lined, you know, ball basically. And they do slowly get larger over time because it's making fluid. But if a bit of it's grown into a solid bit, that's a bit more concerning. If it's pressing on the duct or the duct is dilated behind it, I. E. You know, it's invading somehow or causing pressure. That also makes us worry. So things like so size over three centimeters, I mean, you know, 29 millimeters is still pretty big, but you know, size over three centimeters, we've now got the point that actually if its size alone is the only abnormality, we'll go up to 4cm because actually most of the time nothing much else really happens.
So size of the actual cyst, size of the duct itself. So if the duct is less than 7 millimeters, you normally don't have to worry too much. If it's a bit dilated, it might need watching, or if there's any lump inside there, these are the ones that may need to go for fairly urgent investigation. The others need surveillance. Now who does? That is a very good question. Because actually, as you've already said, pancreas is a bit of a weak point for not even GPS for most people, to be honest with you. Unless it's what you're doing, it's not something that you necessarily know what's going on. There are tons of international guidelines on what to do with these patients and they all say quite different things. So we have our own local regional protocol that we use, but based on most of these guidelines. But it starts with how fits the patient. So if they're elderly or majorly comorbid, it's irrelevant what the, what the scan says. So we break it down, it's a two by two square. You've got low or high risk patient and low or high risk cyst. So if they're both low, you've got loads of time. They probably just need surveillance. If they're both high, well, that's a bit more tricky. But probably they're not going to get surgery. If it's a high risk cyst, low risk patient, they probably need surgery. If it's a low resist high risk patient, then you're probably not going to do anything about that and just tell them, look, you know your underlying heart disease is going to get you long before this does. So we often see that. So we often see them in clinic counselor. I often show them the scan, they often quite like to see the scan. This is what everyone's worried about, this tiny little thing here in your pancreas.
Then depending on its size, if it's less than 10 millimeters, they get a scan in two years. If it's more than 10 millimeters, it's every year and we just put them on surveillance. If they're fit for an operation and it doesn't immediately have any high risk features, they'll go on to surveillance and most will go for probably the rest of their life having a scan and just grow and die of something else. I think we found locally about 2% end up going for surgery. So it's not many. And even those that turn bad, so more of them turn bad, they're just not fit for surgery. So it's often about counseling the patient about risk. So this is all a risk thing. How risky is the cyst? How risky is the patient? And then work out where they're sitting there. So if you've got a very elderly person with a cyst who. Or very, not roughly elderly, but very comorbid person with a cyst who's never going to be suitable for major pancreatic resection, the answer is probably don't worry about it whatsoever. Tell them they've got a cyst but, you know, explain they don't need to worry about it too much.
But there are a group, like I say, who may end up having surgery. There's a group that we would certainly survey that should probably be done in secondary care rather than primary care would be my suggestion.
I'm not sure gps are leaping into want to do this in our region. Even our regional gastroenterologists will do it. So we give them the protocol and they follow it and when something changes, they refer them back and they end up then getting things like endoscopic ultrasound sampling, that kind of stuff. If we're worried and the group do go for surgery, we do try and hopefully what you don't want to do is under treat, I. E. Miss ones, but you also don't want to over treat. The last thing you want to do is do a major operation on someone that turns out have an utterly benign cyst that had no malignant potential. They've gone through a lot of risk. People die of a Whipple's procedure, it's got a 2% mortality. So you've got to have a damn good reason to have it. So quite often we'll kind of go, this is a worrying one. The surgeons will sit on them for another 6 months, 12 months and kind of we'll see. I'm not so sure. You know, these are people who love doing operations. So if they're a bit, you know, not sure about it, they're certainly wants to be to be careful of. So yeah, they're quite complicated and there's a lot of complicated stuff that some of them will end up doing. But the vast majority either need nothing or simply just need surveillance.
[00:57:07] Speaker A: Okay. And I feel like this is one of those good areas where it's Going to be shared decision making. Well, shared decision making to primary and secondary care. You know, gp, getting advice around, kind of where do we go next? And being guided by secondary care. And now finally, John, autoimmune pancreatitis. It feels like there's sort of a growing recognition of this as a kind of distinct entity. Could you explain a, a bit more about how this condition can potentially present and what primary care clinicians ought to know about this?
[00:57:36] Speaker B: Yeah. Okay. It's probably been around longer than we realize, hasn't it? But certainly it's been more recognized. I guess the proper term for it now is probably IgG4 disease, because actually, whilst the pancreatic manifestations are common, I mean, we looked at our local population and some people just present with other parts of the disease and I've come to that.
