Smilow Shares with Primary Care: Pancreatic Cysts and Cancer

Transcript

• 00:00Yeah. I'm Anne Chang and
• 00:02I have been running, Smilo
• 00:04shares with primary care Zoom
• 00:06lecture series,
• 00:08and the idea is that
• 00:10we are focusing on areas
• 00:12of overlap between primary care
• 00:14and oncology,
• 00:16whether that's cancer screening, cancer
• 00:18diagnosis,
• 00:19figuring out what to do
• 00:20with something that might be
• 00:21cancer, or following up after
• 00:23somebody's recovered
• 00:24from cancer.
• 00:27This is our third year,
• 00:28and today's session is just
• 00:30as wonderful, if not more
• 00:32so, than all of the
• 00:33others. And I think,
• 00:34you will find it,
• 00:36excellent. The topic is pancreatic
• 00:39cysts and cancer.
• 00:41As you know, we're finding
• 00:43a lot more pancreatic lesions,
• 00:45and lots of guidance is
• 00:47needed, and, it is here
• 00:49today.
• 00:51As always, we are joined
• 00:52by an NEMG
• 00:54primary care colleague as well
• 00:56as specialist from Spinal Cancer
• 00:59Center.
• 01:00I'll introduce Flora Zarku Power,
• 01:03who is a colleague at
• 01:05Northeast Medical Group.
• 01:07She is a graduate of
• 01:08the University of Medicine in
• 01:10Karol Davila, Bucharest,
• 01:11Romania,
• 01:12and completed her internal medicine
• 01:14residency at New York Presbyterian
• 01:16Hospital in Queens.
• 01:18She joined the medical staff
• 01:20of Yale New Haven Hospital
• 01:22several years ago as a
• 01:24hospitalist before joining
• 01:26into our community practices
• 01:28in Milford.
• 01:29She's now both a practicing
• 01:31physician and a managing partner
• 01:33of PrimeMed, which is part
• 01:34of a Northeast Medical Group.
• 01:36She's an active member of
• 01:38the Milford and Bridgeport area
• 01:39medical community. She served on
• 01:41executive medical staff committee at
• 01:42Bridgeport Hospital
• 01:44and participated in the Emerging
• 01:45Leadership Program through the Yale
• 01:47School of Management.
• 01:48She's a full time active
• 01:50clinician
• 01:51and helps lend her expertise
• 01:54to primary care workflows and
• 01:55especially the Care Signature pathways
• 01:57where she has helped to
• 01:59author more than almost any
• 02:01other primary care clinician that
• 02:03works with us.
• 02:05She strongly believes in Sacrosanct
• 02:07doctor patient relationship as a
• 02:08keystone to great health outcomes,
• 02:10and I think that will
• 02:11come through today.
• 02:12And I'm gonna turn it
• 02:13over to you to introduce
• 02:14our Smiley colleagues.
• 02:17Thank you, Karen.
• 02:18And as always, a pleasure
• 02:20to,
• 02:21host this with you, and,
• 02:24we have a great program
• 02:25tonight. So we have doctor
• 02:26James Farrell,
• 02:27professor of medicine and surgery
• 02:29and director of the Yale
• 02:30Center for pancreatic disease.
• 02:32He's an internationally recognized expert
• 02:34in pancreatic disease treatment and
• 02:36research.
• 02:37In addition to his clinical
• 02:38work,
• 02:39in the on the endoscopic
• 02:41evaluation of autoimmune pancreatitis
• 02:43and pancreatic cysts, he's also
• 02:45known for his development of
• 02:46personalized therapy approaches for pancreatic
• 02:49cancer and early detection biomarkers
• 02:52for pancreatic cancer.
• 02:54He received his medical degree
• 02:56from University College Dublin, Ireland,
• 03:00graduated first in his medical
• 03:02school class.
• 03:03He completed internal medicine training
• 03:05at Johns Hopkins
• 03:07and then both a, gastroenterology
• 03:10gastroenterology
• 03:11and advanced therapeutic
• 03:13endoscopic fellowship
• 03:14at MGH in Hartford,
• 03:16medical school in Boston.
• 03:18After fellowship, he went to
• 03:19UCLA Medical Center
• 03:22where he developed,
• 03:24the largest endoscopic ultrasound program
• 03:27in California and became a
• 03:28founding member of the UCLA
• 03:30Center for Pancreatic Diseases. And
• 03:33in two thousand thirteen, he
• 03:34was recruited to lead the
• 03:35Yale Center for pancreatic diseases
• 03:37at the Yale School of
• 03:38Medicine,
• 03:39while also joining the existing
• 03:41Yale interventional endoscopy
• 03:43program.
• 03:44He currently directs the Smile
• 03:46of Cancer Center high risk
• 03:48pancreas
• 03:48cancer early detection clinic and
• 03:51the Yale Digestive Health pancreatic
• 03:53cyst program.
• 03:55We also have doctor John
• 03:56Kunstmann,
• 03:58and he's MDMHS.
• 04:00He's a board certified surgeon
• 04:02specializing in the care of
• 04:03patients with cancers or benign
• 04:05diseases of the pancreas, liver,
• 04:07bile ducts, stomach, and intestines.
• 04:09He attended medical school at
• 04:11the University of Wisconsin School
• 04:13of Medicine and Public Health.
• 04:15Doctor Kunstmann,
• 04:16completed residency training in general
• 04:19surgery at Yale as well
• 04:20as a fellowship in complex
• 04:22general surgery surgical oncology at
• 04:25Memorial Sloan Kettering Cancer Center
• 04:27in New York City, and
• 04:28he also holds a master's
• 04:29degree from Yale University.
• 04:32He has a special interest
• 04:33in the treatment of patients
• 04:34with cystic diseases of the
• 04:36pancreas,
• 04:37and he maintains an active
• 04:38research program at Yale examining,
• 04:41development of such cystic lesions
• 04:42as well as the genetics
• 04:44of those,
• 04:45of associated pancreatic cancer,
• 04:48and is seeking to improve
• 04:49the outcomes of those patients
• 04:51undergoing pancreatic surgery. So thank
• 04:53you all for attending. And
• 04:54I'm gonna hand it over
• 04:56to Flora.
• 04:59Thank you, Anne. Thank you,
• 05:00Karen, for the warm introduction.
• 05:01I'm delighted to be here
• 05:02with my colleagues.
• 05:05And I wanna say thank
• 05:06you to all those tuning
• 05:07in.
• 05:08So why are pancreatic cysts
• 05:09being identified more?
• 05:12Well, virtually every American that
• 05:14goes to the doctor with
• 05:15abdominal pain gets an abdominal
• 05:17CT. Or,
• 05:19if you roll through ER,
• 05:20you might be getting a
• 05:21CT even if you don't
• 05:22have abdominal pain.
• 05:24So one study years ago
• 05:25show that two point six
• 05:26percent of patients found to
• 05:27have a pancreatic cyst on
• 05:30CT scan.
• 05:32If you add abdominal ultrasound,
• 05:34MRIs,
• 05:36eventually, this leads to a
• 05:38good number of cysts that
• 05:39are identified every year, more
• 05:41than half a million.
• 05:43Next slide.
• 05:45What is the challenge?
• 05:46Well, there's multi
• 05:49faceted
• 05:50challenges here. So one,
• 05:53finding a pancreatic cyst is
• 05:54concerning for the patient and
• 05:55their family.
• 05:57With patients having access to
• 05:58the health record on the
• 06:00system,
• 06:01They might be reading actually
• 06:02their CAT scan even before
• 06:03you you get to, read
• 06:05the report. So that leads
• 06:07to fear and angst.
• 06:09It's challenging for the radiologist.
• 06:11They,
• 06:12hedge from time to time,
• 06:14and, that's the basis on
• 06:15which they operate daily.
• 06:17So it is a hard
• 06:18decision to eventually,
• 06:20decide between an overcall versus
• 06:22a realistic risk assessment
• 06:24when they realize that there's
• 06:26something wrong on the CAT
• 06:27scan.
• 06:28It's challenging for the gastroenterologist.
• 06:31Thank you, James, for pointing
• 06:32this out. It's tough to
• 06:33decide who needs an endoscopic
• 06:35ultrasound
• 06:36and who needs to be
• 06:37surveyed and how.
• 06:40Of course, lastly,
• 06:42but
• 06:43most importantly, probably,
• 06:45it's challenging for the surgeon.
• 06:46Like any oncologic
• 06:48disease,
• 06:49it is a matter of
• 06:50balancing
• 06:51biology of the lesion, which
• 06:53sometimes is not known,
• 06:55with the comorbidities of the
• 06:56patient
• 06:57and certainly,
• 06:59location of the lesion.
• 07:00Pancreatic cysts reside in a
• 07:02very high priced real estate.
• 07:04A pancreas is surrounded by
• 07:05very important structures.
• 07:07And, obviously, considering the technical
• 07:10aspects of the operations as
• 07:11well, which, altogether
• 07:14could lead to certainly a
• 07:15tough decision to make.
• 07:17So what are today's objectives?
• 07:20Well, we're gonna learn about
• 07:21cyst management and surveillance of
• 07:23the pancreatic cyst.
• 07:25We're gonna learn about the
• 07:26most common pancreatic cyst and
• 07:28their characteristic features.
• 07:30We're gonna hear about what
• 07:32tools we have to help
• 07:33distinguish benign cyst from those
• 07:34with malignant potential,
• 07:36how helpful these tools are
• 07:38and how to interpret them,
• 07:40and hoping that,
• 07:41we learn more about identifying
• 07:44cysts at risk for progression,
• 07:46which certainly provides a great
• 07:47opportunity for early detection and
• 07:49cancer prevention.
