E82 Chuck Vollmer Masterclass on Pancreatic Fistulas
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Chuck Vollmer 00:00
You got to know the field, the weather, the conditions, your adversaries' traits. You have to know the risk assumption calculus and we make a point of emphasizing you know, what Bill Belichick does with this in terms of adapting his game plan every game to what he's facing. So, I feel that's what you have to do in the operating room for this problem.
Chad Ball 00:34
Welcome to the Cold Steel surgical podcast with your hosts Ameer Farooq and Chad Ball. We've had the absolute privilege of chatting with some amazing Canadian as well as international guests over the past year. While the topics have been broad in range, rather clinical, social or political. Our aims for the podcast continue to remain the same. We hope to inspire discussion, creativity, scholarly research, and career development in all Canadian surgeons. We hope you enjoy our second season as we continue to highlight some incredible guests, deliver detailed masterclass sessions on a myriad of clinical topics and introduce some fresh new features such as debate and companion formats. We hope you relish the podcast as much as we do.
Ameer Farooq 01:34
We're lucky enough to have Dr. Charles Vollmer join us once again on the podcast. Dr. Vollmer is a pancreas surgeon at the University of Pennsylvania and a previous guest on the show. This week, Dr. Vollmer gave us a masterclass on pancreatic fistulas starting from how to define them, how to predict them, how to prevent them, and ultimately how to treat them. Be sure to check out the show notes for all the resources and materials that Dr. Vollmer talks about on the show.
Chad Ball 02:02
Welcome back once again, Chuck.
Chuck Vollmer 02:04
Well, thanks Chad and Amir for the opportunity to join Cold Steel once again. I'm looking forward to the commemorative jackets like they get on the Saturday Night Live five timers club. But I'll try to distill my career's research concentration from roughly about 25 years, down to about an hour or so if that's okay by you.
Chad Ball 02:28
We can't thank you enough. As always, we know how busy you are and this is a real treat, and a real gift to all the listeners. I want to start by asking maybe a semi personal question, maybe it's a little bit odd. But I want to ask what drives you to study this? Like, why are you into pancreatic fistulas so hard and truly all in?
Chuck Vollmer 02:50
Well, good question. I mean, this has developed over time. And it certainly wasn't the thing that I was thinking about when I started my career, first and foremost, but you sort of get into a lane over time and it takes you to a place. But truly, this is the big one. It's hackneyed phrase, but authentic. When people refer to pancreatic fistula as the Achilles heel of pancreaticoduodenectomy, it truly drives the vast majority of morbidity in the operation. And some of our earlier work on why people die from the operation showed that fistula accounts for a full 1/3 of the deaths from the operation. So if you're invested in doing this, you want to improve, and you've got to attack the big things to make that improvement happen rather than the low lying fruit. I'll take you back to my early experience as a medical student. It was very formative for me. When I was a third, fourth year student doing rounds on my surgery rotation, and of course, I was going to be a surgeon and I was really into it. But this is in the early 1990s. And I was charged with doing rounds on the patients early and getting back to the team. And we've started the ICU. And you know, back then, it seemed like it was the killing fields. I mean, it's a very crude term to say but we'd go in and watch these patients with humors falling out everywhere from their abdomen. All sorts of bags and drains and colors and really sick people and was very harrowing. You know, you can't improve that operation without impacting that particular problem. And that really imprinted on me at that point in time. I actually feel now it's the cornerstone to good results in this operation and that's why I've dedicated so much effort into it.
Ameer Farooq 04:54
Dr. Bowman, can you outline to us through your research and all your studying and thinking about this topic. Can you outline for us what the historical arc is on the work on pancreatic fistula? Like what has been done in the past to get us to this point?
Chuck Vollmer 05:12
Yeah, thanks a lot. It goes way back to the start with Whipple's first case. And not many people know this, you have to read John Howard's recounting of Whipple's career to get this detail. But there's a guy called Hap Mullins who was Whipple's surgical resident at the time, and back then he was doing lab work on the concept of putting the pancreas to the jejunum. So, he was very invested in his inquiry period into figuring that out, and he was one of the first people to operate with Whipple on those early operations. The first procedure on an ambulatory tumor, they tried to put the pancreas back to the duodenum, and it broke down within 30 hours. The patient died. The first case died within 30 hours. And they did an autopsy of that, and realized that the anastomosis had completely disintegrated. And the reason why is that they used catgut, to put it back together, and it basically didn't hold. This lead them in ensuing cases to do duct obstruction thereafter. You have to understand he did about 10 cases before he ultimately got to the first or one stage procedure. But in the early days, it was felt that to obstruct the duct and live with the endocrine, insufficiency was better than having a dead patient. So, you know, that's sort of the the start. And then you could fast forward to about the 1950s when Patel and Warren describe the concept of duct to mucosa anastomosis. In the 1960s, John Howard, you know, the Dean of pancreatic surgery, reported in the last chapter in his seminal book diseases of the pancreas is a chapter on pancreatic fistula and it's mostly centered on pancreatitis, pseudocysts and fistulas from cases of pancreatitis operations. But there's a mention of three or four post-operative pancreatitis fistulas in that situation. I guess you could sort of go ahead to the timeframe when I was describing before the 1990s. When, at that point, these fistulas were becoming more evident. They were probably fueled by the realization that the Whipple could be done for more indications than just cancer. So people were getting a little bit more adventurous and therefore venturing in on more risky glands, so to speak. And the leaks were happening and they were breaking down and causing people to be very sick. There came a point when there were, you know, people were starting to describe this with definitions. And it came to light that there were numerous definitions. Claudio Bassi had a very famous paper that said there were 26 individual definitions of pancreatic fistulas in the literature at that point. And mostly these were based on the local shops conception of what they thought a fistula was. Varying amylase content versus radiographic findings versus length of time that it was studied versus volume coming out. So, it was a real mismatch. I think one of the important concepts brought up by Andy Loewy was that of the clinical condition concept, and that was that a leak of the pancreas was really most important when it brought the patient down, in some way, shape, or form. So, the clinical severity idea came into play. And that's really where the ISGPS, the International Study Group of Pancreatic Surgeons got the idea to validate it. They wanted to really synthesize this down to one defined idea of what it was that everyone could speak on the same language with. And also, they tiered it in a clinical impact process. Beyond that, and this is really where my career started, is right at the outset of that definition, and then we move into the era of risk score development. And then now, since scores have come out, what I'm going to talk to you a lot about today is the pancreas fistula study group contributions. A group that we brought together from around the world. So as I talk to you about more of this later on, there are two things I'm going to refer to going forward. One is this pancreas fistulas study group, which refers to 18 international institutions, about over 8000 whipples at this point, and over 75 surgeons contributing from all around the world. Which we've developed numerous papers and analyses from, and it's really a living, breathing coalition for about 20 years now. And then the second thing I'm going to refer to at times is something called the Masters survey, which is a just published paper in the Journal of Surgery, called decision points and pancreaticoduodenectomy: invited expert opinion on pancreatic fistula. This recounts the opinions and practices and habits of 60 truly international experts on pancreas surgery, where we asked them about 110 questions about their practice. And we were able to identify best performers and what their habits were. So I'll drop in at times evidence from these various important studies that we have.
