Thank you. Dr. Kahl and I are going to talk about pancreatic masses. To start our objectives today, we'll start with the differential diagnosis of a pancreatic mass on imaging. We'll talk a little bit about the evaluation and the risk stratification, go through a couple of case studies, and then we'll end with those key take-home points. When we see a CAT scan such as this one, this is a contrast enhanced CT scan of the abdomen, and it's showing a four by five centimeter enhancing mass in the head of the pancreas. Some of the things that we're thinking about is a pancreatic adenocarcinoma. Neuroendocrine tumors can be solid or they can be solid and cystic. Solid pseudopapillary tumors, lymphomas, and metastatic cancer. We can also see pancreatic masses in more benign conditions, like a focal pancreatitis and autoimmune pancreatitis can be mass-forming. Then there's some less common things like the intrapancreatic spleens, intrapancreatic lymph nodes, and just lesions. How do we evaluate these? Oftentimes, the first step is cross-sectional imaging. That's your CAT scans, your MRIs, maybe a PET scan or a PET DOTATATE scan. The PET DOTATATE scan is certainly more sensitive and specific for neuroendocrine tumors. Endoscopic ultrasound can also be helpful. Blood work, so the CA-19-9, particularly looking for pancreatic adenocarcinoma. Chromogranin A-level, we're thinking possibly a neuroendocrine tumor, and then those autoimmune serologies. Your ANA, IgG4, and total IgG, if there's a strong suspicion for autoimmune pancreatitis. Then there's the endoscopic ultrasound with fine-needle aspiration or fine-needle biopsy. That's important to get that cytology for diagnosis. The fine-needle biopsy can also be used for molecular testing in the cases of adenocarcinoma. Dr. Kaul, do you want to comment on FNA versus FNB? Just a comment I wanted to make on the differential diagnosis of solid pancreatic masses. This is a great list, and this list was created for a reason. The vast majority of the time, at least in the American context, a solid pancreatic mass is almost invariably invoked to be pancreatic adenocarcinoma. Now, whereas statistically in the right clinical setting, that may be true the majority of the time in this country or in the Western world, there's a wide variety of other things that can be between benign and malignant solid lesions, and many of them are listed here. In other parts of the world, tuberculosis can be a differential diagnosis, including other infections that present a solid lesion. So keep in mind that just because somebody has a pancreatic head or body mass, it's not a death sentence like it's commonly invoked, which also belabors the point that it is important as far as possible to get a firm tissue diagnosis in these patients, especially if they are older patients, and especially if it's a disease that's not amenable to surgical cure, because you need to have a firm diagnosis. And there's a bunch of benign entities that can present in this manner. There's also a lot of variables around protocols and quality of imaging, interpretation, standardization versus not of how images are read, the fact that solid lesions can have cystic components, cystic lesions can have solid components. This is not a simple space. So treat a solid pancreatic mass report with a lot of respect, make sure the right people are looking at it, and that the right steps are taken as the next steps in that particular patient. For the next slide, I think the question was around EUS. Most certainly, tissue sampling with EUS is the most efficient diagnostic paradigm that has emerged in this space in the last two decades. And even that has evolved, as Sarah mentioned, from an FNA paradigm to an FNB paradigm. For the most part, if your question is whether a carcinoma is present or not, FNA should be able to answer that. These needles are generally a little easier for the average endosynographer to manipulate. But if the question is that which requires more tissue, volume of tissue, or if it requires further molecular profiling, such as that we use for personalized cancer chemotherapy, then you need some more robust tissue samples, and the core biopsy needles afford you those. And there are other indications for core biopsies outside of pancreatic head tumors. But that's my comment on FNA versus FNB. And here you see at the EUS level, this is a pretty representative sample of hypoechoic lesion, which is relatively discrete in a part of the pancreas, and it's not involving a vascular structure, so that's good. Just looking at this lesion, my guess would be that this could be a representative lesion like a neuroendocrine tumor, or if the patient is really, really lucky, while being, of course, unlucky, but lucky to have such a small adenocarcinoma, this would be the type of lesion that could be completely cured by surgery and have that longer five-year survival. Please go ahead. So we have a couple of cases, and these are representative of patients that we have seen in the last few months in our collaborative practice. So the first one is a 72-year-old female who has a past medical history significant for