During this 20-25 minute pre-recorded lecture, Dr. Michelle K. Kim discusses the topic of neuroendocrine tumors. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards. CME pre-requiste of live Q & A webinar, 8th Annual Mount Sinai Intensive Board Review in Gastroenterology & Hepatology on Sept 29.
Hi this is Michelle can kim uh I am going to spend the next 20 to 25 minutes or so. Talking about some of the A. B. CS of any T. S. And so this is really hopefully everything that a gastroenterologist needs to know about gastrointestinal nano consumers. Well the first thing really to know about nana consumers is that like many things in life location is really key. Uh So they're depending on where the nordic consumers located, whether it's in the stomach or in the pancreas. This will really greatly change how you think about them and therefore how you decide to do the clinical management and what you can expect from a clinical course. So for instance those that arise from the stomach, What's important to know here is that there can be three different types and that you need to identify which type it is in order to best identify the treatment plan. Uh There's going to be the type one that are by far the most common that are often associated with a trophic gastritis and sometimes with pernicious anemia. Uh and this greatly differs against the Type three sporadic cases which can often be much more clinically aggressive. Moving them to the small bowel. Those that are in the duodenum are very different as compared to those that are more distal in the small bowel and the Digimon ilium, those in the duodenum are often going to be non functioning. But when they do have a clinical syndrome associated with them, they often will be gastronome Azaz. And so you'll get that classic syndrome of reflux abdominal pain and diarrhea. In contrast those in the mid gut, Those in the Digimon ilium are often the ones associated with a carcinoid syndrome or an excess of serotonin. This is the classic flushing, wheezing diarrhea syndrome that is often described in textbooks uh in rectal known to consumers. Those are often going to be found incidentally on colonoscopy and often will not be associated with any clinical syndrome at all. So you want to make sure that you are not thinking about uh flushing or diarrhea in these patients or checking five H. I A s. Because this is not going to be relevant to this population. And then finally for those younger consumers that arise from the pancreas, these again will often be found incidentally on cross sectional imaging such as C. T. Or M. R. I. Um and often will be nonfunctioning tumors. About 80 or 85% of the time when they do function. They often will be associated with an overproduction of insulin or gastric is seen here. So, another way to think about murder consumers is to think about the ways in which they may present clinically. And so we've just reviewed a few of the hormonal syndromes that often can be associated with neuronal consumers. And this is really what we learn about most classically during our medical training but often can be a relatively small proportion of patients who actually uh will have no to consumers. And so these are the classic syndromes such as carcinoid syndrome. Gastronome Azaz, the dramatic sync api and priests could be that can occur with insulin. Omagh's more commonly. I would say that we often see patients who have relatively non specific symptoms related to the U. S. And so this can be something like right upper quadrant pain from a liver mass. Or if you have a pancreatic nor the consumer, perhaps uh someone who presents with gastric pain radiating to the back. And then finally, as gastroenterologists, we do a lot of endoscopy ease. Um and so we are often finding incidentally these rectal energy consumers. These incidental gastric and consumers when we do lower and upper endoscopy, respectively. So just reviewing a few of the gastric and consumers, um and the different types, these again will be often detected incidentally symptomatically, uh if they do have symptoms, they will be associated with abdominal pain, G. I. Bleeding or anemia. Generally, there is not a clinical syndrome here. So again, please don't check five H. I. A. S. Or other types of american tumor markers such as those uh markers. Because there will be no clinical syndrome. There will be um uh no association with carcinoid syndrome for these gastronomic consumers. Again, the most important thing to know about gastric known to consumers is that you need to identify which type Type one is going to be the most common. And again, the reason it's important to identify the type is that the natural history and the treatment will differ according to type. And so therefore it's important to know this is an overview of the different types of gastric, better consumers that there are. Again, there are three types. Type one is the most common by a fair margin and these are often going to be associated