Chad Ball 11:26
You know Chuck, you listed so many great sources of knowledge and information in that arc. You know, sitting here in my office on on my shelf, one of the books that I have is, of course, John Howard's Life and Times, Allen old father Whipple, a two-volume set. And we'll link that in the show notes for anyone who's interested. It's a long read, but it's a remarkable life that he led and it touches on a lot of what you've mentioned. The other thing I would say is that the international group, the ISGPS that you mentioned and we'll talk about more is really sort of "must reads". No matter what they put out, no matter what that group comments on, I think it's a must read for anyone that thinks about the pancreas. They don't necessarily believe that's just pancreas surgeons that do elective work like you and I do, or pancreatitis, acute care surgeons, for example. It also includes trauma surgeons that have to think about pancreatic injuries and subsequent fistula. So, it really is high yield reading. I wanted to continue to go down that path then and ask you very simply, at least at 30,000 feet two questions. How do you define a pancreatic fistula? And then, take us through the ISGPS grading system. And in particular, I'd love if you'd comment on the utility or lack thereof, of grade A fistulas, as they're currently defined.
Chuck Vollmer 12:51
You brought up the ISGPS definition. So I'm going to say at the outset here, the best constructed and conceived of all those definitions is the original one, which is the pancreatic fistula study, famously authored by Claudio Bassi. It is, in fact, the most cited work in pancreatic surgery. I think it's been cited over 3000 times since about 2005 when it came out. So it's really important. I conceptualize fistula in this way. I think of it as a continuum of the condition of a breakdown of the pipes, so to speak. Or an anastomotic breakdown, you know for our terms. But conceptually, a pipe disruption. You have to really understand the importance that in in this definition as compared to the other ISGPS definitions, there's an actual biochemical parameter that defines it. And that is the amylase content of the juice that's produced by the pancreas. The other definitions don't have that sort of linchpin to it. So, amylase is the evidence of a physiologic process that is associated with the problem. Otherwise, the definition is dependent on severity. And this is a bit controversial, but the construct is that it's graded on as judged by what the surgeon does. So there's a problem with that because there's variability on how surgeons approach the care of the patient, right? Some are aggressive and some are less aggressive with their interventions. But basically, the grading tier scale has to do with resource utilization. So it starts with Grade A and at the outset, this was felt to be important. I think more about helping the definition come along. But we were the first in our validation study of this paper to show that this grade A transient biochemical leak kind of zone is really worthless. It's not impactful is what I should say. There are in fact no predictors identified for it. It probably represents some minor leakage of side branches of when you cut through the gland, that it sort of drips off and can be found as a low-level amylase content in the drain. More important, though, is what we call clinically relevant fistulas. And that's where we step up into Grade B, and C. So, Grade B represents 80% of all your clinically relevant fistulas. So, this is, you know, the bulk of it. This is predicated on medications, or interventions. Then we've actually subsequently sub classified this into three zones based on the degree of those interventions. It's also associated with prolonged drainage. And this is a little bit arbitrary, 21 days, but people would really understand that, you know, you really shouldn't have a drain in your side for three weeks. So, you could quibble over why that number, but basically, that's sort of your cut off. If you have to keep drainage to prevent from sepsis from happening, then that would get you into a clinically relevant place. For someone to go home with a drain in their side is impactful to them. So, it counts. And then you can step it up to Grade C, which is organ failure. And this is not necessarily ICU use. Some could say that's what the definition says. But it's really when you have an organ failure because people could decide to put someone in an ICU very arbitrarily. So, it's organ failure, and then other consequences of that which ramp up to reoperation, full on sepsis, and death. A death from a pancreatic fistula is Grade C. Grade C accounts for 2% of all the whipples that you will do. So, a little bit, but a real number and they are memorable for you. Together if you want to put the CR pop rates together, it's delineated at a 13 to 15% rate across the world, pretty uniformly over time. That's the number that happens after this operation. 13 to 15% of your patients will suffer this problem. So, to bring this all together, I have a conceptual analogy. It revolves around sort of the degrees of a leak and would look like this. It's sort of a spectrum of sweat off the gland. So that would be a Grade A. A leaky faucet, which would be Grade B. And then finally a sewer burst, or a full dehiscence, which would essentially lead to Grade C with its septic predilection. Finally, if you want to really use the word fistula properly, it's an epithelized connection. I would save this term more for the longer-term condition. If you have juice coming out of the side of the body through a long-term fistula epithelialized tract, I think that's a better word for that rather than the initial leak kind of process. Whatever you want to say about this kind of stuff, the standardized definition has finally allowed for an objective comparison to be made, both for research, for performance, for assessment of interventions, whatever you want to say. We now have something that is pretty well socked in around the world and understood.
Ameer Farooq 19:32
It's a remarkable achievement and all the residents now of course, learn this and hear about this as we go through our HPB rotations. But it's remarkable to think about how this definition came about, and what it entails. Can you talk to us a little bit about you know, now that we have a definition, can we actually now predict who's going to get a pancreatic fistula to the degree that you know, we can do that? And talk just a little bit about some of the many risk scores that are available for predicting whether an individual patient is going to get a pancreatic fistula.
