Well, how are we doing? We're halfway, we're all the way through medical school and halfway through a GI fellowship in two and a half hours. So we've got a lot to cover and we're about, it's about to get worse because we're going through the liver, the gallbladder, and the pancreas here. I'm actually going to just, in the interest of time, kind of skip through some of these questions and we'll ask, we'll go to this one here. Which statement about gallstones is true? Gallstones are common and present in about 50% of adults. Most gallstones are cholesterol stones and if gallstones are present, cholecystectomy is recommended. So which answer do you think is correct here? All right, well you can see that the right answer here is most gallstones are cholesterol stones and we'll cover that during the course of our lecture. Okay, most pancreatic cancers originate in the insulin-producing cells of the pancreas, B the cells that line the duct of the pancreas, C the enzyme-secreting cells of the pancreas or D the bicarbonate-secreting cells of the pancreas. And that is absolutely right. It's the cells that line the ducts of the pancreas or ductal adenocarcinoma is by far and away the most common form of pancreatic cancer. So we have been talking largely about the luminal digestive tract in terms of our disease state so far. We're yet to get into the large intestine, but what we're going to talk about now are the digestive organs, which is the liver and the biliary system or the gallbladder and the pancreas, which hides way deep down in the back of the abdomen and it's an organ that's not very accessible to at least on the surface of either physical examination or otherwise. Let's start with the liver, cirrhosis. You guys have probably heard that term used a lot or you may even know somebody with cirrhosis. And really what cirrhosis indicates is a chronic disease of the liver, usually a chronic inflammation of the liver, that over the course of time can lead to progressive scarring and then nodule formation as a result of the liver's attempt to regenerate. The liver has the unique capacity to regenerate. You take out half your liver, part of it's actually going to regenerate. And in the liver's effort to regenerate in the formation of all this scar tissue, you develop these nodules and that's what defines cirrhosis. It does lead to a progressive loss of liver function and it's generally considered to be irreversible. But if you identify the cause of the underlying inflammation and remove it, you can see some reversal or regression of cirrhosis. These are the common causes and at the top are probably the big three, so to speak, of cirrhosis in this country. And that includes non-alcoholic fatty liver disease, which we're now calling metabolic associated fatty liver disease, alcohol associated liver disease, and hepatitis C. And then there's a whole list of other diseases and there's whole textbooks written about various causes of chronic liver disease. But we'll just spend most of our time talking about the most common causes of chronic liver disease and cirrhosis. So when you have cirrhosis, there are signs and symptoms. And in terms of symptoms, fatigue and muscle wasting are pretty common, especially as the cirrhosis advances. Now early on, there may be no symptoms. And so that's why many people with, say, hepatitis C or even non-alcoholic fatty liver disease that have chronic inflammation and progressive scarring liver may not know it until they get more advanced and actually develop signs and symptoms. These are some of the signs of liver disease that we can detect on physical exam and or patient's experience, including jaundice, because the liver's not able to clear bilirubin. There are endocrine changes that occur or hormonal changes that occur in patients with cirrhosis, so they can develop spider angiometer or abnormal blood vessels on the skin. Or males can develop enlargement of the breasts because of increased estrogen levels in patients with cirrhosis. And then some of the complications that occur with cirrhosis include GI bleeding, and we've touched a little bit about varices in a moment, confusion, which is hepatic encephalopathy because the liver is responsible for clearing toxins in the liver. And when some of those toxins build up, patients can become confused. And then finally, swelling because of alterations in the kidney perfusion that occurs and the increased pressure of the blood vessels in the abdomen because the blood flow can't get through that scarred liver leads to the accumulation of fluid in the abdomen, which is ascites formation, and also increased fluid development in the lower extremities. Now if a patient develops any of these complications, whether it's GI bleeding, encephalopathy, or ascites, we call that decompensation. That cirrhosis has now become decompensated. And that's an important term when we're seeing patients because the prognosis is much different. There's many ways to diagnose cirrhosis, including some simple blood tests, which are both proprietary commercial blood tests as well as just using a calculation based on standard and routinely available blood tests to come up with a score that has reasonable predictive accuracy in terms of whether somebody has significant fibrosis or scarring. And then we can use imaging, primarily ultrasound or even CAT scan imaging, but even some more recent proprietary imaging that uses some ultrasound technology to look at elastography or the stiffness of the liver. And