Podcast Episode E61: Masterclass with Michael D’Angelica on Colorectal Liver Metastases

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Chad Ball  00:12

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, whether 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  01:13

Dr. Michael D’Angelica is a surgical oncologist and hepatobiliary surgeon at Memorial Sloan Kettering Cancer Center. He is world renowned for both his research and clinical expertise in the treatment of colorectal liver metastases. We got to pick his brain on this episode for his approach to colorectal liver Mets, as well as some of his broader advice for prospective fellows, and his experience living in New York through the COVID-19 pandemic. Dr. D’Angelica, thank you so much for joining us on Cold Steel. It’s an absolute pleasure to have you on. Can you tell us a little bit about yourself and where you grew up and your training pathway?

Michael D’Angelica  01:47

Sure. I spent most of my life in the New York area, certainly most of my life in the northeast United States. Actually, believe it or not, I was born in California. But at the ripe age of 15 months, my parents who had briefly gone out to California, moved back to New York, where they were originally from, and they grew up in New York area really just outside of New York City. I got away to go to school in Boston and trained in Connecticut and did my general surgery at the University of Connecticut. And I would say that probably what impacted my career was doing a research fellowship during my residency at Memorial Sloan Kettering, which really led to my career, to be honest, it sort of got me that fellowship at Memorial and ultimately being hired there and sort of that probably had the biggest impact on becoming a surgical oncologist and an hepatobiliary surgeon within that field. Yeah, no, I think I’m a New Yorker to the core. I live in New Jersey now. And my parents thought that was sort of similar to moving to Alabama. But that’s sort the New York feel about things. But I’ve lived in New York City and that area, for most of my life.

Chad Ball  03:06

That’s interesting. Did you always sort of have the assumption that you would end up working in the Greater New York area? Or were you kind of open to wherever life took ya?

Michael D’Angelica  03:16

I was totally open to wherever life took me. Just, it all sometimes looks like a planed thing. But it really isn’t. It’s, I could have easily ended up training somewhere else. I would say life is just full of twists and turns. And I think the people who tell you they’ve got it all planned are not really telling you the whole story. I think you come off, like, oh, this guy’s from New York. And this is his only thing. But it was totally random. It was totally just the way things felt. Never, never, that was never the plan, necessarily. The plan was be a doctor, be a surgeon, be a surgical oncologist then be a hepatobiliary surgeon and then try to make a difference. That was really the plan, not where you do it.

Chad Ball  04:05

So interesting. You know, your group, obviously at Memorial Sloan Kettering is not only world renowned, but you know, and I’m biased I get it. But I would certainly make the argument you guys have the greatest core group? Maybe in North America? I mean, you seem from the outside to get along so well. You guys are so productive. You seem very cohesive, although certainly every group has speed bumps, I get it. But how does the dynamic in that in that group work? And honestly, like, how great is it to be part of it?

Michael D’Angelica  04:38

Yeah, that’s a good question Chad. I’m really glad that we come off that way. And I think, of course, like you say there are bumps but I think that’s part of the success. You know, it’s a group who sort of checks their ego at the door. There’s no lack of ego in our group but we work well together. And I think like everything, it came from the top, you know, when Leslie Blumgart really started the group he, I don’t know how exactly he did it, but I think his field was inclusivity. And you know, he’d invite you down to the OR and say, hey help me with this, or “What do you think of that? And then he’d bring you to his clinic, when you were first starting and say, “Hey, you take care of these cases for me to help develop your practice.” And he sort of led the way that way. And I think that set the tone from the beginning, and it’s sort of continued since then. I also think we’re able to work in a system where there’s, quote, unquote, “plenty to go around”. There’s lots of resources, there’s a very high volume of patients, and that allows, I think there’s less competition among people and that allows for it. So I think it’s the hospital itself, the leadership and I guess I have to give credit to the people that I’ve worked with. And the group has evolved that I’ve worked with over the last 18 years. When I first started, it was Blumgart, Fung, John Egan, DeMatteo. And, you know, John Egan out of that group is the only one left. So it’s a younger group of people now, but it’s, I think the spirit is the same and it’s an amazing place to work. And I would be remiss not to give credit to the group and to the system that I work in that the, for some of the things that we’ve accomplished,

Ameer Farooq  06:28

Dr. D’Angelica, you’re known for many, many things, but I think colorectal liver metastasis is something you’ve clearly had a huge passion for. You kind of talked about this in your training pathway that you kind of had this – that you’re gonna become a surgical oncologist and HPB surgeon and then correct liver metastases seems to be a part of that whole evolution. Why colorectal liver metastases? What prompted that passion in that topic?