So it was called autoimmune pancreatitis because basically that's what it appeared to present us. But it doesn't tend to present with acute pancreatitis. So people often will measure IgG4 levels on the acute pancreatitics and there's absolutely no point. It's a form of chronic pancreatitis. It's a chronic lymphocytic invasion of your pancreas and it causes all kinds of other features we look for on biopsy. There's a big mimicker. So one of the things it often does is presents as a mass in the pancreas. So about it's estimated that roughly 1 in 50 masses in the pancreas will turn out to be IgG4 disease. Now the big difference there is that you shouldn't operate on that one and they should get, you know, immune based treatment, which is what we go for. And we've got a whole bunch of these patients and they do very well. In fact, it's a marvelous thing to treat because the vast majority of course, are steroids. And it absolutely melts away in front of your eyes. There's a group of them who go on to some of the more advanced treatments. So some have gotten things like azathioprine, mmf, or even a drug called rituximab, which is one of the biologics very specifically for the mutations in this disease.
So it presents in a number of ways and often presents acutely. So we often see patients present with jaundice mass in the pancreas. Everyone thinks it's cancer. They go through their workup, we do a biopsy and it comes back as not cancer and a whole load of inflammatory change. You think oh, that's really interesting.
In which case you give them a course of steroids through a very early scan and it's all melted away. It's amazing how it melts away.
But we also now tend to do PET CT on these guys as well because you find it's, it's more of a multi. A group of patients is a multi systemic disorder. So commonly you find infiltrates in the kidneys, things like the prostate.
You get what they called lacrimal gland and salivary gland involvement, sometimes tonsils. There's nearly nothing it can't do.
And a group of our patients have presented to the head and neck guys with some really weird things. So retro orbital masses, fistulas in their palate. Turns out to be IgG4 disease completely. So it does some really weird stuff. So I think the problem is it will present us what some looks like something serious. And then we find, fortunately for the patient, actually it's not that. And it's incredibly steroid and immune therapy sensitive. So, you know, sometimes it's. With the pancreatic mass, there are a few features on scans, particularly from the abdominal side. So you're meant to have what's called like a sausage, pancreas. So rather than just being a mass, the whole pancreas is like some big swollen up sausage. Sometimes the edge of it on contrast is a little bit spared, so you get this rim around it that, that doesn't look abnormal. But not everyone's like that. We had one, we even presented at a meeting not long ago who had classic, you know, Taylor pancreas mass. It even wiped out the vein. And everyone's like, well do a biopsy. This is a cancer. We'll team up for a distal biopsy. In fact, we made us do two biopsies because they didn't believe it.
Both of them shared RTD4 disease, gave him steroid, everything's vanished and even that vein has fully opened up again. So you think this thing, it just mimicked pancreatic cancer? There's just no. If you'd shown, I remember our radiologist said, I've looked at it time and time again, I would call it nothing but cancer. And it's only when you got the tissue that you thought that wasn't very. Occasionally you'll find other features. So if someone's got funny looking pancreas, biliary strictures as well. Sometimes these things where you've got infiltrates in other places in the body and sometimes you get retroperitoneal fibrosis. So aortic related issues. So it often sometimes presents to the kind of connective tissue people like rheumatology, that kind of guys. It's one of the ones to think about.
And if they've got active disease pets, really useful as it shows you about activity.
And if they've got what we call organ threatening disease. So in the pancreas one, we can put a stent in and make the jaundice better. That doesn't worry us too much. But if you've got something, you know, sight threatening or going through your soft palate or something that's a bit more concerning or periaortic, they'll often leap in a bit like they do with, you know, rheumatological diseases these days with quite heavy immunosuppression. But their prognosis is phenomenal. Most of these guys are now growing up and grow Donald and dive other stuff. It's more common in men, more common in slightly elderly men. But, you know, that's just a bit of demographics. We've seen it in all kinds of different people in all kinds of different ways. So big mimicker. But again, it's back to. It's one of the reasons why a lot of cancers these days in the pancreas are now getting biopsy rather than go straight for operation. Because you don't want to miss it and you don't miss something that isn't cancer. And the operations these days, it's such a big thing that if you woke up and they then said, oh, you've been through all this and actually it wasn't cancer, that's probably not the right thing to do. Most patients aren't too worried about that. But one day someone's gonna be like, hang on, could you have told me this beforehand and saved me an operation? If the answer is yes, you may. You know, there's a litigation potential issue there, isn't there? And to be honest with you, I don't really. That's not normally a huge worry. Everyone's so scared it's cancer that they, they think they can operate, they'll go for it, but no, we can get biopsies easily these days and biopsies are better. So when we used to take samples in the pancreas fna. So true. Fine needle aspiration. We now have different needles that give you biopsy so you get core tissue. They can do proper immunohistochemistry. So it now means that they can. So not only can they say it more, more confidently that it's cancer, they're actually More confident to say, no, this is be. This is. Actually, we can do the stains and show this is IgG4 disease. So our biopsies, they're not perfect, don't be wrong. But they've certainly improved massively over the last 10 years, to the point that we can be much more comfortable and confident that we are not missing cancer, but also that we are confidently diagnosing benign disease, which is really, really handy because it used to be the FNA came back as well. It's not cancer, but it didn't tell you what it was. But now it comes back, it's not cancer, it's IGT4 disease. Everyone's like, oh, cool. Over to you guys.
