BTK_NETumors_12Jan

Hi everyone, and welcome back to Behind the Knife. We're your surgical oncology team. And today we're really excited to present a topic, which we all agreed we could talk about for several hours. Neuroendocrine tumors of the small bowel. I'm Elizabeth Barbera. I'm a PGY 6 from Brooke Army Medical Center.

I couldn't join the team for the discussion, but I'm happy to rejoin for our next episode, which is going to be a journal club presentation where we do a panel discussion. Deep dive into the literature for the medical therapies we have to offer for neuroendocrine tumors. I'll let the rest of the team introduce themselves and thanks for listening.

I'm Connor Chick. I'm a second year fellow at Ohio State. I'm Lexi Adams. I'm a first year fellow at MD Anderson. Tim Braylon's staff at BAMC. Otherwise known as Brooke Army Medical Center. We'll start with a case. Lexi, you're seeing a 50 year old man in clinic who's referred for an incidental finding of a mesenteric mass on a non contrast CT scan that was done for kidney stones.

In terms of his history, he has well controlled hypertension, no surgical history, he's on lisanopril, he doesn't smoke or drink. We'll And he has no family history of any cancers. So

what elements of the history do you want to ask about first and then what would you look for on exam? So I would ask this patient about symptoms that could include abdominal pain, change in bowel habits, any obstructive symptoms, weight loss, fevers or chills, night sweats, any other changes to his health.

And then on exam I'd of course look at his vital signs, perform a cardiopulmonary exam to listen for a murmur. Thank you And an abdominal exam to evaluate for a palpable mass. And I would also examine all his nodal basins. Yeah, so he has no other symptoms. So in terms of thinking about the differential, so oftentimes these mesenteric masses represent enlarged lymph nodes.

Those can be regional nodal metastases from somewhere in the GI tract or elsewhere in the abdomen. sometimes a primary lymphoma. Sometimes mesenteric masses can represent a desmoid since these often arise in the mesentery, or they can even be non neoplastic inflammatory diseases or even cystic lesions, which are usually benign.

And then when we think about the GI tract

primary sites nodal mets from neuroendocrine tumors often form a mass in the mesentery, but this could also be a peritoneal metastasis or other nodal metastasis from something like a gastric or appendiceal or colon cancer. So, for this patient, we got some basic labs, including a CBC and a chemistry, and those are normal.

We looked at the CT scan without contrast, and there was a 3. 5 cm mass in the small bowel mesentery with some peripheral calcifications. What should we do next to work this up? Given those CT findings, I am concerned about a nodal metastasis and this could be from something like a small bowel neuroendocrine tumor, but the findings are pretty nonspecific, so I would start by repeating a CT abdomen pelvis, but I'd get it with IV contrast this time, and I'd make sure that I'd ask for both arterial and delayed venous phases.

I would also add some LFTs and then as far as my concern for neuroendocrine tumor some people add chromogranin A's historically, but it's not very sensitive or specific and it doesn't

often change management decisions. There's another tumor marker called pancreastatin that's also a little more sensitive for neuroendocrine tumors, but it's not necessarily part of the guidelines at this point.

Yeah, it was interesting that recently the NANETS guidelines dropped chromogranin from from their, their recommendation. So I think a lot of people still get it, but like you said, it's fallen out of favor because it's neither sensitive nor specific. Yeah, at our institution, we actually don't even include it in our workup anymore.

Yeah, I would say here it's, it's variable. Some people do, some don't. So we get the CT scan. There's there's a mass in the mesentery measuring three and a half centimeters. Yeah. It's in proximity to, but not involving the iliocolic artery and vein. There's no other obvious mesenteric masses. There are a few small liver lesions that seem a little brighter on arterial phase.

And we don't see a small bowel mass. What are our thoughts now about the differential and the next steps? I still am concerned about neuroendocrine tumor.

Generally the primaries are very small and often you can't see them on imaging. Another I would then proceed with a DOTATATE scan to take a closer look at the liver lesions and see if they're avid.