Michael D’Angelica  06:53

Yeah, well, you know again, I could claim it was all some big plan, but that would be dishonest. When I was training, you know, HPB surgery was not such a common or popular specialty, really. I was going to be a surgical oncologist, quote, unquote, and do all the big cancer operations in the belly. And that drove me. And I always did love operating in the upper abdomen. And I always was fascinated by liver metastases and the surgical impact of them. But I never really knew that I would be able to make a career out of it until I was hired onto a service that sort of gave me that opportunity. And I would say, you know, it’s interesting when I first started, believe it or not, I was sort of behind some pretty famous people. And really, what I started studying in the very beginning of my career was minimally invasive surgery. Believe it or not, I was one of the few people who did minimally invasive surgery back then. And I studied ablation, which was a kind of new technique at the time. And then things shifted in the service. And I have to give credit to Blumgart, and actually to Nancy Kemeny, and sort of practices developed, an interest developed, and then you start studying something and I think two things got my interest about colorectal cancer and the liver. One was the fascinating biologic observation that removing a metastasis can actually cure a patient, which goes against everything we understand about cancer. And that’s without chemotherapy. And the second thing that was interesting at the time, while everybody was getting away from intra-arterial to chemotherapy, Nancy Kemeny – and I give her so much credit for this – persisted and continued to study it. And she was so giving and gracious to me and allowed me to be part of her trials and help, you know, we develop trials together. And so it just sort of came together for something that I really enjoyed and was passionate about, and then was given the opportunity to study in terms of studying the natural history and developing clinical trials and translational work. And I don’t know, sometimes I feel like it’s kind of lucky. But I also think luck comes from taking advantage of opportunities. And I think it’s a combination of those two that happened. But it is a fascinating surgical thing to think that a disease in which patients were sent home to die 30 years ago, is now potentially curable with surgery and some other adjuvant therapies. To me, that’s the most fascinating thing that I get to do every day.

Chad Ball  09:34

That’s really well said, Mike. You know, our listeners – big proportion of them anyway – are general surgeons from across Canada and Australia and really the world. And, you know, I’m hopeful that maybe we can take a moment and delve into colorectal liver metastases a little bit more deeply. Because it certainly applies to all of us whether you work in a community setting or an academic setting, low volume, high volume, whatever that means. So I was wondering if you could sort of frame the entire topic at a 30,000 foot level for our listeners. In other words, how common is having colorectal liver metastases? And what does that landscape look like at the very broadest level?

Michael D’Angelica  10:15

Yeah, it’s a great question. You know, obviously, colorectal cancer in the Western world and now epidemiologically growing in the eastern world, probably as, you know, dietary habits change, it’s a very common disease. Probably upwards of 50%, although I think that’s an overestimation in probably the United States or North America, it’s probably somewhere between 30 to 50% of patients with colorectal cancer will develop liver metastases. And yes, I think the 30,000 foot look is that: most of those people are treated with systemic chemotherapy and non-surgical interventions. But I think the key thing that everybody, whether you’re a surgeon, a medical oncologist, or just a primary care doc, or anybody taking care of patients, I’m sure understands that there’s a subset of those patients who really are not quote unquote, stage four cancer that are only treated with palliative chemotherapy, that are potentially curable with surgery and other ongoing treatments. And I think the really important point is to look for the patients who really are those candidates, and get them to the right person to really think a little bit about it. And I still see patients today, young, healthy people who were told, you know, with very resectable liver metastases, who are told: “you have chemo and you have two years to live and that’s it”, and then you look at them going, “no, no, wow, you have resectable disease, you know, with various approaches, we have a chance to cure you. We have certainly a chance to provide long term survival for you, perhaps with chronic treatment, but even with less than that”. And so I think the really critical point is it’s a common disease. But understand there’s a subset of it that’s potentially curable, and get them to the right people. And I think it’s important to educate yourself a little bit about that, so that you have a sense of who those people are.

Chad Ball  12:16

Yeah, you know, I’m glad you said that. The truth is, I think if you have a high enough volume liver practice, we all see that on a disappointingly regular basis. And that’s not to disparage any of these other physicians or groups that you mentioned, but I couldn’t agree more. It’s so important to try and get these patients, you know, to the sites and the multidisciplinary groups that can make those decisions and try and cure them. And I think that’s another important point, too. And, you know, you’re well known for saying this, and you’re exactly right, that, although the liver surgeon may be the sequencer and the ultimate decision maker, this is a real team sport. You know, what we do in a vacuum, we’re in a silo, we need our medical oncology colleagues, whether it’s, you know, Nancy, or whether it’s a run of the mill, medical oncologist or radiation oncologist or palliative care. It’s a big group and that’s what centers like yours and many of the deliver centers across Canada are built to do, hey? Is to try and look after these people.  I’m curious, in particular, when a patient walks in, and you’re talking to them about that concept, how do you deliver that news? And how do you frame that? You know, I assume most people who get to you, know that they have liver Mets, and they’re coming to a liver surgeon. But how do you maybe put them at ease or frame the whole voyage? Which as we know, can be a very long one?