Chuck Vollmer 20:09
Sure. You know, it seems we live in an actuarial world. Now we're consumed with the concept of risk, both predicting and managing, particularly in our field and as surgeons. Actuarial science has crept into medicine over the last two decades. And now risk scores, apparently are a dime a dozen in the academic literature. They're not that hard to make in the big picture. So, you see them popping up everywhere for everything in surgery. But truly, very few have manifest tangible value. So, a lot of people can make a score. But then what do we do with it? And is it actually practically applied? And that's where surgeons have fallen down. Because we haven't taken it to the next level of providing value. With the ISGPS definition being developed, we attacked this concept over a decade ago by first validating that construct in an Annals of Surgery paper, and then searching for factors associated with it. And great credit has to go to a young medical student at Harvard, when I was there, named Wande Pratt, who really attacked this problem for us. You have to start with the realization that risk for pancreatic fistula is multifaceted. And many people are very stuck on the concept that it's just about one thing, and that's the soft gland. But really, we've identified that the median number of factors that people think or consider is three. And you know, there's many more than just three, but that's sort of what people around the world think - that it is a multifaceted approach. But truly, that risk is dominated by the inherent glandular features. These are the things that make it not fun to mess with the pancreas, as the old adage goes. I'm very strong on the relative uselessness of preoperative prediction. A lot of the scores proposed in the literature, very few have gotten through to publication, but a lot of people have proposed preoperative risk scores. These factors that are identified are largely not modifiable, and therefore have no reasonable pre op interventions against them. I think it only adds basically to the informed consent process to know about preoperative risk. But you know, you have to take that to a limit, because the more of this you get into, you can scare patients off by telling them how bad things could get. I think it rarely disqualifies people from an operation. I've never not done an operation that was necessary for other reasons out of fear of a leak happening. I think many people would say the same. And then I'd say this, you know, prediction is like the weather forecast, or today using Google Maps function. Truly unforeseen and actual events change and alter the course of those predictions. I can give you some examples. I mean, the temporal forecast of the weather. If you go on your app, and you take it out 14 days, it's going to tell you basically, that it's going to be a sunny, mild day, where you live. Or it's going to predict for you the norm for that time of year. How many times have you looked at that, and then the day before you get there, it's completely different. Because there are better things to help with that forecast more close to the real time. Same thing goes for road closures on a map function. It'll tell you it's gonna take you seven hours to get from this city to that city. But what you can't understand is if there's going to be a major pile up on the highway on the way. So, you know, prediction has its limits. And really, we would take this. This is why we're very fond of the concept I call times zero with this problem officially. And then anastomosis can't leak until it's made. And everything you talk about preoperatively is just foreplay to this. But you actually have to endeavor on the problem. That part of the operation to me is what we call the critical portion of the operation. This is the one where the attending surgeon has to be there and has to be part of it for relevance. So, this is where it all starts. And it's because at that time, you can size up your field. You know what the gland is like by observation, palpation. As opposed to a surrogate, preoperative radiographic look. It's authentic at that point. You know the tissue quality, you know the physiologic state of the patient, in the midst of the operation. You know what your blood loss is. And you also know the help that you have that day. Who's working with you, and what's their skill level and how you're going to put this anastomosis together. So, I think that you're dealing with the actual at that point. And you can basically go to the measurable and tangible versus the supposed, or surrogate data at that point. And I also think that this is your first opportunity to actually influence the situation with your actions. And of course, as surgeons, we feel that we have that power, right? So then my next thoughts would be post-operative assessment is moving towards confirmation or definition that the fisula is happening rather than prediction, per se. And naturally, as you get closer to the act of a fisula being defined, and farther from time zero, you're going to increase your predictive value and accuracy. So, the factors that you can roll in postoperatively are valuable and helpful. But you got to think of them as sort of being more about the odometer of the disease. One basic question we grapple with is, if you perceive added risk, would you do something different? And if so, what? When we asked that question directly to the masters, and they say that they believe that these scores help. Three fourths of the people claim that. And that 50% of them calculate them. But truly, they struggle with what to do functionally, with that knowledge. And I hope that as we get into this a little deeper, that I can shed some light on that. But that's where we are right now. People, they like the idea of a risk prediction model or tool, but they're not really into how to affect change with it.
Ameer Farooq 27:29
Can we talk a little bit about the fistula risk score that you developed and published on?
Chuck Vollmer 27:36
Sure. We'll call that the FRS for simplicity. It should be said at the outset here that it was derived from a very rigorous modeling process that used 42 preoperative and intra operative factors from over 450 whipples. It has subsequently been validated across multiple domains and conditions for all forms of pancreaticoduodenectomy, including minimally invasive and private practices versus academic and multi practice processes, etc. So, it's really sort of got the primacy in the field of the fisula risk prediction process. FRS risk, or the FRS score is, as it turns out, the most consistent and important driver of the ultimate outcome of CR pop for clinically relevant official. So, in other words, that inherent risk, as determined by FRS is there. And as each point of the score accrues, you add an odds ratio of 1.5 to the hazard of a fistula happening. So, what it does is ultimately it predicts very well, morbidity after the operation, overall morbidity, not just a fistula. The burden of an operation, as judged by the post op morbidity index. Resource utilization, costs, and it even predicts mortality. The higher you get up on the FRS score, the more chance you're going to have of dying. It also aligns with your post-operative day one drain amylase values. So you know what you're going to get the next day already in the operating room, if you figure your score out. There's a stepwise increase in your amylase as the FRS goes up. Now we tried to make it simple along the lines. Some of our modeling early on got very complex with big numbers and things that people couldn't remember. But we made it a very simple process and it basically relies on four components: Gland texture, duct size in millimeters, calibrated to millimeters, not a dichotomized thing. Disease pathology broken down into protective and non protective pathology. Protective is pancreatic cancer and pancreatitis. And then finally interoperative blood loss on a scaled basis. You get various weights to these four things to make a 10 point continuously escalating scale, as you go across from zero to 10. It's utilitarian, and it's easy to remember. You can do this on your two hands, on the fingers of your two hands and on the top of your head. We were then able to delineate it into zones that cluster outcomes pretty relatively. So the lowest risk group is called negligible. And there's a under 1% chance that you develop fistula in that group. And you go up through low risk to moderate risk to the high risk group. That pretty much socks in about a 30 to 35% chance of developing a fistula if you're in the FRS seven to 10 range. I'll talk about that a little bit more later in the talk today. Frequency across the zones also has been defined. 10% of your cases are going to be negligible risk or virtually no chance of leaking. The most common areas, the moderate risk is 60% of all cases undertaken. And then this high risk zone is infrequent. But of course daunting. And that is a 10% chance of encountering a high risk scenario. I use the word scenario because we have recently defined the fact that there are 80 distinct ways you can bring these four components and their weights together. We call these distinct scenarios. And they are made up of the possible combinations of those four elements. This is been outlined in a paper in the Annals of Surgery last year, called the Fistula Risk Catalogue, where each of these 80 scenarios is defined and the outcomes from them understood.