these are two such technologies that are available, FibroScan and ARFI. And finally, the gold standard of diagnosing cirrhosis is a liver biopsy, which is typically obtained percutaneously, really at the bedside, often with imaging. And you can see the representative pathology here, with the red being normal liver cells, but have turned into nodules that are surrounded by the blue scar tissue or fibrosis. And it's that regeneration of the liver tissue between the fibrous scars that leads to the nodule formation. And that nodule formation really creates obstruction to blood flow through the liver. So when you have that obstruction to blood flow through the liver, the blood has to go somewhere. And what it does is it goes to detour blood vessels. And these varices are indeed detour blood vessels. So normally the blood flow is flowing this way up the portal vein through the liver, but the pressure builds up in the liver. And so it finds its way through these detour vessels back up to the heart. And these dilated veins in the esophagus are called esophageal varices. And in about 10% of patients with cirrhosis, or 5% to 10%, they'll also form in the lining of the stomach. And we call those gastric varices. Here you can see the endoscopic view of esophageal varices. You remember that nice flat image of the esophagus you saw before? Well, now you see these tortuous, serpiginous elevations, which are actually dilated veins. They're important because they can rupture and bleed. And when they do rupture and bleed, it is a very significant clinical event for that patient. They clearly need to be hospitalized, typically in the intensive care unit. And as you can see here, their mortality, or their chance of dying from that one bleeding event is upwards of 25, can be as high as 25%. So it is a serious, life-threatening event when it happens. Daniel? Is there any risk when you band the varices to practically treat them, of them bleeding? Yeah, there is. There is a risk of actually precipitating bleeding when you do banding. But in general, we want to do banding whenever we think the risk of the banding doing benefit outweighs that small risk of actually inducing bleeding. How do you, if they do rupture, how do you treat them? Would you try to band higher or lower? Usually the blood flow is coming from below, so you always want to start down at the bottom first and work your way up by placing these bands. But yes, you want to go after that site that's actively bleeding and actually target that and put a band on that. And usually you can stop it that way. So the management, as we've talked about, includes some medical therapies, obviously resuscitation, as we talked about earlier, with standard GI bleeding, and octreotide as a medication, or sandostatin as a medication that decreases the pressure in the portal circulation. So we'll often provide that as medical therapy. Endoscopic ligation, which is the band ligation that we were just talking about, is, and we showed earlier, is designed to place that band and ligate it and interrupt the blood flow in that varix. If that doesn't work, and there's a salvage, another salvage therapy that can be performed is done by our interventional radiologist, and that's a transjugular intraepatic portosystemic shunt, which we call TIPS for short. And the idea there is to place a stent between the hepatic vein and the portal vein that opens the dike, if you will. It basically opens the dam and decreases the pressure in the backed-up portal circulation. By decreasing that pressure, you decrease the forces that are leading to the bleeding in the varices. Okay, ascites is the other, this is the second decompensating or complicating event of cirrhosis, and you can see it's the accumulation of fluid in the peritoneal cavity. This is in the cavity around the intestines. Ordinarily, there's no fluid detectable there. It's actually constantly formed and constantly absorbed in all of us right now. But in patients with cirrhosis, the ability to resorb that fluid is less than the rate at which it's formed, and that's why the ascites develops. And that's because of the increased pressure in the portal circulation that we can't absorb the fluid as quickly. So the management here is a low-sodium diet. The fluid is really the result of excess sodium in the body. Diuretics are designed to get rid of some of that sodium in the body. And then finally, TIPS, by decreasing that pressure in the portal circulation, creating that shunt or opening up the dam at the liver, so to speak, just creating a shunt through the liver, decompresses that portal pressure or lowers the portal pressure and can help with patients that have a difficult-to-control ascites. It's not the first-line therapy for ascites, but in patients with refractory ascites, it's difficult to treat. It can be. In patients that do have ascites, it is at risk of getting infected, and that's another very high mortal event for patients with cirrhosis. If that does get infected, their chance of surviving a year is probably less than 50%. And so we want to manage the ascites, reduce it, and if we reduce the ascites itself, there's a lower chance of it's going to get infected. But if it does get infected, we want to treat them with antibiotics and potentially keep them on antibiotics to lower the chance of them getting an infection again. And finally, the third of four complications, this is in terms of decompensation, the third decompensating event is hepatic encephalopathy, and