breast cancer, treated 20 years ago with radiation and surgery. She also has hypothyroidism. You can see her medications there. Other than that, she really doesn't have a significant family history. She does have a 60-pack-year history of tobacco use, and she presents with a 45-pound unintentional weight loss over the last one year. So her primary care saw her for this weight loss and ended up starting with a transabdominal ultrasound and showed a 3.7-centimeter hypoechoic pancreatic head mass. Ultrasounds are often challenging when we talk about the pancreas. Because of our overlying bowel gas and the gas in the stomach, we can't often see the entire pancreas. When it does show something, certainly it gives us some guidance. But when ultrasounds don't show the pancreas well, if there's a high index of suspicion for something in the pancreas, it's important to follow that up with cross-sectional imaging. So for this patient, she was referred to our office after that ultrasound. And on further discussion, she does admit to dark urine as well as a colic stools for the last one week. She doesn't have any complaints of abdominal pain, fever, chills, early satiety, loss of appetite. So we're essentially seeing her for painless jaundice, a pancreatic head mass on ultrasound, no signs of cholangitis. Her physical exam was unremarkable. And you can see on her blood work that she has that evidence of biliary obstruction with her bilirubin of 3.4 and her alkaline phosphatase over 1,300. Her CA-19-9 was 667. So at this point, prior to moving forward with any procedures, we did get a pancreatic protocol CT scan. And two points I'll make on this. We're showing both the axial and the coronal view. So the axial view are those horizontal cuts. If you're thinking of the magician that we always see on the stage where they put those knives horizontally through somebody, that's really what we're looking at on an image. Everything in medicine is a mirror image. So what we're seeing on the left side is the right of the patient. And this is showing that pancreatic mass. The CT scan shows that it's about four by three and a half centimeters. It is causing compression on the distal conus. As well as some dilation of the pancreatic duct. Dr. Kwon, any other thoughts on these? Yes, if you go to the previous slide, please. So I think take a moment to reflect on these LFTs. This is a patient who has no fever, denies much abdominal pain, and comes with these what we call obstructive pattern LFTs. And comes with these what we call obstructive pattern LFTs. These are pretty representative of an obstructive process combined with a imaging study showing biliary dilatation. So that's kind of sort of how you triage these. And when the referrals come in, you already kind of know what the CT is going to likely show. And then the second point here is the tumor marker CA19-9, which is significantly elevated in the absence of any inflammatory process. Whenever you have a CA19-9, which is a tumor marker for both pancreas and biliary cancer, and there is no inflammation such as acute or chronic pancreatitis, acute alcoholic hepatitis, and so forth, that is very, very concerning for tumor. And in general, the higher the CA19-9 level is, it does tend to correlate the level of the advancement of the disease. In other words, if you see a CA19-9 of 25,000, it is very likely that the patient has metastatic disease, carcinomatosis, malignant ascites, or some other occult malignancy that has gone beyond the abdomen. So it's a useful test when it fits the story. It is not useful when there are confounding variables present. Next slide, please. CT scan, again, is very helpful. As Sarah mentioned, the bottom pictures here are demonstrating to you the nature of the cut. In the left side, you're looking at the patient from the feet, above towards the head, and on the right side, you're looking at the patient face on. And these tell you different images, but essentially the story is that there is a hypodense lesion in the pancreas, very concerning. And the next steps here, Sarah will elaborate on those. It is a contrasted study, which is a bare requisite for this situation. Yeah, so this patient then was scheduled for both ERCP and endoscopic ultrasound. And Dr. Kahl, I'll defer to you on this slide. Yeah, so radiological imaging, ERCP images, these are important for APPs to get familiar with. I am told that there is not a lot of emphasis on this, obviously, in the core curriculum. So here we have an opportunity to review these. This is the endoscope, the duodenoscope, which is the classic scope used to perform ERCP. Somewhere over here is the major papilla. And as you can see, there is no contrast in the distal bile duct. And if you were to do an EOS here or put an image graphic over here, the pancreas would be somewhere over here with the head of the pancreas in this location. So the distal end of the bile duct normally traverses through the head of the pancreas. And whenever the head of the pancreas or the neck of the pancreas has a tumor, this is the first area that gets obstructed. And that is consistent with this proximal bile duct