Chad Ball 32:18
That's absolutely tremendous Chuck. I was wondering if you could just take a second before we move on for our learners in particular because it might not be totally intuitive. When you look at your four components of your FRS and look at the underlying pathology, and you just find it as protective, for example, with pancreatitis and pancreatic adenocarcinoma, or pancreatic tumors that are non neuroendocrine. What's the link with gland texture? And why is that particular element so important?
Chuck Vollmer 32:50
Yeah. So the protective aspect would really have to do with the effects on the gland and what happens when you have an obstructive pancreatic cancer tumor to the pancreatic duct. This is all about what's going on at the duct where you transect it. And also pancreatitis is about fibrosis. So the dilated duct from the tumor makes it easier sewing basically, right? And, the same thing can be said about the fibrosis aspect. Sometimes the pancreatic cancer, you get both of those, obviously. But the fibrosis allows for the sutures to hold better, turning it into a hard gland. The interesting thing here is that you would assume that those are co-linear with the gland texture. Those facts are co linear with the gland texture or the duct size. But they're not in fact, and it's hard to understand. But there's definitely situations where you're going to have a pancreatic cancer that does not obstruct the duct that way. And this accounts for that fact that there are going to be cases where just the fact that you have cancer, or pancreatitis is enough, but you may even have a soft gland or a tiny duct. I can't explain that. But you can understand how conceptually those are protective because largely they do affect the gland.
Chad Ball 34:18
Yeah, absolutely agree. And, you know, I think we all talk to our trainees when we initially frame our Whipple procedure and they come on to our service as: it's a procedure where you have the resectional component and the reconstruction component clearly. And you pay for one with the other. Meaning, if the resection is hard, ie. pancreatitis, for example, the reconstruction is generally, overall, if you take all commerce, it's more straightforward. It's simpler to do and it's lower risk, or vice versa. I'd like to move into certainly a more controversial or maybe hot topic, and that's surgical variants; both in terms of centres and volumes, as well as individual surgeons. How do you think that plays into the story of pancreatic fistula? Clearly, it's not uniformly distributed. How do the outcomes of relevance look, you know, across surgeons, for example? I pick up on a number of the nuances that you sort of tip your hat to in the last segment, which is, you know, the experience of sewing that pancreatic jejunostomy, or pancreatic gastronomy for some folks is so critical.
Chuck Vollmer 35:32
Yeah. So back to the point you just made. I couldn't agree with you more about the two phases of the Whipple. And we say the exact same thing. You usually get one good side of the operation and one bad side. Or tough, or difficult. And rarely, if ever, do you get both the line where you have double good or double bad. So, fully agree with you. I state the exact same things. When I was growing up in this field, I used to consider. Before I got into all the work that I did, I used to consider that it was a defined biologic fact, that it's a 15% rate of pancreatic fistula. That it was an immutable fact. And while I told you earlier that the average in fact is 13 to 15%, it was when I was young. It is now - the definition is there as well. But I actually think it's not a truth that this is a biologically immutable fact. I was fascinated by the idea. I was like, what if you work at a cancer center, and this ties back to what we were just talking about. And you're getting all these pancreatic cancers in your practice with dilated ducts and firm glands. But you're not dealing with cysts a lot or something like that. And your practice is dominated by what we would think would be less risky situations. Would you have better fistula rates? So, I wanted to sort of look into that. And we did that through the fistula study group. That's really why we could put it together, is to be able to look at the broad variance. And it truly shows that surgeons and institutions show great variation in risk assumption. So, there are people, and I don't think it's by choice necessarily. It might be you know, it might be the nature of your practice or not. But there's a huge array of the median FRS and the constitution of the risk zones between surgeons, and that actually also applies to institutions in the series as well. Similarly, not all surgeons are created equal in terms of CR pop rates and outcomes. There is a great variance. 15% is the norm. I'll tell you if you're in the 20% range, you're not doing as well as you think. You shouldn't be up there. And maybe you should be looking at what you're doing and why. There are a few people in the series who didn't have a lot of N or a lot of background who were in the 30% range. Similarly, on the other end, there's a handful of people out there who really have this down and are in the three to 5% range. And that master series paper, actually, we focused in on those people in the world who have a 5% chance or less. And we focus in on what they're doing so that the reader can actually look at their practices. So, there is a variance for sure. This is the hot stuff in our outcomes research now, in all of surgery. This can be normalized now that we have the score to use as a risk adjustment process. And we've now taken this to the concept of performance assessment for whipples, showing that there are definitely people who underperform and overperform despite the risk profile that they have. That was Annals of Surgery paper by Matt McMillan and really shows a nice waterfall plot of both the surgeons and the institutions. Showing the good performers, and you know, the people who were shooting over par and under par.
Ameer Farooq 39:47
So you've obviously now published this paper, talking about what the Masters do, and we have their insights. But what do you think are the biggest obstacles to making tangible progress against this dreaded complication?
Chuck Vollmer 40:01
Yeah, well, here's the big deal. It's very complex. I mean, this is why the Whipple is the pinnacle operation in surgery. This is why everyone, you know, respects it and admires it and fears it, you know? It's just very complex, there's tons of decision making. The way I like to put it, I have a slide in some of my talks, it's a bunch of gears put together. And, you know, there are basically many moving parts going on. And we figured out that, you know, at baseline, there's at least 10 or 11 distinct choices that use the search and can have for putative mitigation techniques. You just can't assess one technique in isolation, as has been the habit historically for this when you look at studies. What is lacking is a more comprehensive assessment of the multiple approaches necessarily employed, in concert together. How do they all interact? What dominates what in those gears to get to the final outcome? What helps you to be more protective or less protective, etc. So this conceptually indicates that randomized control trials are actually inadequate approaches for this. And while yes, we have RCTs on various mitigation strategies in this problem, the problem is that they are basically funneled into just one mitigation strategy alone in isolation. This is actually where multivariate analysis, propensity score matching might actually be more relevant in assessing this story, because it actually accounts for the interplay of numerous factors together at once.