And then I would refer them for a tissue diagnosis of one of those liver lesions as well. So I think a couple of comments there. I think arguably tissue diagnosis may not be needed in all these cases. So. You'll almost never get a tissue diagnosis of the primary because, like you said, the primaries are generally very small and kind of hard to find.

You're not going to go biopsy a node in the middle of the mesentery. And the other thing that's changed now is there's dotatate, right? So there's not a lot of things that are dotatate avid, although there can be some false positives. But most of the time, if all these things light up on dotatate, you kind of have your answer.

Now, you know, if you want to go with medical therapy, the medical oncologist may require a tissue diagnosis. But if you're going to go to the O. R. anyway, you might not need a tissue diagnosis. The other thing is just, if you're going to go to the O. R. you might not need a tissue diagnosis.

The imaging you brought up there is very characteristic of neuroendocrine.

So you guys talked about differential, which I think is good, but this no longer really sounds like a lymphoma. The, you know, when I give a lecture on this, I draw this triangle like a normal, well, not normal, but a GI adenocarcinoma, the primary tumor is big and the lymph nodes are small. So you'll almost always, you know, have some indication of a primary before you have big lymph nodes in the mesentery.

Neuroendocrine being the exact opposite of that. So you can have these big giant nodes and you know, two millimeter primary So you have to kind of invert that Paradigm that you normally think of where the lymph nodes come late and the primary tumor is very big before you see big Visible lymph nodes on a CT scan the exact opposite is true for neuroendocrine.

So you'll have very small primaries Big nodes. And then what's the other weird thing about primaries for small bowel and endocrine that, in my opinion, changes the way you have to do the

operation every time? So they're often multifocal. So you really have to, it's mandatory that you palpate and feel the bowel.

And you're feeling for masses that are sometimes like grains of sand. They can be really subtle. So you, it's not like a trauma X lap running of the bowel. You're very slowly running the bowel and feeling for those tiny little tumors. Okay. Exactly. And you'll see debates about whether or not you should do these cases.

MIS, you know, some people will say, Oh, well just take the lymph node and then take any bowel that's being drained by that lymph node. But in my hands, in my opinion, it's mandatory open operation so that you can run the small bowel with your fingers to find those masses. I don't think there's, I don't think it's possible to adequately run the small bowel for these tumors.

MIS. So these should all be done open in my mind. The other thing is that You're going to go way to the base of the mesentery, which is not very safe MIS, and probably you won't be as thorough in your lymphadenectomy MIS. Yeah, I mean, I would say at our institution, we're, we're

fairly aggressive about minimally invasive approaches.

All of these are done open for that, for that exact reason. The only other consideration for I think biopsy prior to the DOTA is insurance approval for a PET scan. Cause sometimes those won't get approved if you don't have a real diagnosis yet. You know, the alternative in that situation, if there's nothing really to biopsy might be to just get an MRI of the liver to get a better assessment of the volume of disease in the liver with the idea that you're still going to go to the operating room.

It's just a question of what exactly are you going to be doing? I do think most patients are able to get the DOTA tape. Beforehand. So, but in this case, we got a liver biopsy and it returned as a well differentiated neuroendocrine tumors. Grade 1 with a K I 67 of 1%. So just to talk about the.

Pathology for these, so for gastric gastroenteropancreatic neuroendocrine tumors, which is sort of the category of neuroendocrine we're talking about the degree of differentiation and the K. I. 67 are critical components of the pathology report. So

that tells us about disease biology. It tells us about prognosis.

And then it also can influence which imaging modalities we can use, and even which systemic therapies might be helpful. In terms of discerning neuroendocrine versus something else, so like an adenocarcinoma for example Lexi, what are, what are some of the special stains that we sometimes will do to differentiate these?

So sometimes it's challenging for pathologists to identify these well differentiated neuroendocrine tumors. So some of the stains that they use that are specific to neuroendocrine are TTF1, synaptophysin, and chromogranin. And then some specific stains. to GI adenocarcinoma instead of neuroendocrine would be CK7 for upper GI cancers, CK20 for lower GI, and neoplasms.