dilatation. This is the wire over here. And so this is the area of interest. This is certainly somewhere where we will perform tissue sampling and potentially intraductal biopsies as well. And as you can see here in the next area here, there's some sampling going on, some additional contrast being put to delineate the structure. And in the final image here, you can see a stent. So Sarah, you can elaborate what went on in this ERCP as described here. Yeah, so during this ERCP, the first thing that was noted was that her duodenal anatomy was unfortunately distorted because of tumor compression. And we know that she did not have an obstruction because on her CAT scan, we didn't see that the duodenum was significantly dilated. But it did make for a difficult biliary cannulation. That stricture, as Dr. Qualt mentioned, in the common bile duct was seen. Sphincterotomy was performed, so cutting the papilla and being able to then put the catheter with the balloon dilation. And then ultimately, that stent for drainage. And in the same session, she also had the endoscopic ultrasound with fine needle aspiration. And that cytology confirmed a pancreatic ductal adenocarcinoma. And what we wanted to highlight here is that when you use endoscopic ultrasound for FNA of these pancreatic masses, their accuracy is quite high, 94%, with a specificity of 100% and a sensitivity of 83%. Here again, you see an EOS image showing the FNA being performed. And a lot of these questions have come over the years about the efficiency of EOS FNA with regards to a diagnostic capability. And I think that debate is pretty much settled. We can talk about it offline as well. But a competent endosynographer performing FNA with experience, and of course, a lab that is used to looking at these samples should be able to come to a 90% to 95% accuracy and diagnostic yield in the vast majority of cases. There are still some difficult cases where the results are not clear from the first sampling, but they then undergo salvage procedures such as core biopsies or some other type of dual modality tissue sampling. And most of these cases we're able to diagnose pretty accurately. And so just an overview of pancreatic adenocarcinoma. For the purpose of this talk, we don't have the time to go into all of it. That could be a talk of its own. But this is the third leading cause of cancer-related death in the United States after lung and colon cancer with a lifetime risk of one in 64. It's more common in males, African-Americans, and it's rare less than 45 years old, although we certainly have seen that. There are several risk factors to be aware of. Some of those are hereditary, chronic pancreatitis, and then certainly the environmental risk factors as well. And there are known genetic mutations that put you at higher risk for pancreatic cancer, such as the BRCA genes, BRCA1 and 2. And so once a patient's diagnosed with pancreatic adenocarcinoma, they are referred for multidisciplinary evaluation and consultation with medical radiation oncology and surgical oncology. They may require systemic chemotherapy prior to surgery, very frequently do. If they are found at an early enough stage, surgery is the treatment of choice. And then there is a role for endoscopic palliation. Dr. Kal, do you want to speak to that? Right, so, you know, the treatment management really is the right word. Management of pancreatic adenocarcinoma obviously is well known to most of us, but for those who are coming in new into the space, the only real modality for cure is surgery, which is what I referred to about a few minutes ago. You have a small tumor in a young, surgically fit patient, surgery is the only curative therapy that we know. Short of that, systemic chemotherapy and bits and pieces of endoscopic palliation and therapy are really what most patients, about 80, 85% of patients will undergo. And then there are many paradigms around protocols and trials and our neoadjuvant therapy. Some people have even used protocolized radiation before and after surgery, very limited role. Other types of percutaneous and endoscopic ablations, but a lot of that new stuff is still kind of not mainstream. But once you get to obstructed duodenums and obstructed bile ducts, you're looking at stenting in non-surgical patients and the median time to survive varies, but has extended a little bit from two decades ago, but the vast majority of these patients will not make it to five years. So it's a difficult space. There is some hope with immunotherapy and some newer treatments, but I think overall the space remains difficult for those patients who don't end up with surgery. So this patient had neoadjuvant chemotherapy. She was stented to alleviate that biliary obstruction. Unfortunately, she was found to have liver metastasis just shortly after diagnosis and she passed away about 11 months later. So changing our focus a little bit, this is a different patient who came in, a 22-year-old female who really doesn't have a significant medical history. She has a history of exercise-induced asthma, which was well-controlled with just an inhaler as needed, and a history of migraine headaches. No