Well, ampullary and duodenal adenomas are uncommon. They're rare. Most present as incidental findings, and frankly, when patients present symptomatically, it typically is a signal of locally at least advanced disease. Occasionally they'll present with anemia or obstruction. Sporadic lesions are distinct from those with FAP, and my comments today regarding the duodenal adenomas are strictly related to sporadic duodenal adenomas. What's special about removal of ampullary and duodenal adenomas? Well, the duodenum is a fixed segment of bowel. It has a narrow lumen. It's retroperitoneal in its location, and it's surrounded by a lot of perilous structures like the aorta, the pancreas. It has a relatively thin wall, maybe three millimeters of thickness. It has a very rich vascular supply, and of course it houses the pancreatic obiliary orifice. So these features present some technical challenges. It requires some specialized equipment and techniques. There's an increased risk of both acute and delayed bleeding. There's a risk for pancreatitis. Perforation in the lesser sac can be lethal. And patients are often older and with comorbid disease, and there are generally poor operative alternatives for duodenal resection. What's the differential diagnosis for sporadic non-ampullary duodenal adenomas, or SNADA? Well, they're brunner gland hyperplasia. These can be recognized usually in the bulb or at the junction between the bulb and the second portion. And while they can mimic adenomatous features, with careful inspection you can discriminate that, and certainly the biopsy forceps tissue sampling will confirm. Occasionally we'll see sporadic or syndromic hematomas, and we'll see neuroendocrine tumors. Carcinoids, which arise in the deep mucosa. Rarely serrated adenomas are described in the duodenum. And of course, when you see duodenal polyposis, particularly if it's multifocal, you should think about MYH polyposis or attenuated FAP, if not full-thrown FAP. So a clinical history, family history is important in these circumstances. And of course, you need to distinguish the non-ampullary origin versus ampullary itself. Ampullary adenomas constitute about 7 percent of duodenal polyps. And of course, they have a malignant potential that is similar to that of colonic adenomas. This is a little scrapbook of duodenal adenomas that I have known, and you can see that they can vary tremendously in their size, their configuration, their location in relationship to the ampulla. And we use the same type of imaging techniques that have just been covered in the colon, the esophagus, and the stomach to discriminate the margins as one would plan their management. And so we start off with inspection. And commonly, we'll use a duodenoscope. And this is used principally to identify the ampulla of otter to confirm the non-ampullary orientation. And I'll typically use a duodenoscope for resection for lesions on the medial and the anterior walls. For posterior wall lesions, we often have better success using a pediatric colonoscope, usually with a cap on the tip to deflect folds. It just puts the working channel in a better orientation. We'll commonly use injection techniques, and so I preferentially use a wire coil needle because it works very well with the elevator lever of the duodenoscope. My standard injectate is methylene blue tinted normal saline with epinephrine 1 to 10,000. We use diluted epinephrine in the duodenum because there is such a high rate of back bleeding that it diminishes the degree to which bleeding from the puncture site can compromise your visual field. Certainly, other enthusiasts use other viscous agents, which can be exchanged readily. I preferentially use a stiff 15 millimeter diameter snare. We call it the mini snare in our unit. I preferentially use a coag current, but endocut is also very satisfactory. Retrieval of the specimen, of course, is important, and you need to avoid dropping it into the airway, so we use secure nets. We'll occasionally use a suction trap for piecemeal resection. And we have to be ready to manage bleeding. You can use clips, snare tip soft coagulation, or coag grasper has also been recently described. And miscellaneously, of course, you really need to use CO2 insufflation when you're working in the duodenum. It can be very uncomfortable for patients, and so we preferentially will use max sedation as well. So this is how we kind of get started. You can see the lateral extent of this lesion. It's maybe three to five centimeters. It extends over several folds and maybe incorporates about 30% of the luminal circumference. We're using a duodenoscope here, and we're able to demonstrate its orientation or relationship to the ampulla vata. And then we'll simply begin with a submucosal injection here. And this, of course, will serve to elevate the lesion away from the wall. Because we've used some diluted epinephrine, it immediately staunches that back bleeding. And I commonly will attempt to lift the entire lesion. And you can see that as you begin to efface those folds that these lesions can often turn out to be even bigger than you might have thought at the onset. And then we'll use that relatively stiff snare to engage the tissue, a gentle mechanical retraction. And we'll take our time with these. We're satisfied, based on visual inspection, that