• 07:53So a few words about
• 07:54prevalence and incidence.
• 07:56So, overall,
• 07:57the risk of malignancy in
• 07:59pancreatic cyst is zero point
• 08:00five to one point five
• 08:01percent, and the annual risk
• 08:03of progression is about zero
• 08:04point five percent.
• 08:07So
• 08:08the good part the good
• 08:09news tonight is that most
• 08:11pancreatic cysts are benign. Even
• 08:13though we recognize and we
• 08:15find actually, on imaging so
• 08:17many,
• 08:18most pancreatic cysts, the vast,
• 08:20the vast majority are benign.
• 08:21So if I want you
• 08:22to take a home message
• 08:24tonight, I think this
• 08:26is underlying that they are
• 08:28most of the times benign.
• 08:30Only a subset, though, has
• 08:31malignant potential.
• 08:33So in,
• 08:34imaging studies, we've been seeing
• 08:36that prevalence is probably two
• 08:38to fifteen percent.
• 08:39Autopsy data suggests a prevalence
• 08:41that's higher as high as
• 08:42fifty percent.
• 08:44And there are some premalignant
• 08:46lesions
• 08:47that were,
• 08:48recognized as the, the sole
• 08:51precursors
• 08:52of malignant transformation
• 08:53on cross sectional studies.
• 08:55And those were introduced in
• 08:56nineteen ninety six. The terms
• 08:58mucinous cystic neoplasm
• 09:00and intraductal
• 09:01papillary mucinous neoplasm
• 09:03were introduced at that time,
• 09:05to describe the most common
• 09:07premalignant cysts.
• 09:09Historically and interestingly enough, back
• 09:11in nineteen thirty four, pancreatic
• 09:13cystic lesions were considered very
• 09:15rare, and they became recognized
• 09:17more common and potentially premalignant
• 09:19over the years, over the
• 09:20decades.
• 09:23So here's a bunch of
• 09:25studies that look at various
• 09:27rate number of radiologic,
• 09:29studies,
• 09:30CAT scans and MRIs to
• 09:32again demonstrate the prevalence of,
• 09:35of defining,
• 09:36a pancreatic cyst, which could
• 09:38run from anywhere one to
• 09:40forty.
• 09:41One in forty to one
• 09:42in three imaging showing pancreatic
• 09:45cysts.
• 09:46Again, the good news is
• 09:47that the risk of cancer
• 09:48at the time of imaging
• 09:49is very low, zero point
• 09:51twenty five percent.
• 09:55A modern estimate of cyst
• 09:56prevalence, this is from the
• 09:57West Coast,
• 09:59shows us that if you're
• 10:00eighty years old, you have
• 10:02one in two chances
• 10:04to
• 10:05be identified with the pancreatic
• 10:06cyst on an imaging.
• 10:08If you're seventy, one in
• 10:09three.
• 10:10If you're sixty, one in
• 10:12four, and it goes just
• 10:14like that. If you are
• 10:15fifty,
• 10:16one in five.
• 10:17Majority of cysts are small.
• 10:19Obviously, the risky ones are
• 10:21those that are larger.
• 10:26And here's the map and
• 10:27placing some cysts on the
• 10:29pancreatic map.
• 10:31So
• 10:32if you were to have
• 10:33a cyst,
• 10:34probably the best one to
• 10:35have will be the serous,
• 10:36cyst adenoma.
• 10:38These are benign. They do
• 10:39not have malignant potential.
• 10:41They're easy sometimes to recognize
• 10:43if they're classic on an
• 10:44imaging. They have this central
• 10:46calcification as you see on
• 10:47this, pictogram.
• 10:49And,
• 10:50again, they,
• 10:52do not pose a risk
• 10:53unless they grow
• 10:55in size.
• 10:56Then we are dealing with
• 10:58occasionally, with benign,
• 10:59pancreatic cysts. Those are inflammatory
• 11:01cysts, which you could see
• 11:02in the tail.
• 11:04And then we are dealing
• 11:05with the mucinous cysts, which
• 11:07are the IPMNs.
• 11:09And you see here an
• 11:11IPMN of the main pancreatic
• 11:12duct and then IPMNs of
• 11:14the side branch ducts
• 11:17and the
• 11:18mucinous cyst adenoma or pseudobapillary
• 11:22neoplasm.
• 11:23So the mucinous cyst actually
• 11:25become
• 11:29the most common cyst that
• 11:30could transform into into cancer.
• 11:34So talking about the benign
• 11:35cysts,
• 11:36they actually are about fifteen
• 11:38to twenty five percent of
• 11:39all the pancreatic cysts.
• 11:41And the mucinous cysts,
• 11:43amount to about fifty percent,
• 11:47of, the cysts that are
• 11:48found incidentally on imaging for
• 11:50other indications.
• 11:53So
• 11:55when dealing with,
• 11:56an asymptomatic patient who has
• 11:57a pancreatic cyst,
• 11:59one of the most important
• 12:00aspects is identifying
• 12:02what type of cyst we're
• 12:03dealing with.
• 12:06And
• 12:07obviously,
• 12:08considering,
• 12:09the risk factors, comorbidities,
• 12:11and then what strategy
• 12:13will be employed
• 12:15to treat this patient or
• 12:17surveil
• 12:17or follow-up over time. So
• 12:20on the left side here,
• 12:21you see the non neoplastic
• 12:23cysts, the pseudocyst,
• 12:26the inflammatory cysts. In the
• 12:27middle section, you see the
• 12:29neoplastic cysts, which could be
• 12:31serous.
• 12:33These have
• 12:34no, molecular potential,
• 12:36as in serocyst adenoma
• 12:39or the mucinous,
• 12:41cyst, which are the IPMN
• 12:42and then MCN, the mucinous
• 12:45cystic neoplasm.
• 12:46So from left to right,
• 12:50the malignant risk increases. And
• 12:52on the very right side,
• 12:53we have obviously the ductal
• 12:55adenocarcinoma
• 12:57and maybe a neuroendocrine
• 12:58tumor.
• 12:59So,
• 13:01again, the risk of malignancy
• 13:02here is higher.
• 13:06Again, a pictogram to show
• 13:08that when we are dealing
• 13:09with a pancreatic cyst, we
• 13:10wanna think first of what
• 13:12type of pancreatic cyst we're
• 13:13dealing with.
• 13:15What is the risk? Malignant,
• 13:17no malignant risk, or maybe
• 13:18cancers.
• 13:20And what is the strategy
• 13:22we're going to employ to
• 13:23manage this cyst?
• 13:25Again, on the left side,
• 13:26we have the the benign
• 13:28cyst, the pseudocyst,
• 13:29the sero cyst. These carry
• 13:31no malignant potential.
• 13:34And then in the middle,
• 13:35we have the IPMN and
• 13:37the mucinous cystic neoplasm. These
• 13:39are mucinous cysts. Again, they
• 13:40are the bulk of cysts
• 13:41that eventually,
• 13:43could lead to malignant transformation.
• 13:45And then on the right,
• 13:46the pancreatic cancer, the malignant
• 13:48lesions.
• 13:49So the strategy
• 13:51depends on the type of
• 13:52cyst,
• 13:53and obviously could run from
• 13:55no surveillance needed for the
• 13:56benign cysts to
• 13:58surveillance
• 13:59and surgery, a combination of
• 14:01those in the mid category,
• 14:03the mucinous cysts,
• 14:04and obviously surgery when we're
• 14:06dealing with a pancreatic tumor.
• 14:11What are the common types
• 14:12of pancreatic cyst and characteristics?
• 14:13Again, there are about more
• 14:15than twenty epithelial and non
• 14:17epithelial pancreatic cysts.
• 14:20However,
• 14:21the majority
• 14:22belong to the six, histologic
• 14:25categories that you see here
• 14:26on this slide.
• 14:28And I'm gonna slice it
• 14:29for you so you take
• 14:30away actually
• 14:31the message. The top two
• 14:33are benign. So they carry
• 14:36no malignant potential, zero, as
• 14:38you can see on the
• 14:38right hand side. And these
• 14:40are the pseudocysts and the
• 14:42serocyst adenoma.
• 14:45Pseudocysts are usually
• 14:47diagnosed
• 14:48in the setting of
• 14:51pancreatitis. So people patients have
• 14:53to have a history of
• 14:54pancreatitis.
• 14:56And the diagnosis of pseudocyst
• 14:58in the absence of history
• 14:59of pancreatitis should be made
• 15:01very carefully,
• 15:03since you might be dealing
• 15:04with a different type of
• 15:05cyst.
• 15:07The,
• 15:08serocyst adenoma,
• 15:09predominantly in women,
• 15:11occurs in fifth through the
• 15:12seventh decade of life. They
• 15:14are mostly asymptomatic. Again, they
• 15:16carry no malignant potential.
• 15:19And they have a typical
• 15:21presentation when they are classic.
• 15:23The challenge occurs when they
• 15:24are non classic looking on
• 15:26the imaging. So the classic
• 15:27is sort of, with a
• 15:29central calcification,
• 15:31and they,
• 15:32have no communication with the
• 15:33pan pancreatic duct. They occur
• 15:35in the body.
• 15:36Pseudocyst, as you see, first
• 15:38category are mostly in the
• 15:40tail, in the, left side
• 15:41of the the pancreas.
• 15:44Then we have the middle
• 15:45category, the next two, the
• 15:46IPMN and the MCN or
• 15:48mucinous
• 15:50cystic neoplasm.