prior surgeries, no significant family history, and she presented with a complaint of progressive fullness in the left upper quadrant for one year. She initially said that she had noticed it, but it really wasn't bothersome, wasn't causing any other symptoms, kind of thought maybe she was a little bit bloated, but over the last 12 months, she was noticing that it was becoming more prominent. And when I saw her in the office, she really had no complaints. She was eating well, didn't have any nausea or vomiting, denied early satiety, hadn't had any weight loss, no other changes that she could think of. On physical exam, she did have a palpable non-tender mass in the left upper quadrant, and this really was best appreciated when she was exhaling or when she was sitting. Did routine blood work, CBC and CMP, which were within normal limits. Those were actually done prior to coming into our office. And she had this ultrasound. So this ultrasound showing a nearly 12-centimeter, pretty solid vascular-appearing mass within the left abdomen, and hard to tell definitively, but looks like it's coming from the pancreatic tail. And then she had an MRI with and without contrast. And what we can see, if we look at the last image, you can see that it's enhancing on that arterial phase of the MRI. We can also appreciate that there is some extrinsic compression on the stomach. Even though she wasn't symptomatic, it certainly is large and it's starting to cause that compression. Dr. Call, thoughts on this? Right, so, you know, this is a patient, clearly a different type of situation. It's a lesion, which is very large. And we are thinking of a different differential diagnosis here. You know, typically the appearance of this lesion on the MRI is a little different compared to your usual adenocarcinoma cases. The patient, I believe, is a little bit young, if I remember correctly from the previous slide. And so I think in this particular case, I'm invoking some different differential diagnosis, maybe not your garden variety adenocarcinoma type of patient. And most certainly, then the question comes is, should we perform an EOS on this patient? Should we refer the patient directly to surgery? And so forth. So these questions do come up. And I think in this particular case, we did proceed with an EOS serum. We actually went straight to surgery. And so question just for our audience, while we're kind of going through and talking through this, based on the age and the appearance and her presentation, any thoughts on what this diagnosis could be? So as you've rightly pointed out, the usual suspects are here, but there's also an interesting entity here listed as a pseudo-papillary tumor. And, you know, that needs to be considered. And metastatic cancer certainly is a possibility, but we'll see what the audience thinks about. Yeah, so I got a mixture there. Sorry? I said a good mixture between solid pseudo-papillary and pancreatic neuroendocrine. Yes, I think I did agree. Which makes the most sense, based on her age. Sorry, go ahead. So for this particular case, we had actually referred her to surgery because of the size of it and the fact that it was starting to compress on the stomach even though she wasn't symptomatic. The thought process was that she would have to eventually undergo surgery either way from a symptom standpoint. During the surgical consult, they felt that she was a good surgical candidate, and so she went forward from there. And even just in the interest of time, I was gonna move forward from here. That's okay. So this was one of the cases that Dr. Call and I talk about quite a bit, when we see these patients, which ones are appropriate to not have endoscopic ultrasound versus those that should have a cytology diagnosis? And that's really where we invoke that multidisciplinary discussion in those consultations with the surgeon directly. Dr. Call, thoughts there? Yeah, I mean, I think that's why I mentioned, a lot of the times our hand is forced to perform EOS on these patients. And you could almost say, you could almost have this discussion around whether direct to surgery is good, EOS is good, some patients want to know the diagnosis, some surgeons want to know the diagnosis. And actually, if you remember correctly, last week, we had a patient be diagnosed with a sort of epileptic tumor. And then also a month ago, we had a younger female patient that we sent directly to surgery. So I was almost gonna say that, the practice patterns reflect what the real discussions are. I don't think there's a right or wrong answer here, but I think direct to surgery is fine. In some cases, there is a concern around certain other diagnoses where chemotherapy prior to surgery might be the right approach. So then the patient goes to the tumor board and the final decision is based on consensus. Please go ahead. The big takeaway here is that these are predominantly found in females, over 90%. They're often pretty large, the mean is 10 centimeters, and they have a high risk for malignant transformation. And so surgical consult is appropriate. Like Dr. Call was saying, sometimes they need that endoscopic ultrasound