Michael D’Angelica  13:52

Yeah, it is interesting. I think some people come, this sort of highly educated group comes sort of knowing, in a way, what’s going to be talked about. But there’s a group of people who still show up, and they’re not quite sure why they’re there. You know, they’re like, oncologist told me to come see you. And that was the level of discussion. Not even really sure what I would say to them. I think the discussion, actually, it’s a great point, Chad. It’s not really talked about, how you should talk to patients about this. It sort of depends on the stage of the disease. But if you take the patients with straightforward resectable colorectal METS, I sort of, I’m not a huge fan of giving people detailed statistics. I’m always telling people like I could give you the statistics, but you know, to think that you’re going to be the mean, or the median, or the average is not accurate. More important that we give you the range of outcomes here. And so I actually try to simplify it as best I can, in terms of you know, for straightforward resectable disease, I say there’s three groups. And I’ll start with the bad. The bad is we do this operation and whatever other treatment we give you around the time of surgery, and if it doesn’t go well, you recover quickly and you end up on chemotherapy. And I think it’s super important that you talk about the bad. And then I say, well, let’s talk about the really good. The really good is: we do this, and it never comes back. And you’re cured. And that’s a reality, that is not a made up outcome. That’s a real outcome. And then I say, well, there’s also a sort of third group that I think also is a good one, and it’s that it comes back, but it’s still manageable. And you may not be cured, but you can be managed for many, many years. And I think that’s a particularly relevant outcome for the younger people. And I really do think about this, if you’re 80 years old, you might not be so concerned about that group. But if you’re a 40 year old with young kids, and it’s important that you, I don’t know, see them get married, or see them go to their high school graduation, or whatever it is, getting that extra period of time, even if it is difficult and chronic therapy, may be well worth it to them. And those are the three groups that I kind of put it into. I think there’s a spectrum of staging of the disease where, you know, the outcomes are a little different. But I think for the straightforward resectable one, those are the three ways I think about it.

Chad Ball  16:15

Yeah, I think that’s brilliant. And you know, I probably emulated it from you, but that that’s what I try and do too. And I, you know, I always make the statement, yeah, your “median survival” or this language that we use is only good on a population basis. It has very little relevance to you as the individual, right? I think that’s probably, you know, when you say, we all have friends and family and meet folks every day that say, “my uncle had cancer x, and they told him, he was gonna die in nine months, and he’s alive 29 months later”, well, that’s probably because he was given some median number that had no relevance to his biology.

Michael D’Angelica  16:51

Yeah, my least favorite thing is to hear, “my doctor told me I had a year to live”. That’s crazy. Like there’s a time clock above them that’s gonna go off suddenly in one year. It’s just an insane way to think about biology or medicine.

Ameer Farooq  17:04

Dr. D’Angelica, what’s your approach? You know, like you have this patient, you’ve sort of broken the news to them that they have colorectal MET. How do you approach working these people up? Is there any other you know, specifically imaging or workup that you would do? Or is it usually that, people have already been worked up as much as they need to be by the time they get to you?

Michael D’Angelica  17:27

Yeah, it’s really pretty simple. I mean, I think really what people need is good quality cross sectional imaging. And I think in most of our centers, we probably end up repeating a lot of imaging. Unfortunately, there’s a lot of heterogeneity in how CAT scans or MRIs are done. You know, it comes down to a lot of details. And a lot of people don’t appreciate, you know, how contrast is administered, how much radiation they use for the CAT scan. There’s a sort of trend to giving less radiation, which of course gives you very suboptimal pictures. So I think straightforward, good cross sectional imaging of the chest, abdomen, pelvis. If the primaries are moved or they, you know, if they need a colonoscopy sort of within a year or so of their diagnosis. Of course, if it’s synchronous disease, you have to work with someone who does the colorectal part of the operation to assess the primary tumor. I think that scan has been largely discredited by a randomized trial done out of Toronto, the yield of that is low. I think it’s a helpful problem solving tool, if you see some imaging findings that are concerning, but you’re not sure. So it could be a targeted or selective use of PET. There’s a lot of data now that MRI of the liver with Eovist or hepatobiliary contrast, can better stage the liver. And I think that’s a reasonable thing to do. It’s particularly helpful for patients who’ve been on chemotherapy, or who have a fatty liver. Although I have to say, my anecdotal experience is that it doesn’t change much if you have good imaging to begin with before they start chemotherapy. But I think it’s quite reasonable to use MRI pretty liberally. And that’s really it. I don’t think you need much more than that. I think that’s really the bottom line.

Ameer Farooq  19:17

I think one of the perennial questions that, you know, everyone struggles with, whether you’re studying for your board exams, or if you’re an actual practicing colorectal or HPB surgeon is the timing of chemotherapy versus upfront surgery. Can you talk to us a little bit about that, like what’s your paradigm in terms of the timing and sequencing of various therapies?

Michael D’Angelica  19:46

Yeah, when I talk about that, I think, and I do think the biggest problem is the overuse of chemotherapy, in particular in patients with straightforward resectable disease. And so what I mean by that is limited number of tumors in the liver. No extra hepatic disease as best you can tell on your workup, and an otherwise healthy patient. So you know, the number of tumors is debatable, but let’s say four or less tumors or something like that, because those patients are potentially curable with surgery. And I would say that the chemotherapy, despite the fact that it’s so popular to use doesn’t change the outcome after surgery based on randomised trials. And the chemotherapy beforehand for that actually doesn’t help you select patients. The truth is, in two or three months, 95% of those people will have stable or responsive disease. So to use chemotherapy, which, by the way, has its own set of very serious complications. I mean, neuropathy from oxaliplatin is a real serious problem for patients. So to give a bunch of drugs that won’t really help you select patients very well. That doesn’t necessarily improve survival, or if it does improve survival, it’s by a very small amount. So I’m not a fan of giving chemotherapy. Now the use of chemotherapy in patients with say, higher stage disease, or we’re shrinking the tumors, really helped situation in terms of shrinking tumors. It’s very helpful, you know, so if you can change an operation to a more predictable preserving operation or safer operation with chemo, that’s helpful. So I’m not a huge fan of it, just to give it for the heck of it, because it doesn’t really make a difference. But the other situation is people with more advanced disease. You’ve got 20 tumors in your liver or you have limited extra-hepatic disease, the role of chemo there is much more important so that’s a different situation, where I think more liberal use of chemo. But I’m constantly fighting with people who want to keep giving more and more chemotherapy to people with potentially curable disease with surgery. We know it changes, we know it provides side effects on patients. We know it complicates surgery a bit. Every liver surgeon now is starting to see that “ugly chemo liver”. And so I’m always constantly fighting the overuse of chemotherapy. I guess that’s the best way I would say it.