that's really due to the inability of the liver to clear the normal toxins that are present in our body. Those toxins make their way across the blood-brain barrier and make normal neurologic processes and transmissions altered, typically in a way that slows them. So they become lethargic or slower, if you will. And finally, as it progresses, they can progress to a coma. In very early stages of hepatic encephalopathy, it may be subtle cognitive changes. Maybe they're not calculating as quickly as they used to. Maybe they have a little bit more difficulty reading. There may just be harder for them to write or articulate the way they used to. As it progresses, it becomes much less subtle. They actually have trouble verbalizing their words. They get slurred speech. And then finally, they can actually become lethargic and even comatose because the toxins have developed at such a high level. The diagnosis is really made in the right clinical setting with somebody with cirrhosis that has altered mental status, and there are some blood tests that can help corroborate that diagnosis, but it really is a clinical diagnosis that you're making based in the right clinical setting. When we have a patient with encephalopathy, we're going to want to make sure we understand if there's any precipitating event, something that threw them over the edge that made them more confused, and that would include an infection, any alteration in their electrolytes or other acid-based disorders, metabolic disorders. And then finally, medications, some medications that may make us more confused. Even in the normal state, patients with cirrhosis are much more sensitive to it, so if they're on medications that could be the culprit, we want to remove those. And then once we've addressed all precipitating events, we then have specific therapies that help us clear the toxins or reduce the rate at which toxins are formed, and therefore the liver is able to kind of catch up and clear the toxins that ordinarily are present, and that includes lactulose and rifaximin. The last complication that can occur in cirrhosis is hepatocellular carcinoma, and it is a frequent complication of all forms of cirrhosis, but particularly viral hepatitis, so hepatitis B and hepatitis C. It is a very deadly cancer. As you can see, it's the fourth leading cause of cancer death across the world. Here you can see a normal liver over here and a massive, large hepatocellular carcinoma on the right side of this person's liver on a CAT scan. Because the risk of hepatocellular carcinoma is so high in patients with cirrhosis, it is recommended that they have an ultrasound or some imaging test every six months to screen for and detect hepatocellular carcinoma early so it's more treatable. When we do diagnose hepatocellular carcinoma, the treatment, if it's early stage, can be liver resection or potentially liver transplant if their liver is sick enough to warrant that otherwise. Or there are some interventional radiology techniques where we can embolize or ablate the lesion with either cryotherapy or heat or radiofrequency ablation to destroy the tissue. If somebody has very advanced hepatocellular carcinoma, unfortunately it's mostly chemotherapy and it's palliative care as opposed to any attempt to cure the cancer. So if a patient develops progression of their disease and decompensation or, as I just mentioned, even hepatocellular carcinoma, all of those could lead the patient to be a candidate for a liver transplant. You can see here that cirrhosis and hepatocellular carcinoma are perhaps the most common reasons for undergoing a liver transplant, but some patients that present with acute liver failure, say either to Tylenol toxicity or a severe bout with acute viral hepatitis, they may actually also be a candidate for a liver transplant. There's a scoring system that our transplant hepatologists and surgeons use to help prioritize liver transplants to the sickest and the neediest patients, and that's called a MELD score, a model and end-stage liver disease score, and the NA is the sodium that's been added to that more recently. In the United States, within a couple years ago, you can see that we performed about 7,700 deceased donor liver transplants, meaning a cadaveric liver transplant, and then about 450 live donor transplants where a relative or a living donor donates part of their liver. And again, remember, the liver has the unique ability to regenerate, so you can donate a portion of your liver and your liver will grow back, and the half liver you gave to somebody will also regenerate and increase in size so that one liver can actually serve two different people. The one-year survival of liver transplant is over 90% now. The waiting list remains high, and so there's always an effort to try to come up with new ways of, number one, increase the organ availability, but looking at new ways outside of transplant to replace the liver. Unfortunately, we cannot live with a liver. We certainly can live without a kidney on dialysis, but we really don't have an acceptable way to do that for the liver right now. Only about 2,000 people every year die while waiting a liver transplant because of this shortage. Okay, let's talk about some of the common liver diseases. Alcoholic liver disease is obviously due to excessive alcohol ingestion, and in a woman that really is, women are a little bit more sensitive to men in terms of the amount of alcohol it takes for it to cause significant liver injury. Alcoholic hepatitis