And of course, there are many others in the alphabet soup, but these are some of the most common. I would say the most important things to look for, like we said, are the, you know, well differentiated versus poorly differentiated. And then the K I 67. So that

also will help us determine the grade. And, and in most cases, actually based on the K I 67.

So in terms of next steps for this patient who has a well differentiated, likely small Ballender endocrine tumor, it's grade one, K I 67 is 1 percent that has lymph node metastases and liver metastases. He has no symptoms of carcinoid syndrome. So that's one of the things that we should know beforehand, but in general, we're going to move.

forward with surgery. So to get a better sense of the extent of disease, we're going to get a DOTATATE scan. So DOTATATE is a PET scan that demonstrates areas with high expression of somatosatin receptors. So DOTATATE is the molecule that's used instead of FDG. And DOTATATE refers to a gallium 68 labeled somatosatin receptor analog.

So the DOTA part of that is a chemical that binds gallium 68 and then the T A T E or the TATE at the end stands for tyrosine 3 octreotate. So that's the somatostatin

receptor binder. It's amazing how few people understand this. So, you know, you don't need to know what these, all these fancy words mean, but When you talk about a PET scan, most people mean an FDG PET, which is tagged glucose and it lights up hypermetabolic areas, either from an aggressive cancer or from infection.

A low grade neuroendocrine tumor, very slow growing cancer, will not light up on an FDG PET. So you have to get a DOTATATE PET. Which, like you said, is going to light up things that have somatostatin receptors, but it's amazing. You'll have like medical oncologists that will order FDG PETs for a neuroendocrine tumor.

So that's a really key thing to understand when you're ordering imaging for these, because you're going to order a PET scan, but you don't get an FDG PET, you get a DOTATATE PET. So sorry to harp on that. You know, if this, if our patient, instead of having a well differentiated neuroendocrine tumor, had a poorly differentiated or a neuroendocrine carcinoma, for example, Sometimes those tumors actually can lose this amount of satin receptor expression because they're so poorly differentiated

and dota can actually be less sensitive for those than it is for well differentiated.

So that's 1 of those that's kind of counterintuitive. Like you're saying, the FDG pet typically will light up brighter and more aggressive disease. And DOTA is the total opposite. So now we have hit the DOTATATE scan, and the mesenteric mass is highly avid, and there's a few avid lesions within the small bowel, but it should be noted that DOTATATE's not good for looking for intraluminal neuroendocrine tumors because there's physiologic uptake within the bowel anyway so that's really no substitute for DOTATATE.

Feeling and running the bow and the or but the patient also has 1 3 centimeter liver lesion and segment 5 and then 4 or 5 smaller lesions located peripherally and segments 2, 3, 6, and 7. So, as we've mentioned before, the mainstay of treatment for these well, differentiated tumors or surgery they don't particularly respond well to chemotherapy and while somatostatic, Somatostatin receptors can play a role in slowing disease

progression.

They're not likely to shrink or eliminate the tumors like chemotherapy sometimes does for more aggressive cancers. Yeah, so one of the other systemic therapies we should talk about, and we will get into more detail on this later on, is PRRT. So that is, that stands for peptide receptor radionuclide therapy.

Which sort of falls under this category of Theranos tics. So it sounds really cool. But basically what it is, is it combines an advanced imaging technique with a therapeutic. And so in this case, it's using that same somatosatin receptor expression. That dotatate uses and then instead of using using gallium 68 to light up on a scan dotatate is coupled with lutetium 177.

And so the brand name for this is ludothera. The in general, it's referred to as PRT and the goal is to deliver targeted radiation to areas that express the amount of satin receptors. Now. In this patient, the thing

we need to think about is the mesenteric mass, because when you give PRRT, often it will cause this dense fibrotic reaction and you get this desmoplastic reaction within the mesentery that can actually do a bowel obstruction.

So for patients like this who have their primary and nodes intact, that's not a great option for this patient at this point. Although there certainly could be a role. Down the road and we'll talk about that later on. Yeah, I think just to simplify that a bit. Lutathera is cool it works on the same technology as Dota Tate if you light up on Dota Tate, you should respond to PRT But it should be way down the algorithm like it's kind of a last ditch effort really for the most part and that's in part because what you talked about in part because it has Real and meaningful side effects that a lot of the other therapies don't But the mainstay, of course, is surgical resection.