• 15:52So these two are mucinous
• 15:53cysts. They're the most prevalent.
• 15:56And,
• 15:57starting with the IPMN,
• 15:59these are with, equal sex
• 16:01distribution.
• 16:02They occur, in the fifth
• 16:04through the seventh decades of
• 16:05life.
• 16:07They may cause pancreatitis.
• 16:09So, clinical pearl when a
• 16:12patient presents with acute acute
• 16:13pancreatitis,
• 16:15and we identify a cyst,
• 16:17doesn't mean that's a pseudocyst.
• 16:19It could be simply the
• 16:20cyst causing the pancreatitis.
• 16:22The IPMNs
• 16:24are of, few types. The
• 16:26main
• 16:27IPMN,
• 16:28which carries a higher malignant
• 16:30potential,
• 16:31and the branch duct IPMN.
• 16:33And there's also a mixed
• 16:35type that involves the main
• 16:36duct and the branch duct.
• 16:38So
• 16:39with the main duct IPMN,
• 16:42they cause dilation of the
• 16:43main pancreatic duct
• 16:45and they have a hallmark,
• 16:47when, when this is present,
• 16:48the fish mouth papilla.
• 16:50So when you look at
• 16:51the opening of the main
• 16:52pancreatic duct in the small
• 16:53intestine, you would see just
• 16:55as in in the photo
• 16:56to the right,
• 16:57you will see this fish
• 16:58mouth papillae with, expression of
• 17:00mucin since they're mucin productive.
• 17:03The mucinous
• 17:04cystic neoplasm
• 17:06of the second one in
• 17:07the mucinous category,
• 17:09tends to involve
• 17:10the tail.
• 17:13It could be
• 17:16it carries a malignant potential,
• 17:18certainly,
• 17:19but they are less common
• 17:21than IPMN. So I wanna
• 17:22highlight this early on so
• 17:24you understand that,
• 17:26IPMN
• 17:26is the battlefield.
• 17:28That's where most of the
• 17:29hedging and most of the
• 17:30debate goes on in terms
• 17:31of how to manage them,
• 17:33how to work them up,
• 17:34and certainly surveillance to eventually
• 17:37prevent cancer or intervene actually
• 17:39when they develop high risk
• 17:41features, intervene at the right
• 17:42time to for curative,
• 17:45intent with surgical,
• 17:47approach.
• 17:48So the mucinous
• 17:49cystic neoplasms,
• 17:51almost exclusively occurred in women,
• 17:53and they,
• 17:55occur a little earlier in
• 17:56the fourth through the sixth
• 17:57sixth decade of life.
• 17:59They're mostly asymptomatic.
• 18:01And, sometimes they have this
• 18:03actual calcifications,
• 18:04but not all the time.
• 18:05About one out of four
• 18:07of the cyst will have
• 18:08that.
• 18:10And
• 18:12they
• 18:13are
• 18:15showing ovarian like stroma.
• 18:18So they tend to be
• 18:19a unilateral,
• 18:20and they have a specific
• 18:21presentation.
• 18:23So the last two cysts
• 18:25are less common, and I'm
• 18:26not gonna go through them.
• 18:27So we'll move on for
• 18:29the sake of,
• 18:30interesting cases we have,
• 18:33next. I'll turn it to
• 18:34James.
• 18:35Right.
• 18:36Thanks, Laura, for for a
• 18:38great overview of these pancreatic
• 18:39cysts, and thanks, Dan and
• 18:40Karen, for the organizing this.
• 18:43So,
• 18:44for the next phase, I
• 18:45just we just wanna focus
• 18:46on how we approach these
• 18:48pancreatic cysts. And as kind
• 18:49of Flora rightly pointed out,
• 18:51yes, there's a very long
• 18:52list of pancreatic cysts, but
• 18:53really where the battlefield is
• 18:55is is in these IPMNs.
• 18:56And the vast majority of
• 18:57cysts that we're dealing with
• 18:59are likely gonna turn out
• 19:00to be some form of
• 19:01an IPMN and likely some
• 19:02form of what's called a
• 19:03branch type IPMN. So we're
• 19:04gonna use these terms interchangeably
• 19:06when we talk about the
• 19:07cases and kinda going forward.
• 19:08That's really what the focus
• 19:10is on. Not ignoring making
• 19:11a diagnosis, serious diagnosis, and
• 19:13so on, but really just
• 19:14trying to focus on this
• 19:15particular area.
• 19:16So when we approach these
• 19:17page patients and try to
• 19:19figure out what do we
• 19:19do, and a lot of
• 19:20these patients are picked up
• 19:21incidentally for on scans done
• 19:23for other reasons, You know
• 19:24before we figure out are
• 19:25we going to do nothing,
• 19:27follow them or or send
• 19:29them for surgery, we have
• 19:30to kind of make an
• 19:31overall assessment of the patient's
• 19:33condition,
• 19:34competing health risks and so
• 19:35on. And then also look
• 19:36at some other pancreatic cancer
• 19:38risk factors like family history
• 19:39of pancreatic cancer. Does a
• 19:41patient have a germline mutation
• 19:42that would increase the risk
• 19:43of pancreatic cancer? And then
• 19:44it gets into the issue
• 19:45of making,
• 19:47a a a decision and
• 19:48a shared decision making process
• 19:50process
• 19:51with the patient while we
• 19:53assess the risk.
• 19:54And the way we approach
• 19:55this is really trying
• 20:01IPMNs
• 20:02into three broad categories. We
• 20:03talk about high risk pancreatic
• 20:05cyst or IPMNs, intermediate risk,
• 20:08or low risk.
• 20:11So we'll move to the
• 20:11next one. So with respect
• 20:13to the high risk IPMNs,
• 20:15these are patients that have
• 20:17cysts but in addition they
• 20:18have imaging features such as
• 20:20a very dilated vein pancreatic
• 20:22duct at the presence of
• 20:23a solid mass which would
• 20:24be very concerning for that
• 20:26this cyst has turned into
• 20:27a malignancy
• 20:28and even biliary obstruction. And
• 20:29when we see these cysts
• 20:31you know we're concerned we're
• 20:32concerned that there's something significant
• 20:33and serious going on And
• 20:35these are the sorts of
• 20:36patients that we would think
• 20:37about sending to surgery or
• 20:38at least for a surgical
• 20:39evaluation.
• 20:40For the next group of
• 20:41cysts, the next slide,
• 20:43these are the intermediate,
• 20:44risk IPMNs.
• 20:48And this is kind of
• 20:49the intermediate group and these
• 20:50patients have features on imaging
• 20:52that are a little bit
• 20:53worrisome to us. They include
• 20:55things like well the duct
• 20:56is a little bit dilated
• 20:57not very dilated or there's
• 20:58a change in calibre of
• 21:00the main pancreatic duct for
• 21:01example
• 21:02or the cyst size is
• 21:03actually greater than three centimeters
• 21:04which would strike most people
• 21:05as big but it's a
• 21:06worrisome feature.
• 21:07Maybe there's a small nodule
• 21:09in the cyst,
• 21:10maybe there's some lymph nodes
• 21:11or maybe the cyst has
• 21:12gotten bigger over time or
• 21:14maybe over a year it's
• 21:15increased in size by greater
• 21:17than twenty percent or so.
• 21:18And these are patients that
• 21:19we classify as having intermediate
• 21:21risk factors.
• 21:23So for
• 21:24these intermediate risk factors
• 21:27what we end up doing
• 21:28is evaluating them further. And
• 21:29typically these are the types
• 21:30of patients that would undergo
• 21:32an endoscopic ultrasound. Really to
• 21:34kind of parse out if
• 21:35there's something more serious going
• 21:36on. And I won't get
• 21:38into too much detail about
• 21:38the endoscopic ultrasound, but as
• 21:40most of you know, it's
• 21:41a type of endoscopy where
• 21:42the camera is passed down.
• 21:43We get very good views
• 21:44of the pancreas throughout,
• 21:46throughout its stages.
• 21:48And one of its
• 21:49great advantages is just visualization,
• 21:52but another advantage is the
• 21:53ability to biopsy these cysts.
• 21:55And when we biopsy these
• 21:56cysts, we're able to look
• 21:57at the cells that we
• 21:58get back from the cyst
• 21:59fluid, but also a variety
• 22:01of,
• 22:02markers, including DNA markers that
• 22:04have a very high specificity
• 22:06and sometimes sensitivity
• 22:07for not just making the
• 22:08diagnosis of it being a
• 22:10mucinous,
• 22:11but also maybe telling us
• 22:12that this is potentially a
• 22:13high grade dysplasia or even
• 22:15a cancer. So endoscopic ultrasound
• 22:17is very useful again for
• 22:18teasing out these, intermediate
• 22:20risk,
• 22:21pancreatic cysts.
• 22:22Next slide.
• 22:24But really kind of what
• 22:25the the again the main
• 22:26battle to get to get
• 22:27back to this issue is
• 22:28the other group. These are
• 22:29the low risk IPMN. So
• 22:31these are your cysts again
• 22:32presumed branch duct IPMNs
• 22:34that don't have a single
• 22:35worrisome feature. They don't have
• 22:36a single high risk feature.
• 22:38And these make up the
• 22:39vast vast majority of patients
• 22:40these are the five millimeter
• 22:41the ten millimeter cyst that
• 22:43you see on routine scans
• 22:44done for other reasons and
• 22:46yes they are presumed branch
• 22:47strict IPMNs
• 22:49but you can see from
• 22:49this data that if you
• 22:50were to follow this group
• 22:51of patients for long periods
• 22:53of time or up to
• 22:54five years,
• 22:55yes, the cyst some of
• 22:56the cysts will get bigger.
