E133 Masterclass with Charles Vollmer on Types and Workup of Cystic Neoplasms of the Pancreas
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Chad Ball 00:12
Welcome to the Cold Steel podcast hosted by Ameer Farooq and myself, Chad Ball. We consider it an absolute privilege to bring you guests from around the world who are truly experts in their craft. Our mission is to offer you a combination of not only masterclasses on clinical surgery topics, but also insights into achieving personal growth, productivity, and fulfillment as both a surgeon and perhaps more importantly, as a human.
Ameer Farooq 00:42
Dr. Charles Vollmer is the chief of GI surgery at University of Pennsylvania and director of pancreatic surgery. He's a repeat guest of the show. We were lucky enough to have him do another masterclass for Cold Steel, this time on cystic neoplasms of the pancreas. In part 1 of this masterclass Dr. Vollmer gives us an overview of cystic lesions of the pancreas, as well as their diagnosis. Make sure to check out part 2 as well, where Dr. Vollmer specifically focuses on IPMNs.
Chad Ball 01:14
We're thrilled to have you give us a masterclass today on something I think that probably a lot of trainees all the way into faculty of varying specialties think of maybe as not overly exciting, but the reality is that pancreatic cystic disease, cystic neoplasms and so on, are increasingly common. I think we all know this, based on the imaging that we have the incidental findings that have really skyrocketed with that use of imaging. I know we're going to get into IPMN specifically, a diagnosis that's been around for about 40 years. And certainly, as we generate a better understanding of that disease, things get a little bit easier. But I was wondering for the trainees, if you could frame for us how you initially look at a patient with a pancreatic cystic lesion. They show up in your clinic. How do you think of that patient? How do you work that patient out? How do you approach that patient?
Charles Vollmer 02:09
Yeah, okay. So let me take a step back to the first part of what you're talking about. And that was the historical arc of this. And I'd like to say that actually, it is exciting. For those of us in the field, the advent of this cystic process in my career, 20 some years now (30 if you include the training), this has been — I've been living right in the takeoff of this process. Now, it used to be that pancreatic surgery was reserved just for cancer. And it was, actually, there was a point in time where it's thought to be heretical to be doing pancreatectomies with their bad outcomes for anything beyond the most dire issue of pancreas cancer. And it's basically, I guess, John Cameron at Hopkins, who was really the forerunner of that, starting to show some papers of advancing the indications for it along the way. When I started out in the field, you would have thought a pancreatic surgeon or HPV surgeon, or pancreatic surgeons specifically, would basically only be dealing with 2 disease processes: cancer and pancreatitis. It turns out that as I matured into my career, my actual attending career, that this whole element came into the drama. And it's something that's somewhat newish, since the diagnosis of IPMN was really only founded about 1982. But I now refer to this as being like, the third pillar of a pancreatic surgical practice is the cystic disease element to it. It's actually quite voluminous in terms of names, numbers of patients that you get. And I also have a slide and a lot of my talks on this, that is a Venn diagram, and it puts those 3 things together — cancer, inflammation, and cysts — and puts them all together because there's overlap between all 3 of those in what the pathologies cause or present as. So it's actually been an infusion of intellectual energy to our field, in the midst of my career, and I've actually embraced it as being sort of maybe even more primary to me than the pancreas cancer. At least, probably here at Penn, I'm more known for the cyst element of things than pancreatic cancer surgery. So it's an interesting thing, guys, because I've asked some of the forefathers in the field: What were you doing back in 1980 with this? Were you doing resections for cysts and the likes? It was interesting because they said no, not really. And it's very hard for us to fathom that a new disease just sort of popped up in the midst of 20 or 30 years out of nowhere, right? Like, this had to have been going on back in the time. What they didn't have is the imaging elements that were so prevalent, bringing understanding of it. And they also