this is not a malignant lesion. And so while you'd like to take large pieces off, you want to temporize that with the risk of perforation. So we'll incrementally come around with that 15-millimeter snare. And ultimately, we'll conclude, as standard EMR technique developed in the colon, we'll try and get a little collar of normal tissue surrounding the lesion so as to reduce the risk of local residual recurrence. After resection, we'll generally place our patients on clear liquids overnight. We'll routinely place patients on a proton pump inhibitor for four weeks. This has been demonstrated from the gastric resection experience to reduce the risk of delayed bleeding. And it helps enhance resolution of the iatrogenic ulcer. Selected patients, if they have considerable comorbid disease or elderly, we may observe them overnight in the hospital because there is an increased risk of delayed bleeding. We typically have a structured follow-up at 6 to 12 months on an individualized basis. I mentioned delayed bleeding. And so we preferentially will close, currently, most resection sites if we can. And certainly, we're committed to doing it in patients who are going to be resuming anticoagulation therapy. It can't be done in all cases, but you should strive to. And of course, there are some challenges in using clips through the scope clips with the duodenoscope. I want to skip over that. This was one of our papers from our first paper that we published on endoscopic management of duodenal adenomas in 2010. And the purpose of this paper was to acknowledge that size matters. And we used the extent of luminal circumference. And while we were able to curatively resect the vast, almost 100% of lesions that were less than or up to 25% of the luminal circumference, this diminished considerably as you went up to 50% and beyond 50%. Now I will tell you, our endoscopic resection techniques have improved since that time. And we can boldly go where we did not go before. But the extent of luminal circumference is the best predictor of outcome in that regard. And failure, recurrence, and bleeding were more likely for lesions greater than 50% of the luminal circumference. This is some pooled data that came out of the Chicago group. Usma, who's going to be on the panel, helped put this together. And importantly, and this is our most recent series published this past year, showing that our average size of 25 millimeters, that will have success rates, clinical success rates greater than 90%, acceptable adverse events rates, and pretty predictable residual recurrence both early and late. But most of these will respond to additional therapy. And our data mirrors that published by the Chicago group, a Michael Burks group that focused on particularly large and giant lateral spreading lesions of the duodenum. Again, in the high 90% rate, residuals can be expected, but virtually always can be effectively treated. Importantly, no mortalities in any of the large published series. Finally, our most recent series with 162 patients, we would summarize, and it summarizes this section, that EMR can be performed safely and effectively for most sporadic non-ampullary duodenal adenomas. Increasing size of the adenoma is associated with increased recurrence and bleeding after EMR. No association with recurrence was noted with endoscopic or histologic features. Focal recurrence can be managed with additional endoscopic therapy. And importantly, metacognitive lesions don't occur for these sporadic. Moving on to ampullary tumors, these make up 5% of gastrointestinal neoplasms. And again, we're focusing on sporadic. We recognize that virtually all patients with FAP will have ampullary adenoma. Occasionally, we'll encounter neuroendocrine tumors, pseudotumors, and adenocarcinoma. And so it's important to confirm histopathology. The vast majority of these are incidental, and symptomatic presentation typically is associated with local advanced disease. They can be confined to the ampulla, they can extend up into the ampulla, and they can extend around the ampulla. And that's going to stir management. So what are the options? Well, you can observe with interval imaging and repeat tissue sampling looking for progression. You can use operative resection. Interval excision is not really done very much because of the high local recurrence. Most patients would be offered a Whipple resection or pancreatic duodenectomy, and we recognize its high morbidity. And so the preferred approach today is papillectomy, and occasionally thermal ablation for palliation only. It's important to recognize that what we do through an endoscope is truly papillectomy. That ampullectomy would require removing the entire ampullary structure, and that's only done operatively. Again, another scrapbook of ampulla, ampullary tumors that I have known, and again, they can vary considerably in their extent and their configuration and their prospects of extending up into the ampullary orifice. So management, of course, is very much dictated by the morphology of the lesion itself. We begin with inspection using duodenoscopy. As routine, we'll do repeat biopsy forceps tissue sampling. I have been referred at least a half dozen patients where the outside pathology claimed adenoma and was reviewed as being hyperplastic tissue of normal ampulla only, so