• 22:57So some of them will
• 22:58increase in size. The vast
• 22:59majority do not.
• 23:01The vast majority do not
• 23:03end up ever requiring surgery,
• 23:05and the vast majority
• 23:06never develop into pancreatic cancer.
• 23:08And therein lies the challenge
• 23:09because it makes up such
• 23:11a large volume. Patients are
• 23:13worried, we're worried, everybody's worried.
• 23:15So next slide.
• 23:17So as a result of
• 23:18this as we kind of
• 23:19work through this process of
• 23:20trying to stratify patients into
• 23:22are they high risk, are
• 23:23they intermediate risk or are
• 23:24they low risk you see
• 23:25how it it falls out.
• 23:27So for the the high
• 23:27risk patients, this is the
• 23:29group of patients that we
• 23:30would say, hey, we're concerned
• 23:31about this group based on
• 23:32their imaging. We need to
• 23:33have a multidisciplinary discussion. We
• 23:35need to have our surgical
• 23:36colleagues involved in making decisions.
• 23:38Is this something that needs
• 23:39further workup and potentially surgery?
• 23:41For the intermediate risk group,
• 23:43we do further investigations including
• 23:45endoscopic
• 23:46ultrasound.
• 23:47But for that low risk
• 23:48group that's there, again, the
• 23:49vast majority group, if we're
• 23:50comfortable with the diagnosis, if
• 23:52we're cult comfortable with the
• 23:53imaging,
• 23:54then we get into the
• 23:55discussions of saying well maybe
• 23:56we're not going to do
• 23:57surgery, maybe we're not going
• 23:58to do endoscopic ultrasound but
• 24:00we're going to have to
• 24:01follow you and how do
• 24:01we follow you is a
• 24:03real challenge.
• 24:04Next slide.
• 24:08I can cover these. So
• 24:09the the key points that
• 24:10we've talked about thus far
• 24:12are the fact that pancreatic
• 24:14cysts are common,
• 24:15discovered at an increasing rate.
• 24:18The goal which I think
• 24:19has to be emphasized is
• 24:20that we're trying to emphasize
• 24:21that small percentage of cystic
• 24:23lesions that are associated with
• 24:25a substantial risk of cancer.
• 24:27Combinations of imaging, symptom assessment,
• 24:29laboratory tests could help distinguish
• 24:31several benign cysts from the
• 24:33low, intermediate and high risk
• 24:34cysts that we've talked about.
• 24:36EUS can be considered for
• 24:38patients that have equivocal findings
• 24:39when we're trying to figure
• 24:40out the diagnosis,
• 24:41but really for those intermediate
• 24:43risk cysts. And then there
• 24:44is a really significant role
• 24:46for endoscopic ultrasound
• 24:47and sampling these cysts to
• 24:49not only diagnose, is it
• 24:50a serosyst, is it an
• 24:51IPMN, but also to risk
• 24:53stratify.
• 24:54And then this gets into
• 24:55discussions of and we'll hear
• 24:56from doctor Kunstman
• 24:58about surgical evaluation,
• 25:00as well as surveillance for
• 25:01low risk cysts. Next slide.
• 25:05And I'll hand you over
• 25:06now to doctor Kunstman.
• 25:09I'll be happy to introduce
• 25:10the case,
• 25:11the first case, for John.
• 25:14So this is a ninety
• 25:15year old male with worrisome
• 25:16changes in presumed mucinous pancreatic
• 25:18cyst.
• 25:19He has a history of
• 25:20previous urologic malignancies, prostate cancer
• 25:22testicular seminoma, and remission developed
• 25:25hematuria
• 25:26in twenty twenty two, which
• 25:27led to
• 25:28imaging, and that revealed multifocal
• 25:30pancreatic cyst.
• 25:32He doesn't have any history
• 25:33of pancreatitis or jaundice, no
• 25:35family history of pancreatic or
• 25:36BRCA related cancer, no diabetes,
• 25:38no exocrine insufficiency.
• 25:40John?
• 25:42Oh, additionally,
• 25:44some past medical history,
• 25:46skin cancer, atrial flutter, dyslipidemia
• 25:48GERD, hypothyroidism,
• 25:50glaucoma,
• 25:51surgical bisurgical history. Patient had
• 25:53a right orchiectomy, radical prostatectomy,
• 25:55an inguinal, hernia repair.
• 25:57The medications are as listed.
• 26:00He is married, semi retired.
• 26:01He consumes one standard eTOH,
• 26:04alcoholic beverage a day, and
• 26:06he's a twelve pack year
• 26:07smoker.
• 26:09Yeah. I would say just
• 26:10even before we advance the
• 26:12slide,
• 26:12if we could go back.
• 26:14I mean,
• 26:16and it's nice to meet
• 26:17everybody, and thank you for
• 26:18the lovely invites,
• 26:19Karen and Anne.
• 26:22You know, I think from
• 26:23my perspective,
• 26:24you know, obviously, a ninety
• 26:26year old male being referred
• 26:27to surgical oncology clinic
• 26:29might raise some eyebrows,
• 26:31but the history here is
• 26:32really interesting. It was incidentally
• 26:35found. And then to doctor
• 26:37Farrell's points,
• 26:38you know, he doesn't have
• 26:39any of those worrisome findings
• 26:41right away on the history
• 26:42like pancreatitis, John does a
• 26:44strong personal or family history,
• 26:46of malignancy that might be
• 26:48related to the pancreas. So,
• 26:49you know, right away, I'm
• 26:50already thinking this might be
• 26:52a lower risk lesion, and
• 26:54then maybe we can go
• 26:55to the imaging
• 26:56now.
• 26:57So he was eighty eight
• 26:58when this was found.
• 27:01So just looking at his
• 27:02scan,
• 27:05I don't know if we
• 27:05can scroll through it or
• 27:07not.
• 27:08There we go.
• 27:09It's probably gonna go right
• 27:11past it since it's on
• 27:11a loop, but,
• 27:13I'll just kinda describe as
• 27:15it goes through there. You
• 27:16know, the pancreas there in
• 27:17the middle. You can see
• 27:18the calipers going past quickly.
• 27:21You know, basically,
• 27:22what we see,
• 27:24from my perspective
• 27:26is three small cysts. They're
• 27:28they're all very bland appearing.
• 27:30The largest is sixteen millimeters
• 27:32in greatest dimension.
• 27:34There was no,
• 27:35additional features that made us
• 27:37worry like,
• 27:38main duct dilation or nodularity
• 27:41within the lesion like doctor
• 27:42Farrell was referring to. There
• 27:44was a tiny area of
• 27:45calcification, but that alone doesn't
• 27:47convey any,
• 27:48significance. Now since,
• 27:51the patient does have
• 27:52an excellent quality of life,
• 27:54he's still working. In fact,
• 27:56his performance status is excellent.
• 27:59Despite his advanced age,
• 28:01he was recommended to undergo
• 28:03surveillance.
• 28:06So we can head on
• 28:07to the next one. So,
• 28:09as many folks do, he
• 28:11got an early interval
• 28:14repeat imaging study at six
• 28:16months because
• 28:17as alluded to by, Flora
• 28:19and James, you know, the
• 28:20size is a risk factor,
• 28:22but one
• 28:23independent risk factor is the
• 28:25rate of cyst growth.
• 28:27So,
• 28:29our practice is typically
• 28:30for presumed new IPMN without
• 28:33any other worrisome features
• 28:35is to get a six
• 28:36month interval scan to determine
• 28:38whether it's one that's rapidly
• 28:39growing or not.
• 28:42There was a little bit
• 28:43of growth, nineteen millimeters, but
• 28:45no other worrisome features. I
• 28:46would just point out that
• 28:48scan was ordered without contrast,
• 28:50which is perfectly reasonable for
• 28:52surveillance.
• 28:53But if there are some
• 28:54features that you're following in
• 28:56particular,
• 28:57contrast can be helpful because
• 28:58enhancement of a nodule or
• 29:00enhancement of septations within a
• 29:02nodule,
• 29:03those are are risk factors.
• 29:05So he didn't have any
• 29:06of those, so I think
• 29:07an MRCP was perfectly reasonable.
• 29:09And based on those findings,
• 29:11he was recommended
• 29:12to get another scan at
• 29:14a one year interval.
• 29:16So that was done in
• 29:17twenty twenty three as you
• 29:18can see.
• 29:20The largest cyst had grown
• 29:21again a little bit. You
• 29:22know, the typical natural history
• 29:24of these cysts is slow
• 29:26progressive growth.
• 29:28This time, the largest was
• 29:30twenty two millimeters, again, with
• 29:31no worrisome features.
• 29:33Many times in patients
• 29:35that are perhaps,
• 29:37you know, younger
• 29:38or, you know, really exquisite
• 29:40performance status,
• 29:41that two centimeter threshold oftentimes
• 29:43triggers in EUS.
• 29:46It did not in this
• 29:47case after a shared decision
• 29:49making conversation with the patient,
• 29:52which I think was very
• 29:53reasonable, but another annual
• 29:55surveillance interval was recommended.
• 29:58That scan, which we'll show
• 29:59on the next slide, I
• 30:01believe,
• 30:02showed quite a bit of
• 30:03change.
• 30:05So you can see there,
• 30:07you know, this is the
• 30:08MR.