with autoimmune. A trophy Kasparaitis patients will often be B 12 deficient. Sometimes there can also be an association with an autoimmune thyroid disease. Uh the Gaston will often be quite high and I think something that it's important to know here is that we're often taught that a gastric greater than 1000 is highly suggestive of gastronomy. And while it may be suggestive of gastronomic, it can also often be seen in patients with autoimmune. A trophic asteroid. As you can see very high gas trains in this situation uh and so high gas tree in um uh seen here is is a very common scenario on endoscopy will often see multiple small lesions um uh throughout the body of the stomach. The path of physiology here is that you have a clear head ria. And so recalling the path of physiology of pernicious anemia. Autoimmune, a trophic gastritis. You have a clear head real, which is then driving um a surge to try to produce asset, which explains the hyper gastronomy a that we see here. Um and uh and so but what ends up happening is that you of course are making gas stream but not able to produce acid. And so there's sort of this endless cycle where the ACLU history continues um to stimulate production of high gas trian. The treatment here is uh endoscopic surveillance patients who have Type one gastric carcinoid often do quite well uh and so they can be managed endoscopic lee um Often with the surveillance endoscopy, sometimes with endoscopic ultrasound, sometimes with endoscopic mucosal resection, depending on the size of the lesions. In relatively rare situations we have considered and checked me for those who have rapidly progressive disease that is not able to be controlled in other ways. Type twos are the least comment of the gastric kind of consumer family. Um These are often going to be associated with genetic syndrome or with a uh with gastronomy. And so you can see here, there is an association with gastronome. A Z E N M E N. The gas train here again will be often very high. But the path of physiology is very different. So rather than having situation as we do in type ones where you have hyper gastronomy a from UCLA hydra in Type two is you have the reverse, which is actually a very high gas train with a very high acid environment. Uh these are often going to be multi multifocal lesions and these can be managed again, endoscopic lee or surgically. And finally, Type threes are not associated with either of these um uh syndromes at all. These are gonna be sporadic. So there is no association with a trophic gastritis, no association with Z. E. R. M. E. N. And the key defining factor here is that the gastric is normal. And again, this contrast with the other two types, these are often going to be solitary lesions that we see on endoscopy and what's important to know here is that the biology is much more aggressive and for that reason we often recommend surgery with lymph node dissection. These should often be treated very similarly to how regular gastric adenocarcinoma are treated. Uh So you want to be very careful here if we're going to treat this endoscopic lee that needs to be selected very carefully. So thinking a bit about small boundary known to consumers. Again, location, location, location, in terms of what's common. Uh Most commonly we're going to see these in the ilium. Next most common in the duodenum and then least frequently of all the Katrina. Um and in thinking about these lesions again, we're going to go for gut versus mid gut and so forgot will be those lesions of the duodenum. Often you're going to find these rather incidentally an upper endoscopy often will be non functioning if you do have a functioning syndrome. This is going to be associated with a high gas train um causing gastronome A. And causing the classic um try out of symptoms including reflux abdominal pain and diarrhea. These can often be misdiagnosed as good or I. B. S. And so certainly something to keep in the differential there Again to remember that there is no carcinoid syndrome here that's associated with these lesions. Uh And so we're not going to be checking for five H. I. A. S. Or serotonin with these types of lesions now moving down further into the genome of a liam. Um We're seeing these quite a bit um incidentally and colonoscopy as gas technologists are going into the T. I. Um and finding these um completely by accident. Um And so that is one way that we find them. Incidentally if they are symptomatic, they can present with val obstruction with gi bleeding or anemia most famously but perhaps least commonly. We also see carcinoid syndrome with flushing and diarrhea, wheezing uh palpitations. These patients are often misdiagnosed as IBD or I. B. S. For a very long period of time before they actually are found correctly to have carcinoid syndrome and a small bondage consumer. Um and then finally going into the pancreas. Again the vast majority of these will be nonfunctioning patients often will present with more advanced