is really, when we drink alcohol, typically we will have fatty liver develop initially, and if enough alcohol is consumed over a long enough period of time, you can develop alcoholic hepatitis or an acute inflammatory destruction of the liver as a result of that toxicity and dying liver cells. Over time, many patients, if not the majority of patients with alcoholic hepatitis will then progress on to cirrhosis. Some patients never really have this intermediate step. They can just go from fatty liver and over the course of years and years and years of drinking end up with it being detected as cirrhosis. And so a woman probably has to drink about 40 grams of alcohol, which is about three drinks per day for over six months to develop significant chronic liver disease, and a male is probably about 60 grams or about four and a half drinks per day. Not everybody that drinks three drinks per day or four and a half drinks per day develops alcoholic liver disease and why some people do and some don't. We really don't have a clear understanding. It's probably related to genetic differences and predispositions. The treatment for alcoholic liver disease in general is stopping the alcohol, you know, taking away the alcohol because that's the underlying cause. And it can take up to a year of being abstinent from alcohol to see the full benefits of that recovery. So sometimes patients will stop for two months and they're still jaundiced and they say, what the heck, I'm just going to start drinking again. But they've got to be educated that it can take up to a year to see that full benefit. And in the old days, when we weren't transplanting people that have alcohol liver disease as frequently as we are now, we would require patients to be off alcohol for six months, usually with documented AA attendance, because of that very reason. They may not need a transplant if their liver recovers being off alcohol for six months. But now we're getting more aggressive in terms of transplanting patients with alcoholic hepatitis, particularly if they don't respond to medical therapy like prednisone and staying away from alcohol for a month or so and they're continuing to worsen. Non-alcoholic fatty liver disease, as the term implies, is a very similar disease with fat throughout the liver that can lead to chronic inflammation, but it's not related to alcohol ingestion. And the vast majority of these people are obese and have type 2 diabetes or have dyslipidemia, elevated cholesterol. And so that's why the term metabolic-associated fatty liver disease, or MAFLD, is now the term in vogue, because it's really a metabolic disease. Non-alcoholic doesn't really describe what the underlying cause is. It is really now the most common cause of liver disease in this country, because we have an obesity epidemic, a diabetes epidemic, and because of that, this is now the most common cause of chronic liver disease and now the most common cause of cirrhosis needing transplant in this country. The treatment is obviously addressing the type 2 diabetes and or the obesity and trying to promote weight loss exercise. We don't have any specific medications at this point that are approved for non-alcoholic fatty liver disease. We don't have any under investigation, and I suspect within the next three to five years, we're going to have multiple agents available for that disease. Hepatitis C was the most common cause of chronic liver disease in this country, but we've made such strides with hepatitis C, it has now been replaced by non-alcoholic fatty liver disease. It's still very common in this country. About 2.4 million people have the infection, and it was really the opioid. It's still increasing to some degree because of the opioid epidemic, and it's transmitted through blood-to-blood contacts, so IV drug use and in the old days, blood transfusions before we had ways of testing hepatitis C were the most common means of transmission, but IV drug use is certainly now the most common means of transmission. Because of the frequency of this and because we have very effective, very well-tolerated strategies, it is now recommended by the CDC that all adults 18 and over be tested at least one time for hepatitis C, and so I remember that point. I think it might be on a test somewhere. All individuals over the age of 18 should be tested at least once, and then obviously all pregnant women, just like they're tested for hepatitis B, are getting tested for hepatitis C now, and if somebody has risk factors, let's say they're in rehab, but they're in a controlled rehab for their IV drug use, or you know that they're being exposed through IV drug use, it's reasonable to retest those people periodically. As I mentioned, there are numerous agents now, cocktails of agents that are available with cure rates above 95% that are extremely well-tolerated and can often be done within just six weeks. Many primary care doctors are now treating hepatitis C because it's so easy to treat those, especially those without cirrhosis. Hepatitis B is the most common worldwide form of hepatitis. It's not as common in this country, but is really endemic in parts of Africa and Asia. And you can see that it's about 260 million people that are living with hepatitis B. It is also a chronic hepatitis. It can be an acute, it certainly can be an acute hepatitis, present acutely with jaundice, nausea, vomiting, illness, but most people have a chronic form that's with them throughout their life. In the United States, we have to be