you don't want to do an ampullectomy on those patients. We'll commonly do an endoscopic ultrasound exam at those times. You might consider ERCP to look for pancreas divisum up front, and we'll do the cholangiopancreatography at the time of the papillectomy. Han and Kim published criteria that are favorable for endoscopic papillectomy, so size less than four centimeters and less than one-third of the luminal circumference, no ulceration and clear recognizable margins. The lesion should be soft and mobile. There should be little or no intraductal extension and no invasive carcinoma on histopathology. So this is how we'll begin with our visual inspection. I'll use just the forceps here to probe the lesion, and what I want to do is ensure that the lesion is fully mobile, as you can see here. It's not fixed. It's not ulcerated, and we get a better idea of the dimensions of the lesion and how we're going to be able to attack it. Endoscopic ultrasound can be valuable. It does detect invasive carcinoma into the ampulla of vata. We see a nice preservation of the wall layer here. It can also give us information about intraductal spread. It does not accurately discriminate T1A versus T1B lesions. Chalangiography at the time of ampullectomy can rarely demonstrate the extension of intraductal tumor, and that's going to require some modification and management. Technique-wise, again, we'll use max sedation, CO2 insufflation, use a standard 25-millimeter snare because we want to do an on-block resection, if feasible. Electrosurgical injection has been championed by some. I limit it really just for lesions that extend laterally. In this case, electrosurgical current is important. You should be using a microprocessor-controlled electrosurgical generator with an endocut mode. And ideally, we'll do on-block versus piecemeal and post-papillectomy stenting and prorectal endomethicin. Retrieval of the specimen, of course, is critical. And it will provide the histopathologic prognosticators. We'll often use prophylactic IV glucagon to paralyze the bowel to enhance retrieval of the specimen. We'll use retrieval baskets. We'll want to protect the airway. If you lose the lesion, we'll go back with an enteroscope to pursue it. And, of course, we have a conversation with our pathologist to let them know what to expect. Very quickly, there's a literature on the use of pancreatic duct stenting, specifically in endoscopic papillectomy. And it's obvious that the stented group is favored. Now, of course, this was in the pre-endomethicin era. But we place a priority on pancreatic duct stenting. It's the first order of business after we do the papillectomy. Recognize that the pancreatic orifice will typically come in at about 5 o'clock from the bowel duct. We'll use a blunt-tip catheter to cannulate and place a 3 to 5 French stent, which we'll typically have removed in two weeks if we've not used one without internal barbs. This should be avoided in pancreas divisum. And, of course, we'll use endomethicin as well. Interprocedural bleeding is a common nuisance. And we'll treat this with injection of diluted epinephrine. Occasionally, we'll use clips or contact coagulation. And of course, we want to control the pancreatic duct orifice for that. For lesions with lateral extension, we'll do a piecemeal resection, isolating the ampulla, and then we'll chop that off on block. When we see incomplete resection or local recurrence or intraductal extension, we'll use a variety of tools and techniques. Typically, it'll involve extending the sphincterotomy and then using additional snare resection and ablation using multipolar electrocautery, RFA, APC, PDT, and even cryotherapy is making some inroads into this realm. Pooled data shows high success rates, 80 percent for long-term remission, complications higher than for the duodenal adenomas, but for the most part, excellent expected results. Spanning in pancreatitis can be expected in the 3 to 25 percent, but again, a very acceptable mortality. So, post-procedure, again, these are patients that we'll often keep overnight for observation at 23 hours. We'll manage that stent with a plain film in a week to ensure that it's spontaneously migrated, sphincterotomy is individualized, and again, a programmatic follow-up. Just a comment about FAP. This is an autosomal dominant genetic disorder. These patients have an unrelenting biologic behavior. They all have adenomas involved in the ampulla, and I think that resection is futile and does not alter the patient outcome and should be reserved only for selected patients with high-grade dysplasia who wish to postpone pancreatic duodenectomy. So, I'll leave you with these practice pearls. That endoscopic therapy for ampullary duodenal adenomas employs modifications of standard endoscopic protection techniques. It is technically more demanding. It's safe and effective in the majority of cases and compares favorably to operative resection and observation in most patients. Larger lesions are more challenging and are associated with increased adverse events as well as increased likelihood of residual or recurrent neoplasia, but outcomes are likely improved when performed at expert centers. So, thank you. Thank you.

ampullary adenomas

duodenal adenomas

endoscopic resection

follow-up recommendations

endoscopic therapy