So, we should talk about that. I do want to just make a broad point about surgical resection of these

tumors. This is a very slow growing disease, right? We just heard 1%. If this patient's like 80, the chances that this disease is what gets them is very, very low. Even if they're 60, you know, the chance that this is what kills this patient is pretty low.

So the majority of the time we're operating on these patients, it's to alleviate some kind of symptoms. Now, most patients will have. bowel symptoms by the time they present. So this patient did not present with that. But a lot, a lot of patients that you'll see in clinic will have some vague quasi obstructive symptoms.

And so just keep that in mind and let's, you know, talk about what operation to do and why to do it. The other symptom I feel like I've come across a couple times is almost a chronic mesenteric ischemia type symptom where patients will have postprandial pain and almost kind of food fear when these mesenteric masses get really big.

And it does get better when you take those out. So I just think that's really

interesting. Yeah, absolutely. In terms of the operation. So for this patient who we think has a small bowel primary, most likely has mesenteric Mass or, OR nodes and then some, what seems like pretty low volume liver disease.

So our plan for this patient would be exploratory laparotomy, small bowel resection, resection of the mesenteric mass, and then liver resection and or ablation. So in terms of the sequence of the operation, there's probably a few ways you could go about this, but lexi, you want to kind of talk through what, what would your approach be for this particular patient?

So, I would plan on an open operation and do an exploratory laparotomy with planned small bowel resection along with resection of all the associated mesentery. So as far as logistics of how that looks, I would start with running the bowel. That would be kind of a slow, palpation feeling for tumors that can be as small as a grain of, of sand.

And then

I would also look at the mesenteric disease and identify which pedicle it ran with and plan for a high ligation with all of the associated mesentery in that area, but also do a thorough inspection of the peritoneum and look for any peritoneal disease that we could take as well.

Yeah, I, I think that's exactly the right way to start. A couple comments. I always mark the what I think is the most proximal and distal tumor before I start cutting anything. And then I run the small bowel twice. So every once in a while, you'll find that by the time you've run the small bowel and felt all the primary tumors, there's like 10 or 12 and you know, you're only gonna be left with a hundred centimeters of bowel or something like that.

And you may be in some of these cases, you may be stuck with the decision of knowingly leaving behind a tumor or the other kind of wild thing that I've done before is you literally just cut out the piece of small bowel that has that tumor and then close it primarily in two layers. And that, you know, that, cause if there's

one tumor that's like 40 centimeters proximal to the next one you don't want to necessarily take the 40 centimeters of inner intervening bowel.

Even though that's. Oncologically very unsatisfying. Sometimes you have to make compromises in these cases where they have small bowel neurodegenerative tumors basically throughout their entire ileum and part of their jejunum and things like that. So you run the bowel, you mark the proximal and distal tumors, run it again, make sure you're happy before you cut any bowel.

The other thing is, much like a Whipple operation. This, a lot of this operation is planned in my head before I go to the operating room based on the CT scan. So you can, you know, with a triple phase scan, you can get a lot of detail about the mesenteric vessels, which ones you are going to take, which ones you're going to leave, what bowel you're going to leave behind and how it's going to be perfused before you get to the operating room.

Every once in a while, you'll be surprised. And there'll be, you know, certainly more primary tumors than you expect, but. Particularly around that ileocolic vessel and what vein is gonna be left to

drain the, you know, the co, the right colon if you're gonna leave it. Those are things that I really try to plan out in my head, and then as I'm exploring the mesentery, I try to kind of match those things up.

Sometimes I'll use a ultrasound to understand the relationship between the SMB and the tumor. And then that mesenteric resection, it all comes down to the SMV, just like every GI operation, in my opinion, comes down to the SMV. You know, it's, it's like a right colon in my mind. You know, the first thing I do is that medial dissection.