very wary of this. Again, in IV drug users, because it's transmitted from blood to blood, just like hepatitis C is. But in immigrants that are coming from parts of Asia and parts of Africa, we have to be very vigilant about testing those individuals for hepatitis B. Transmission is through sexual contact and blood-borne, and also vertical from mother to child. So that's why it's important to test all pregnant women for hepatitis B, so that we can mitigate the risk of transmission to the child. And there are certainly ways to do that. There's a very effective vaccine for hepatitis B. Unlike for hepatitis C, we do not have a vaccine. And so universal vaccination is now recommended for all children since the 1990s. And hopefully we'll continue to make strides at getting rid of that virus through universal vaccine. In patients that are exposed to hepatitis and or mothers that deliver children that are active hepatitis B replicators, there's an immune globulin that can be delivered to decrease the risk of acquiring hepatitis B if you've been exposed to it. And there's a number of antiviral therapies that are available. The important thing is that it's unclear whether we ever cure the virus. The virus is integrated into the cells, into the hepatocyte DNA, but the goal here is really to suppress the replication of the virus enough so that it's not causing disease in the patient. And that's really what the therapies are primarily accomplishing. In patients with hepatitis B, we have to be careful about the fact that it is a virus that can be hiding, as I mentioned, lurking in the hepatocytes. And if you then expose that patient to a very immunosuppressive event where their immune system is suppressed, the virus can reactivate, and the patient can develop a very severe case of hepatitis that can be fatal. And I've seen that happen. And so we always want, anytime we're gonna be exposing a patient to immunosuppressive therapy, we want to test them to see if they're carrying hepatitis B, and if so, potentially treat them and put them on medications to prevent that reactivation while we're suppressing their immune system. So these are some of the agents that we might give somebody. If you give an agent that depletes their B cell or very potent chemotherapy agents, the chance of reactivation of hepatitis B in somebody that has hepatitis B, the chronic carrier of hepatitis B is over 10%, whereas some of the agents that we use more frequently in GI like TNF-alpha inhibitors for inflammatory bowel disease or integrin inhibitors or tyrosine kinase inhibitors that are often used as chemotherapeutic agents, the reactivation is a little bit lower, but still substantially enough that you would want to put those patients on a hepatitis B agent to suppress the virus while you're treating with the immunosuppressive agent. Primary sclerosine cholangitis is a condition that we deal with in advanced endoscopy that can lead to chronic scarring and liver disease. It is due to an inflammation of the bile ducts that leads to stricturing. Most of the patients with primary sclerosine cholangitis have underlying inflammatory bowel disease. Upwards of 90% have ulcerative colitis. On the other hand, about five to 10% of patients with ulcerative colitis have PSC. And it can occur also in patients with Crohn's disease. These people can develop infection of their biliary system, cirrhosis and scarring, like any form of chronic liver disease. And the one dreaded complication is cholangiocarcinoma or cancer of the bile ducts. These patients with primary sclerosine cholangitis, particularly when they have underlying ulcerative colitis, have a very high rate of colon cancer. And this is the one condition, one of the few conditions where we still recommend an annual colonoscopy if you have a patient with PSC and underlying ulcerative colitis. The diagnosis is really made by imaging because it's a disease of the large bile ducts. We can see this, instead of that beautiful branching tree that we saw earlier of the biliary system, here you can see that there's scarring and narrowing in various parts and almost beading of the bile ducts. And that's diagnostic of sclerosine cholangitis. Now let's move on to gallstones. This is a condition that's very common. It's not 50%, as the question said earlier, but it's probably about 10 to 15% of the U.S. population will develop gallstones. A little bit more common in women than it is in men. And the vast majority of them are made of cholesterol stones. These clear and they're very hard stones that are formed in the gallbladder, as the name implies, but they can migrate out of the gallbladder into the bile duct and cause havoc elsewhere. The two other main types of gallstones are pigmented stones, which are made primarily up of bilirubinate crystals, and then brown stones, which are made up of lecithin, as well as some bilirubinate, which it's the bilirubinate that gives it the color of the brown and black stones. And there's very little bilirubinate in the cholesterol stone. So these pigmented stones, the difference being is that they have bilirubinate in it. The black stones are often in patients with hemolytic disorders, where they're constantly hemolyzing and excreting elevated levels of bilirubin in their bile. The symptoms of gallstones, many, if not most, have no symptoms at all. And they may be detected on an ultrasound that's being done for other reasons, or a CAT scan that's being done for other reasons. We don't do anything about