firmly believed back in that time, like when I was a student, it was said that 90% of the system, the pancreas plus are going to be from pancreatitis. And they're going to be pseudocysts from pancreatitis. And I think we've now turned that — that's been disproven — and turned that around. So I asked them, like, certainly this disease was going on, didn't you do resections for this? And the old-timers, they basically don't have any insight on that, like they don't remember doing it. Now it turns out that the cystic things ultimately, first came to light in the 1990s through symptomatic problems. And so we were dealing with a lot of gross disease stuff with that, like, advanced stuff, because it got to the point where it was symptomatic. And then about the year 2000 on, the ubiquitousness of CT scans and MRIs and axial imaging, and then also ultrasound made this, as the as — I think you brought up the term "incidental-oma" — era was ushered in. And the nature of how we'd seen these things and understood them has changed a whole lot. So now we'll get on to your question. And that's, you know, how do you size these things up? Well, you're not necessarily born with cysts in the pancreas. It's really rare to be born with something. So these are generally acquired issues. So if a cyst is found in the pancreas, it's not supposed to be there, and you've got to be curious about it. The problem is that so many people in the medical field don't have insight to what this is, and anything pancreatic gets very charged up, and is scary to not just the patients, but also a lot of practitioners. So you get these cysts in the pancreas, or lesion in the pancreas, that's found, and people really, you know, freak out. Well, it's not supposed to be there. So it's incumbent upon us then to decipher what's going on with that. And the way I think about it is they can be good, bad or ugly. And you got to sort of get to the base of it. One of the cardinal principles here is you have to have a framework in your head of what the possibilities are, and the scope of what the cysts are and how they behave biologically. And we could detail that here in this talk if you wanted, but essentially, as I approach the thing, I've got this sort of algorithm slide in my mind, and I go from A to B to C to D along the MIDAS points to figure out where we stand. Radiography is so key to it, which is take a step back and say the HMP matters, okay, so, there definitely is symptomatology that can come from these things. And it's usually in the order of it's causing jaundice, which is obvious; it's causing overt pancreatitis; sometimes some exocrine insufficiency; steatorrhea presentations can come from it; and sometimes early satiety or weight loss because of a giant space-filling cystic lesion in the area. So those are kind of things that you can kind of hunt or glean from the HMP, but it's all about the pictures. And now because since 2000 on, everyone's getting a picture for anything, you go to the emergency room, you're going to likely get some sort of imaging. Now, it's just basically been thrust on us: Oh, we found this, the patient's not symptomatic, but here it is. And I think that's a good take-off for your kind of broad question there as to how I look at it. It's a matter of putting those things together. I think another thing you want to understand as you get into this is chronicity of it. So is it only at the time that you're seeing things, or has there been a history or prelude to it? So we always try to understand if there's been imaging prior to that — could have been 3 years ago, 7 years ago or 10 years ago. Did you have a car crash and you got worked up and you had a CT scan back at that point in time that we could refer to? Because you would kind of like to see, was it there at that point in your life? And did it, is it here now out of nowhere? Or has this been something that you had, you know, brewing in you for a long time, and it's getting, you know, it's changed a little bit over time? So I always ask to get that sort of, can you get us your radiographic history behind that?
Chad Ball 10:40
Yeah, that's a beautiful approach. You know, I think the reality that we all know is that if these patients come to the emergency department to a referral to a general surgeon, for example, usually that ends up in a CT-scan-type referral. If they come through a family doctor's office, then oftentimes, it's maybe an ultrasound that led to the CT scan, for example. How do you see the radiologic workup for these patients? So, where does MRCP fit in? Where does EUS fit in? Where does CT fit in?