And we're. We manage these people. They're great to manage. You have to spend a bit of time kind of unpicking because everyone's only got cancer until proven otherwise. And then you're saying it's actually not cancer. At least don't think it's cancer. We're going to give you this treatment instead. And let's see what happens. And they normally take a little bit of time to come to terms the idea. They're not getting an operation for what they were told was cancer to come out the other side. They often get diabetes as well if they've got pancreatic involvement. So the inflammation goes away, but it doesn't normalize the pancreas. You end up with some of them get very strict thin pancreas. It kind of atrophies afterwards. So they commonly get pei. You have to manage that. And they commonly get diabetes.
But I remember one lady who was, you know. In fact, they did an intraoperative biopsy before they're about to do a Whipple and it came back as this. And they went, oh, okay, fair enough. So they did a bypass because she was jaundiced and she's still alive eight years later. Her biggest problem is her sugar control. That's it. That's the thing that bothers her the most. You know, she's. She's not died of pancreatic cancer. And so you kind of have to get a year down the line. And they're like, I'm still here. I'm like, yeah, exactly. You know, this wasn't cancer. We wouldn't be here if it was pancreatic cancer. As simple as that. Particularly with no treatment. So, yeah, it's a. It's a. So it's quite rare. Still comes in the rare disease group of less than 1 in whatever number it is. They go for 10 and 100,000 or something. So it's pretty uncommon. Newcastle alone, we've got maybe 200 patients between a group of us.
I'd say that's from a population of about 4 million. So that's how pretty unusual it is.
I'm sure there's people getting missed and it's got several causes. Some people have one attack and it never comes back. Others we've had had to go on to, you know, heavy immunosuppression because they've got more persistent disease. But you just have to follow them to work that kind of stuff up. And we're learning more about it as we go. We work very closely with one of our rheumatologists who delivers the rituximab for those patients. She's got a connective tissue interest, plus she's married to one of my colleagues, which makes it probably a little bit easier to. To refer anyway. But yeah. So unusual disease will probably present quite starkly, but usually the prognosis is utterly different to the thing you thought it was. Even if it's one of these head and neck things, you know, it vanishes with immunotherapy and sorry, not immunotherapy with immune based therapy. So steroids and, or you know, some of these other agents and they, they get better very easily.
[01:06:14] Speaker A: Amazing.
Wow, we have covered so much there, John. I can't believe what we've. I'm just thinking about what we've covered. We've basically unpacked the pancreas. We've told everyone exactly what it. Well, you've told everyone exactly what it is. We've covered chronic pancreatitis, we've talked about blood tests, imaging, abnormal findings on ct. We've talked about pancreatic insufficiency, talked about immune autoimmune pancreatitis, IgG disease. Wow, we have covered so much there.
And yeah, I feel really much more knowledgeable just having just spent this time with you. So thank you John, so much for spending the time to talk to me today.
[01:06:53] Speaker B: No worries.
[01:06:55] Speaker A: And thank you, our audience, for listening to this episode. I hope that you found it really useful. I've got some sort of take home messages. I mean there's so many. But some of my things that have really sort of jumped out are just getting that better understanding of what the pancreas does with the role with lipase. Just helps us to understand why we develop some of the problems when it's not going well. It's also really helpful talking about how difficult it can be to make that diagnosis with that pain. You're really thinking about that sort of searing, deep pain as a possibility to guide us towards the pancreas, but also thinking about kind of family history, risk factors. So it's got to be on our radar. We've got to be thinking about it before we're ever going to start picking it up.
And Connecticut imaging sounds like it's the way forwards. Someone with exocrine insufficiency, CT sounds like a sensible option to try and identify the cause. But not forgetting that you've got other conditions, things like celiac disease, simple things that we could be looking for and doing in primary care. And then kind of that final thing was just as you'd mentioned, osteoporosis. And not forgetting that in those people with chronic pancreatitis, easily, probably, easily forgotten, not through any malice, but just can happen. We know it can in lots of other conditions. So, you know, quite a nice quality improvement project might be kind of looking at your chronic pancreatitis patients across your patch and have they had their DEXA scan? Have they had their bone health looked at? So some really helpful things there, John. So thank you so much for those listening. That was the end of part one. We're going to be back with part two, so please tune in for that. And we're going to be talking about malignant pancreatic conditions.