Chad Ball 41:49
I want to go backwards again, to explore or unpack. In particular, I think that the term used is time zero, ie. the construction of that pancreatic anastomosis. And as surgeons, we certainly all, I think, fundamentally believe that at a high-volume capacity that we have the ability, the power, the luck, whatever term you want to use to influence the outcome of that technical endeavor. Whether that's colorectal hookup, like a low rectal hookup, or whether that's pancreatic hookup. So in terms of the anastomosis, the reconstruction, is that really true? Where does the tipping point lie between surgeon and disease or surgeon and other non-sort of self-interested factors?
Chuck Vollmer 42:44
Yeah, I go at this with a yes answer to that, and a no. I believe that technique matters. But the technique probably doesn't. So, you must start with a foundation of a sound and anastomic construction physically. Again, times zero. You're making it. This is when it starts, okay. The Masters series indicates that they're unanimous about this. They fully believe that the surgeon has the power to do this. Well, they believe that good surgeons do well and bad surgeons don't, so to speak, okay. Now, the manner of placement, the type, and the caliber of the stitches probably doesn't matter. There's actually been very little studied on this. But I'll also temper that by saying don't use catgut. As they figured out at the beginning. Because of the enzymatic degradation issues. But other than that, what caliber you use and what type, that's not really going to make an anastamosis keep together better than another one. But how well you place them and tie your sutures probably does matter. And the bigger risk you have with the gland, it's the most important thing. The pancreas requires a great deal of respect. You know, one of the things I try to teach my residents is you have to have fine motor skill on this. There's a very real tendency when you're tying these fine sutures to bob up and down with your hands. And you can just see the the pole of the suture pulling up and ripping against it. You can't do that on a fragile gland. Same thing on, you know, like tying a portal vein so to speak. So we all know that you got to respect the tissue. The technique papers, they're out there a dime a dozen in the literature. And so many have been scuttled in the review stage because they're not good. They're generally poorly designed and underpowered. It's usually one surgeons idiosyncratic technique. It's usually reviewed retrospectively and has a limited end where they're looking at like 50 cases and trying to tell you what a fistula rate is, that has changed in that case. That's ridiculous. No study accounts for all the moving parts I've mentioned earlier. It's generally about one feature of the anastomosis in isolation alone. The randomized controlled trials cannot account for these variations, since randomization is to one facet or another. And furthermore, virtually none have been risk adjusted, say, for the recent Verona's study in JAMA surgery on high-risk glands, and stent use. So let me emphasize some emerging evidence by Max Trudeau in the Annals of Surgery last year, about the importance of limiting blood loss. There's a reason it is a signature element, the official risk score. You can decrease rates by up to 20% overall, and 50% in the high-risk zone if you knock down the FRS points attributed to blood loss; the three points of that scale. If you were able to eliminate that down and get your blood loss under 400. Hypothetically in theory, you'd be knocking down your fistula rates. And secondly, there seems to be potentiation of vulnerable, or what we call charged up glands. Those being soft glands with the small ducts. When you add blood loss on top of that, you get worse outcomes because of it. And you can even get fistulas in a protected gland. They will leak when you have the setting of considerable blood loss. So, a lot of our work recently has gotten into that, as one of the main influencers at the time of your anastomotic construction.
Chad Ball 47:08
Beautifully summarized. You know, it makes me think of a couple of papers that I was lucky enough to be involved in that sort of highlight your comments. The first was a review that John Cameron had asked Tom Howard, you know, the great Tom Howard that I think is a mentor, both clinically and non clinically, to you and I, to write about pancreatic anastomosis. I did that as a fellow. I went back and I read just over 1000 technical reconstruction papers going back, as you know, over 100 years, and what became very evident very quickly was that you're right. The specific technique didn't matter. But the attention to detail, the technical nuance, the foundational surgical principles, I think that we try and teach folks that rotate onto our service at the chief resident level, as well as our fellows, of course, before they move upto practice are critical. You know, using the curve of the needle, just as one example. Critical. And I also remember, you know, Henry Pitt and I published NHPB, a paper using the initial sort of round of NSQIP data on blood loss and Whipple procedures. And I remember the experience of presenting that at the International... Yeah. And it was funny, because you asked a great question. But my sense in talking to people after that presentation was that a lot of people hadn't really bought into the idea that blood loss was relevant or significant at that point. And it's amazing to see how you and your group have taken that to where it is today. Really emphasizing that that initial signal was in fact, correct. Like, it's an amazing voyage for sure. Yeah. And it makes sense, right? It makes sense biologically, and it makes sense technically.
Chuck Vollmer 48:56
We've been criticized a little bit about that in some of the reviews of our work. Because people say that, of course, every surgeon has that as a tenant - that they don't want to lose blood. That it's sort of naturally built into us. You know, no surgeon is out there bloodletting basically. That's true. But very few, I think, go to the level of actively trying to prevent blood loss and do the things necessary to minimize it. With the way they dissect, the way they approach things, etc.
Chad Ball 49:36
Obviously, I'm biased, but I couldn't agree more. And you know, the technical part of it is interesting to really think of at a 30,000 foot level. In Calgary, and I think probably in a lot of places, we talk a lot about with the residents, you know, if you're on a colorectal rotation or you're in a general surgery rotation and you're sewing bowel to bowel, that's sort of a soft, mobile flexible structure to another soft mobile flexible structure. That is technically, motor memory wise mechanically very different than sewing a flexible structure to a relatively fixed structure. So, bowel to pancreas, bowel to bile duct, bowel to liver. Those are such different skill sets that you really don't learn in a general surgery residency nor do you really need. And I think those foundational, almost how do you sew soft things like cardiac muscle or like pancreas - really do play into the underlying message of what you're talking about. If we move on a little bit, I wanted you to just briefly touch on the absolute dizzying myriad of mitigation strategies beyond what we've talked about, in terms of reducing pancreatic fistulas. Whether that's pharmacologically or, you know, ERAS wise or drainage. Any of those topics. What's your overall summary of the bells and whistles, so to speak?
