We'll move on to our next talk. We'll be given by Vanessa Shammy from University of Virginia. Unfortunately, Dr. Shammy could not join us physically, so we will watch a recorded talk that she did for us very kindly late last night. I'd like to thank the course directors for the privilege of speaking with you today. Why care about pancreatic cysts? Well, we know a subset of pancreatic cysts are premalignant and may become a cancer. In a meta-analysis of 6,200 patients with IPMNs, 0.24% developed malignancy. Understanding the nuances of various cysts and the multiple guidelines is critically important for their management. Now, cysts with malignant potential are what we're talking about. We're talking about the mucinocystic neoplasms and the IPMNs, and these are the ones we're concentrating on. Now, some pancreatic cysts will become cancers. How do we identify which cysts to survey and which to resect? Now, let's look at the timeline of guidelines for management of pancreatic cysts. Now, first, we had the Sundai Guidelines in 2006, and this is based on the fact that this guideline was developed in Sundai, Japan. It was then revised in Fukuoka, Japan, in 2012, and finally again in 2017, and it's called the International Consensus Guidelines. Then we have the European Guidelines, which were developed in 2013 and revised in 2018. The AGA Guidelines, which were developed in 2015 and a little bit different and more controversial than the other guidelines. We'll talk about that. And finally, the ACG Guidelines in 2018. We are going to concentrate on the most updated guidelines here in this red box. So, before we start, I really would like to go through some no-brainer concepts. If the patient is symptomatic from the cyst, they're going to undergo surgery. If they have an associated mass, they're going to undergo surgery. Consider surveillance only if the patient is a surgical candidate and willing to undergo surgery and or the patient is willing to undergo systemic therapy. Now, let's first talk about MCNs. Now, these are treated like IPMNs in the majority of the guidelines. The only one that recommends resection in good surgical candidates is the International Consensus Guidelines, so keep this in mind. Now, this is a 60-year-old gentleman with an incidentally found cyst in the tail of his pancreas. It measures 2.5 centimeters. Remember this case as we go through the guidelines. Now, first, the International Consensus Guidelines. You look for high-risk stigmata, which include obstructive jaundice, enhancing neural nodule greater than 5 millimeters, and dilated main pancreatic duct over 10 millimeters. If the patient has any of these, they go to surgery. If not, then you look for worrisome features, which include clinically pancreatitis, imaging-wise, a cyst greater than 3 centimeter, enhancing neural nodule, thickened, enhancing cyst walls, main pancreatic duct size of 5 to 9 millimeters, abrupt change in the caliber of the pancreatic duct with distal pancreatic atrophy, lymphadenopathy, increased serum level of CA-19-9, cyst growth rate of greater than 5 millimeters over two years. If you have any of these, they'll go to EUS. If not, they're going to enter a surveillance program based on size. What you can see is that this is heavily based on EUS more than any other guidelines. So EUS makes it into the surveillance for any cyst that's 2 centimeters or greater. Now, in terms of our patient, they had no high-risk or worrisome features. The patient's size cyst was 2.5 centimeters. So if you follow this guideline, the patient would undergo an EUS in three months. So the main criticism of this guideline is that it's fairly aggressive in surveillance intervals. You can see if the cyst is greater than 3 centimeters, the patient's going to go MRI with EUS every three to six months. That's pretty taxing. There's little mention of when to stop surveillance. Then we have the AGA guidelines, in which case you need two high-risk features in order to undergo EUS FNA. So if you have a dilated main pancreatic duct and or a 3-centimeter cyst and or a solid component, again, two out of three of these, then you undergo EUS FNA. And I remember that you need two because AGA has two A's. Simple, but something I remember. If not, the patient undergoes a surveillance MRI program in which they undergo MRI in one year and then every two years to the five-year mark. If there is no change in the cyst size at five years, then you're done with surveillance. So very different, again, in the number of high-risk criteria and also the fact that you stop surveillance. Now, if you look at our patient with a 2.5-centimeter pancreatic tail cyst, they