Ameer Farooq  22:13

Yeah, I think that makes a lot of sense, and is a very good approach. But also, I mean, it underscores again, that every patient’s requires individualized planning and thought, when deciding their treatment sequence in therapy. I was curious, you know, a lot a lot of junior residents and potentially medical students listen to this podcast. Can you define what the difference is between metachronous and synchronous, colorectal liver METs are? And does that kind of change how you think about the workup or planning for their treatment?

Michael D’Angelica  22:53

Yeah. So it’s a great question. I actually think the biggest mistake people make is that they try to look at those two, synchronous and metachronous diseases totally, biologically different situations. They’re probably not, they’re probably all really synchronous disease that just take some time to sort of show itself on scans. I think that  the most practical way to think about it is, synchronous diseases, when you’re diagnosed with colorectal cancer on a schema imaging study, you see metastases at that time. From a biologic point of view, people sort of have divided it. If you find it within one year of diagnosis. And that, I think that’s a helpful way to think about it biologically. But I don’t think it’s a helpful way to think about it practically from a point of view of treatment. The real treatment problems is when you have got a colon tumor or a rectal tumor in place and metastasis at the same time, then it becomes different. I don’t necessarily think it changes the surgery. But it often changes the preoperative therapy, particularly for rectal cancer, because the paradigm rectal cancer, which I think has not really been applied in every hospital, but is coming soon, is probably going to be the use of total neoadjuvant therapy with a significant percentage of patients never needing surgery. So the use of chemo and radiation and prolonged periods of chemotherapy or radiation in rectal cancer complicates the treatment of the liver disease. And I can’t say that I have an answer. But my first question is usually tell me what you need to do for the rectal cancer. And then we’ll sort of work in how we want to manage liver metastases. And that almost always involves some neoadjuvant therapy because that is a well founded idea if you can give chemo and radiation then never need an APR or a low interior resection. That really is a game changer for a lot of people. For colon cancer, I think it’s more straightforward. I think it staves the liver disease. And and if it surgical, I think you do it. But again, I want to say very clearly, I think the idea that synchronous presentation is an absolute bad prognostic factor as a complete misinterpretation of data. Most studies do not show it as a major prognostic factor. And I think you should think about it the same way as if it shows up six months or a year later.

Chad Ball  25:13

That’s so well said, Mike. Thank you. You know, a little bit earlier, you mentioned Dr. Kemeny and sort of very briefly touched on hepatic arterial chemo infusion. For our listeners who may not be familiar with that, could you sort of give us a ballpark technical description as well as when you guys particularly use it and when you don’t?

Michael D’Angelica  25:37

Sure, so hepatic chemotherapy is really a fascinating therapy. It’s based on studies done in the 1950s that show that liver metastases are largely fed by the hepatic artery, whereas the liver has sort of the blood supply. So it gives you a mechanical advantage to deliver a therapeutic to a tumor and spare the normal liver. And the way we give it, we give it with a drug called floxuridine or known as FUDR. And the cool thing about that drug is that it is totally metabolized by the liver. So if you infuse it into the liver, it really is completely taken up by the liver. So you basically have this sort of really cool pharmaco kinetic advantage of giving high dose chemotherapy without physically isolating the liver, just using sort of pharmaco kinetics, and you give it by infusing it into an artery, you’re able to give high dose chemotherapy and isolating it to a single organ. And this is really old stuff. This has been worked out in the 1960s and 70s. It’s really kind of interesting. That what’s old is new again. And in unresectable disease, I mean, the response rate to combinations of hepatic artery and systemic chemotherapy are very, very high. In the first slide, it’s 90, at least 90%. In the second line, it’s 50 to 75%. And if you compare that to systemic therapy, it’s nearly double the response rates for systemic therapy. So for unresectable patients, it’s an extraordinary treatment. And I think the interesting historical thing was in the 1990s, when quote unquote, modern chemotherapy, (which by the way is the longer modern, it’s 20 years old now), came around, a lot of people abandoned hepatic artery chemotherapy, and I have to give credit to Nancy Kemeny. She said, no, let’s not abandon it. Let’s combine it with systemic chemotherapy. And that’s exactly what we’ve done and shown these very high response rates, conversion to resection, and even cure for a group of patients. But the other way to think about it as adjuvant therapy after complete resection, which makes most people very uncomfortable. But if you look at the data, the truth is adjuvant systemic chemo alone does not improve overall survival based on multiple randomized trials, whereas a single trial done in the 1990s, with pump chemotherapy really did show a durable long term progression for each survival advantage to pump chemotherapy, there really has not been a modern trial that’s compared the two again, and we like to say that it’s the only proven adjuvant therapy. And while it’s a bit unpopular to say, from a strict data point of view, that is actually true. In our long term survival, if you give an adjuvant pump chemotherapy, the difference in survival is two years, the cure rate is probably doubled. So that’s where we stand. I would be remiss to not talk about the toxicity of pump chemotherapy. That can cause very serious biliary cirrhosis, that would be a whole long discussion. But there’s definitely a downside to it. So when the fellows asked me, who do we do this in? What’s the indication for pump chemotherapy? I sort of say the presence of colorectal liver metastases. Because the truth is it hasn’t been worked out exactly who among the group is most likely to benefit. It can be unresectable disease, it can be an adjuvant situation where you resected all the disease. So it’s all sort of in there.