I try to get out the SMV, understand where it's at, peel the tumor off of the SMV, leave as much as you can, and then take what you have to take. And again, usually, That branch that you have to take will already be occluded by the tumor. And so you're, you know, that, that can be planned out before you get to the operating room.

And then you want to make the anatomy look in the operating room like it did on the CT scan. And that's how you avoid getting in trouble. I think the way that people get in trouble in these cases. Is they use a ligature impact,

they cut the bowel, and then they go chomp, chomp, chomp with the ligature impact and they end up taking a big branch of the SMB that they didn't need to take.

And then they end up having to take more bowel than they need to, or they're doing an asthmosis to bowel that's kind of sketchy and then they have a leak, things like that. So I think starting central and doing a really thorough job of understanding the branches of the SMB and the SMA. That's how you stay out of trouble in these cases because you really are going to be high in the, in the mesentery and higher than a lot of people are comfortable.

So I think the other operative consideration we should talk about is how to approach the liver. So in this patient, we said there were small peripheral lesions in seconds, two, three, six and seven. You know, if, if these are all. Peripheral and, and, you know, visible on the external surface of the liver.

We may just do some wedge resections for all of those. I think the, some, one of the, some of the harder decisions are when there's lesions that are a little bit deeper. You know, maybe not the very central lesion right on the right. Inflow or the right

hepatic vein, but you know, something that would require a bigger resection.

So Dr. Vreeland, can you kind of talk to us about how you approach some of those more intermediate. Liver tumors. Yeah. Yeah. I think that ultimately the question you have to ask yourself on these cases is why am I here? Why am I in the operating room? Right? And again, this isn't. colorectal liver mets, assistant pancreas cancer, these things are not going to grow quickly.

They are going to grow very slowly. There is medical therapy that can keep them at bay. So you always need to live to fight another day. Don't do a dangerous resection to clear these patients liver. There's also a bit of confusion, I think, because there's a body of literature about debulking these tumors, right?

So, you know, there's literature that says you should debulk 80 percent or 90 percent and that's considered a successful resection. A couple things to keep in mind there. One, the majority of that is retrospective data. And so the patients who, you know, are able to be debulked

are going to do better because they have less disease.

Got it. Great. So debulking is good if you look at it from a retrospective standpoint. Two, debulking makes a lot of sense to me in a tumor that's making hormones. So we haven't done a lot of discussion about. How these can be hormonally productive. But you guys talked about carcinoid syndrome. So if you have a patient with carcinoid syndrome and a bunch of liver mats, then debulking those liver mats to try to get them down to a very small volume of disease or no disease that is producing that hormone makes sense.

And you should be a little more aggressive in those patients because you want to stop them from producing those hormones. So, and then, so, that's one reason, right? So to debulk the disease. That's one reason to be in the operating room. Got it. The other one is to render them disease free. Why do you need to render them disease free?

In the case of colorectal liver meds, you know, you want to get them off chemo, basically, in my mind. So you want to give them, one of my mentors always called chemo free survival time. Here,

you want to offer them an opportunity to not have to go on a somatostatin analog. So if you can clear all the disease that they can see on imaging, then they don't have to be on medical therapy.

If you leave a tumor behind, that's where things get a little complicated. A KI 67 of 1%. If there's one Little lesion that's deep in the liver and i'm gonna have to like do a big liver resection Or let's say you get in there and you can't find it on ultrasound because it's two millimeters and it's in the back of the liver I don't sweat it because this is a two millimeter or five millimeter lesion that has a ki67 Of one percent it's not going to grow over, you know multiple years so it might be four or five six seven years before that patient has meaningful growth in that lesion and requires a somatostatin analog or some medical therapy.

And so you just have to always keep in mind what disease you're treating and what your goal is. So I know that's, you know, and it is very nuanced and very complicated, but I think to your point, if it's

easy to get rid of, go ahead and get rid of it because then we don't have to stare on it on the next set of imaging and decide whether or not to start medical therapy.

