All right, thank the course directors for having me here today. If you're looking at my title, and you don't really have any idea what I'm going to be talking about, you're not alone, because this is pretty much exactly how I felt when the topic was assigned to me. After all, I mean, when we're talking about commonly encounter upper GI lesions, that's going to mean different things to different people. So for example, if you're Dr. Sachinwani, you ask him, what's the most common encounter lesion? He's going to tell you it's Barrett's esophagus. If you're Doug Rex doing an upper endoscopy, that's probably what you would see. That's a lateral spreading granular tumor, and that's how good his adenoma detection rate is. But all joking aside, because of time constraints, I decided to pick two cases that hopefully all of us as gastroenterologists can relate to some extent, irrespective of our subspecialties. So these are my disclosures. The first case is the case I like to call the case of the diminutive polyps. So you have a 65-year-old woman who presents with anemia, no significant past medical history, some hypertension, GERD. So she gets referred to her GI doctor, the colonoscopies are remarkable, and this is what he sees on upper endoscopy. See fairly bland mucosa, probably some atrophy. And then on closer inspection, you see these kind of very small sessile polyps in the fundus. So the endoscopist proceeds and does biopsies of the stomach, as well as these polyps. The biopsy report shows chronic atrophic gastritis, no intestinal metaplegia, dysplasia, H. pylori. Stomach polyps show fragments of polypoid gastro mucosa with well-differentiated neuroendocrine tumor. So the questions are, what are the significance of these findings? How do we work these patients up? What should we do to manage them, and how do we follow these patients? So gastric neuroendocrine tumors, or GNETs, they are thought to arise from histamine secreting into chromaffin-like cells, or ECL cells. They constitute 2% of all gastric neoplasms, and they're traditionally subdivided into three types, with type 1 being overwhelmingly more common than type 2 and type 3. So in order to understand GNETs, we have to go back a little bit to the pathophysiology. So normally for acid production, we have the G cells in the antrum. They're going to secrete gastrin. This is going to bind to the ECL cell, resulting in the production of histamine. Histamine then binds to the H2 receptor in the parietal cells, which leads to acid production. This will then stimulate the D cells, who are going to secrete somatostatin, and that kind of stops the entire pathway. So when you have type 1 gastroendocrine tumor, the problem is you have a depletion of your parietal cells, right? So now you don't have that inhibitory arm on the pathway, which results in unchecked excitatory stimulus of gastrin on the end of chromaffin-like cells, resulting in ECL cell neoplasia. With type 2, the problem revolves around the ectopic production of gastrin from ectopic G cell neoplasia, which then somewhat escapes the inhibitory pathway as well, again, resulting in overstimulation of ECL as well as parietal cells. And with type 3, you don't have a disruption of the pathway at all. The problem is you just simply have sporadic ECL neoplasia. So in this table, I kind of highlight some of the main clinical features of the different types of genets. If you look at it, the main thing you want to remember for type 1, it's an aclyritic state, right? Because you have depletion of parietal cells. It's associated with chronic atrophic gastritis, pernicious anemia, and so forth. When it comes to the lesions, as you saw in that endoscopy, they tend to be fairly bland, small polyps, primarily in the fundus. And this is quite different from type 3, where these lesions tend to be more ominous in appearance. They tend to be larger, they can be ulcerated, mostly in the distal aspect of the stomach. If you do a gastrin level, it's going to be high for both type 1 and type 2, but for different reasons that we already went through. The way to differentiate is the gastric pH is going to be high for type 1, right? Because you have a depletion of the parietal cells, as opposed to with type 2, the ectopic production of gastrin, the stimulation of the parietal cells, results in low pH. And again, both of these are going to be normal in type 3 because there's no disruption in the pathway. The main thing to remember is type 1, again, is the most common one that we're going to be encountering. And it's associated with an excellent prognosis as compared to type 3, which is rare, but it's associated with a very poor prognosis. So how do we approach these lesions? Well, when you do the endoscopy, you want to do a good assessment, you want to characterize the size of the lesions, the number, the distribution, and so forth. Obviously, you want to do not only biopsies of the polyps, but also of the residual of the rest of the stomach. It's very important to pay attention to the rest of the stomach, and we'll elaborate on that. Laboratories, you can order different laboratories, as you see from the slide. Not only do these labs can help you differentiate the different type of Gnets, but it can also potentially highlight some of the associated conditions, such as autoimmune gastritis, or even MEN type 1 in the setting of type 2. Histology is important, right? So K167, the mitotic index, is going to give you an idea of the tumor differentiation, and therefore the tumor grade. Imaging is generally not