Chad Ball  29:13

So that’s so well described.

Michael D’Angelica  29:15

That’s the best way I can do that in five minutes.

Chad Ball  29:18

That’s absolutely, superb. You know, I have sort of two quick questions about it. The truth is that there’s many groups across the country in the world really, that have tried it, but, you know, it’s been a challenge, I think, to make that technique common across the globe. And I’m curious, outside of Dr. Kemeny, and maybe that is the answer. And yourself. Why do you think that is? And then I’m also curious as a second part, has the improvement of systemic chemotherapy changed your view and your use of that over time as well?

Michael D’Angelica  29:57

Yeah so, I think there’s lots of hurdles to using this and to say that it’s an easy treatment or that it’s a treatment free of problems would be be a terrible disservice. It requires some surgical expertise. I think people like to think of the operation as a simple one. It’s not a simple one. I like to tell the fellows it’s a thankless operation. If it goes well, nobody cares. And if there’s a problem, everybody’s going to pay attention. But it’s a real vascular operation. It requires some expertise, for sure. And it certainly requires some ability to handle abnormal arterial anatomy and all the complexity that comes with that. So there’s that surgical bit. There’s definitely complications that people have to understand. You do occasionally get pseudo aneurisms, and you do occasionally get bleeds, and you do occasionally a catheter erode into the duodenum. And most importantly, when you’re infusing it into a liver, and this is actually much more common in the adjuvant setting, you can get very serious biliary complications. You know, and it’s upwards of 5% in the adjuvant setting, that that can happen. And that can be a life threatening complication. It can. It’s very uncommon and very rare that it’s truly life threatening, but it’s a serious problem. And I think it scares people. It’s sort of interesting to me that people have been less tolerable of that. But they’ve sort of tolerated things like bevacizumab that has an associated 1 or 2% rate of bowel perforation, which can be a life threatening complication as well. So every drug has its serious side effects, you know, and oxalicplaten, although it’s not life threatening, some people have lifelong neuropathy, which is no minor thing for people to live with. We’re learning in pancreas cancer, that modified folfirinox in a neoadjuvant setting has a real mortality rate to it, that’s probably similar to a pancreatectomy. So all these drugs have prices to pay. But I just, I have to say when you’ve seen bad biliary cirrhosis, it is a scary thing, and it is something that has to be taken very seriously.

Chad Ball  32:07

That’s interesting. Yeah, there’s no doubt. You know, I wondered if you would do us the favor of very superficially, maybe sort of defining or at least chatting very briefly about, you know, one stage hepatectomy, versus two stage when vein embolization is, and maybe the role or not the role of ALPPS. Not really at the fellowship level, but, you know, again, in maybe just introducing some of these advanced technical approaches that we use to some of the listeners, in an attempt to just sort of open the curtain, so to speak, and encourage some of those referrals.

Michael D’Angelica  32:52

Yeah, it’s a tough one to do in a cursory way, but I think there’s a couple of really important points. Historically, the presence of quote unquote, by bilobar metastases was considered unresectable. And I think some of that still persists a little bit, if it’s on both sides of the liver, you can’t do it. And I think maybe the underlying theme of liver surgery, is leaving enough liver behind that is well perfused and well drained. And that can regenerate and sustain a patient. Because if you overdo liver surgery, and every liver surgeon knows this, you then have to watch a patient slowly succumb to liver failure, which is a horrible thing, and it’s the nightmare of every liver surgeon. But it happens, and it’s lethal, and it’s not always explainable in ways that you would think. So that’s the point. And the techniques that you describe: two stage resections, portal vein embolization are essentially attempts to create a situation where you have enough liver at the end of that operation, whether it’s one or two operations that will sustain a patient. And I think you’d much rather have say, two operations than have a serious risk of liver failure. But I think it gets into real technical detail. And you know, you can’t really get into all of that, but I think that’s the basics of it. And I think the other thing that people have lost track of is that our, you know, liver surgery used to be you take out the right lobe or you take out the left lobe, and that was really why you couldn’t deal with bilobar metastases. We now understand you can sort of carve out small pieces of liver or leave blood vessels behind narrow margins probably don’t make much of a difference. I think it gets into incredibly complicated decision making when you’re deciding whether to do it in one operation or two. But I would say that I often go to the operating room with patients and I say, “We make do this in one, we may do this in two, but I’m going to decide that in the operating room, and you’d much rather me be a bit conservative rather than take a big chance with taking out too much liver. I guess the main point when I think about this, Chad and Amir the when I think about this is probably the thing that has changed this the most is not really what we talked about most of the meeting – the two stage resection, the ALPPS and all that sort of stuff. But rather the use of small wedge resections and intra operative ablations, I still see patients who have a right hepatectomy because they have a single, deep, tiny little tumor, that can easily be ablated with equal efficacy, and this is easy to debate, equal efficacy tool to resection. You know, if you have a one centimeter tumor deep in the liver, not next to any major blood vessel, if you’re reasonably fascicle with interoperative ablation, that will work as well as resection. And to do a right hepatectomy, especially in the context of some complicated by bilobar resection, whether it be one stage or two stage is unjustified in my mind because then suddenly, you’re putting the risk of liver failure there. Even if you are the best surgeon in the world, even if you do that operation perfectly with minimal blood loss and minimal trauma. Taking out that much liver is a huge problem. So I think the use, the creative use of all our tools Chad has made this much safer for patients and sometimes unfortunately it’s two operations. Sometimes it’s ALPPS, sometimes it’s other things. But that’s kind of the way I think about it. I guess I’ll end on ALPPS, which seems to be waning in popularity, the way I actually think about ALPPS is that we haven’t found a single patient at our hospital who needs one. And we’re generally not accused of sort of being you know, non aggressive with patients we’re accused of the opposite usually. And so I’m not sure where exactly fits in. But I think it’s very rarely necessary. Very rarely necessary. With all the techniques we have to sort of optimize a future liver, be it surgical techniques, embolization techniques or two stage resections, we simply haven’t found someone who needs it. So that makes me think that a lot of people are using it unnecessarily.