• 30:09Now we're
• 30:11seeing multifocal
• 30:11mixed phenotype with both the
• 30:13main ducts dilated
• 30:15and multiple cysts clustering together
• 30:18in essentially the entire pancreas
• 30:20from the uncinate
• 30:21all the way to the
• 30:22tail.
• 30:23So a number of concerning
• 30:24features of progression,
• 30:26with just one year of
• 30:28surveillance, and he was recommended
• 30:30to undergo in the US.
• 30:32So he got that endoscopic
• 30:33ultrasound,
• 30:35that noted the cysts did
• 30:37appear to be mucinous upon
• 30:38aspiration.
• 30:40And there was some nodularity
• 30:42in the junction of the
• 30:43body and the tail that
• 30:45was biopsied.
• 30:47That biopsy you can see
• 30:49there,
• 30:50red out is again a
• 30:51mucinocystic
• 30:52lesion, not not unexpected,
• 30:54but there was dysplasia and
• 30:56that dysplasia was high grade.
• 30:58You know, high grade dysplasia
• 30:59is essentially
• 31:01the pathologist telling us that
• 31:02they're seeing pancreas cancer like
• 31:04cells. They're just not seeing
• 31:05it invade into the underlying,
• 31:08you know, pancreatic parenchyma still
• 31:10within the cyst itself. Generally,
• 31:12this is considered a very
• 31:14high risk finding,
• 31:15and it triggered a referral,
• 31:17to surgery.
• 31:21So I just wanna talk
• 31:22briefly
• 31:23for a patient like this,
• 31:24what types of surgeries
• 31:27might be a consideration? You
• 31:28can see on the right
• 31:29side, that cartoon there again
• 31:31showing what we would call
• 31:32a mixed IPMN where there's
• 31:34main duct involvement
• 31:36and branch duct involvement.
• 31:38And in this case, again,
• 31:39pretty much the entire pancreas
• 31:41was involved.
• 31:43The red star is about
• 31:44where it is, where the,
• 31:46dysplasia biopsy was taken. So
• 31:48when we're talking about surgery
• 31:50for IPMN disease, first and
• 31:52foremost, the question is there
• 31:54cancer there? Now, in this
• 31:55case, we didn't have an
• 31:56overt diagnosis of cancer, although
• 31:58we did have a diagnosis
• 31:59of dysplasia.
• 32:00Certainly with any operation,
• 32:02we wanna try and minimize
• 32:04the future risk
• 32:05that IPMN could convey to
• 32:07the patient.
• 32:08So in his case, the
• 32:10entire gland was affected, so
• 32:12there's going to be risk
• 32:13regardless unless he undergoes a
• 32:15total pancreatectomy.
• 32:16Now we also wanna minimize
• 32:18any complication risk. Generally speaking,
• 32:20that means that, you know,
• 32:21distal pancreatectomy
• 32:23is a lower risk operation
• 32:24than a Whipple procedure, but,
• 32:26certainly the cancer and the
• 32:28risk considerations
• 32:29supersede that.
• 32:31And then just alluding to
• 32:32that total pancreatectomy,
• 32:34we also wanna try and
• 32:35minimize any long term effects
• 32:36on the patient's digestive health
• 32:39or metabolism
• 32:40now.
• 32:41Certainly, patients can and do
• 32:43develop diabetes or exocrine insufficiency
• 32:45after a pancreatectomy
• 32:47of any size.
• 32:49So it's important, especially from
• 32:51a primary care
• 32:53standpoint,
• 32:54that those considerations are discussed
• 32:56both with the patients
• 32:57and their primary care provider
• 32:59beforehand. And if if you
• 33:01can mitigate some of them
• 33:02by, say,
• 33:03an additional referral or additional
• 33:05conversation with a diabetes specialist,
• 33:07etcetera, nutritionist,
• 33:08Those are steps we certainly
• 33:09take in our multidisciplinary
• 33:10clinic. So, as far as
• 33:12the operations themselves,
• 33:14if you can hit the
• 33:15the next button,
• 33:17you know, Whipple procedure is
• 33:18the resection of the pancreatic
• 33:20head.
• 33:21Now, as you may or
• 33:22may not know, you know,
• 33:23the way the reason a
• 33:24Whipple procedure is done the
• 33:25way that it is with
• 33:26the duodenum being resected as
• 33:28well as the lower part
• 33:29of the bile duct is
• 33:30all those structures, the duodenum,
• 33:32the pancreatic head and the
• 33:33lower portion of the bile
• 33:34duct share the same vascular
• 33:36supply.
• 33:37So during the operation, the
• 33:38gastroduodenal
• 33:39artery gets ligated.
• 33:41As a result, all those
• 33:43structures,
• 33:44then need to be removed
• 33:45to unblock and and reconstructed.
• 33:48Go ahead and hit next.
• 33:51Conversely, a left sided operation
• 33:52or a distal pancreatectomy,
• 33:55doesn't require the reconstruction
• 33:57that one would have with
• 33:58a Whipple procedure.
• 34:00You simply close the divided
• 34:02neck of the pancreas,
• 34:03either with sutures or staples
• 34:05or a number of different
• 34:06techniques. Generally speaking, when this
• 34:08operation is done for any
• 34:10risk of malignancy
• 34:12or a known malignancy,
• 34:13we perform a splenectomy
• 34:15concomitantly
• 34:16with that. Reason being, almost
• 34:18all of the lymph nodes
• 34:19in that area cluster along
• 34:21the splenic artery and splenic
• 34:22hilum.
• 34:24So removing the pancreatic tail
• 34:26alone for a cancer or
• 34:27possible cancer
• 34:29is not an oncologically adequate
• 34:31operation.
• 34:33Next. Yeah. And then a
• 34:34total pancreatectomy.
• 34:36So just a quick word
• 34:37about that, you know, for
• 34:39patients with
• 34:40the entire gland being involved
• 34:42with IPMN, that is a
• 34:44consideration especially in a younger
• 34:45patient where you expect them
• 34:47to develop a cancer in
• 34:48any remnant pancreas.
• 34:51You know, I would say
• 34:53it it is an operation
• 34:54that obviously has severe long
• 34:56term metabolic
• 34:57effects for the patient.
• 34:59That being said, in the
• 35:00era of exocrine,
• 35:02you know, enzyme replacements
• 35:04and insulin pumps, you know,
• 35:05this has been well studied
• 35:07in our literature. Patient quality
• 35:08of life is actually very
• 35:09good.
• 35:10But it does take six
• 35:12to twelve months to resume
• 35:13their preoperative quality of life
• 35:15after a total pancreatectomy.
• 35:17So why don't you go
• 35:17ahead to the next slide?
• 35:22So this patient's,
• 35:24after a period of shared
• 35:26decision making and imaging,
• 35:28despite his advanced age,
• 35:31was interested in undergoing surgery.
• 35:34You know, I felt it
• 35:36was appropriate given that his
• 35:37performance status was as good
• 35:39as most sixty or seventy
• 35:41year olds,
• 35:42and I felt his other
• 35:43medical comorbidities could be well
• 35:45managed.
• 35:46And again, it was a
• 35:47decision between the patient, myself,
• 35:49the gastroenterologist,
• 35:50and the primary care physician.
• 35:53So he underwent an operation
• 35:55where we remove the left
• 35:56side of the pancreas, and
• 35:57we extended it a little
• 35:59bit because we wanted to
• 36:00remove as much of that
• 36:01main duct that was affected
• 36:02by IPMN,
• 36:04but we didn't wanna subject
• 36:05him to a total pancreatectomy.
• 36:07He had a little bit
• 36:08of postoperatibilis,
• 36:09but essentially no complications.
• 36:12The main complication we watch
• 36:13out for in any pancreatic
• 36:15surgery is a pancreatic fistula
• 36:17or leak. He had he
• 36:18did not have that. You
• 36:19can see the gross specimen
• 36:21there that's been,
• 36:22divided there in the pathology
• 36:23lab and right dead center
• 36:25in the middle.
• 36:26Lo and behold, he actually
• 36:27did have a fairly large
• 36:29adenocarcinoma,
• 36:31arising within the IPMN.
• 36:34The surgical margins were negative,
• 36:35so it was completely resected.
• 36:38He did have one out
• 36:39of forty eight harvested lymph
• 36:41nodes that had regional disease.
• 36:45So, you know, after surgery
• 36:46in this particular patient,
• 36:48you know, systemic chemotherapy is
• 36:50generally considered standard of care
• 36:53for any adenocarcinoma
• 36:55of the pancreas. However, you
• 36:56know, again,
• 36:57at his advanced age, there's
• 36:58certainly pros and cons, to
• 37:00consider with the toxicity for
• 37:02the multi agent regimens we
• 37:03generally use now. So that's
• 37:05an ongoing discussion.
• 37:07He did not have any
• 37:08issues with diabetes or exocrine
• 37:10insufficiency.
• 37:11People do need to be
• 37:13vaccinated
• 37:14if they are,
• 37:16having a splenectomy against encapsulated
• 37:18organism. Now he had an
• 37:19excellent primary care physician,
• 37:21so he was already actually
• 37:22vaccinated,
• 37:23for for his pneumococcal
• 37:25vaccinations.
• 37:27But we did give him
• 37:28meningococcal
• 37:29and haemophilus vaccinations.
• 37:32And certainly, he'll undergo surveillance.
• 37:34I think the take home
• 37:35points for this case, this
• 37:36is actually a great
• 37:38demonstration of everything that Flora
• 37:40and and and James had
• 37:41talked about. You know, he
• 37:42had a lesion that had
• 37:43some risk.