Charles Vollmer 11:08
Okay, so actually, the most common way they're referred to us if you want to look at the numbers is through the GU track. So hematuria and or kidney workups [inaudible] ultrasounds and then ramp that up to the CT scan kind of thing. The second thing would be gynecology-based assessments where an ultrasound is put on the abdomen, down low, but then they start looking around because they can, right? So those are our 2 most fertile grounds on that kind of stuff. You can also get this stuff through cancer surveillance screening processes, so oncologists will encounter this because they're getting their preferred scanning kind of things. And sort of the last thing would be the quote-unquote, executive workup, executive health workup screening kind of thing, where someone is worried and or their insurance company allows them to go get screened, to assure that they don't have anything going on, right? So these are sort of our portals of entry. And we can get any of those imaging things or all of them at one time. What you need to know about the cystic process is that the workhorse for this — the best thing — is MRI. And the reason is that you want to be looking at the plumbing system of the pancreas through this, and how do you do that? Well, MRI is the best thing to look at the ductile elements. And it relies on basically the fact that on a T2 image, you're assessing standing fluid, or non-pulsatile fluid. So if you want to look at the plumbing system of the body, you're using the MRI. So the cyst elements, we can get into the nature of this a little bit down the line in the talk here, but it's basically the epicenter of the problem is going to be in the tube of the ductal system of the pancreas, and MRI will outline that the best for you. CT scan should be thought of as being more for parenchymal elements. You will be able to understand things about cystic lesions, and duct dilations and stuff with CT scans, but they will be on a grosser level and probably reliant on that cyst being a little bit more advanced, bigger, or more biologically involved with things. So I tend to, if someone comes with a CT scan, I tend to get an MRI immediately at the outset as a baseline to go off of that, because most of the screening will go off of that. There will be people who can't get MRIs, but even that's, in today's world, changing to the point where they know — pacemakers can be, you can have it. People with claustrophobia can be dealt with. There's open MRIs -- actually saw something the other day — there's actually an upright MRI, you sit in a chair, and you can get that done. So we're sort of getting away from all those disqualifiers, so I would urge you if you can do that, you can do that. Now ultrasound in general, and transabdominal ultrasound is an easy, quick, efficient way to kind of peer at the pancreas. It's kind of like getting a chest X-ray of the chest. It kind of tells you a little bit, gets some basics for you, but it's not going to be as well detailed. And of course looking at the pancreas through bowel and such, it's often obscured and you can't get a good, full look at it, but there's definitely times when an ultrasound, looking at a gallbladder, and they sort of peek over, oh, I found something ahead of the pancreas too. So that's sort of your entree level of kind of thing. But then you brought up the idea of an EUS. So that would be where you pair, the ultrasound imaging [inaudible] process can actually biopsy or access the cyst. And that will be done by a gastroenterologist. There's a whole lot to say about that. So you could think of that as being your best way to target the biological nature of the cyst. Heretofore, we just talked about radiology and I can tell you, for the vast majority of all these people that we deal with, we can totally rely on radiology because the numbers and the odds, and the features that we see on that are very, very clear cut now, okay? But that's not the case for every case. So the best way to go to the target lesion itself is to go down through the stomach. And essentially, you understand the stomach sits right in front of the, the corpus of the pancreas, so you can look right through onto it most directly. And then you have the ability to access the fluid within, which is going to tell you more of the biology of it. There are some caveats to that, okay? So it's more invasive, there are definitely side effects that can happen. They'll quote you a 1 to 2% risk, it's probably a little bit higher than that, but it's not, you know, outstanding risk. But things can happen. And I have absolutely seen people in my career whose pancreases have been blown up by getting pancreatitis from an FNA biopsy, to the point where it distorts the gland itself, and you don't even know where the cyst is anymore. And you can't even surveil it over time. And sometimes you get to a point where it's so bad that you can't even operate, or at least you have to delay any operative intervention from it. So you've got to be a little bit leery of the complication process to it. And the second thing is you can't biopsy all cysts, and we can get into this later, nature of what we're finding, but there are a full spectrum of size and morphology of these cysts. And the general rule is, to get anything out of a cyst, it needs to be about 1 centimetre in size or equivalent of 1 cc of fluid. So the concept that all these