Ameer Farooq  37:19

That’s Dr. D’Angelica, I’m going to ask you another tough question in the sense that this is again, a huge topic. But again, keeping it sort of at the 30,000 foot level as Dr. Ball loves to say, can you talk to us a little bit about sort of your planning preoperatively? When you’re looking at these colorectal liver metastases? What are the important principles that go into your mind when you’re thinking about a resection? And then a little bit about sort of preoperatively and intra operatively. How you plan your operations. Are there some big things, big principles in your head that stick out to you?  Even like I’m thinking here, keeping the CVP low? Like all these different considerations that might go into your mind as a high volume liver surgeon?

Michael D’Angelica  38:13

Yeah. So I think first and foremost is technical ability to deal with liver surgery, because if you’re going to do creative breakable, sparing operations, or ablation or things like that, you need a few basic techniques. One is yes, to not lose blood in the operating room. Your anesthesiologist is very helpful with low CPP. And if you’re staring at the vena cava, it’s very, very easy to tell them what that CVP is. I think the judicious use of pringle maneuver if necessary. I don’t use it a lot. But I think that’s just from experience. I actually constantly tell my fellows if you need it, if it’s a little bloody, or you can’t see well, just pringle. There’s a million trials that show that it’s not dangerous, but it’s actually, the outcomes are the same. So if you need it, use it. And then basically you need to be able to sort of work your way through this opaque three dimensional organ with the use of ultrasound and with some technique of dissection through liver tissue. And I think you know, basically you have to sit at a CAT scan, see where a tumor is define the anatomic structures near it and have all the techniques to sort of carve out that tumor whether it’s taking out a lobe or taking out a small sub segmental piece of liver and basically desecting through liver without a lot of blood loss down to specific structures, recreate what you see on that cat scan in an operation with those techniques: with ultrasound, with dissection techniques that do not necessarily require sophisticated instrumentation. I largely do it with a Kelly clamp and the right angle or things like that. And if you can do that, then you can probably do any liver operation, you may do it slower than the more experienced surgeon, but you can do it. The other thing I teach fellows is that when you come across, say a vascular structure inside the liver, and you’re unsure of where you are, and anybody thinks that sounds crazy, has not been in a lot of liver surgeries, you can easily get lost inside a liver. And then you can clamp things and use ultrasound. And you know, every once in a while, you’ll be on something and you’ll clamp it and go, “Oh, my God, that’s not exactly where I thought I was, I don’t want to take that” and clamping and looking at ultrasound flow and all those techniques. So you need to do that, first and foremost, you need to develop that technique. And I think having a reasonable volume of surgery is necessary for that. And then I think how you use all that, my goodness, it’s almost sort of endless variation about how you do it. But it comes down to the basic idea of making sure that you preserve enough well perfused liver at the end of the day. And, you know, and I think it would take forever to go through specific examples of where to do a two stage or where to do with single stage or when to use portal vein embolization. And that would take a long time to go through. But I think understanding that there are times in operations where you have to pause and say “am I going to continue?” That’s kind of the way I think about it. Sometimes I’ll carve out a bunch of tumors on the left. And I have to do a substantial operation on the right side of the liver. And I’ll look at my fellow and we’ll say, Okay, let’s stop, let’s look at the liver. Do we think this liver can tolerate much more surgery? Or should we delay this for another day? And I tell all my patients, I’ll be quite conservative about that decision. Because if I overdo it, there can be lethal consequences. And so even if that event is rare, you want to minimize that event to a tiny number, if at all possible. I hope that answered your question. I think there’s a lot of detail that can go into that. That probably requires a year long fellowship, to be quite honest. But those are the basics of it I think.

