During this 20-25 minute pre-recorded lecture, Dr. Christopher J. DiMaio discusses the topic of chronic pancreatitis. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards. CME pre-requiste of live Q & A webinar, 8th Annual Mount Sinai Intensive Board Review in Gastroenterology & Hepatology on Sept 29.
Hello and welcome in this lecture. We will be covering chronic pancreatitis. Both the diagnosis and management of this very complex uh disease chronic pancreatitis is a condition characterized by marked inflammation and fibrosis of the pancreas with result in loss of asana and eyelet cells, the development of paranormal and ductile calcifications resulting in pancreatic duct distortion and obstruction. These morphological and pathologic changes can manifest in a number of ways, including severe abdominal pain, recurrent acute pancreatitis, execution insufficiency with associated weight loss, fat soluble vitamin deficiency or osteoporosis as well as endocrine insufficiency, which is now reclassified as Type three C diabetes, Chronic pancreatitis itself is a relatively uncommon condition with an incidence of up to 10 per 100,000 person years Both morphological E and symptom wise patients may present anywhere along the spectrum. Classically, patients will present with numerous calcifications throughout the pancreatic land as well as pancreatic stones and strictures resulting in a dilated pancreatic duct. However, many patients, they have a normal appearing pancreas gland with no calcifications and or no changes in their pancreas ducts. So called minimal change disease. For symptom symptom Atallah gee the majority of patients will present with abdominal pain up to 90% with roughly half having execution and or endocrine insufficiency. We'll start with a question which of the following patients are the most likely to develop chronic pancreatitis a 68 year old female with a 2.4 centimeter branch duct. I. P. M. N. A 31 year old male who has consumed 2-3 drinks a few times a week for the past 10 years. A 54 year old man with two bounce of Gallstone pancreatitis in the past five years. A 75 year old male with recently diagnosed autoimmune pancreatitis. Or a 24 year old male with two bouts of acute pancreatitis over the past year and who was discovered to have a P. R. S. S. One gene mutation. The correct answer is the last 24 year old man with a genetic ideology of his pancreatitis. There are a multitude of ideologies for chronic pancreatitis which are listed here. Most common ideologies include alcohol and tobacco smoke, but we also must remember patients with hyper calc mia and hyper triglyceride anemia or chronic renal failure are at risk for this condition, idiopathic causes include tropical pancreatitis or true idiopathic uh disease. There are a number of gene mutations with an association of developing chronic pancreatitis, the P. R. S. S. One uh which is the cat ionic trips in a gene gene as well as autism or recessive genes such as CFTR mutations and Spink one mutations. Autoimmune pancreatitis is a condition that's being increasingly recognized. Uh And both the Type one and Type two subtypes can be associated with chronic pancreatitis, particularly if they are if it's undiagnosed and left untreated as the pancreas can become a trophic and burnout. Uh Any form of recurrent or severe acute pancreatitis such as necrotizing pancreatitis can render the pancreas uh a trophic with loss of asking ourselves and eyelet cells as well as exposure to vascular diseases and ischemia or radiation effects can all lead to chronic pancreatitis and then any type of chronic obstruction being pancreas to visa. Uh Speaker of od dysfunction or or papillary stenosis or any kind of duct obstruction, be it from a solid or cystic nia plasm or from strict chronic strictures from post trauma, all of which can lead to chronic pancreatitis. Alcohol is the most well established factor and ideology of chronic pancreatitis. Alcohol metabolites are known to injure a solar cells as well as activate stealth lights and Stella cells resulting in uh fibrosis. It is thought that patients need to drink on average more than five drinks a day or 35 drinks a week to be at significant risk of chronic pancreatitis. Uh there is a latent period of about 15 years before onset is seen. But what is interesting, less than 10% of alcoholics develop chronic pancreatitis and in fact, patients who are alcohol abusers are much more likely to develop chronic liver disease rather than, rather than chronic pancreatic disease. All lending itself to a second hypothesis that alcohol exposure alone may not be sufficient to result in this condition. Smoking has recently been discovered to be an independent risk factor for the development of pancreatic insufficiency, pancreatic calcifications and severe morphological changes. Uh there is no association of smoking with diabetes or the development of pseudo cysts, but it should be recognized that smoking in and of itself is a significant risk factor for chronic pancreatitis, particularly chronic calcification, create type, as mentioned earlier, pancreatitis is really a spectrum of diseases where on the one end we can have acute pancreatitis. Uh And on the other extreme patients may have chronic pancreatitis, but you'll see in the middle that some patients with recurrent acute pancreatitis may transform from the acute form to a more chronic. So the question is, who, which patients with recurrent acute pancreatitis are most likely to develop chronic pancreatitis. These two studies do shed some light. Uh this first is a Dutch study looking at 669 patients who