necessary, so that's something to remember, that for type 1 with these small little polyps, whether it's EUS, whether it's cross-sectional imaging, it's not going to be very helpful, and probably you want to reserve it for lesions that measure more than one centimeter. In terms of management, it's not going to be possible for you to go and resect every tiny little polyp in type 1. Most of the time, surveillance, endoscopy, one, two years, is more than reasonable. For lesions more than 10 millimeters, you can consider endoscopic resection, and then management of type 2 certainly is focused on the management of the gastroenteritis and the MEN 1. Type 3, as I mentioned before, it's associated with worse prognosis, so these patients do need to undergo extensive surgery, as well as systemic therapy. So back to our patient, you know, we did do the EUS as requested by a provider. The EGV and EUS were unremarkable. We recommend the follow-up in one year. So let's move on to our second case. This is the case I like to call the case of the benign polyp. So you have a 50-year-old man with naphel cirrhosis, persistent anemia, and fecal cold blood. We sent him for endoscopy and colonoscopy. This is what you see on endoscopy. He's got multiple polyps. Some are larger, some are smaller. Some are sessile, some are peduncleated. You have that larger one that's kind of multilobulated. They have these ulcerative appearance. They tend to be friable to touch, and they'll kind of ooze. So the questions are, when do you consider resection of these polyps? What is the risk of cancer of these polyps? And what about recurrence rate for these polyps? So gastrohyperplastic polyps arise from this excessive proliferation of foveolar cells. Remember, it's almost part of the normal regenerative reparative pathways in the stomach. Therefore, it's commonly associated with conditions that result in mucosal injury, right? So H. pylori or states of hypergastroenemia, where you have overstimulation, you're going to see gastrohyperplastic polyps. The risk of neoplastic transformation is traditionally considered pretty low, and that's for the most part. Some factors that are associated with a higher risk of cancer have been studied, and those measuring more than two, two and a half centimeter, have a significantly higher risk of cancer. Patients in which they have adjacent gastrointestinal metaplasia also have a higher risk of cancer as opposed to those that don't. So going to recurrence after endoscopic resection, we all know this happens. So it's been reported to be about 23 to 78% of the time, and this is probably the only time you're going to hear me say this, that MBLOC and R0 resection does not matter in this type of case. Because if you think about it, whether you piecemeal resect the polyp, or you resect an MBLOC with ESD or whatever, the pathophysiology, the reason they recur is the regenerative process, right? So it's not because you left hyperplastic polyp behind. It's because these polyps will tend to recur. Interestingly, some studies have demonstrated that patients with cirrhosis also have a higher risk of recurrence. It's not well understood, and perhaps it's associated with another mechanism, but it's thought to maybe due to capillary proliferation, neoangenesis in the setting, and portal hypertension. So when should we resect hyperplastic polyps? I mean, the obvious answers would be, well, a patient who's symptomatic, if they're bleeding or the polyp is causing obstruction, but this is going to be very rare, right? So most of the hyperplastic polyps you see are not going to be causing a problem. Same thing with the large gastrohyperplastic polyps. Most of the polyps we encounter are not that large. Should we be resecting every polyp that measures more than one centimeter or between one to two? I'm not sure. I don't know if we have the answer. Some people say we should because the risk of cancer is there. But I think you have to weigh in the risk and benefit ratio, because if you look at the recurrence rate after a second resection, it's about 70 to 80%. So again, you have to determine that. I think the main take-home message of this is, rather than focusing just on the hyperplastic polyp, is you need to do systematic assessment of the remainder of the stomach for the associated conditions that we talked about. Because most often than not, that is the reason why the patient showed up. So the anemia is not due to the hyperplastic polyp you found incidentally in the antrum. The anemia was probably associated with chronic atrophic gastritis, pernicious anemia, or whatnot. So back to our patient. We resected the larger multilobulated polyp, no intestinal metaplasia or dysplasia. There was no H. pylori. We're recommending surveillance in one year. So in summary, remember, management of gastrointestinal tumors should be based on the subtype. Small lesions, less than one centimeter, especially if they're multiple. Surveillance endoscopy every one to two years is recommended. You don't really require any additional imaging besides that. Large hyperplastic polyps should be resected due to the risk of cancer. The question whether we should be resecting those less than two, particularly those closer to one centimeter, I think it's debatable, particularly given the high risk of recurrence. And the main take-home message, like I said, is to make sure you evaluate the rest of the stomach in both of these scenarios. Thank you.

upper gastrointestinal lesions

anemia

GERD

gastric neuroendocrine tumors

hyperplastic polyps