disease symptoms can range from those from mass effect including abdominal pain, weight loss, pancreatitis and jaundice. And we're seeing these increasingly with increased availability and accessibility to different imaging techniques. When you do think about the clinical presentation of these tumors. Um Again the non functioning will be the most common. But if they do function the insulin um was the gastronomes are really going to be the dominant clinical syndromes. Uh I think especially as gastroenterologist, we are going to be in a position to diagnose those who have gastronomes. And so for those patients who have peptic ulcers reflux, secretary diarrhea, um those who seem to be unusually attached and dependent um on their on their PPS perhaps consider gastronome and some of these patients, what certainly is um something that may be hard to reconcile is that um it's a very easy test to obtain to just check a gastric level if there's any suspicion of gastronome. A and so for that reason it really behooves us to think of these lesions and to at least check a gas train if we have any clinical suspicion. I think one thing I really want to drive home today is that the grade of the tumor is incredibly important. Um And so what this means is um essentially um when a tumor is biopsied or removed, um it is graded according to K. 67 index or my taught account per 10 high powered fields. And as you can see here, there is a range from uh um er G. One to G. Three. Um and that the higher the chaos case seven index which is a proliferation index or the higher than mitad account the more advanced the tumor grade. And so we really have no business in managing any tumors that are G. Three. Those often should go to an oncologist. Um or at the very least to a very specialized narrow consumer provider. Um We really should be managing the G. Ones um and we can manage some of the GTs. But again, I would be very careful here. I would say that um you know, anything beyond the G. One tumor should probably be referred. So now that we've gone over some of the um uh some of the review of the background, why don't we go through a few cases? So um the first is a case that came to me several years ago, a 29 year old woman with abdominal pain had been seen by multiple gastroenterologist. She had had hpai Laurie, she's had symptoms including abdominal pain, nausea, vomiting, diarrhea. She's lost weight, she's regained the weight. She's had um multiple E. R. Visits for her symptoms. She was admitted at one point found to have an ulcer. She notes that if she's not on NexIUM, she has continuous vomiting diarrhea. She sometimes vomited blood and sometimes had brought up but correct um um She continues to have a bitter taste in her mouth. The burning in the chest stress definitely makes her symptoms worse, but her weight is currently stable. And so the first time I saw her actually just got some regular labs and everything really seemed to be within normal limits. Um And then I saw her on a follow up visit. Um And she reported feeling pretty well she was taking a pee pee I every day. But she does note that she forgot to take it once and had diarrhea. So perhaps thinking about what are the next best tests. And I'll give you a few minutes to take a look. Is it upper endoscopy colonoscopy a gastro level A. C. T. Or A. U. S. Well so as you may or may not have guessed the best answer here is see gas train And let's take a look. Her gastric actually end up being over 1000. It was actually closer to 2000. And this really I think brings home the question about gastronomy rosie. So remembering that this is a non beta islet cell tumors that secrete gastric associated with a very hyper secret story state of gastric acid associated with really um uh permanent often peptic ulcer disease. Oftentimes can be a malignant process. Um And actually you can have two types here where you have a sporadic type as well as an M. E. N. One associated type. Um And remembering here that there's actually a gastronome a triangle here extending from the duodenum and also encompassing the head and neck of the pancreas. And this is often where these tumors will be found I think for a gastroenterologist when should we suspect gastronome a well. Um If there's not really a clear reason for ulcer disease. So if you don't see h pylori if you don't see insets I think um you know it's very reasonable to at least think about the gastronomy. Again it's a very easy test to obtain. You just get a cm gastronomy. If sort of there are more ulcers and you've ever seen ulcers in strange places. Um if a patient has um the classic symptoms and so this is often reflux, nausea, vomiting and diarrhea. Uh And so I would say that you know our patients will often have reflux so often have diarrhea. They don't necessarily have both. Um And certainly um these symptoms don't both improve on a P. P. I. Or worse than off of P. P. I. Um And so I think thinking about patients who have some a combination