had their first episode of acute pancreatitis. Following these patients out recurrent pancreatitis developed in approximately 17% of patients, whereas chronic pancreatitis developed in about 8% of patients. And alcohol and non biliary causes were the most common reason for patients developing chronic pancreatitis after their first round of acute pancreatitis. A meta analysis of almost 8500 patients showed that similarly, a very low percentage of patients who have one bat of acute pancreatitis will go on to develop chronic pancreatitis roughly 10%. However, once you have recurrent acute pancreatitis. Your risk of developing chronic pancreatitis rises to about 36%. And again, the risk was highest among smokers alcoholics and men. So tip, the typical patient with one attack of boston pancreatitis has an extremely low risk of developing chronic pancreatitis. Also increasingly being recognized is the impact of gene mutations in the development of pancreatitis. There are multiple gene mutations that have been uh described to be associated with development of either recurrent acute pancreatitis or chronic pancreatitis, many of which fall in the uh over activation of trips in or decreased inhibition of active trips. Uh The most notable is a mutation in the cat ionic trips in a gene gene Known as p. r. s. s. one. This gene mutation is autism, a dominant though it does have incomplete penetrates but it is associated with early onset recurrent acute pancreatitis and chronic particularly chronic calcification pancreatitis And can be identified in young people particularly under the age of 40. It is important to note that patients with P. R. S. S. One mutation have a very high risk of developing pancreatic cancer. And while unfortunately there are no set guidelines and had the best monitor these patients. Uh certainly any change in symptom Atallah gee must be taken seriously as they may be developed. May have developed near plaza. So in the diagnostic work up for chronic pancreatitis were really assessing two separate variables. One is the morphological assessment and we're looking at a bankable changes and ductile changes uh Such as strictures duct dilation, pancreatic duct stones. Dilated side branches. Karen Campbell calcifications and atrophy. Many if not all of these findings can be seen when present on good cross sectional imaging such as a contrast enhanced ct or M. R. C. P. Or an endoscopic ultrasound. And the presence of these can often the right clinical context can often give you your diagnosis of chronic pancreatitis. However some patients require functional testing if especially if they lack any of these morphological findings. We can do indirect functional testing by assessing for fat malabsorption uh typical stool tests or we can directly measure their pancreatic pancreatic execute function uh by doing a secret and stimulation. And here are just some examples of imaging studies. So here you see uh numerous calcifications located throughout the pancreas which is classic for chronic pancreatitis. Here again you see uh calcifications as well as a dilated main pancreatic duct. This is an M. R. C. P. Showing a massively dilated main pancreatic duct with a possible stricture in the mid duct and numerous dilated and cystic changes of side branches in the distal body and tail pancreatic stones and strictures can occur anywhere in the pancreas. And this is an example where a patient has a stone in the distal pancreas resulting in focal upstream dilation. This was a patient with renal failure who was found to have an incidental abnormality on imaging uh and underwent endoscopic ultrasound which discovered this pancreatic duct stone. Endoscopic ultrasound plays a role in the diagnosis of chronic pancreatitis as us provides the Anderson ah gra for the ability to look at uh very fine detail and some features of the prank. Um And and the duct that may not be appreciable on cross sectional imaging you can see on the right side of the table the paranormal features and the ductile features that are associated with chronic pancreatitis. And the presence of major and minor features depending on the number can help guide whether or not this patient has chronic pancreatitis or or other causes should be considered. Lastly, stool tests are used in the work up of chronic pancreatitis, mainly to diagnose pancreatic endocrine insufficiency uh In this day and age. The most readily available is the pancreatic the last taste test. Uh a normal value is greater than 200 micrograms per gram of stool. Uh This test is extremely sensitive in detecting severe Execute insufficiency which is less than 100. It loses some sensitivity in detecting mild disease, but the overall specificity is high with few false positives. It should be noted that patients with watery diarrhea should not have samples submitted for a last testing as the delusional effect of the watery diarrhea may create a falsely low concentration. Uh huh. Mhm. We'll move on to another case presentation. This is a 53 year old female with chronic klauscivic pancreatitis with dilated pancreatic duct, numerous dilated side branches and multiple pancreatic duct stones. She's been hospitalized three times in the past year for bouts of acute pancreatitis. She complains of chronic pain sciatic area and weight loss. She was referred to you for an ercP which of the following statements is most accurate number one, successful decompression of the dilated pancreatic duct will result in improvement in all of her symptoms. To endoscopic management of pancreatic duct stones and strictures may result in improvement in chronic