Chad Ball  42:00

That’s amazing, Mike. You know, the masterclass, you’ve just given us in hepatic resection, we can’t thank you enough for it. I was wondering just before we finished, if you don’t mind, we switch gears a little bit and, you know, pull it back out and ask you as a New York City guy, what it’s been like a little bit if you’re comfortable talking about it with the latest COVID-19 onslaught, particularly in New York. And I would imagine just being a bit of an optimist, maybe delusional optimist by nature that, (myself) that there’s probably been some great things that have come out of it as well, again. I’m curious how that’s going there.

Michael D’Angelica  42:39

Yeah, I’m with you, Chad. I think if you’re an HPB surgeon, and you’re not an optimist, you’re in the wrong field. You have to be an optimist in this world, because you’re always fighting something quite difficult. Yeah, so you know, when COVID hit New York City, it was right at the beginning of everything. I was actually at the HPBA meeting, when things really shut down, and things were really becoming real. And I think at that time, you know, looking back on it, it’s kind of hard to remember how little we understood at that time, and how whether masks would be important, whether social distancing really mattered. It was really a lot of unknown stuff. And I will tell you Chad, I think it’s really important. I think a lot of people see pictures of crowded emergency rooms and incredible situations. And I want to be really clear, everybody, and I work at a cancer hospital. And yes, we had plenty of COVID patients. But we were not like the real heroes, in my view, who were at the city hospitals, at the bigger general hospitals in New York City, who really took the brunt of this, who really put themselves at risk, and I am in awe. And just so respectful of the people who really did the work, many of whom will never, ever be recognized for the things they did places like in Elmhurst, Queens, and parts of Brooklyn that really saw the real badness. And I was a bit sheltered from that. And I want to be super upfront about that. But what happened in New York was we saw the power of an infectious disease just take over in New York. And I have to say, we went through this period of time where we all kind of shut down and said, Okay,  we’re ready to sort of use our hospitals to deal with this. And anytime someone says to me that, you know, I don’t think this is a really dangerous virus. I say, well, look, we had refrigerator trucks in New York City, because the morgue couldn’t keep up with the dead bodies. That usually illustrates quite well the situation and how this can overtake a crowded city like New York. And I think there are many cities that are similarly crowded in parts of New York. And I think I would also point out that the people who suffered in New York were the underrepresented, the minorities and the poor because they live in places where they can’t distance right? And you know, people like me, it’s easy for me to distance. But they can’t because they’re on top of each other in apartment buildings and they suffered the most. And I think we should never, never forget that. But with being the optimist Chad, you know, we came out of it and I am so proud of New Yorkers. I really am. I mean, New Yorkers just stepped up. I don’t walk around New York City and see people sort of not wearing masks, or I think people are just aware. They’ve seen it all, they understand the danger. And I even remember this during 911, when you know, when the towers went down. New Yorkers got in line to donate blood. Sadly, the blood wasn’t necessary, the lines are so long that they had to be turned away. And I think they’ve stepped up again, and just done whatever is necessary. And that’s meant economic troubles, it’s meant that a lot of businesses have collapsed. But New York will rise again. And it already is. And I’m with you, Chad. I’m an eternal optimist. And it’ll come back. The New York right now is not the New York I know, but it’ll come back. And we’ll beat this. And I will just say again, I’m just proud of the New Yorkers who just do the right thing and really fight and do whatever is necessary to help their own. And it’s been really, it’s been quite a trip. I’ve lived through the AIDS crisis. I’ve lived through 911 in New York. And this is this is something that I never imagined could happen. But I guess the people who studied this stuff knew it was coming. Most of us were, sadly a bit naive and didn’t know it was coming. But we’re getting back. And I think we’ll see bits and problems here and there. And hopefully, with a vaccine, we’ll get back completely. But it was quite a time, I’ll tell you that. It was quite a time to live in New York. I remember walking around the avenues of New York with no cars on the street, mid late March. And that’s an eerie thing in New York City. But that’s coming back, we’re getting there.

Ameer Farooq  47:00

That’s a beautiful and moving description of a city that’s seen so much adversity in the last few years. The last few decades. Just to make one more pivot here, you’ve been the Fellowship Director at Ms. K, at a very high volume center. What is your advice for prospective fellows? Whether in terms of like even applying, and then subsequently as a fellow, and I’m being a bit selfish here, given that I’m a fellow right now, what tips and tricks do you have for for applying to a good fellowship? And then getting the most out of it?