trivial ditzel kind of cysts are things that 1 centimetre or below are important or valid, etc., that you need to go put a needle into that, that's really probably overdoing things. And then the other thing I'll tell you is your fidelity of your biopsy is going to be based on your size as well. You start poking 1 centimetre cysts, I believe that there's going to be a larger, false-negative/false-positive process from that, than when you have the larger 2 to 3 centimetre cysts, or in essence, the cysts that are actually more biologically relevant for the concern, okay? So I do worry about over-aggression. And this is an interesting thing, because we're talking to a general audience here. It really kind of depends whose hands you fall into as a consultant, as a patient, what kind of consultant you're encountering, initially. A gastroenterologist is likely going to be more aggressive and do what they do, okay? A surgeon, likewise, can be more aggressive and do what they do. But we also know that our aggression is really extreme. So I think we have a little bit more measure on like a we're when we take someone to the operating room. But a gastroenterologist is likely going to apply that technology because it's their skill set and they make living off of it. And it's, their culture is ingrained. That's but, you know, we, the same person could go to a surgeon and they'd look at it and say, I can pretty much figure this out by the radiology and by the history and physical, and it's not really a big threat in my mind. So I don't really feel the need to go do that sampling at this point in time. So definitely in our own cyst clinic group here, we definitely have different approaches — and not to say that one's better or worse — It's just the fact on that, okay? I personally resolve or leave the endoscopic ultrasound aspect for more advanced cases that are going to help me make a choice to go to the operating room or not, okay? So if I want to know what the paver is, what is going on inside that cyst biologically at the cellular level, then I'll invoke a EUS approach. And I will generally use that because it needs to be an additive layer of qualification to help me make the determination to go to the operating room. That's that.
Chad Ball 20:31
I think that's perfectly said, right? I think we all use EUS in that way that it's an additive test, when you're when it may tip you one way or the other way, i.e., into the operation or out of it. So you've triggered your EUS on this given patient, and you get back a report that has a number of different values: glucose, amylase, lipase, cytology, perhaps a CEA level, maybe even a CA 19-9 level. For our audience, can you break down those 4 or 5 elements and what they mean to you?
Charles Vollmer 20:31
Yeah, so that's, I was about to go into that. And that's exactly it. So you've got 2 purposes or 2 ideas of what, a by a cytology FNA can yield you. And it depends [inaudible] And this is why I'm saying like, you have to be selective. The smaller cyst, you're not going to get a lot of fluid back. Sometimes, you're going to be forced to choose between the 2 thought processes. So one is what is the biology that I'm dealing with? Can we use that cyst fluid to give an additive insight to, on top of the radiology, as to what the discrete category of the cyst is? The second would be, can I get to the aggressiveness and the worry element of this cyst; i.e., is this cancer or in the pre-cancer element at some, or dysplasia zone, at some point? Sometimes you have to choose between one or the other: you can only get a cc off, you can't send them for both, and you have to be sort of judicious about what you're looking for and what you're asking. Now, let's start with the biochemistry. This is to determine what kind of cyst it is. So you're basically pulling the fluid off, all right? The other thing you should understand about cysts, people worry about the size of cysts, okay? And they're like, oh, my God, it's a 4-centimetre cyst. Well, you know, a 4 centimetre pancreatic mass is almost unheard of, okay? So people freak out, like, oh, my God it's 4 centimetres, right? You should just think of it like that 4 centimetres is not necessarily a proliferation of millions of cells, like a solid mass is. That size is a fluid sac — it's basically a bunch of fluid. Yes, you could argue that their surface area, of the neoplastic or disease process that is added there, but you shouldn't get so worried about like a large cyst, or the size of the cysts changing so much. It's so, you know, Red Alert, Red Alert kind of thing. Let's get back to the fluid. There's a number of things you can get out of it. So first of all, since it's in the duct system, putatively the cyst should have amylase in it, okay? Now, if it's truly connected to the whole pipe system, it will have amylase because that's what the glandular elements are producing, okay? There are a few types of cysts that are trapped, unilocular things that are not part of the pancreatic duct system. And this is where that differentiation helps you, okay? So an amylase would indicate connection to the pancreatic duct system. You're going down the line of pseudocyst or IPMN with that thought process. If the amylase is not in that, it could be more on the lines of a mucinous cystadenoma, which is just a singular trapped cystic cavity within the pancreatic parenchyma but not fueled by the