Buddha in Minneapolis and, you know, has been focusing on pre-malignant conditions of the upper GI tract and has been quite proficient in publishing both on Barrett's esophagus as well as gastric intestinal metaplasia. So his back-to-back presentations are entitled Eight Pylori, Atrophic Gastritis and Gastric Intestinal Metaplasia, followed by the second talk, which is on gastric polyps and cancer. And again, we specifically selected this along with the ASGE MSET committee was because we do encounter these very frequently, random biopsy showing gastric intestinal metaplasia, what to do, seeing multiple polyps in a patient who's on PPI, do you biopsy every single one of them or just one of them? So very practical points. And I think Madhav is going to put all those queries to rest at the end of his presentation. So Madhav, thank you for joining us and the floor is yours. Well, thank you so much, Dr. Sharma, for this wonderful introduction. Thank you, Dr. Sharma, Dr. Konda for this invitation. I don't have any disclosures to make. So this is an important topic as Dr. Sharma highlighted, and we face this issue probably on a weekly basis or daily basis sometimes of H. pylori. And what should we do when we encounter this and what's the role of atrophic gastritis as well as GIM? So my topic will be focused on H. pylori, atrophic gastritis and GIM. And I will try to kind of tackle this in like next 10, 15 minutes. And briefly, kind of, I want to highlight what's the prevalence of helicobacter pylori, what are the consequences, and then move forward my talk to the risk of cancer progression when you have atrophic gastritis and GIM. And finally, role of endoscopy in these two conditions. How should we be looking for this? How should we sample and will that help in terms of management? Now, the H. pylori is very, very prevalent. And as highlighted here in different parts of the world, the prevalence is more than 70%. So every other individual actually has it. In the United States, this is around 35.6%, according to a large scale systematic review. That means that every, you know, one in three individuals could be having H. pylori. So you need to be mindful whom to sample. That's my first point. Second thing is that the most rare complication from H. pylori is gastric cancer for most of us. United States is a low incidence country for gastric cancer, and incidence of gastric cancer per year has been declining overall. Now, gastric cancer, when occurs through H. pylori infection, progresses through a stepwise fashion, and referring back to the chorea cycle from our med school days, that this occurs in a gradual pattern of infection leading to chronic inflammation over several years, sometimes, you know, starting in childhood to young adulthood, moving on to atrophic gastritis in the middle-aged years, and finally, through signaling pathway involvement and changes, development of intestinal metaplasia or GIM. At that stage, further molecular changes happen leading to dysplasia and finally to gastric cancer. So it's a very gradual process. And in that stage, when H. pylori is very prevalent, it is important to explain to your patient that finding of H. pylori is not enough, and once it's treated and eradicated, the risk of cancer goes substantially down. Now, who will develop or how many will develop cancer when they have infection? So, 1% or less than 1%. H. pylori, because of its oncogenic potential, has been labeled as a potential carcinogen from World Health Organization. It accounts for almost 90% of cases of non-cardiogastric cancer all over the world. So it's definitely the most common cause of gastric cancer, apart from some rare genetic mutations. But gastric cancer or mild lymphoma is not the most common complication. In fact, after having infection, 100% of the individuals will develop some form of gastritis, mostly chronic, leading to atrophy in only 5% of the cases. On the other hand, peptic ulcer in stomach or duodenum is more common in almost 10% of the cases. So when do you or when are we looking for H. pylori? Generally, we sample the stomach when there is a finding of gastric or duodenal ulcer, gastric intestinal metaplasia, or gastric cancer. This is when the prevalence or sensitivity of detection of H. pylori is highest. After that, if you see nodular changes, erosions in stomach, you may get H. pylori. But for abdominal pain, and especially if it's not typical dyspepsia and anemia, the utility of getting H. pylori is substantially lower. Now, especially in the PPI era, when many individuals have tried PPI over-the-counter or they're taking PPI over-the-counter, I want to highlight this fact that you may not be able to actually get H. pylori. So these individuals may be found to have non-H. pylori active or inactive gastritis, since PPI may not eradicate the H. pylori, but can reduce the densities substantially. Unfortunately, this may lead to appearance of gastric intestinal metaplasia in these individuals in the later stage. Final point regarding the prevalence is that whenever you encounter certain populations, especially United States veterans, and especially if they are from African-American ethnicity or Hispanic ethnicity, middle-aged prevalence is substantially higher, almost to 50%. So every other veteran