• 37:45It was felt to be
• 37:46appropriate to surveil him. He
• 37:48had some changes that triggered
• 37:49a further workup that led
• 37:51him to an operating,
• 37:52to the operating room. And
• 37:54ultimately, you know, we were
• 37:55able to resect his pancreas
• 37:57cancer before it metastasized.
• 38:00So, you know, again, he
• 38:01he was ninety, but I
• 38:02do think it was the
• 38:03right thing to do and
• 38:04certainly he'll enjoy a survival
• 38:05benefit from this intervention.
• 38:08Okay. So I'll try and
• 38:10get through the next couple
• 38:11cases a little quicker.
• 38:12Our second case is a
• 38:14sixty four year old female
• 38:15with history of ankylosing spondylitis
• 38:17and increased epigastric
• 38:19and back pain.
• 38:21So,
• 38:22HBI,
• 38:24it's significant for chronic back
• 38:25pain, but recent increased episodic
• 38:28pain.
• 38:29And careful,
• 38:31ROS revealed that patient had
• 38:33postprandial
• 38:34exacerbation.
• 38:36The primary care doctor ordered
• 38:37a CT of the abdomen
• 38:39and pelvis, and that revealed
• 38:40a pancreatic cyst.
• 38:42Also relevant is that patient
• 38:45had remote history of pancreatitis
• 38:47attributed to gallstones,
• 38:49no history of jaundice,
• 38:51family history of breast and
• 38:53GYN cancer,
• 38:54and no history of pancreatic
• 38:56cancer,
• 38:57no diabetes and no exocrine
• 38:59insufficiency.
• 39:00Additional
• 39:01past medical history significant for
• 39:03asthma, diverticulosis,
• 39:04hypertension, Graves' disease, and attention
• 39:06deficit disorder.
• 39:08By,
• 39:08surgical history,
• 39:10she had cholecystectomy,
• 39:11tonsillectomy, breast biopsy,
• 39:13home medications,
• 39:14as noted,
• 39:17and by social history, she's
• 39:19married, no tobacco,
• 39:20and consumes
• 39:21one to two alcoholic beverages
• 39:23per week.
• 39:27K. So, yeah, I think
• 39:29hitting all the important points
• 39:30again,
• 39:31you know, in this particular
• 39:34case, you know, the imaging
• 39:35shows
• 39:36a somewhat
• 39:37concerning cyst for somebody that
• 39:39had previously had imaging with
• 39:41no cysts
• 39:42in the past during workups
• 39:43of her chronic back pain,
• 39:46and that remote history of
• 39:47cholecystectomy.
• 39:49You know, here we have
• 39:49this three point four millimeter,
• 39:52or sorry, thirty four millimeter
• 39:53cyst. There's no clear nodularity,
• 39:55but quite thick,
• 39:57walls with some enhancements.
• 40:00In this case, you know,
• 40:01kinda contemporaneously,
• 40:03the the primary care physician
• 40:05actually referred her to both
• 40:07gastroenterology,
• 40:09and to my clinic,
• 40:10with these findings. And so
• 40:12I,
• 40:13had the luxury of having
• 40:14endoscopic ultrasound being done at
• 40:16the time she presented to
• 40:17my clinic.
• 40:20And as those we we
• 40:22had the ultrasound done, but
• 40:23we didn't have the biochemical
• 40:25analysis
• 40:26just yet.
• 40:27So we spoke to her
• 40:28about the possibilities
• 40:29of IPMN
• 40:30or MCN with a picture
• 40:32like this. But what really
• 40:34stood out to me was
• 40:34the history of pancreatitis
• 40:36in the distant past. Now
• 40:37again, that had been attributed
• 40:38to gallstones, which may have
• 40:40been the case, but she
• 40:41had now undergone cholecystectomy.
• 40:43But the post prandial
• 40:45exacerbation
• 40:46of her pain,
• 40:47really made us wonder a
• 40:48little bit because pancreatitis that's
• 40:50attributable to a cyst,
• 40:52as alluded to can sometimes
• 40:54be a diagnostic dilemma. Is
• 40:55the cyst causing the pancreatitis
• 40:57or is the cyst secondary
• 40:59to the pancreatitis?
• 41:00So
• 41:01we sent her for the
• 41:02EUS,
• 41:03and those findings are as
• 41:05listed there. In this case,
• 41:06the CEA on biochemical analysis
• 41:09was about as close to
• 41:10zero as you can get,
• 41:11And the cis fluid amylase
• 41:13was quite high, and a
• 41:14biopsy showed inflammation only.
• 41:16So next slide.
• 41:18You know, the way that
• 41:19we would interpret that
• 41:21is as a pseudocyst rather
• 41:22than a mucinous cyst.
• 41:25Interestingly enough, as we were
• 41:26awaiting,
• 41:28those biochemical results,
• 41:30she actually ended up in
• 41:31the emergency department after going
• 41:32to a holiday party,
• 41:34with serum lipase of over
• 41:35a thousand as you can
• 41:36see there after having a
• 41:37few glasses of red wine.
• 41:40So in this case,
• 41:41the diagnosis was made of
• 41:43acute on chronic pancreatitis
• 41:45with pseudocyst formation.
• 41:47We recommended the patient to
• 41:49have a bland diet and
• 41:50stop drinking,
• 41:52and she basically returned to
• 41:53her baseline level of of
• 41:54back pain. It was quite
• 41:55satisfied, and we did get
• 41:57a follow-up scan to ensure
• 41:58that things were improving,
• 42:00which it did. The cyst
• 42:02was gradually reducing in size,
• 42:03which is the natural history
• 42:04of most pseudocysts,
• 42:06that are under about five
• 42:07or six centimeters.
• 42:08So this patient needs no
• 42:10intervention and also needs no
• 42:11surveillance other than,
• 42:13you know, some reminders to
• 42:15to be cautious from a
• 42:16pancreatitis standpoint.
• 42:18And, and and she moved
• 42:20on with her life. So
• 42:25Our next case is a,
• 42:27patient with a worrisome cyst
• 42:29and a frail patient.
• 42:30This is a seventy three
• 42:31year old female with left
• 42:33lower quadrant pain who underwent
• 42:34imaging revealing diverticulitis
• 42:36and pancreatic cyst.
• 42:38Diverticulitis was treated nonoperatively.
• 42:40Patient is wheelchair bound, secondary
• 42:42to chronic low back pain
• 42:44and severe degenerative arthritis.
• 42:47She has no history of
• 42:48pancreatitis or jaundice. There's no
• 42:50family history of pancreatic, BRCA
• 42:52related cancers.
• 42:54She has long standing type
• 42:56one diabetes. She's actually on
• 42:58an insulin pump, and she
• 43:00has no exocrine sufficiency.
• 43:03For,
• 43:05other,
• 43:05past medical history, dyslipidemia GERD,
• 43:07obesity, hypertension,
• 43:09radiculopathy,
• 43:11by surgical history. She had
• 43:12the gallbladder out, appendectomy,
• 43:14and, foot fracture that was
• 43:16operated.
• 43:17Medications
• 43:18as noted, statin, insulin pump,
• 43:21an SGLT two inhibitor that
• 43:22was in,
• 43:24blood pressure,
• 43:25medications,
• 43:26anti inflammatory, pregabalin, tramadol probably
• 43:29to manage her pain. And
• 43:30by social history, she's widowed,
• 43:32no tobacco or ATOH
• 43:33she used, and lives with
• 43:35an adult child.
• 43:40So this was an incidentally
• 43:42found lesion.
• 43:44Just for the record, her
• 43:45diverticulitis did resolve,
• 43:47with antibiotics
• 43:48only,
• 43:49and she was referred to
• 43:51my clinic.
• 43:53And her pancreatic,
• 43:56she really had a pancreatic
• 43:57body, sis, a little error
• 43:58there on my part,
• 44:00that measured over three centimeters,
• 44:03with some enhancements in the
• 44:04wall. No clear nodularity,
• 44:07but certainly one that would
• 44:08be in that intermediate risk
• 44:10category as doctor Farrell was
• 44:12was, delineating earlier.
• 44:14An EUS was performed that
• 44:16confirms
• 44:17the
• 44:18diagnosis
• 44:19as an IPMN.
• 44:21You can see the CEA
• 44:22level is quite elevated.
• 44:25The amylase level is low.
• 44:26A biopsy was performed. The
• 44:27epithelium was bland. No evidence
• 44:29of dysplasia.
• 44:30So here we have an
• 44:31intermediate
• 44:32risk lesion. So what's to
• 44:34do next? Kinda next slide.
• 44:37Yep. So the diagnosis confirmed
• 44:39as a branch deck to
• 44:40IPMN.
• 44:41As,
• 44:43Flora was was alluding to,
• 44:44you know, this patient was
• 44:45quite frail.
• 44:46When we evaluated in our
• 44:47clinic,
• 44:48she really had challenges with
• 44:50the get up and go,
• 44:51frailty test.
• 44:53I would call her from
• 44:54a from a oncologist point
• 44:56of view, you know, ECOG,
• 44:57you know, two on a
• 44:58good day, kinda three on
• 44:59a bad day.
• 45:00She did ambulate some at
• 45:02home.
• 45:03And, again, you know, the
• 45:04diagnosis of large branch doctor
• 45:06IPMN, but without additional worrisome
• 45:08features.
• 45:10So we had a long
• 45:11discussion with her, and and
• 45:13these can be challenging discussions,
• 45:14but it's important to understand
• 45:16what people's values are,
• 45:18how they view their quality
• 45:19of life, etcetera.