pain and decrease the incidence of recurrent acute pancreatitis. three. There is no role for extracorporeal shockwave with a trip c. s. wall in this patient Or four pancreatic enzyme supplements will be highly effective in relieving her pain. Understanding how to best manage pain associated with chronic pancreatitis. Uh It is inherent to understand the different mechanisms that can cause pain in chronic pancreatitis. Uh Some mechanisms include obstruction from pancreatic duct stones and strictures, uh chronic swelling and edema can lead to pancreatic land uh compartment syndrome with associated ischemia and a low ph environment. There's chronic inflammation of the nerve fibers which innovates the gland and then there's associated biliary obstruction and uh duodenal obstruction from both inflammation and fibrosis. All of these factors can lead to pain and it's important to understand what may be driving the pain in your patient in order to understand how the best treat. So the targets of endoscopic therapy for the most part are obstruction of the main duct being from either strictures and or pancreatic duct stones. This will lead to pancreatic duct obstruction which can cause pain recurrent acute pancreatitis and disruption of the pancreatic duct resulting in leaks and collections such as pseudo cysts. Again biliary obstruction and do a dino obstruction should be recognized when available. And we're looking mostly at the use of ERCP for ductile relief though in some instances endoscopic ultrasound can play a role in uh drainage of collections or relief of pancreatic duct obstruction as well as having a role in celiac plexus blockade, which we'll talk about later. What is unclear is what the impact of endoscopic treatment is on non pain symptoms such as endocrine function, execute function and weight loss in general large series to show that these symptoms do not have a significant improvement after relief of pancreatic duct obstruction. And they can be managed medically with with uh with insulin and other diabetic agents as well as pancreatic enzyme replacement therapy and nutritional support. Here we see an example of a pancreatic duct stricture in the middle of the pancreas on an E. R. C. P. In the main stay for treating pancreatic duct strictures is stenting. Uh Looking at large series, we see that the use of temporary plastic stents is associated with a high rate of early pain relief. Uh and sustained pain relief can be seen enough to 90% of patients. The patients who respond best to this treatment are those in whom pain has developed early in their course as opposed to patients who have had chronic pain for years and years who may again have centralization of their pain and managing uh morphological changes at the local level may not result in any pancreatic duct stones are a bit different than biliary stones. These are made of calcium carbonate due to precipitation of calcium carbonate. In a inspo stated pancreatic juice. These are extremely hard, they're very difficult to crush and crack and they can often become impacted in side branches and the main pancreatic duct and telescopic management options for pancreatic duct stones includes the traditional E. R. C. P. Uh where balloons and baskets are used to try and remove the stones, but in some cases where the stones are impacted or too large to be removed, we can rely on little trips E or breaking up the stone. Mechanically, this can be done introductory using either electro hydraulic with a trip see or laser little trip see or can this can be done non endoscopic lee by the use of S wall or extracorporeal shockwave with the trips. And here is an example of S. Wall. Uh So the patient has the stone identified under Flora Skopje. Uh And then a water bath is placed in close approximation to the area of the stone. A shockwave is applied to this water bath and that shockwave creates a sharp up bubble which will fragment the stone. Uh and usually patients in our center undergo this for about an hour receiving anywhere from 3000 to 5000 shocks procession. Large Meta analysis and systematic review looking at over 300 patients undergoing as well for treatment of pancreatic stones showed excellent results with 50% of patients having complete relief of their pain. And another third of patients only having a reduction to mild or moderate pain. You see that the quality of life is markedly improved and the need for narcotic use is markedly decreased in these patients And you can achieve a complete ductile clearance rate of around 70%,, Although it should be noted that as well can induce pancreatitis and the and the aggregate risk is approximately 4%. This is another series, looking at the outcomes of endoscopic decompression of the, of the main pancreatic duct in patients with painful chronic pancreatitis. This is over 1000 patients uh with a mean five year follow up, You see that about half of the patients had strictures uh and uh 18% had stones while 30% had both strictures and stones And long term success for pain relief with endoscopic management. In this group was about 65%. About a quarter of patients went on to require surgery as noted. There was no significant improvement in patients pancreatic function, either endocrine or execution uh after undergoing endoscopic decompression and complications are not are not rare. Uh And the most common being acute pancreatitis With overall complications being up to 13%. What are the predictors of long term pain relief with endoscopic therapy. So what has been shown through again, numerous studies is that those patients who do best and have the best outcomes