Chuck Vollmer 50:58
Yeah. So in general, our work through last decade, looking at these with risk adjusted analyses, finally, has tempered the enthusiasm for the bells and whistles. And in my career, I have stripped these things down for sure. These were shiny objects when I was a fellow and a resident, and ooh yeah look at all the things you can do. But I'll quickly summarize our findings of over about 10 papers or so. First and foremost, there's an incredible variation across the world in the application of these strategies. Matt McMillan's HPB paper was a survey of practice around the world really defines what people are doing and why and it has regional variation. This is probably propagated more by local habits and training paradigms and influences, rather than the best evidence available in the literature. Sometimes it's about where the papers are derived from. There seems to be regional proclivities to doing strategies based on where the strategy has been studied the most. And a lot of times, I think your habits are basically by what the professor told you to do when you trained. So I'd like to introduce to you some thoughts that are a little bit more ubiquitous, rather than than what you learned in your fellowship. So, in general, the first and foremost thing is, is PG versus PJ. It's controversial. The idea would be that pancreatic gastrostomy would be a protective thing in general. But the literature absolutely over time, study through RCTs, etc, certainly doesn't show that PG is better. Okay. So it's barely applied actually internationally. And our work at the risk adjusted level would actually tend to suggest the PG does worse, particularly in the higher risk cases that you think would do better. There's been a lot of energy about PG, you know, over time for something that's really not as relevant in real day practice is what I'm trying to say. Dunking and invaginating is not superior to ducting the Kozel. There's competing RCTs on this. Our work has shown that even in the trickiest glandular scenarios, a small ducts and soft glands, there's no improvement in doing a dunking invaginating over a duct mucosa. There are times for doing them. And I'll talk about that later. But this is not the best way necessarily, right. We've found that selective drain placement probably is safe and equivalent to using drains in every case. More drains are not better. So we have a new paper in review right now that shows that putting two versus one does not improve outcomes. And the drain type that you use is not influential. Whether it be a closed suction or gravity type of thing. We're very strong on indicating that internal stents are not good. They're generally detrimental. They are not valuable in decreasing fistula rates, and they can have other collateral problems associated with them. In terms of external stents, there's probably a limited value to them. It's certainly not useful across all risk zones. You can understand putting an external stent in a nine-millimeter duct that's an FRS zero is not going to help you in any way, shape or form. Our work has shown that you need to actually look at the aggregate risk profile, not just one risk factor in isolation like small duct or soft gland. And our work has shown that the high-risk group is the area that derives value from external stents, whereas not so much on the rest of the risk profile. A very big point that I'm vocal about, and it's very controversial, is the avoidance of somatostatin analogs. By using the FRS, we were actually able to do a first-time risk adjusted analysis of this, and it actually shows that octreotide shows more harm than good. The odds ratio for the fistula development is constantly between two and four when octreotide is used. And that has been consistent as we've grown our series from 1000 to 8000 cases. I think the use of sealants are useless. It's generally a hail mary in the case. I did it a couple times early in my career, they broke down anyway. They're just not good. They're not the sort of strength of glue that you think that they are. For an enzymatically charged anastomosis. There's an idea of using roux limbs to divest the pancreaticobiliary secretions. There's really no substantial data that would show that is an improvement or valuable. And then finally, I'd say patches are anecdotal. They may have some value. They're often applied to prevent gastroduodenal artery stump bleeding. It's very common in the eastern hemisphere. But there's really nothing that says wrapping a anastomosis in omentum or something like that is going to protect you.
Chad Ball 57:00
And that's a beautiful summary. I will push back a little bit about the internal pancreatic duct stance and just sort of nuance that out a little bit and say that, in that one to two mil duct that you're that you're sewing in, it is a helpful mechanical tool for the actual hookup. Whether you leave it there or not, I think more is more reflective of what you're referring to. Leaving it in place is certainly not helpful, and it's been shown, as you and others have pointed out. But it can be a mechanical help, just to use as a bit of a deep guide. There's no doubt. Let me make you take us into the operating room then and ask you, you know, you're doing a whipple today. You're all charged up, you're ready to go, your team's electric, so to speak. How do you actually integrate the FRS into a practical informative decision making in the OR?
Chuck Vollmer 57:54
Sure. So yes, we use it in the operating room. For me, it's on the top of my head. I've lived this for a decade. So it's easy. And that's because it's easy to use. I mean, anyone can get to that point. But for my partners and such, we put a cheat sheet up on the wall. So the FRS scale thing is there. And look out in the future, because our next endeavor is we are creating a web based and app device app coming later this year that you can use right at your fingertips to figure this out down the line. So it's there, you know, in our face in the operating room to calculate and then adapt to. In every operative note, I put a paragraph. I say, you know, we put the pancreas together in this fashion, blah, blah, blah. And then it is: today's specifications for the pancreas were a soft gland, a duct that's two millimeters in size, pancreatic neuroendocrine tumor as the diagnosis and a blood loss of 400 cc's. Therefore, the fistula risk score is seven. And this makes it a high-risk case. Accordingly, we applied the following mitigation strategies. Boom, boom, boom, boom, boom. So that's there for research purposes. I can look back at every case and say, here's what I did. And we knew where the state of the situation was at the point of the anastomosis. Furthermore, we've developed the basic playbook in some of our papers that are applicable to the relative specificity you may wish to key on. It could be the FRS number, it could be the FRS zone that the case is in. Or it could be the distinct scenario. And from those, we can play out and tell you best mitigation strategies for that scenario available.
Ameer Farooq 1:00:00
Dr. Vollmer, I want to circle back here to something that you were talking about earlier. And that is that whole idea of very high-risk situations. You talked about low risk and moderate risk, and then very high risk situations. Can you first talk a little bit about what those high-risk situations are? I think you've alluded to them in terms of the soft gland and small duct, but can you elucidate that a little bit more? And then how do you think those types of situations should be approached?
Chuck Vollmer 1:00:31
Yeah, so these, you know, are particularly harrowing, even to the most seasoned pancreatic surgeons. These can now be explicitly identified. Through using the fistula risk score, there are 20 distinct scenarios. So that's 1/4 of all the combinations possible. But they account for just 10% of all the cases in terms of frequency. So each is rare, but fact. Thus, they are high stakes situations. Essentially, we've been able to identify an optimal mitigation bundle, as we put it, that includes the following combination: pancreatic jejunostomy, rather than PG. Stent use, external stent that would be. Placement of a drain because of the severe risk. And obviation or not using octreotide or semana statten agents. We could show that if you took it from using all the counter arguments to those, it would be like a 30 to 50% chance of leaking, if you use this particular bundle, it takes it down to 13%, even in the high-risk zone. Okay. So that's about a third of an impact for you, or two thirds impact. You need to have a multifaceted toolkit for anastomotic creation. You need to know the gambit of options. And this is only coming really upon me in the last 10 years of my career. I'm now 20 years into my career. Okay, so after riding the horse for quite a while, now I'm sort of seeing the understanding. I've seen enough cases to understand the value of this. You need to try out these different anastomotic approaches to the PJ, not just the traditional Kotel Warren. Not just the balloon guard. You got to be able to do both, you got to be able to do the way Whipple did initially - just putting a single layer together. You need to be able to dunk sometimes. Sometimes two layers, sometimes one. You have to try them out. Too often people are paralyzed with fear of something that we haven't done yet. And when you get humming in your career and you're on the horse, you just don't want to get off of something that's a little uncomfortable. You need to do that as you mature in your pancreatic surgical career. Because there are going to be times when a certain morphology of the gland demands a certain attachment approach. I'm getting more adaptable, the older I get with that.