of these symptoms can be helpful. The patient can sometimes just describe feeling really unwell off a. P. P. I. Sometimes are not able to really describe why. And I think also we should keep in mind that although gastric over 1000 is a very common thing that we see in these tumors. We also have seen Gaston's not be that high and they can just be in the in the few hundreds. All right. So our second case is a 56 year old gentleman who had generalized abdominal pain while abroad. He was found to have um an upper endoscopy with a large mass of the angular areas. Um erythematosus mucosa here with some ulceration and a cat scan demonstrated the same thing. I'll tell you that he was actually taken to the O. R. And the pathology demonstrated large 5.5 centimeter note of consumer with a low my todd account um with all margins negative and multiple lymph nodes also negative for tumors. So what would be the next most appropriate test here? Again we'll give you a few minutes. Um And so whether it should be a C. T. Scan, whether it should be an F. D. G. Pet cT scan and US gas trian or a chronograph at A. Level. And so as some of you may have thought checking a gastric is the important thing here. And the reason is that referring back to our review slide here um You really want to understand the reason why somebody has a gastric net and the easiest way to do so is to check a gastric level. That should really be a first step. Um and so a normal gastric level tells you that this is a Type three. And in somebody who's had a solitary lesion um taking out of the O. R. Solitary large lesion that's often going to be a type three gastric turner consumer. And so that's why that's the right answer. And so thinking about this a little bit more. You do want to check the castro in the chroma granite A. Is important but it's not necessarily critical. The tumor has already been removed. U. S. Might have been helpful perhaps before the surgery. If there was some question of the diagnosis? Um And if you want to do let's say a fine needle aspiration. Um An F. D. G. Pet is not something we typically obtain in these patients. You could consider something like some out of staten receptors. Integra fee. These were the Austria tied scans that I think we have had for many decades that now have been replaced by gallium 68 pet cts. But in F. D. G. Pet ct is not helpful under the consumers in general. Uh So in this particular patient the gastric was actually normal. The chroma graham was normal. You actually did have a knock tree types can post operatively because this was something that was done about a number of years ago, almost 10 years ago. And so this is a type three sporadic consumer. Okay so another case a 53 year old gentleman comes to see you for a screening colonoscopy. He recently had a rectal polyp removed by snare politic. To me, This was found to be a well differentiated and a consumer. This had a low cases seven of less than 2%. But as with many of these cases that you are extended to the cauterized margin. And so he wants to know what is the next best step. Do you want to get some blood work or chronograph? And a or 24 year and five H. I. A. A. Do you want to get a cat scan a colonoscopy? Do you want to do a flex sig and erectile? Us. And so the right answer here is actually e flexible sig microscopy and rectal us. And so I can tell you hear that in this patient there was actually not a tumor seen on the flexing or on the U. S. But we did see the scar where the politics to me was performed. Um There was no peri rectal lymph retinopathy. And so we actually didn't E. M. R. At the scar and found a little bit of residual two millimeter tumor. With clear margins. And so with this E. M. R. And the clear margins the patient is very likely cured. I think what I really want to make sure that everyone recalls that this would be a different type of um scenario. If this patient had a G. Three tumor with a higher cases have an index to hire me to count. This is something that you have to be a little careful about managing endoscopic lee. But because this was a G. One tumor, something that was less than 2% because you have an index. And the metadata count was low. This is an appropriate management for this patient. So talking a little bit about director learner consumers often detected incidentally um if they're symptomatic perhaps associated with thematic asIA. But again generally no clinical syndrome. You want to ensure that these are G. One U. S. Low grade. You want to consider us and make sure there's no peri rectal retinopathy treatment will really be according to size if they're under a centimeter that can be managed endoscopic lee. If greater than two centimeters you want to think about surgical approach. And if they're in between this is where There is a grey zone. You can think of transitional excision or perhaps endoscopic 70 causal dissection. The next case is now a 47 year old female with long standing I. BSD who presents to the