are those that have obstruction at the pancreatic head As this is often much easier to reach and disc optically and much easier to clear after an as well procedure patients with a short duration of disease. In other words, patients who have not had pain ongoing for years and years and years, but perhaps just for months. Those patients who have who have low frequency of pain attacks seem to do better than those who have a high frequency complete ductile clearance is associated with better long term pain relief, absence of a stricture similarly, and I think most importantly, is discontinuation of alcohol and tobacco as both of these are independent risk factors for ongoing pain in chronic pancreatitis and they work synergistically when taken together what is the role of surgery and pancreatic decompression. This was a recently published study in Jama randomized controlled trial of 88 patients who all had chronic pancreatitis with associated pain and a dilated pancreatic duct patients were enrolled could either be on strong opioids for less than two months or weak opioids for up to six months and they were randomized to either surgical drainage or an endoscopic approach. First, The results showed that after an 18 month follow up the surgery group had overall lower pain scores compared to the endoscopy group. However, there was no difference between the groups in terms of complete or partial pain relief, no difference in complications, mortality number of admissions, uh endocrine and execute function and quality of life. So the debate continues. As to when would patients with chronic painful chronic pancreatitis and pancreatic duct obstruction. Uh When would surgery be the best um intervention? Uh And in this, I think in this study uh the jury is still out on what its overall strong outcomes are. Move on to another case. This is a 45 year old man with pancreatic type pain. He drinks 18 beers a night for over a decade and he smoked a half a pack a day for about 30 years. Uh Initially he had an extensive outside work up uh and the diagnosis for his symptoms was not able to be identified. He underwent an endoscopic ultrasound which demonstrated four of the rosemont criteria for chronic pancreatitis and a stool alas taste was obtained which was low consistent with pancreatic execution insufficiency. So based on the EU. S criteria, the execute insufficiency and uh the clinical condition and symptoms, This patient has all the features of chronic pancreatitis, but without the strong morphological changes of calcifications. Stones are dilated duck. So with this patient which of the following interventions will have the most impact on his disease and symptoms. Would it be alcohol and smoking cessation, pharmacologic pain control, celiac plexus blockade, pancreatic enzyme replacement therapy or antioxidants. The answer is alcohol and smoking cessation. So again, there are two different forms or rather chronic pancreatitis can present on a spectrum of morphological changes with the classic being um numerous calcifications and stones and a dilated duct. Uh those patients such as this can have a non dilated duct with a minimal morphological changes. It is worth noting that morphological features on imaging have no correlation with patients symptoms. So as a perfect example, this patient on the right has no evidence of stone strictures or duct obstruction, yet they have severe pain. Whereas you can have a patient with the picture on the right who can be completely asymptomatic in terms of minimal change, chronic pancreatitis. There are a number of treatment interventions, clearly when alcohol and or smoking are the cause implicating this or in patients who do smoke or drink and have other ideologies of chronic pancreatitis cessation of these activities has the largest effect on improving their outcome. This is one study that that looks at patients who have alcoholic chronic pancreatitis and it shows that those who smoke have a considerable acceleration of progression of their disease. Compared to alcoholic chronic pancreatitis, patients who do not smoke. Pain control can be a can be thought of as a step up approach with initial management using acetaminophen or insets and then moving on up to non opioid analgesia such as traMADol. The next class would be neuroleptics. And then finally opioids, it is certainly not uncommon for patients to be given opioids upfront. But again, a step up approach may be beneficial as patients can quickly become opioid dependent and again, that can lead to centralization of their pain. Yeah, this study looked at the use of pregabalin or Lyrica in reducing pain. And chronic pancreatitis is a randomized controlled trial and see that compared to placebo, the use of this drug had a significant reduction or a significant improvement in pain relief and an overall improvement in patients health status. What about the role of pancreatic enzymes? This is a meta analysis looking at six randomized double blind placebo controlled trials examining the effects of pancreatic enzyme replacement therapy on pain and chronic pancreatitis. only 52% of patients found a relief and the conclusion was that there was no significant benefit to relieving pain in chronic pancreatitis. That being said, many of these patients do have underlying execution pancreatic insufficiency. So, pancreatic enzyme and and that may be playing a role in some of their pain symptoms. Perhaps bloating gas diarrhea. So, so while there may not be strong statistical proof that there is a benefit. I do believe that patients, because it's uh this is an easy and safe treatment