• 45:20Certainly,
• 45:23even a distal pancreatectomy, if
• 45:24done laparoscopically,
• 45:26that risk is is,
• 45:28still considerable.
• 45:30It's a it's a major
• 45:31operation, and we really felt
• 45:32that that risk was prohibitive
• 45:34for this particular
• 45:35patient unless there was clear
• 45:36evidence for a cancer there.
• 45:38And even then, it might
• 45:39not have been the right
• 45:40thing to do.
• 45:42You know, so oftentimes, the
• 45:43way that conversation gets steered
• 45:45is
• 45:47if we were to discover
• 45:48a cancer, we'd know that
• 45:49you don't have a cancer
• 45:50now based on our best
• 45:53guess,
• 45:54would you want that cancer
• 45:55to be treated? Would you
• 45:56want chemotherapy? Would you want
• 45:57radiation therapy?
• 45:59You know, if the answer
• 46:00is yes, then it's very
• 46:01reasonable to consider surveillance
• 46:03with the understanding that if
• 46:05there was a change that
• 46:06was concerning before any treatment
• 46:07could be rendered,
• 46:09you know, they would need
• 46:10to have a repeat biopsy,
• 46:11and there would be options
• 46:13for them that they could
• 46:13choose.
• 46:14But if the answer is
• 46:15no,
• 46:16and, you know, when explained
• 46:18to a patient in this
• 46:18way, they actually oftentimes do
• 46:20say no. I say, yeah.
• 46:21You know, doc, I'm I'm
• 46:22just not interested in that
• 46:23chemotherapy. If something happens, you
• 46:25can manage my symptoms.
• 46:28But but I'm not having
• 46:29surgery. I'm not having chemo.
• 46:31And expectant management is very
• 46:33reasonable. And we, you know,
• 46:34we give these patients, things
• 46:35to watch out for and
• 46:36the contact information.
• 46:38But as,
• 46:40said several times in this
• 46:41talk, these are frequent findings
• 46:42and, you know, this is
• 46:43really a disease of older
• 46:45patients.
• 46:46So, you know, deciding where
• 46:48we wanna deploy our surveillance
• 46:49resources is oftentimes a really
• 46:51meaningful conversation to have.
• 46:53You know, in this particular
• 46:54case, she did opt for,
• 46:56continued surveillance,
• 46:58but at a at a
• 46:59low frequency. So
• 47:04we'll pass it back to
• 47:06doctor Farrell.
• 47:08Great. Thanks very much, John.
• 47:10So it's very, interesting cases.
• 47:12So
• 47:13I think it's also important
• 47:15to stay as most people
• 47:16realize that the the vast
• 47:17majority of all cysts, not
• 47:18just,
• 47:19the IPMNs, never undergo any
• 47:21sort of, you know, surgical
• 47:22management,
• 47:24but yet we make decisions
• 47:25about following them. And this
• 47:27is often a very confusing
• 47:28area, and the guidelines have
• 47:29been changing and will continue
• 47:31to change.
• 47:32The references here, if anybody
• 47:34wants to email me, I
• 47:35can send you the actual
• 47:36article with this with this
• 47:37table in it. But, basically,
• 47:39surveillance for patients that you
• 47:41decide or you're going to
• 47:43survey
• 47:44is really based on the
• 47:46size of the lesion.
• 47:48And so the smaller that
• 47:50the lesion is, the more
• 47:51likely you're gonna use noninvasive
• 47:53imaging studies like MRI, MRCP.
• 47:55The bigger the the lesion
• 47:56gets, you're going to include
• 47:58endoscopic ultrasound because those are
• 47:59lesions you're concerned about may
• 48:01maybe not planning to operate
• 48:02on, but you're worried about.
• 48:04And then over time, the
• 48:06surveillance changes as well, whereas
• 48:07upfront, we kind of get
• 48:09more frequent imaging because we
• 48:10are concerned about trajectory trying
• 48:12to understand the cyst. But
• 48:13over time, we back off,
• 48:15especially if there's stability.
• 48:17And as we'll mention very
• 48:18briefly at the end, there
• 48:19may now be some discussions
• 48:20about stopping surveillance based on
• 48:22stability as well. Next slide.
• 48:25I have two cases, but
• 48:26I'll quickly go through them
• 48:27so you can just keep,
• 48:29forwarding.
• 48:29And I'll just you can
• 48:30keep forwarding here. This is
• 48:31just one of those cases
• 48:32where it's a small
• 48:34cyst, and you're saying to
• 48:35the patient, oh, probably nothing
• 48:37will happen, but you can
• 48:38stop there. But over time,
• 48:40this patient's cyst grew
• 48:41and, ended up going undergoing
• 48:43endoscopic evaluation.
• 48:45The pancreatic duct got bigger.
• 48:47And so this is a
• 48:47young JIT patient,
• 48:49with a relatively small cyst,
• 48:51like eleven millimeters to begin
• 48:52with. But ultimately, because it
• 48:54grew and the duct size
• 48:55was big,
• 48:57the patient actually elected for
• 48:58surgery. So go to next
• 49:00slide.
• 49:01And next slide.
• 49:02And at the time of
• 49:03surgery, again, for a patient
• 49:04that started with a small
• 49:05cyst over time go back
• 49:07one slide. This ended up
• 49:09being a, an IPMN with
• 49:11high grade dysplasia.
• 49:12Next slide.
• 49:15This is one of the
• 49:16more challenging patients. This is
• 49:18like an eighty one year
• 49:19old gentleman. So you can
• 49:20begin to kind of have
• 49:21that discussion saying, well, should
• 49:22this patient even really be
• 49:23in surveillance?
• 49:24But this is your pickleball
• 49:26playing eighty one year old
• 49:27who comes into clinic and
• 49:28wants everything done and is
• 49:29adamant that they want everything
• 49:30done. Often a very difficult
• 49:32conversation.
• 49:33But a patient with a
• 49:34relatively large cyst and we
• 49:36presumed it was branch checked
• 49:37IPMN and greater than three
• 49:39centimeters and so we do
• 49:40these alternating strategies but we're
• 49:42constantly saying to him look
• 49:43you know we'll reevaluate this.
• 49:45Next slide.
• 49:47So in fairness twenty twenty
• 49:49nine went by twenty twenty
• 49:50went by twenty twenty two
• 49:51twenty twenty three
• 49:53He's now,
• 49:55developed a second cyst in
• 49:56the uncertain process, and his
• 49:57original cyst has got a
• 49:58little bit bigger.
• 50:00Next slide.
• 50:01And so he finally comes
• 50:02into back into clinic, and
• 50:04this time now, he's eighty
• 50:06six years old, still healthy,
• 50:07still tells me he's playing
• 50:08pickleball.
• 50:10But we wanna have one
• 50:10of these discussions, and it's
• 50:12kind of part of the
• 50:12broader discussion about, like, I
• 50:14think it's easier for us
• 50:15to to get into surveillance
• 50:16with patients, but the really
• 50:18challenging thing is how do
• 50:18we stop surveillance with a
• 50:20lot of these patients? It's
• 50:21an issue if it doesn't
• 50:22make sense. It's resource utilization.
• 50:24It's comparison with,
• 50:25you know, their other competing
• 50:27with their other medical,
• 50:28issues. And so we had
• 50:29the conversation with this patient
• 50:30and said, look. You're eighty
• 50:32six years old. I know
• 50:32you're very healthy. I know
• 50:33you wanna go all the
• 50:34way, but let's let's bring
• 50:36some sanity to the situation
• 50:38and he negotiated himself to
• 50:39one final endoscopic ultrasound rightly
• 50:41or wrongly we said look
• 50:42if that's completely normal
• 50:45we're done we're gonna stop
• 50:46next slide
• 50:48Long story short, we sampled
• 50:50both cysts.
• 50:51One of them had high
• 50:52grade atypia in it, and
• 50:54the other had a molecular
• 50:55marker in the cyst that's
• 50:57very suggestive of an advanced
• 50:58neoplasia. High grade
• 51:03selected
• 51:04to stop surveillance because of
• 51:05other cardiac issues that arose,
• 51:07and so that made the
• 51:08decision. But just they use
• 51:09this case just to illustrate
• 51:11how challenging some of these
• 51:12folks are,
• 51:14especially when we're getting into
• 51:15the the time frame when
• 51:16we should really be backing
• 51:17off surveillance, not just for
• 51:19pancreatic cyst, but probably for
• 51:20other diseases as well. Next
• 51:22slide.
• 51:23So back to this kind
• 51:24of bigger topic
• 51:26of stopping low risk,
• 51:28IPMN pancreatic cyst surveillance. So
• 51:30for sure we're not applying
• 51:32this or not having this
• 51:33discussion for patients with the
• 51:34sorts of patients that John,
• 51:36ends up seeing, patients with,
• 51:37you know, large cyst patients
• 51:38who are on their way
• 51:38to surgery. But there are
• 51:40these groups of patients with
• 51:41one centimeter, two centimeter cyst.
• 51:43And now there's an evolving
• 51:44discussion that perhaps if they
• 51:46are of a certain age,
• 51:48maybe over the age of
• 51:48seventy five, if the cysts
• 51:50are stable for five or
• 51:51ten years,
• 51:52that maybe we should stop
• 51:54surveying them because their long
• 51:56term outcome is very similar
• 51:57to the general population. And
• 51:59so this is beginning to
• 52:00creep into guidelines,
• 52:02and there's more and more
• 52:03data accruing. So I think
• 52:04people need to be aware
• 52:05of that. And, again, it's
• 52:06probably one of the more
• 52:07challenging things we we do
• 52:08in PANCIS clinic is having
• 52:10frank discussions with people about
• 52:12stopping
• 52:13surveillance. Next slide.