may have this condition. Now, endoscopically, it is not that straightforward to identify H. pylori compared to chronic atrophic gastritis or GIM. Internal nodularity and enlarged gastric folds are somewhat sensitive, but there are no specific features of chronic H. pylori gastritis that can be utilized. So you have to rely mostly on the clinical features and also is the test indicated. H. pylori eradication is of benefit from several standpoints. Most importantly, population health standpoint and preventing the spread of infection overall. But most importantly, at the individual level, it has substantial risk reduction from the incident gastric cancer and the mortality related to gastric cancer in future, almost 33% per systematic reviews and meta-analysis. The benefit also extends to individuals who already had gastric cancer, but at an early stage, and they had endoscopic resection performed. Several studies, including four different meta-analyses, have shown that H. pylori eradication reduced future metachronous gastric cancer after endoscopic resection of early gastric cancer. So definitely when you find it, finally, you want to do everything to eradicate and confirm the eradication. Finally, again, regarding H. pylori and PPI linkage, there was a large-scale retrospective study from Hong Kong of almost 64,000 individuals showing that after successful eradication for H. pylori, the future risk of gastric cancer in next eight years was substantially low at 0.24%. However, when they stratified the individuals who were taking PPI, they had somewhat higher risk compared to those who were not taking it. And this was linked to number of years and the duration-dependent increase in the risk. So again, emphasizing the second point that when you do not need PPI after eradication of H. pylori, think about stopping it because it can mask H. pylori and allow slow growth over years, leads to GIM and increased risk of gastric cancer. Moving on to the two important aspects of our talk, which is chronic atrophic gastritis and gastric intestinal metaplasia. Now, chronic atrophic gastritis is described as loss of gastric glands with or without metaplasia in the setting of chronic inflammation, either from H. pylori infection over years or autoimmunity. And finding of chronic atrophic gastritis invariably implies that there might be metaplasia or that vice versa. Finding of GIM invariably applies that patient already have developed chronic atrophic gastritis. So look for these changes in your histopathology report. The risk of progression in these individuals is anywhere from 0.1 to 0.3% per year. And this could be higher based on the extent of chronic atrophic gastritis and GIM changes in the stomach, meaning that is it limited to interim or is it pen involvement and severity of these changes. And we'll go into it in a minute. Second thing with chronic atrophic gastritis is that it also increases the risk of neuroendocrine tumors, especially in the setting of autoimmune atrophic gastritis. And that is why a careful examination, meticulous examination during your endoscopy is important. Risk of neuroendocrine tumor is anywhere from 0.4 to 0.7% per year. We need to do a better job. And I think we all need to understand this entity very well, because right now we are not well equipped, at least in the United States, in terms of recognition and doing a proper sampling, because, you know, we are not looking for it. And that impairs our strategy to risk stratify and increases the number of endoscopies when we get finding of GIM focally on random biopsies. Four principles features which could help endoscopically determine whether the patient is having chronic atrophic gastritis. Gastric mucosal paler, pale mucosa, loss of gastric folds. And whenever there is a loss of gastric folds, sometimes they have developed an atrophic border, as shown in the image here, distinguishing atrophied mucosa and remaining folds. And finally, prominence of blurred vessels, which could be appreciated as prominent, you know, vessels, mainly in antrum, but also in body on a closer inspection. So this probably will be the most important slide from my talk, and this is very useful. I substantially refer this every time I'm thinking of doing endoscopy in these individuals. This will help you identify patients who has limited involvement, you know, more of an entire body or stomach involvement or pain involvement. And this is helpful in terms of risk stratification. So updated SIDNEY classification should be utilized in terms of endoscopic staging of these patients. This includes obtaining biopsies from five different sites, including from antrum on the posterior and anterior wall, as well as incisora, and then from the lesser and greater curvature of the stomach. Now, these are random biopsies, and you should be doing a close inspection of the mucosa under high-definition white light, as well as some form of chromoendoscopy, including narrowband imaging, preferably with near focus. It would be a good strategy to send your biopsies in different bottles, at minimum two bottles, one from antrum and incisora, and one separately for the corpus. And this will help you understand if they have extensive involvement in the stomach or not, or is it just limited