If it's really difficult to get rid of. Only do it if there's a reason now, if it's a big tumor and you're worried that it's going to start producing hormones, I think it's reasonable to respect. Especially if they're kind of young and healthy again, if they're 80 and they have this disease, you really should only be operating if they're symptomatic because, you know, it's not going to, it's not likely to kill them and then it gets even more complicated when now we have a little bit higher K I 67 and now we are worried that it's going to progress.

And should you, you know, should you respect in those cases? The reality is that even if you clear the liver, you know, there's microscopic stuff that you're leaving behind. And so you always have to sort of keep that in mind, is that, you know, heroics in, you know, in other diseases, we clean up with chemo or we treat with chemo, and so we're gonna be surgically a little more aggressive because of microscopic stuff

we can take care of with chemo.

In neuroendocrine tumors with a low Ki67, Chemo doesn't work. You, as you guys said, you can give medical therapy, but it's more static than cital. So it'll prevent progression, but it's not going to kill microscopic disease. And so, you know, you just always have to keep these things in mind that we can only do so much with surgery and In a very slow progressing tumor, you should not go doing big whacks for small tumors that aren't going to have a clinical consequence any time soon.

So it is very case by case and nuanced, but I think those are kind of the general principles, is really understand your why when it comes to operating on metastatic disease for a well differentiated indolent disease like this. And I think another important tool to remember is ablation, whether it's an OR and you can see it on ultrasound and ablate it there, or if it's small and you can't find it, again, remembering that if it grows in

8 10 years, that IR can always ablate it later.

Yeah, and I've had that case come up where I can't, I can't find it on ultrasound in the operating room and I wanted to ablate it. And I just leave it alone. And when it gets bigger, then I are going to bleed it, like you said. So if it's too small to see, then it's too small to have clinical consequence and it'll get bigger eventually.

And then it'll be easier to treat. But I do think that the primary tumor is the more important thing to resect here, not because it's more curative or anything like that. It's because the, you know, one thing we didn't mention on the imaging early. Okay. Is that these tumors have this very severe desmoplastic response around them in the mesentery and they tend to suck the bowel into the mesentery and so they almost uniformly will cause a bowel obstruction if you don't operate.

And so in my hands, everybody with a small bowel neuroendocrine tumor gets a surgery because if it hasn't caused a bowel obstruction yet, it's going to. And what you don't want to

do, especially if the patient's not super reliable, is, you know, a lot of times these patients present to the hospital because they have a bowel obstruction.

And now it's like you have to operate and they're malnourished and you're like putting them on TPN per week just to get them tanked up a little bit and then having to operate. in that kind of acute setting, it's great to avoid that. And so if you have a patient who's a little bit obstructed, I would go ahead and operate then because eventually they're going to be more obstructed.

And the primary tumor is what kills these patients in the majority of the disease. So what are the, most of these patients die of eventually? Bowel obstructions. Yeah. So even if you do a great job, they may recur in their mesentery and that'll suck the bowel in and they die of malnutrition from bowel obstructions.

So be extremely aggressive in the mesentery. and be less aggressive in the liver. It's kind of a weird paradigm shift, but that, that really, I think is the best approach to these is that the nodal burden is super, super important in this disease. So be as aggressive

as you can. That being said, sometimes you'll see like periordic lymph nodes and lymph nodes that are away from the bowel and are not going to cause symptoms in the setting of stage four disease.

I don't think there's a huge rationale to go after those. They're not the ones that, that are going to be in the mesentery and cause that small bowel obstruction. And so being super aggressive about doing a periortic lymph node dissection and things, those things don't make a ton of sense to me because they're not going to cause symptoms.

You are, you're at, your why for these is generally either causing symptoms or you're going to try to clear them of all disease so they don't have to go on to medication. How do you handle lymph nodes in the porta hepatis? What I would say is that those lymph nodes are generally not that hard to take care of.

You know, there tends to be that like lowest node on the common bile duct, the one that's kind of right on the corner of the, you know, on the patient right of the common bile duct on the top of the pancreas there next to the duodenum. I've seen that one obstruct the duodenum for sure. And so I think those low portal

nodes can cause duodenal obstructions.