would undergo MRI in one year since they have no high-risk features. So again, the controversy of the AGA guidelines are that you stop, you discontinue cyst surveillance after five years if there's no change in cyst size. And also, when there is a – you need two out of three high-risk stigmata or features in order to undergo EUS. Next, we have the ACG guidelines, which are very similar to the international consensus guidelines in that if you have any high-risk – if you don't have any high-risk features or worrisome features, then you look at size and you enter surveillance program based on size. The difference is this is not as EUS-heavy. And the only time you get an EUS is if you are unsure what the cyst is and the cyst size is two to three centimeters. In the case of our 2.5-centimeter asymptomatic cyst, patient had no worrisome features, no high-risk features, cyst size was 2.5. Again, we were unclear whether the patient had an IPMN or MCN, so the patient should undergo EUS FNA. This is just to demonstrate the comparison. The ACG and international consensus guidelines, again, are very similar. The ACG guidelines are just less intense in terms of surveillance in the first year and are less dependent on EUS. Finally, we've got the European guidelines. What's kind of unique about them is they actually tell you if the patient is unfit for surgery that no follow-up is required. The other guidelines don't, although they imply it. Again, if you have absolute indications, which are very similar to the others, for surgery, then you go on to surgery. Relative indications, it depends on the operative candidacy of the patient. But if the patient has no high-risk features or relative indications for resection, then they undergo a surveillance program like our patient would undergo. And that surveillance program, if we look at it closer, would be a clinical evaluation, serum CA-19-9, and an MRI or EUS every six months. And this is what would be recommended for our patient with a 2.5-centimeter cyst. Now, keep in mind that the guidelines are pretty similar. In terms of indications for surgery, high-risk cytology, obviously suspicious cytology, solid component or a large mural nodule, dilated pancreatic duct, these are all similar in all of the guidelines. Let's simplify this. So what do none of the guidelines consider? Well, fluid analysis and molecular markers. And that may work itself in over the next few years. Now, my partner did a very unique modeling study where he took patients that had IPMNs, and they were surveyed through the AGA guidelines and the consensus guidelines. And this was estimating 0.24% cancer over a 15-year period. And what he saw was that it cost $1.2 million per additional cancer identified, so quite expensive. Now, all-cause mortality was similar. With the AGA guidelines, which were a little bit more conservative, more patients died of pancreatic cancer. However, with the consensus guidelines, which was more aggressive, more people died of surgery. So do you die of surgery or do you the treatment or do you die of the disease? And again, there's no easy answer to this. There are a myriad of studies that have been done, and the bottom line is following the AGA guidelines would result in fewer unnecessary surgeries at the expense of missing malignant cysts. So back to our case of the 2.5-centimeter incidentally found pancreatic tail cyst. If you follow the international consensus guidelines, they were recommended in the U.S. in three to six months, AGA, MRI in one year, ACG, U.S., and European guidelines, U.S. and or MRI in six months. If you look at it, AGA and the European guidelines would recommend waiting, and so would the Fukuoka a little bit, but the ACG guidelines would recommend. So we perform an EUS, we see a cystic component, and lo and behold, there's a solid mass, and we do a fine-needle aspiration, and the patient has adenocarcinoma, much to our surprise. Much to our surprise. So if you follow the AGA guidelines, you would have waited a year for an MRI, but on the other hand, we know the AGA guidelines preserves many people from going on to surgery. So again, there's no right or wrong answer. Follow a guideline and also use your clinical judgment. In conclusion, use your brain and the guidelines. Don't survey. If the patient is not a surgical candidate, review the surgery or systemic therapy. Despite differences in controversy, guidelines suggest a roughly similar approach. You want to evaluate for surgery if the patient has a dilated PD, mural nodule, associated mass, or positive cytology or biopsy. Thank you.

pancreatic cysts

guidelines

surveillance

surgery

clinical judgment