gallstones if they're not causing symptoms. We leave them alone. Now there's a chance those patients will develop symptoms, and if they do, then we'll act upon it. But when they do develop symptoms, it is, we use the term biliary colic, but it's really a misnomer. It's not a colicky pain, like a crampy pain. It's really a pain that occurs typically right in the epigastric, right in this area right here where my fist is. It's a squeezing sensation that comes on gradually but steadily, and stays that severe squeezing pain until it resolves, which typically 15 minutes, 30 minutes, maybe 45 minutes later. So it's not like a crampy, colicky pain that we think of, but it's really more of a steady, boring pain. And it lasts minutes to hours, often occurs with eating. It typically means a stone is trying to get out of the gallbladder, and it's obstructing the cystic duct, and then when the obstruction, if the stone falls away from that obstruction, the pain goes away. Here's how we diagnose gallstones. An ultrasound is a very accurate way. You can see this is the gallbladder, which is showing up black on ultrasound. Fluid is black. And a stone would occur as a very bright, echogenic focus inside the gallbladder, and then you see the shadowing, or the blackness on the other side, because all of the sound is being reflected by the stone, and that's why we see that shadowing. And that's classic picture diagnostic of a gallstone. Now, what if that stone that was trying to get out of the cystic duct, trying to get out of the gallbladder, and trying to get out here, that caused the biliary colic, and remember I said it falls back in, and then the pain resolves. What if it gets stuck there, and the obstruction doesn't become relieved? Well, then that's when you often get cholecystitis, and that's inflammation of the gallbladder, and that's due to an impacted stone at the cystic duct. The patient's developed not only the pain, the pain then starts to localize to the right upper quadrant. They often have signs of infection, including fever and an elevated white count, because there typically is an infection that is getting set up inside that obstructed gallbladder. We diagnose this also by ultrasound, is one of the most common ways, and you can see a thickened gallbladder wall here. Sometimes you'll see fluid around the gallbladder. We call that pericholecystic fluid. And when the radiology technician is doing the examination, and pushing the probe on the gallbladder, it hurts right at that spot, and we call that an ultrasonographic Murphy sign. All of those features help us to diagnose a patient with acute cholecystitis. The treatment includes antibiotics, and then surgery, or some sort of decompression, or relief of the blockage of the gallbladder. In patients that are healthy, surgery is by far and away the best thing to do. If somebody's not very healthy, and they can't tolerate a surgery, there's other ways for us to drain the gallbladder. So this is what the before and after looks like for a cholecystectomy. The surgeon would go in, and they would dissect out the gallbladder, put usually a couple of clips across the cystic duct. The cystic duct is leading from the gallbladder to the main bile duct, and removing the gallbladder, which is the diseased organ. Now, this can create havoc, because if the surgeon places clips on this area, that's a bad problem. And that can happen, and that's why we as gastroenterologists sometimes see patients that have complications after a cholecystectomy due to ductal injuries, or leaking of these clips with bile leaking into the abdominal cavity. Choledocal lathiasis means that the stones have migrated out of the gallbladder through the cystic duct, but now into the bile duct, and we should never leave those alone. We never leave stones in the bile duct, unlike stones in the gallbladder that are not causing symptoms. If there's a stone in the bile duct, even if it's not causing symptoms, we want to address that, because it can't, almost certainly will, cause symptoms or problems over time. When they do obstruct the bile duct, the patients will develop jaundice, because this bile duct is draining the whole liver, and if bile can't get past that stone, the liver's not able to clear the bilirubin from our normal excretion process, and the patient's skin will turn yellow, and their laboratory abnormalities will worsen as well. They often become infected. Whenever anything is obstructed in the biliary tree, it's very common for there to be an infection upstream from it, especially with stone disease, I should say, and they'll develop jaundice and fever and pain in the right upper quadrant, because the whole liver is infected, and this is an emergency. It really needs to be dealt with within 24 to 48 hours, because that patient can get sick very quickly when your whole liver is full of pus. So the way to treat that primarily is with an ERCP, and here again is our ampulla vata in the second portion of the duodenum. We place a catheter up the bile duct. We can shoot a normal cholangiogram here, but here's a patient where we put the catheter up the bile duct, and you can see the bile duct here is very enlarged, dilated, because these stones that are showing up as filling defects in the bile duct were obstructing the bile duct, and we can take tools through our endoscope and make an incision, what we call a sphincterotomy, to open up this opening of the bile duct. Here you see a cartoon characterization of that, and then once that