• 52:15And so when we think
• 52:16about stopping
• 52:18pancreatic cyst surveillance,
• 52:20there's multiple factors that come
• 52:22into play. There's one group
• 52:23of factors which obviously has
• 52:24to do with the pancreatic
• 52:25cyst itself. You know, what
• 52:27type of cyst is it?
• 52:29Has a patient had surgery
• 52:30for the cyst before?
• 52:32What does a cyst look
• 52:33like? Do they have low
• 52:34risk features, or are there
• 52:36high risk features?
• 52:37The issue of cyst stability
• 52:38is very important because people
• 52:40are beginning to understand that
• 52:41maybe if cysts are stable
• 52:43over a long period of
• 52:44time, it denotes a certain
• 52:46biology that may not progress
• 52:48further.
• 52:49But then there's patient factors,
• 52:51and we don't really have
• 52:51an absolute age yet. We
• 52:53don't say seventy five, we're
• 52:54done. Eighty, we're done.
• 52:56But we certainly take age
• 52:58into account. We take comorbidities
• 53:00into account. Also, because some
• 53:01of the comorbidities
• 53:02influence progression like diabetes.
• 53:05And then as John alluded
• 53:06to, like, patient preference, this
• 53:07is kind of shared decision
• 53:08making. This is like, well,
• 53:09what's important to you? Do
• 53:09you really do wanna be
• 53:10coming in for endoscopies and
• 53:12MRIs for the next five
• 53:13years?
• 53:14But there's other issues maybe,
• 53:16race and ethnicity kinda plays
• 53:18into decision making as well
• 53:19as ultimately resource utilization from
• 53:21a health system perspective.
• 53:23So this is an evolving
• 53:24topic,
• 53:25and I will leave you
• 53:26with this notice that there's
• 53:27a large number of, very,
• 53:32expert and, well trained individuals
• 53:34at Yale both on the
• 53:35surgical side as well as
• 53:36on the gastroenterology
• 53:37side. But, also one of
• 53:38the beautiful things about pancreatic
• 53:39cyst, it's a really multidisciplinary
• 53:41specialty. So we have wonderful
• 53:42pathologists and radiologists,
• 53:43you know, who help us
• 53:44manage these patients. And so
• 53:46I think the sorts of
• 53:47patients that we end up
• 53:48seeing in clinic in terms
• 53:49of co management,
• 53:51with primary care include next
• 53:53slide.
• 53:54You know, it is when
• 53:55it comes down to trying
• 53:56to figure out what type
• 53:57of cyst it is, and
• 53:58we can certainly help with
• 53:58that. And again, the vast
• 54:00majority of times, as I
• 54:01said, these small cysts turn
• 54:02out to be branched out
• 54:03IPMNs.
• 54:04But also how do we
• 54:05help with those branched out
• 54:06IPMNs?
• 54:07At what point should we
• 54:08be thinking about surgery?
• 54:09When should we be thinking
• 54:10about an endoscopic ultrasound, especially
• 54:12for those intermediate features?
• 54:14But, actually, what I think
• 54:15is the larger and bigger
• 54:16picture and the big, big
• 54:17problem is trying to figure
• 54:19out what to do with
• 54:20all the low risk branch
• 54:21direct IPMNs
• 54:22and decisions about do we
• 54:23start surveillance?
• 54:25How do we
• 54:26survey? How frequently do we
• 54:28survey? And when do we
• 54:29think about stopping surveillance?
• 54:39We can
• 54:40I was just, I was
• 54:42just answering one of the
• 54:43questions in the chat,
• 54:44but, James, Flora,
• 54:46I'm curious, before I type
• 54:48anything to Jill?
• 54:50You know, the question is,
• 54:51can you talk about how
• 54:52to use a one c
• 54:53and c a nineteen dash
• 54:55nine levels should PCPs be
• 54:56ordering them for SIS follow-up
• 54:58or or not?
• 55:00You know, that's actually a
• 55:01really good question.
• 55:02There's arguments for following them
• 55:04and and for not.
• 55:06They generally are not included
• 55:08as firm recommendations in the
• 55:09guidelines.
• 55:11My personal practice is for
• 55:12somebody who is nondiabetic.
• 55:14We don't follow the a
• 55:15one c at all.
• 55:18In terms of cyst surveillance,
• 55:20James, I'm curious what you
• 55:21do. And CA nineteen nine,
• 55:23I like to get a
• 55:24baseline
• 55:25level and correlate it with
• 55:26any imaging changes,
• 55:29keeping in mind that nineteen
• 55:30nine should always be sent
• 55:32with concomitant
• 55:33LFTs.
• 55:36Somewhat similar. I think it's
• 55:37a you know, to go
• 55:38to the end of the
• 55:39discussion and say it's a,
• 55:41a very practical issue from
• 55:43a patient management perspective because
• 55:45we get the results back.
• 55:46And a lot of our
• 55:47patients have mildly elevated hemoglobin
• 55:49a one c's, mildly elevated
• 55:50c a ninety nines that
• 55:51leads to other tests. And
• 55:52so the question is, is
• 55:53it really worth, you know,
• 55:55going going down this road?
• 55:56We know that c a
• 55:57ninety nine is not a
• 55:58great tumor marker for pancreatic
• 55:59cancer, but I do agree
• 56:00it's good to have a
• 56:01baseline,
• 56:02you know, just in case
• 56:03it rises later on in
• 56:05the patient's course. Because you're
• 56:05gonna be following these patients
• 56:07for four, five, six, ten,
• 56:09fifteen years.
• 56:10The hemoglobin a one c
• 56:11and the diabetes is a
• 56:12slightly different story because there's
• 56:13growing data about the role
• 56:14of just diabetes in accelerating
• 56:17progression of patients with branch
• 56:19of IPMNs, IPMNs, but also
• 56:21the role of just new
• 56:22onset diabetes as a risk
• 56:23factor for the development of
• 56:25cancer.
• 56:26So it works kind of
• 56:27both ways. Yes. It's a
• 56:28it can be a good
• 56:29biomarker,
• 56:30but it can also be
• 56:31a way of trying to
• 56:31decrease that risk in these
• 56:32patients who we're surveying. We
• 56:34don't have all the data
• 56:35there, but I think it
• 56:36is worth following.
• 56:37I think there are a
• 56:38lot of patients out there
• 56:39who, you know, I think
• 56:40can obviously benefit from, you
• 56:41know, healthier lifestyles and better
• 56:44controlled blood sugars. It's certainly
• 56:45challenging. But I do actually
• 56:47monitor the hemoglobin a one
• 56:48c a little bit more
• 56:49closely than the c n
• 56:50nineteen nine.
• 56:53Fantastic.
• 56:55And while we're on the
• 56:56hour,
• 56:57Flora, did you wanna say
• 56:58something the last? Week. Yes.
• 57:00Well, I have a question
• 57:01for James, and,
• 57:02that pertains to how far
• 57:04are we in research these
• 57:05days with endoscopic ultrasound and
• 57:07using of,
• 57:08laser optical cameras to get
• 57:10a microscopic view of the
• 57:12cyst wall. And is that,
• 57:14in development? Is it coming,
• 57:16down the pike soon or
• 57:18using AI as well to
• 57:19analyze the images and to
• 57:20identify the high risks,
• 57:23eventually with the cyst transforming?
• 57:25Yeah. No. There's definitely a
• 57:27lot of,
• 57:31put small cameras into assist
• 57:33to get more imaging. It's
• 57:34still considered a research tool.
• 57:35May not well be applied
• 57:36to the to the broader
• 57:38spectrum. I think there are
• 57:40still,
• 57:41exciting developments in understanding
• 57:43how cells develop and how
• 57:44they progress and understanding
• 57:46if there's diagnostic tests, like
• 57:47molecular tests that could help
• 57:49us understand that. And, of
• 57:50course, you can't get through
• 57:52any,
• 57:53conference these days without mentioning
• 57:54the word AI. And so,
• 57:56yes, AI is right there
• 57:58in analyzing and coanalyzing with
• 58:00radiologists,
• 58:01MRI images, CT scan images
• 58:03to kind of quickly get
• 58:05to what are the worrisome
• 58:06features, what are the high
• 58:07risk stigma, or are things
• 58:08being missed. And the very
• 58:09kind of scary piece of
• 58:10data
• 58:11about the fact that for
• 58:12some patients who go on
• 58:14to develop cancer,
• 58:16if you go back and
• 58:17use AI to look at
• 58:18their imaging studies with cyst,
• 58:20you know, twelve months, eighteen
• 58:21months before they develop cancer,
• 58:23that there may be signs
• 58:24there. So I I you
• 58:25know, I'm classically
• 58:28a late adopter, but when
• 58:30it comes to stuff like
• 58:30AI, I think there's great
• 58:32potential. And so you'll be
• 58:33seeing a lot more about
• 58:34AI AI and imaging recognition
• 58:36and so on when it
• 58:37comes to the medical system.
• 58:39Topic for for a a
• 58:40future
• 58:42Smilo shares. But I'm gonna
• 58:43have to close this. We're
• 58:44after the hour.
• 58:46Thank you all for attending,
• 58:47and thank you so much
• 58:49for for putting on this
• 58:50program. I learned a lot,
• 58:52and take care. Bye bye.
• 58:54K. Thank you. Bye bye.