involvement. All right. So American Gastroenterology Association has a document on best practice advices, which I strongly encourage everybody to refer to. This highlights the same, you know, points that I discussed during our talk today. And this will help in terms of management. So if the patient was found to have significant involvement of the stomach, also finding of gastrointestinal metaplasia, positive family history, those factors will help you understand if patient is at a high risk for development of future cancer. And then in a shared decision, you know, model, they can be offered endoscopy every three years. But again, to highlight is that they should have individualized assessment. Gastrointestinal metaplasia is the next step in this pathway. And definitely there is a higher risk of gastric cancer among these individuals. This has been reported very variably, but overall poor prevalence of finding GI among gastric biopsies in Western world is anywhere around 5%. And this, you know, helps identify patients who could benefit more from surveillance. It definitely increases the risk, you know, to almost 10 fold compared to individuals from the general population. This is a table highlighting different categories with gastric intestinal metaplasia and their risk of gastric cancer. So just having a finding of GIM has a risk of 0.16% per year or 1.6% in 10 years. And if they have a finding of family history with gastric cancer, they are at a higher likelihood. And similarly, incomplete GIM compared to complete GIM or extensive GIM compared to limited involvement has a higher risk, you know, of progression. Two other important points to highlight here is that although the yearly risk of progression is low, you know, the risk of progression to dysplasia is high. It's almost 15% at three to five years. And in a minority of 0.5% of individuals, they may have a finding of prevalent gastric cancer that goes undetected. So look carefully whenever you have patients with findings suggestive of gastric intestinal metaplasia. Now, these are the individuals who may have more specific features, which will help you determine your strategy during the endoscopy. During a white light exam, they may have mortal patchy erythema in antrum. They may have this gray, white, slightly raised plaques. On NBI, they appear more distinct with grooves in between. And during NBI or any form of virtual chromatoscopy, there might be specific patterns that may help you identify GIM. One of them is a light blue crest sign. These are fine, faint blue white lines on the crest of the mucosal surface as highlighted here. When you use your NBI with near focus or magnification, you may be able to appreciate this faint white lines, as well as a thicker gray band-like pattern around the grooves. And this is called a marginal turbid band. So look for this, and then you can target your biopsies that will help you capture GIM. Studies and meta-analysis have shown that use of NBI improves detection of GIM as well. So how should you be managing GIM? So first and foremost step is to assess severity and the extent of underlying GIM, as well as coexistent atrophic gastritis. The second important step is here to identify if they have underlying H. pylori or not, because transient changes from H. pylori are common, and after eradication, these changes may resolve. So you need to do a good job at identifying coexistent H. pylori at the same time. And this will eventually help you understand the involvement and pattern of GIM, which should go into a shared decision-making with your patient to identify who could benefit from surveillance. In the United States currently, guidelines do not recommend routine standard surveillance for everybody. However, you know, patients who have multiple risk factors, including incomplete type of GIM, extensive involvement, positive family history, and certain minorities, they could benefit. And individuals who put higher emphasis on early detection of cancer and cancer prevention are certainly eligible for endoscopic surveillance. And in them, it should be performed every three to five years. This is my personal approach, which basically goes over the same factors that I highlighted, that before the endoscopy, as Dr. Sharma highlighted, that getting a proper history of family history of involvement, et cetera, is very important. And this will help you determine your strategy during the endoscopy. Be careful of, you know, looking for certain lesions, and that will, you know, help you do target biopsies. And they should be sent in separate jars. After that, you should be doing a modified SIDNEY protocol biopsies, at least in two separate bottles. So that information will help you review the case and determine the management after your endoscopy. So in summary, H. pylori is not completely benign, so know your indications well. If found, look for consequences at the same time, and that can be improved by doing a proper sampling. Discuss the eradication therapy and confirm the eradication after it has been found, and stratify the risk and determine surveillance with your patient. And for that, a meticulous exam is key. Thank you so much.

H. pylori infection

atrophic gastritis

gastric intestinal metaplasia

gastric cancer

eradication therapy