And so you, if you, if you see those, you should clear them. Doing a pair of periordic lymph node dissection that has a lot of morbidity, you got to do a lot of surgery and it doesn't make a ton of sense. So to shift gears a little bit, you mentioned carcinoid syndrome. So let's say that our patient that we talked about now has some concerning symptoms.

He's having flushing, diarrhea. So Lexi, before thinking about surgery, what kind of things do we need to rule out? And then what things would we do differently in the operating room? In the setting of carcinoid syndrome, you can develop carcinoid heart disease which should take priority over the operation initially.

Because that can lead to acute heart failure and even hemodynamic instability in the OR. So sometimes these patients may even require a valve replacement prior to the operation. And their symptoms can be managed with somatostatin receptor analogs in the meantime. It's also, we've now, Multiple times

mentioned how slow to progress.

This disease is so it's not a huge rush. Typically for us to go to the operating room. We have time to optimize the medically. We have time to get their heart ready for the case. So, ultimately, we just medically manage them until their cardiac symptoms are taken care of before proceeding to the, or when you do bring those, these patients with carcinoid syndrome to the, or you want to have a, Good pre op discussion with anesthesia.

You can start them on an octreotide infusion perioperatively to prevent intra op carcinoid crisis. One thing is that the long acting octreotide analogs have, have helped a lot with that problem. Because if you get somebody on a long acting octreotide analog and they're on it for a few months, And then you give a dose kind of like a week before the operating room, you don't see the carcinoid crisis nearly as much in the operating room.

So, I think, in some ways, that's a little bit of a problem of the past, but it's certainly something that gets anesthesia all excited and they'll have their

drip ready and not typically use it. But I think before we had the longer acting ones, it was more of a problem. But most of these patients now get established on a long acting I treat out an analog and it's less of a problem.

So, let's change our scenario again. So now, instead of having a mesenteric mass, the patient actually presented with a near obstructing mass in the duodenum. It's biopsied endoscopically and returns as a grade 2 neuroendocrine tumor with a Ki 67 percent or, excuse me, Ki 67 of 10%. And on imaging, there is resectable metastatic disease in the liver.

Would your approach to managing this patient change at all? So again, you're trying to avoid heroic measures to debulk this disease. So if it's respectable endoscopically, that would be the first line for the duodenal mass. If it's not then you could proceed with a segmental duodenectomy with, Reconstruction or if it is very close to the ampicula, you might have to consider something like a Whipple.

But again, you're trying to maximize your other options before getting to that point. I think if it's obstructing, it's probably not going to be. You know, endoscopically respectable, but obviously that's best. The ones that I've seen of these, they've D1. I think that's probably the most common spot.

And a lot of times you can do kind of an anthrax to me. And then. Just really push pretty far onto the duodenum and do an antrectomy D1 resection and get away with that. In the study of metastatic disease, I probably wouldn't do a Whipple, honestly, I just think it's too morbid and these Whipples are not easy Whipples because they all have soft pancreases and normal ducts, right?

So it's not like pancreatic cancer where you have the big, Duct in the hard pancreas where you don't worry so much about the leak. These are the ones that have leaks because they're their pancreas is very normal Now that we're creeping up on the ki 67, right? So we've gone from 1 percent to 10 percent You know, the cutoffs are 1 to 3 3 to 20 and 20 and above for the

different Grades, but in that kind of 10 percent range is when I start worrying about them not being so friendly anymore now They're a little more aggressive I think one trick is honestly to get, you can't always get it improved by insurance, but to get both types of PET scans, right?

So if you get a DOTATATE PET and an FDG PET, it kind of helps you tie break on whether this is a chemo kind of neuroendocrine tumor or a somatostatin analog kind of neuroendocrine tumor. And so I might do that in this case with a, you know, with a KIC 7 of 10 percent and I'm not real sure what to do. If it's FDG avid, I would probably give some pre op chemo and see if I can get it to shrink down where I can do more of a segmental resection and see whether or not it's worth being aggressive in the liver.