Ameer Farooq 1:03:15
I'm clearly listening to you and Dr. Ball talk about this. It's obvious to me that this is not for the occasional dabbler in Whipple surgery. This is something that you need to be immersed in, day in and day out, as you said. There's so many moving parts and so many factors that you really have to take into account. So, to me, it seems obvious that that volume is going to have an impact on outcome. But can you enlighten us a little bit on the data around surgical experience and fistula development? And what that data shows?
Chuck Vollmer 1:03:50
Yeah, sure. This is our latest work actually. It was just published in surgery about a month ago by Fabio Casciani from Verona. So essentially, we focused in on the high-risk cases, and there was something like 850 of these in our series, thinking that this is you know, where you need to have the best proficiency, right? And it truly did delineate an experience factor. Those surgeons who had done over 400 case whipples, or had 20 years’ experience or more, but did better. And I think the odds ratio was like point 0.5 too, so you're doing twice as well if you have that career profile. And what we also found about this is that these surgeons tend to use better mitigation strategy profiles. So there's something about that. Not only do they have a skill set that's more refined, maybe, but also, they tend to use the better package. It's their concept; their construct for it. We're actually going to have forthcoming data that shows this process correlates also to the full spectrum of risk. So that experience is...this paper shows the most... discrete paper to show that experience matters in pancreaticoduodenectomy for not just fistula outcomes, but all outcomes that you care about. And finally, I'd say this. You know, what's the take home from this? It's that, less experienced surgeons starting their career not quite to that glorious 400 case level, may benefit from relying on their partners, or getting true intra operative collaboration. You know, there's papers out there. There's places in the world where there are two surgeon whipples. People coming in just to do the reconstruction aspects. Sort of like being called from the bullpen in baseball. So that idea is out there. And also you can look at some of this work if you're younger an think about adopting the best practices that we've been able to delineate.
Chad Ball 1:06:14
I love the fact that you just bought a sports analogy into that. I think it's quite out. You know, we're getting close to the end here, Chuck, and you're provided us with such an amazing, comprehensive masterclass. But I do want to take a little bit of a sidebar here and make you talk about your Annals of Surgery paper: a commentary called "Of Fistula and Football" and I don't know if I'm allowed to say this, but you know, I was lucky enough and obviously, because of my bias to review that for the Annals of Surgery. And it's one of my favorite pieces I've ever read. Could you walk us through that analogy between pancreatic surgery and fistula in particular and American, NFL football?
Chuck Vollmer 1:06:56
Yeah, well, thanks Chad for accepting it. I didn't know that. But that's great. Yeah, I really liked this paper. It basically provides a philosophical analogy to a competitive sport. It basically shows an uncanny association with the kicking game in American football. In other words, fistula rates correlate to field goal rates in the NFL, and it's identical. The numbers are identical across the zones of risk assumption. The paper also emphasizes situational adaptation. You got to know the field, the weather, the conditions, your adversaries, traits. You have to know the risk assumption calculus, and we make a point of emphasizing what Bill Belichick does with us. And in terms of adapting his game plan every game to what he's facing. So, I feel that's what you have to do in the operating room for this problem. You know, it's about the hash, where are the hash marks on the field, the wind conditions, how sloppy is your plant foot, etc. You know, the same thing happens for what you can size up in your field, the operation. To make it pretty simple, you know, low risk situations should be automatic. So, point after attempt in football is like a 99% chance of being made. Negligible risk in pancreas surgery is a 99 plus percent chance of not leaking, etc. For moderate risk, you get into the concept of using accuracy. You're going to have to be more precise with what you do in those low-risk situations. You know, it's like sort of shooting on a goal without a goalie there - you really can't miss, right? You can go be blindfolded and probably hit the goal. But moderate risk, you're going to actually have to have a skill set of accuracy. And then high-risk kind of is, do you actually have the leg to make a 50-yard field goal? Do you have the skill level for that? And that's probably where we get into this, what we just talked about with the experience thing. What the paper does, is it underscores the impact of specialization, to the improvement of outcomes both in the football level with specialized kickers practicing every day, day after day what they do, and only that, and for us, the specialization of pancreatic surgeons alone.
Chad Ball 1:09:40
Yeah, that's a must read for anyone who's interested in this topic, there's no doubt. Chuck, before we end, maybe a bit of a discussion on post-operative period care and maybe a summary. I was wondering if you could just very quickly, you know, again, despite us sort of dancing around it and sprinkling this conversation with the evidence of it. I wonder if you could talk to us and summarize the FRS catalogue paper that was published last year in Annals? Because it really is sort of a penultimate, quite beautiful summary of a lot of what we've talked about.
Chuck Vollmer 1:10:14
Yeah, thanks a lot. It's probably the paper I'm most proud of, because it is. It's the pinnacle of all the work that went into it to this point. So, you know, I consider this to be precision medicine for the surgeon. I mean, let's not just leave this to the chemotherapy world. You want to attack every case, for the variables that are unique to that case, or that patient, okay? So, what we found from this is that the frequency of occurrence of these various scenarios is inversely related to severity. So, you're actually more likely to encounter low risk cases in your practice, then you are high risk. And in fact, the most common scenario is FRS zero. That's the one that can't leak basically. It's a 0.5% chance of a leak. That happens 10% of all the cases. It's the single highest frequency scenario. So, you're more likely on any given day to go in the operating room and encounter a case that can't leak and won't be a problem than you are otherwise. So, what we also got from that paper is that we're able to sort of hone down into the 10 most impactful scenarios. This would be a combination of both the frequency, and the severity of that particular risk combination. These 10 most impactful groups account for 36% of the frequency of cases, and half of all the fistulas. And we would argue that if you want to make way on improving this problem, you got to go figure out how to deal with those situations. Because they will have the biggest impact on changing your numbers. Ultimately, this gets to the balance of standardization versus specialization in surgery. Or uniqueness, I should say. And I think the master’s paper will say that there is a very big tension in our field between the people who say, you've got to just figure out what you do, and do it repetitively and do it all the time that way, and that's what makes you excellent and a master; versus the others who would say there's nuance to things. And a real expert is going to be able to understand, size things up and be adaptable for any given case with a full toolset to be used. I would be on that second...among the second group of that. But there's a big tension in the pancreas surgery world about that question.