duct system, okay? So that helps you with that kind of distinction there. Glucose, I don't find a lot for that, necessarily, but I think that that is one of the newer frontiers that's going to be a marker that is going to help you understand more about aggressiveness of a neoplastic lesion. So I say future attractions there, but not yet proven. This was all figured out, I guess in the late 90s. Bill Brugge at MGH was the guy who really sort of pioneered this and the landmark paper was from them, I think it was a New England Journal paper, actually, if I recall. Basically like they sucked all these the fluid out, and they just looked at all these biomarkers along the way. And what did they find out? The key finding was that CEA, carcinoembryonic antigen, was elevated. If that was elevated, it was trouble. Now, that is CEA the same as what you draw for colon cancer, survivorship or analysis from the blood. But, and you always have to make this very clear to your practitioners as well as your patients, that we are not talking about that and we are not talking about this being a tumour marker for colon cancer. This is a specific look at pancreatic juice. All right. So you get that and that's elevated. The threshold is somewhere around 180 to 200. If you're above that, this does not mean you have cancer. And this is the fallacy. This is actually an ABSITE question that's been known to happen for the surgical residents. But it's also the most common misconception by any of the practitioners you deal with, oncologists in particular, and primary care doctors. Oh, the CEA tumour marker is high; this must mean it means cancer. It does not. What it means, instead, in this case is that you are talking about a cyst in the mucinous family. And that basically means IPMN, or mucinous cystadenoma, or possibly the non, the very rare, nondysplastic mucinous lesion, which is really benign. So, that's the big thing you need to know. So you get a CEA that's up, and again 180, 200 is your threshold; however, there's also data that takes that down lower. So if it's actually like present, I've seen cases of IPMN where the level is 50, or something like that, and it's clearly IPMN, or we can show by diagnosis or pathology too. So there's, you know, there's a spectrum for what that number could be. But that's up, that's an indicator. And I think that's a bit [inaudible] is that you've just got to understand that it is not a cancer diagnosis by using that. Now the other thing would be glucose, or I'm sorry there's some some added extracellular kind of biochemical things you can get. It's it escapes the top of my head right now, but there is something a little bit more specific for serous cystadenomas and the serous, which is a benign condition, and if that is elevated, then that gives you a little bit more comfort that you're dealing with this lesion that's benign and probably doesn't even need to be followed thereafter. Very interestingly, you can make some comparisons with what we're dealing with in the pancreas here to the ovarian cystic lesions that all surgical residents had to remember, but they never really deal with anymore. We had to do it for our board test and understand the differences of the ovarian cysts and how you treat them in the operating room. Well, here you have the same thing. You have the differentiation between serous and mucinous lesions. The mucinous stuff is bad, okay? That is pre-malignant and has the malignant potential that serous generally does not, okay? And so you have the same components as cystic lesions in the pancreas, and this is one of your differentiating points in the biology. The last thing about the aspiration — if you go down the other course or maybe you're lucky and you got enough fluid you can do both at the same time, you then can look at the cytology elements. One thing before I get to that though, is another finding that you can have when you're they're doing the EUS is they're going to pull this fluid back through the scope, and they're going to see a string sign on it in some cases, and it's just very obviously viscous, so it's called the string sign, and essentially that you could know even before you get any, you know, biochemical numbers back to you from your visual on it. Let's go to the cytology element. This is where it gets very vexing and this is where my point before about maybe overuse of EUS is a problem. What you're looking for is to get exfoliated cells that are just sort of floating around the that are indicative of what's in the neighborhood, okay? You're never going to get -- the best thing is a final pathology where the whole tissue and the architecture of the neighborhood is visible to the pathologist and then they can put it all together. But essentially you're getting a glimpse to it by just getting these cells out and having a cytologist look at them. You need to remember that that is an art form — cytopathology is an art form of a field. And it's in the eye of the beholder, and there's certain skill levels, and you have to have trust in who you work with on that kind of stuff. There's absolutely false positives and false negatives. Essentially, you want to know where in the spectrum of disease does this fall: benign, dysplastic in some way, or cancer in terms of overt cancer or even invasiveness if they could go that far.
Ameer Farooq 30:56
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