So, there are different chemo strategies here, but capecitabine and It's Cape Tam, I think it's temozolomide is kind of the standard of care for, for these well, what are called well differentiated neuroendocrine tumors that are more grade two or grade

three. And I think it, it'd be worth a shot in this case.

And if they progress through that, then surgery is probably not going to help them. Then they're acting more like a higher grade. If they respond, then you kind of treat it like an adenocarcinoma, and you, you know, can be more surgically aggressive after some response from chemo. And one other thing to think about, you know, as we start moving up higher in those grades, so there was a recent trial called NETR2 that looked at the addition of PRT to somatosatin receptor analogs, and their response rates were actually really impressive.

So in a patient who maybe has already had surgery for the, for, you know, a small ball primary with nodes and has liver disease primarily or something where you need a response and they can tolerate PRT, that may be a regimen to start to think about since there is randomized data for that now.

Yeah, and I think that's where the two types of PET are helpful, right? Because if they, if they're light up on DOTATATE, then they should respond to PRRT. If they don't, and instead they're lighting up on an FTG PET, then PRRT

is not going to be helpful. That's where you have to use chemo, usually in the form of CAPETAB.

One more scenario, and one that probably comes up more on exams than in real life, but there's a patient who had an appendectomy for what was thought to be perforated appendicitis. But on final pathology, there's a two centimeter neuroendocrine tumor. It's well differentiated, but grade two ki 67 is 12%.

There's no disease in the liver. How would you approach this patient? So I would counsel the patient on the need for a completion rate hemiflectomy with the goal of getting all of the of the high iliococcal pedicle to get all the lymph nodes associated with the area. So again, I think that principle of like small tumor, big nodes, like even though it's a two centimeter tumor, there's a real risk of lymph node mets because these, these tumors go to the lymph nodes so early.

And then what about let's say instead of a, you know, well differentiated neuroendocrine tumor the pathology comes back as a neuroendocrine carcinoma. So how does that change things? Just so all the listeners kind of have it in their head, neuroendocrine carcinoma should be

thought of as a totally different disease.

It is not a neuroendocrine tumor and it's, it's treated more like a small cell lung cancer. then it is like any GI cancer. So it's given, you know, cisplatin it's given a lung cancer regimen basically for for chemo. Now the new thing is kind of immunotherapy, but it's really not treated like a GI cancer.

Cause it's this very weird tumor that is very, very aggressive. I remember the medical oncologist who gave us our lecture on this and fellowship said, if I ever find out about you operating on a neuroendocrine carcinoma, I'm going to find you. And, you know, I can't remember what his threat was, but he was basically like, don't operate on these.

So, you know, every once in a while, you may be in a situation where you're going to operate on these, but I would argue it should always be after chemo. So these, these are very aggressive and they tend to blow right through chemo and the patients unfortunately do very poorly. And so if you ever get pathology back, that's as.

Neuroendocrine carcinoma, not neuroendocrine tumor,

don't be confused. That is a wildly different disease that you as a surgeon probably have very little to offer that patient. And the other thing I would say is if you get a neuroendocrine tumor that is done by an inexperienced pathologist, and the KI 67 is crazy high and they mention like some weird features, you may want to send that out for expert pathologic review because they may be looking at it.

Neuroendocrine carcinoma and not knowing exactly what they're looking at. Yeah, the other really weird one that I've come across is a mixed adenocarcinoma neuroendocrine tumor, which is something that is really, really, really rare. So definitely one that should be looked at by an expert pathologist.

And generally very bad. You have two pathologies on one pathology report, something bad is happening. That concludes our case presentation today. Thanks everyone for listening. Just to review, we talked about the presentation of neuroendocrine tumors, key points of their workup, including what labs to and maybe not to order, as well as imaging studies.

We talked about what a dodotate skin is and its relationship to PRT, as well as other medical therapies. And finally, we talked

about operative management. Key aspects reviewed here include careful running of the entirety of the small bowel and the ever important mesenteric dissection of these tumors.

We ended with some case variations, including poorly differentiated tumors and neuroendocrine tumors in other areas, such as the duodenum and appendix. We're your surgical oncology team. Thanks for listening. And until next time, dominate the day.