E. R. With worsening abdominal pain, nausea, vomiting Her last almost 24 hours before presentation. She's obese. She's flushed. She's a little hypertensive and tachycardic. She has a distended into pathetic abdomen. Um And an N. G. Tube yields about 2.5 liters of dark fluid. With a significant improvement in campaign. Her diarrhea had really been attributed to I. B. S. With you no more than six water and non bloody bowel movements a day. Um It often weeks her from sleep and she's spending continent a few times. Remember abdominal pain has been rather more severe in the last year. No longer responsive to the usual medications. So the question is what's the next best step colonoscopy capsule ct scan, V. I. P. Or smash that separates into graffiti. So the right answer here is a C. C. T. Scan and so this really a sort of supposes that you are thinking. This patient may have carcinoid syndrome. This is a patient who often will have elevated 24 every year in five H. I. A. A. Um You can certainly get a serum serotonin that can be positive as well. Um Just to let you know there are a lot of different reasons why you can have um false positive elevations of five H. A. A. There are often related to diet. Similarly there's often a reason that you can have false positive chroma ground and a being elevated and non consumer cases most commonly it's related to appease. And so this here is a differential of carcinoid syndrome um and can be um mixed up with a lot of other syndromes that we see much more commonly I. B. D. And I. B. S. Um I think the fact that oftentimes these patients will have nocturnal diarrhea. Um And just really quite extreme symptoms in terms of the volume of their diarrhea and the number of times they're going to the bathroom. Also these patients will often also be uh flushing as well. You want to remember that it's all by location. And so if you do see a patient like this um that these are going to have tumors in the genome of a liam. Um And particularly with those that have carcinoid syndrome. Often with metastatic disease which is why you do the cat scan to just look for tumor that can be associated with these patients. Um And so again this is going to be patients with mid gut the genome and alien tumors. Okay, and so this is the last case, I'll just go very quickly through this lady who had had a history of gastric carcinoid. Her last upper endoscopy was three years ago. She mentions that she's been anemic B-12. And so what do you think is the next best study? Well, I just give you the answer here. The gastric gastric was quite high. Chroma granted was also high. She's also had some equivocal findings in terms of parietal cell antibody, intrinsic factor antibody. So what type of gastric net is this? And how can you confirm the diagnosis? Well, um just give you a look at what her endoscopy looked like. Um And so you can see that's very smooth that there's not really too much in the way of rugal folds. Um and so you know how can you manage this patient? Well, um this is somebody who has type one gastric carcinoid. And so um she's got the hyper gastronomy a she's got the gastric atrophy that we often see in these patients. And so you can often just manage them endoscopic Lee with surveillance and mapping biopsies every 1-3 years. And so again, just remembering what some of these um um uh what your treatment algorithms should be if your gastric is elevated. Um one thing you can do is um uh I think that this is perhaps excuse me if the gas trian level is not elevated and you have a gastric net, this tells you immediately to type three gastric owner consumer. And so you want to do a full staging evaluation with surgical resection. Um and if it is elevated, then you have two scenarios. One, there is an autoimmune, a trophic gastritis. Um and the other less common option is that you have M E. N. And Zollinger Ellison. Okay, so in terms of some of the take home message is for all the other consumers, you can um Uh you can and should identify tumor grade again, making sure that these are G1 low grade tumors. Um and so um understanding that gastric nets can be different types and that one is going to be the most common. The duodenum are most commonly going to be non functioning, but you'll have gastronomy as general Leonardo consumers. You can present with obstruction or carcinoid syndrome. Uh and that pancreas under consumers are most commonly going to be non functioning but also have gastro number insulin, oma. And finally, with rectilinear consumers that you should ensure grade one, perhaps consider directly us in these patients. Finally, I just wanted to offer a little bit of um you know, if this is on the boards um if there is a rash associated with another consumer, you want to know what this is, This is going to be neck politic uh migratory erythema which is associated with glaucoma, which we didn't really talk about, but is one of those, um, very rare not to consumers. Thanks very much and good luck.