for diagnosis, other times, just depending on their appearance and their symptoms and their size, they may go direct to surgery. And so these graphics are representative of the surgery that she had. You can see on the top graphic that the red arrow is pointing to the tumor. It is in close proximity to the spleen and it's part of the tail of the pancreas. So she underwent a distal pancreatectomy and splenectomy. In the bottom image, the blue circle's representative of the portions that were removed. And the pathology came back as a T3N0 solid pseudopopulary neoplasm. The total size was 12 centimeters. It was confined to the pancreas with no lymphovascular invasion, negative surgical margins, and she's doing quite well. And Dr. Call, I'm gonna let you speak to this when we talk about patients who have acute pancreatitis, particularly that idiopathic acute pancreatitis and looking for pancreatic cancer. Right, no, I know that we are pretty much on the end of time, but this is an important paradigm that all of you in practice will see, which is a lot of pancreatitis is out there in the community, they come in, and every so often, some of those patients, and we did the study, found that about nearly 3.5 to 5%, depending on the situation, will have a pancreatic malignancy. So it is very difficult to identify bona fide pancreatic neoplasia in the setting of inflammation. So the take-home message here is whenever there is an acute pancreatitis that is not easily explained, the patient continues to have persistent symptoms, do not just let those patients go, follow them up with a follow-up CT scan, have a relatively low threshold for EUS, and you can see here, this patient came into the hospital and then soon after had an EUS, and you can see the resolution of the EUS in terms of finding the pancreatic lesion was much better than the CT scan, and this patient had a malignancy. So in some patients with acute pancreatitis, a very small percentage, the reason for the pancreatitis will be a pancreatic cancer. Don't miss that. That is the message here. This is like a proposed algorithm for the workup of idiopathic acute pancreatitis. This is a paper from a few years ago, actually right before COVID, and it basically talks about the same concept that I just explained, signs and symptoms of acute or chronic pancreatitis. These patients have a clear etiology, manage the etiology, that's fine, and then you're done. But if you have an unclear etiology, then you need to follow through with high-quality imaging. If there's a mass on that imaging, follow it up with FNA and EUS. If there's no mass, then you continue to follow until resolution or until you find the problem. So that is the message from this paper. It's one of the few on this topic specifically and something worth looking up. Sarah. And we'll just real quick look at a couple other diagnoses that we see that come as a pancreatic mass. So this was a mass-forming chronic pancreatitis or autoimmune pancreatitis that presented with a three and a half centimeter pancreatic head mass. There were also multiple enlarged peripancreatic lymph nodes and the bile ducts at the time of diagnosis were dilated. This patient had been treated after we evaluated them and they had the endoscopic ultrasound, which gave us a little bit more diagnostic ability. And they were started on azathioprine and prednisone and that mass actually completely resolved. And this is a serocyst adenoma, so it has a honeycomb-like appearance. The individual cysts are generally quite small, usually less than two centimeters, but it looks like a multi-cystic lobulated mass. And this patient also has quite a few gallstones that you can see. And then this one was a pancreatic neuroendocrine tumor. This one's quite a bit smaller like the endoscopic ultrasound image that we saw early on in this talk. It has homogenous enhancement on the arterial phase and it's well-defined. And then this patient had a pancreatic adenocarcinoma in the head of the pancreas and it was causing a common bile duct stricture, which is what the red arrow is pointing to on this MRCP image. And so to summarize, transabdominal ultrasound unfortunately rarely visualizes the entire pancreas. And so pancreatic protocol CT scan is the most frequent used imaging modality for pancreatic masses. This is most helpful when it's dual phase, arterial and portal, and contrast enhanced. As Dr. Call was informing us, endoscopic ultrasound with fine needle aspiration is the gold standard for sampling pancreatic masses. MRCP is very helpful for biliary and pancreatic duct stricture evaluation, but the quality of the imaging, the diagnostic certainty and multidisciplinary management are the key to good outcomes. Any final words, Dr. Call? No, this was excellent. I think if we follow these final principles regularly, consistently across the board, we're likely to not miss too much cancer out there and also be able to provide the state of the art management to our patients. That was well done. Thank you.

pancreatic masses

differential diagnoses

evaluation methods

multidisciplinary consultations

adenocarcinomas

neuroendocrine tumors