Michael D’Angelica  47:42

Yeah, it’s a tricky question. I’m going to start by saying something that maybe is a little controversial. I actually think medical training is, particularly for people who want to go into academics, is kind of broken. I think, you know, we’re graduating fellows now who are closer and closer to 40 years of age. And if you think about it, there are people who’ve gone into other businesses, who have sort of already been working for 20 years. So I don’t know, I think the problem is that people have gotten so good at trying to get into the best fellowships or the best schools or best residencies, that they take take time off here and there. And they take more and more years and years and years of additional stuff to get into fellowships that, you know, by the time they’re done, they’re they’re almost 40 years old. And I don’t know if that’s the right way to do this, I think we have to fix this system. And that’s my backdrop. That’s my frustration. But I’ll answer your question more directly, within the system that we have. First of all, I want to say that working with the fellows at a place like Memorial is truly the greatest privilege of my life. I mean, it is incredible, they are bright. They are our conscience, they constantly challenge us to think. And frankly, they allow us to do the other things we do by simply taking care of our patients by allowing us, by helping us do research, by just being smart people who keep us on our toes all the time. Our fellowship has become, I think, focused on sort of more academics. You know, the people that we take are very accomplished, MD, PhDs, incredible researchers, and I think that you know, but I usually say when people ask me, what I’m looking for in our fellowship, is I’m looking for people who are going to go out and contribute things beyond the care of the patient, not to say that going out and being a surgeon and just caring for patients is a bad thing. I think that’s an awesome thing. But I will, I think what we, the resources we have, are best suited to train people are going to go out and go into academics, or education or even administration to help run programs. And so that’s what we focused on. But I think there are other programs which should be focused on other things based on their strengths, whether its political strengths or academic strengths, because we don’t want to just train a bunch of people who are going to go into academics. That’s that’s not what the world needs, the world needs every kind of surgeon. So how do you get into a good fellowship? Well, I would say, Ameer, your generation has gotten very good at it. I did not think very hard about it in my life. And I guess maybe I was lucky. But I think unfortunately, to get into good fellowships, you need to do some research, you need to publish a little bit to get recognized. But I would say that publishing, excuse the term, publishing “garbage” or publishing a million papers that you don’t know much about is not necessarily going to help you. Good fellowship directors will see through that. But doing meaningful research or meaningful activities, people will see that and they’ll see true passion rather than people who are simply trying to play a game. And so I think being genuine is really important. Because I think people can see through that, and being yourself and also starting to realize what it is you really want to do. I mean, a fellowship at a really academic place is not necessarily the right thing for someone who’s going to not do that with their career. Frankly, it’s a waste of time. I also think that getting people to advocate for you is quite important. It’s very difficult to select residents or select fellows. And getting people to advocate for you, whether that’s a phone call, or a really strong letter, is super helpful. And I think honestly, that’s how life works. Getting people to advocate for you is how you get yourself into positions of power. And when I say power, not power simply for the sake of power, I think of power as… if you’re using power for that, then something’s wrong. But if you’re using power to accomplish things that will really move a field forward, then that’s good use of power. So that’s my best advice. I actually think my best advice is don’t worry about trying to get into the best programs, my advice is get into the programs that will best suit what you want to accomplish in your career. And if that’s to be the best surgeon, find the place that does the most surgery or has the best teachers. If it’s to be a basic science researcher, find a place that will help you do that. If that’s to be a program director, find a place that really has a big education program. And stop worrying about being the guy with the best grades, and focus on what it is you really, really want to do with your career. That’s my best advice.

Ameer Farooq  52:40

That’s fantastic advice. In closing, and this has been a wonderful discussion. And thank you again for giving us your time. If you could go back in time and give yourself advice as a trainee. Now that you’ve you had your long and very successful career, what advice would that be?

Michael D’Angelica  53:03

Cool, my career’s not that long. I learned that a little while ago. Probably a little bit of what I just said to you: it’s to, I think when I was a resident, I was focused on just being the best surgeon I could be. When I was in medical school, I was focused on learning the human body as best I could. And then when I went and did a research fellowship, I was focused on being the best researcher I could be. I think at the time, nobody gave me the advice to really think a lot about what it is you want to accomplish in your career. I don’t want to sound like I didn’t get advice, or I didn’t have mentorship or teachers. But I kind of feel like I figured it out on my own with experimentation. And I wish that I had put more thought into what my strengths were and what I could do, and I’d be a little bit more focused. I think if you looked at my career, it looks like I knew exactly what I wanted to do. But that would not be true. I wasn’t exactly sure. And I wish I had thought more about it and thought more about what my career should be like. I think I sort of fell into certain positions where I met certain people who really changed my life and gave me, whether it was intentional or unintentional, mentorship. I saw examples of things that I wanted to be and that’s really what I focused on. Ultimately, as I move through all this, I just feel that I’m just very fortunate. I fell into situations that gave me opportunities. If i were to give myself some credit, I really took advantage of those opportunities and that was good. But I myself, I would sit down and say really think about what you want to do. Do you want to be a researcher? Do you want to be an academician? Do you want to be a community surgeon? Ultimately, I fell into exactly what I wanted to do, kind of by responding to the stimuli around me. But I could have easily gotten lost in that system. And I think if I was unlucky, I would not be in the position I’m in now, I wouldn’t have had the opportunities to take advantage of certain things. So I wish I was given advice about that, about really thinking about my career. When I went into residency, all I thought about was, I’m going to be a surgeon, I didn’t think much more about it. It sounds simplistic, but I wish I was thinking more about long term career goals. And I think the current generation all thinks they want to be academicians. But I think that’s because they’ve been told that to get into the best programs, to get into the best residency, you have to be academic. The greater majority will never ever do any academics. And that’s not a bad thing. That’s just because that’s the way the world works. And nobody gives them advice to get into the best of the best instead of thinking about what it is they really want to accomplish with their life. And I think as Americans and Americans in medicine, we have what I call a prolonged adolescence. Where we’re children, and we grow up much later than most other professions. And so that’s really what I wish people talked to me about when I was younger. And helped me think more about that when I was younger. I know it looks like it was all perfectly planned. But trust me, that’s not the way.

Ameer Farooq  56:30

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 podcast.cjs@gmail.com or connect with us on Twitter @CanJSurg. Thanks again.