intervention. I do feel strongly that patients with painful chronic pancreatitis should be tried or given a trial of enzyme replacements. Similarly antioxidants have been studied uh with the idea that these will be scavengers for free radicals and reduce oxidative stress in the chronically inflamed environment of the pancreas uh use of cocktails such as vitamin E riboflavin and others as well as l Matthiasson in beta carotene, vitamin C. E. And selenium uh have been shown to have some benefit in patients. But again we see a double blind randomized controlled trial of 70 patients followed for six months. Uh there was a decrease in pain scores in both the placebo group and the antioxidant oxidant group which was more or less equivocal and there was no difference in the quality of life need for narcotics or a number of admissions. Again, this is a safe and easy intervention and uh in my in my opinion it is worth trying on patients as they may experience some uh some pain relief which in conjunction with other interventions, maybe celiac plexus blockade is a longstanding intervention used to treat chronic pain. The idea is to oblate the notes. Receptive not receptive nerve fibers which carry pain a sensation from the area of the pancreas back to the spinal cord and the brain. Uh This is traditionally has been done per cutaneous lee by the use of Flora Skopje. But endoscopic ultrasound guided celiac plexus blockade is a mainstay in the toolbox of the of the interventional endoscopy pissed. Unfortunately while safe again this meta analysis shows that us Celiac blockade is effective in relieving abdominal pain in roughly only 50% of patients. What we do know is that this is a safe treatment when it works. Uh it can provide some relief for weeks to months. It is safe to repeat and in some patients who respond to a blockade using steroids, one can consider doing a pleat complete neural ISIS using ethanol injection as well. Next question. Despite alcohol and smoking cessation, the patient has no improvement in pain or quality of life. He inquires as to whether surgery has any role which of the following surgical interventions would be appropriate for this patient, whipple resection, a post oh procedure. A total pancreas attacked me or a total pancreatic To me with auto islet cell transplant, correct answer is total pancreatic to me with auto islet cell trans. So T. P. I. A. T. Uh is increasingly being recognized and incorporated in the management plan for these patients. Uh indications for its use are patients with recurrent acute pancreatitis, hereditary pancreatitis, causing either recurrent acute or chronic pancreatitis. Patients with refractory pain. In patients with minimal chains are small duck disease that are otherwise not amenable to endoscopic interventions such as uh stenting This large men analysis, looking at over 1000 patients shows that over time there is an opioid free rate improved from 0 to 15% patients up to 63% of patients. Uh but that the insulin free rate decreased from 90 to 100% of patients to about 30% of patients. Over time. These patients do experience a significant improvement in the quality of life. It appears that those with hereditary ideologies do achieve significant benefit. But not surprisingly, those with underlying alcohol ideologies do have worse outcomes. So to conclude in looking at our algorithm of managing patients with chronic pancreatitis, we start by looking at the mechanism of their pain in those patients with a dilated main pancreatic duct due to pancreatic strictures and or stones intervention. Uh by way of stricture management with stricture dilation and stent placement and stone management by way of ERCP as wall or introduction with the trip. See uh is a first line therapy for patients who have inaccessible strictures that cannot be reached easily by ERCP US, guided drainage can be considered as a backup. Mhm modality. But ultimately these patients may require surgery. Surgery should not be considered a failure of treatment in this disease. Uh but actually a a large component in managing these patients. On the other hand, those with minimal change or small duck disease who have no targets for endoscopy treatment will focus on alcohol and smoking cessation when applicable pain management should focus mostly on neuroleptics and avoidance of opioids until uh they have failed all other pain control techniques. We talked about the potential benefits of endocrine enzyme replacement therapy, antioxidants and celiac plexus blockade. Again, the data is not strong. It's basically a coin flip as to whether or not any of these modalities would work, but they are all safe and may provide some benefit. In addition to other modalities. And then lastly, patients who fail all modalities should be considered for a total pancreatic to me with autologous islet cell transplant. Lastly, these patients do develop biliary strictures, pseudo cysts and duodenal obstruction, all of which can contribute to their pain and should thus be managed accordingly. We should we should look for and manage pancreatic execution insufficiency as a significant portion of these patients will have that. And lastly, all of these patients are elevated risk for pancreatic cancer unless any major change in their symptoms, pathology such as jaundice, acceleration of weight loss or change in pain pattern should be taken seriously, and an investigation for cancer should be pursued. Thank you very much for your participation in this uh course. Uh I can be reached at my email. Should you have any questions or cases you would like to discuss? Thank you.