sphincter of OD or the sphincter at the bottom of the bile duct is opened or incised, that allows us to pull these stones out of the bile duct and pass into the intestine and relieve the blockage. Okay, we're gonna lastly move on to the pancreas and talk about pancreatitis, and as the term implies, it means inflammation of the pancreas, and the pancreas lays deep within the darkness of the abdominal cavity. Like I said, it's really not an organ accessible to physical examination, and there are two forms of pancreatitis, acute pancreatitis, meaning that the symptoms come on suddenly and the inflammatory process is a sudden increase in inflammation, or chronic pancreatitis, and chronic pancreatitis means it's going on over months and typically associated with scarring and damage, chronic damage to the pancreas. You can think of chronic pancreatitis as sort of the cirrhosis of the pancreas. So acute pancreatitis, acute onset, usually patients find one minute, within 30 minutes, they are very sick and very uncomfortable, and there's a very wide range of severity. Some patients have very mild symptoms and might even be able to get away without being in the hospital, and many just don't even report to the hospital, but some become deathly ill, acutely ill, and require ICU care. So the mild patients may have some nausea and vomiting, pain radiating to the back, often resolves in days, whereas the patients with severe acute pancreatitis, they have fever, their shortness of breath, they can develop confusion, multi-organ failure, they often go into shock and it can be life-threatening, and if they survive, they often end up in the hospital for months at a time. The causes of acute pancreatitis, the two main causes are heavy alcohol ingestion and gallstones, and particular gallstones are one of the most common causes. There's a number of other things listed here on your slide, including, by the way, ERCP. Anytime we're manipulating that ampulla botter, we can cause pancreatitis, and it gets back to our risk-benefit strategy we talked about before. We are only gonna take that risk of doing ERCP if we think the risk of us causing ERCP is lower than the risk of us helping the patient. So how do we diagnose acute pancreatitis? Well, it's usually blood test-based. Amylase and lipase are pancreatic enzymes that show up in the blood, and when you have acute inflammation of the pancreas, those levels are elevated much higher than normal, and in addition, we often have the right clinical setting with the patient presenting with acute abdominal pain, and then often imaging is part of that diagnosis, and here you can see the pancreas in a patient with mild acute interstitial pancreatitis where there's some very subtle fogginess to the fat around the pancreas. Ordinarily, fat on CT scan is black, but you can see it's a little grayer over here, and that's because fluid is accumulating around this inflamed pancreas, and on the right, you see probably the end sequelae of a very severe episode of pancreatitis where there's really no pancreas left there at all. The treatment of acute pancreatitis is really intravenous fluids, correcting electrolyte abnormalities, and initially resting their intestine, but we've gotten into the habit of feeding them more, feeding them sooner now. There's really no medications that we can use to suppress the inflammation in patients with acute pancreatitis, at least none that are effective. If somebody has gallstone pancreatitis, if there's a gallstone that's stuck at the ampulla vater and that impacted stone right at the intestine is what's causing and perpetuating the inflammation of the pancreas, we can go in and relieve that just like we did earlier with a stone obstructing the bile duct. Chronic pancreatitis, as I mentioned, is really kind of the cirrhosis equivalent in the pancreas. Fortunately, you can live without your pancreas, not very easily, but you can live without your pancreas. You can't live without your liver, but when the chronic damage and scarring occurs to the pancreas, patients develop typically chronic abdominal pain. They also don't make enough insulin to keep their blood sugar under control, and they don't make enough digestive enzymes to help completely and efficiently digest their food, and so the exocrine insufficiency leads to malabsorption, and the endocrine insufficiency leads to diabetes. Remember, the pancreas has two functions. One is to make digestive enzymes to help us digest our food, but also makes hormones, including insulin, that keeps our blood sugar regulated. Two completely separate functions in the same organ, and both of those are typically deranged in patients with chronic pancreatitis. The exocrine insufficiency and the diabetes, we have medications to control. We have pancreatic enzymes they can take by mouth that helps replace the pancreatic enzymes that the pancreas ordinarily make, and we have insulin to help control their blood sugar. The pain, on the other hand, is a little bit more challenging to control. We diagnose chronic pancreatitis often by imaging, and in the right clinical setting. You can see this calcification on a plain x-ray is picked up here, because these patients often have dense calcifications due to that chronic inflammation and scarring throughout the pancreas here. You can see that same calcification on a CAT scan, and on an MRCP or an MRI that is really designed to highlight the pancreatic duct anatomy, you can see that the pancreatic duct is dilated. It's not