Ameer Farooq 1:13:00
I love that description of that tension. And it's really something that we're I think, in particular in the HPB world, obviously, but surgeons everywhere are struggling with. So, I really love that description of that tension. And talking about variation or standardization. One of the fun things to do is to go on Twitter and get HPV surgeons talking about how they manage patients postoperatively. When do they check drain amylase, all these kinds of things. Can you talk to us a bit about post-operative approaches? What works and what doesn't?
Chuck Vollmer 1:13:32
Yeah, I'll be brief because I know we're running a little long here. But that master’s paper really dives into this heavily. And there's so much rich information about it regarding how people use the amylase thing. But in general, a couple of thoughts. Early drain removal within three to four days is valuable. This is an RCT based proof. The Baussi paper from Verona was really important in this, but it holds up. It's hard to explain this mechanistically however, you know? Why is it that if you take a drain out earlier, it's better. But if you leave it longer, it's worse. But the RCT really shows that it's true. Drain amylase assessment, you should consider to be the odometer of the problem. It helps you understand how the rides going after the operation. As far as using that, there's a tension here also between using positive predictive values and negative predictive values when you're using the amylase concept. A negative predictive value is going to give you the certainty that you're not going to leak. And to me, that's really the more important zone. So far, our data has been more centered on positive predictive value, saying that if you had a level, it would be indicative that the league is going to happen. But in terms of determining if you're going to take a drain out or not, you're going to want to know with good certainty if you're not going to leak if you do that. So I would say that the the push is going towards a negative predictive value concept. We've melded this into a dynamic drain management process. This includes the FRS principle in the operating room. Preventing drain placement for a full third of the patients for which it won't help. And then using stepwise drain fluid and analysis thereafter. And we've pushed this along in a couple of papers most recently in the Journal of American College of Surgeons last year. Our most recent thoughts on this is about the kinetics of the drain management afterwards. And this has just been accepted in surgery, it'll be published in the next month or so. Where we're actually trying to show that it's a story and evolution afterwards. You can't look at just one day of drain amylase and know where you stand. It's gonna be very helpful for you to know if that number is going up, down or in between. And we have a nice analysis of what those kinetics mean. In other words, use your real time data to your value. The Masters series also values the characteristics of drain output more than volume. What does it look like drives the decision making rather than the amount of fluid coming out. And I will tell you also that the masters are generally cautious regarding drain management. They think of it as a security blanket, for the most part. Another thing I would again, emphasize from my belief on this is: avoid somatostatin analogues in the post-operative period, as we've intimated before. And I'll tell you that if you want to use that for therapeutics, you're usually using it too late, and I really don't think there's really strong data out there that says putting octreotide on to dry up a fistula really works. Finally, I'll say nutrition support in the post-operative period has very little proven value yet. But it could certainly be explored better.
Ameer Farooq 1:17:06
If you have a real and clinically impactful pancreatic leak, what do you do in that post-operative setting?
Chuck Vollmer 1:17:13
This gets down to you know, how do you treat patients basically. So I think that the things that come through is you need to respect this entirely. So, you need to not be cavalier with these patients. Manage them to the hilt. Transfer them to the ICU, higher acuity settings, when a patient starts to fall off the cliff. Don't waste hours on that. The masters are very strong about that. It's almost unanimous that you have to put these people in the ICU. What's really come around and I think we've taken a big lead from necrotizing, pancreatitis care, is that the percutaneous approaches are preferred. And that you need to maximize your drainage process to keep people from getting very ill or dying, so to speak. This is the difference between what I started out with, with the killing fields. In those cases, those patients had open bellies, you know, all the humors were coming out because the multiple reoperations, etc. Now, a patient is spared all that because of percutaneous aspects. Not all collections can be drained. And you need to know that. And nor do all collections need to be drained. You don't have to go into overdrive with this, if a patient isn't that sick. Antibiotics alone may suffice in certain scenarios, just like we learned in necrotizing pancreatitis. My biggest take home for this is: let the body catch up to the healing. Almost all the time, the body will seal and heal a fistula, almost all the time. It just takes time. On the other hand, there's a balance. You don't want to be keeping drains in for two to three months. When they do, they fistulize externally. So, there's a good zone there. But almost always when you remove your drains, that body is going to seal it up and patch it up and you're not going to have intra-abdominal leaking. And I think the last point here is what do you do when that patient is in extremis? What we call the Grade C leak. When it's basically a full dehiscence of the anastomosis. And you can see this radiographically and your patient is tanking. It's a tough scenario. And it's not well optimized in literature because it's infrequent. I mean, there's no way we're ever going to have a study that's going to optimize the best approach. But the first and foremost concept is avoiding a reconstruction attempt in that setting - in the septic abdomen like that. You're going to fail. It failed the first time, it's no better when you go back in. The second thing is, what could you do otherwise? Actually, a completion pancreatectomy is favored by most of the masters at 30% of the time. However, an almost equivalent number fully avoid doing such a thing. And with its attendant physiologic downfall, you also have to understand that doing a completion pancreatectomy can harbor as high as a 50% mortality rate from that reoperation. The other alternatives for you are wide drainage, or stenting processes: either a bridge stent approach that we've popularized into the bowel, or just a pure external Wirsung ostomy, Wirsung ostomy. Drainage externally and live to fight another day on that.
Ameer Farooq 1:20:57
You’ve been listening to Cold Steel, the official podcast of the Canadian Journal of Surgery. If you’ve liked what you’ve been listening to, please leave us a review on iTunes. We’d love to hear your comments and feedback. So, feel free to email us at [email protected], or connect with us on Twitter @CanJSurg. Thanks again.