perfectly smooth. There's kind of a rough edge to it, and there's even a stone or a filling defect sitting in this main pancreatic duct, which are all characteristics of chronic pancreatitis. The treatment I've alluded to already, and that includes abstinence from alcohol if that is the underlying cause. Smoking cessation is really important, because tobacco use, we've learned, is just as important as alcohol in terms of perpetuating and causing chronic pancreatitis. And then, in addition to controlling their diabetes with insulin, we use analgesics and pancreatic enzyme supplements by mouth to control the exocrine insufficiency that leads to maldigestion and malabsorption. Okay, finally, we're gonna talk about pancreatic cancer. It is, as many of you know, a very deadly cancer. It is the fourth leading cause of cancer death in the US. The two main types, there's several minor types, but the two main types are adenocarcinoma, which develops from the ducts that line, or the cells that line the main pancreatic ducts, and then neuroendocrine cancers develop from the hormone cells in the pancreas, the insulin-producing cells of the pancreas, but these tumors are not always insulin-producing, but there's other hormones that these endocrine cells produce. Neuroendocrine tumors of the pancreas, which is what Steve Jobs had and Ruth Bader Ginsburg, typically the survival's much longer. Adenocarcinoma has a very poor five-year survival, even today. It's gotten a little bit better, but even today, it's a horrible prognosis. The risk factors for adenocarcinoma include family history. We think about 15% of pancreatic cancer actually runs in the family, or heritable. Age, nothing we can do about that, but it is more common as we get older. Smoking and alcohol, obesity, and diabetes, particularly smoking. Smoking is a major risk factor for pancreatic cancer. The symptoms of pancreatic cancer, because the bile duct travels right through the pancreas, a tumor in the head of the pancreas, the most common area, will obstruct the bile duct and cause the patient to develop jaundice. It's often painless initially, and so when a patient presents with painless jaundice, we're always worried they may have pancreatic cancer, especially if they have weight loss and a poor appetite. Later, as the tumor progresses, they do often develop abdominal pain. We diagnose pancreatic cancer often by getting a biopsy, and that is very much facilitated with endoscopic ultrasound. Again, we're using a linear echo endoscope here, and we can see the target. In this case, it's a cyst that we're targeting in the pancreas, and we can direct a needle directly under ultrasound, real-time ultrasound guidance, into that target, and this could be a mass in the pancreas as well as a lymph node or any abnormal tissue that we see anywhere in the upper digestive tract. The treatment of pancreatic cancer includes surgery for the lucky few that still have a resectable or early-stage tumor, and if not, it's usually chemotherapy, which is often palliative. When patients do develop obstruction of the bile duct, here you can see a tumor surrounding the bile duct that's obstructing it. We can intervene as gastroenterologists endoscopically, and here, using an ERCP scope, place a catheter into the bile duct and then deploy a stent, which is a tube-like device that opens up the bile duct and allows bile to drain freely into the intestine. Here's a closer-up cartoon of the stent opening up the bile duct and allowing this obstruction to be bypassed that was created by the tumor. Here's the ERCP radiograph, or the cholangiogram. You can see where the tumor is compressing the stent, but it still opens it up enough for the bile to flow normally, and this is the endoscopic view from that deployed stent. Okay, that's it. Let's deliver the gallbladder and the pancreas. Question? If you had a person that lived with a pancreas, then why is the mortality rate so high for a pancreatic cancer? Well, it's the cancer in that case. It's not so much you're destroying the pancreas. It's the cancer that then metastasizes throughout the body, and it's the tumor that takes the patient's life. It's not the destruction of the pancreas itself. Question? So when you were talking about some of the symptoms from liver disease, it also kind of triggered in my mind some of the issues that we see with heart disease. Is there ever a linkage between the two? Yes, there actually can be. What you notice is the fluid accumulation that you see in cirrhosis is very similar to the physiology of the fluid accumulation in patients with heart disease. Similar to the physiology of the fluid accumulation in patients with heart failure. What's happening is in both states, the perfusion of the kidneys is compromised. In the heart failure state, it's because the heart can't pump blood well enough. In the cirrhosis state, it's because of the changes in the blood flow of the mesenteric circulation that blood flow to the kidneys is compromised and altered, and in both cases, the kidneys are trying to retain as much sodium because the blood flow, the kidneys are not seeing adequate blood flow. So they're thinking, I gotta retain more sodium to get more fluid to see more blood flow. So the physiology is related in many ways. Both of them lead to fluid overloaded states. Okay, in the interest of time, I think we'll move on to the next talk. Great.

liver

gallbladder

pancreas

cirrhosis

varices

ascites

hepatocellular carcinoma

pancreatic cancer