Hello guys and welcome to taking the pain out of feline pancreatitis. So this talk is an approach to the diagnosis and management of feline pancreatitis in the general practise setting. So we're going to go through the causes of pancreatitis, how it can be diagnosed in primary care practise, and how it can be managed as well, looking at both acute and chronic forms of the disease.

So pancreatitis has been considered traditionally a rare diagnosis, although with the improvements over the last few years in technology, particularly abdominal ultrasonography. And accessibility to, pancreatic lipase testing, it is something that we're probably recognising a lot more frequently, than we used to. And it's certainly not, I would think these days, an uncommon, cause, of, of illness in our cats that are presenting in primary care practise.

So I think traditionally it has likely been somewhat undiagnosed. It certainly is not the most straightforward problem to diagnose as as we'll talk about later on in this talk. So it perhaps should be thought of a disease that is becoming more common with time.

And we have to be aware of it as well, because of its association with various other comorbidities, that we'll touch on a little bit later on. And one thing that we have to be aware of as well is that there's probably a proportion of cats out there in the population that actually have subclinical pancreatitis. So what about the definition of pancreatitis?

Well, acute pancreatitis is reversible, whereas chronic pancreatitis should be considered a disease where there are irreversible histopathological changes, and we'll talk about those in more detail a little bit later on. But I think when we're defining pancreatitis, we do really think about it initially as, as acute or chronic, and they are sort of really quite different in their diagnosis and, and somewhat different in their treatment. But some patients as well may have both acute and chronic pancreatitis at the same time that we have to be aware of.

Sometimes acute and chronic pancreatitis can be actually quite hard to differentiate clinically. Again, we'll touch on that a little bit later on, and certainly with acute pancreatitis, the severity is really quite varied, with some patients presenting extremely unwell. Are requiring intensive hospital-based care and despite best efforts succumbing to their disease, whereas other patients may present as outpatients and can be managed successfully as outpatients with the more mild forms of the disease as well.

So we're going to talk a little bit about the aetiology of feline pancreatitis, and some of the things that we need to be aware of, are that there are no actual age, sex, or breed predispositions for feline pancreatitis, which is somewhat different to dogs. And also there is no association with obesity, diet, or drugs, again, which is, you know, somewhat different to dogs. The, the cause of diets will, will, sorry, the role of diet even in the management of these patients as well is, is different than in dogs, and we'll touch on that, a little bit later on.

Infectious causes can cause pancreatitis, such as toxoplasmosis, which of course is a systemic protozoal disease of cats that can affect various different organs in the body. And actually infectious causes are really quite rare. And we'll talk about the utility of antibiotics a little bit later on in the talk in these cases.

And manipulation during surgery traditionally has been considered one of the potential causes of pancreatitis, but there's some publications that have looked into this and really found no strong evidence supporting the association with surgical manipulation of the pancreas and pancreatitis. Pancreatic neoplasia certainly, can induce pancreatic inflammation and can present, many, in many ways similar to feline pancreatitis. But fortunately, feline pancreatic neoplasia is really, quite rare.

Certainly when compared to the, the frequency of, of feline pancreatitis, we'll talk a little bit how we can differentiate the two, a little bit later on as well. But certainly trauma and ischemia are possible causes of feline pancreatitis. Both of which can happen, in a variety of settings, but potentially, you know, ischemia can be something that is seen in patients in hospital that perhaps would be undergoing procedures for other reasons, and transient ischemia of the pancreas can set off pancreatitis, for instance, due to hypoxemia, under general anaesthesia.

Mm. So whilst some of those previously listed causes can incite pancreatitis, generally, most cases should be considered idiopathic. So about 95% or more of cases are, are in fact idiopathic.

There are some patients who may have an autoimmune form of pancreatitis. Again, not dissimilar from certain breeds of dog, and some of these actually may respond successfully to immunosuppressive therapy. But otherwise, pancreatitis should be considered idiopathic and should also be considered in light of multiple other comorbidities as well.

So we know that with cats there is an association between chronic enteropathies, so inflammatory bowel disease if you will, inflammatory liver disease, which we refer to as cholangitis, and pancreatitis. So together we might refer to this as triaditis. And certainly, when we are investigating a patient with pancreatitis and considering how we're going to treat them, we should be aware of the various comorbidities and do a various, well, do a degree of screening for them as well, based on our index of suspicion, because it might actually alter the outcome for that patient, and how we treat them.

Lippidosis is an important sort of comorbidity to consider certainly when we're approaching, the treatment of these patients. diabetes mellitus, of course, is something, that we might well see in patients with chronic pancreatitis, due to, Loss of islet cells, you know, and functional, endocrine pancreatic tissue. And, as well, we sort of probably have to be aware of exocrine pancreatic insufficiency as well, in these chronic pancreatitis cases, which of course is due to the loss.

Of exocrine pancreatic function, due to replacement fibrosis, because of chronic inflammation in, in these patients. So with respect to the pathophysiology of feline pancreatitis, it's worth knowing a little bit about this just to help understand how how the process of pancreatic inflammation starts and then progresses. But ultimately in acute pancreatitis.

The inciting event really is the early activation of tripsinogen within the pancreas. So tripsinogen is a zymogen, so essentially it's a substance that is normally converted into its active form, trypsin within the small intestine in the duodenum. And trypsin acts as a, protease, so an enzyme that that breaks down proteins.

However, tripsinnogen activation occurs within the pancreas in pancreatitis patients, and as a result of that, as it's converted to its active form, it starts the process of auto digestion of the pancreas, as well as activation of other digestive enzymes as well within the asin cells of the pancreas, which further sets off this cascade of inflammation and variable tissue necrosis. . Hypo perfusion, and thrombosis as well, may be inciting factors, of pancreatitis in these individuals.

In chronic pancreatitis, trips in activation is, is generally not the inciting event. And instead cholecysticinin and oxidative stress have been suggested as activators of injury and tissue necrosis. When making a diagnosis of feline pancreatitis, I think there's certainly 3 main things that we should consider, and they are a combination of compatible clinical signs, imaging findings, and pancreatic lipase testing that together all support a diagnosis of pancreatitis.

Now the diagnosis of pancreatitis, I think, is one of the harder aspects of feline pancreatitis, and it's something we're going to spend most of the talk concentrating on. But as you'll find, the clinical signs of feline pancreatitis are not always consistent or that obvious. The imaging findings can be variable and often hard to detect, certainly in primary care practise.

And pancreatic lipase testing, whilst a bit of a godsend also can have its pitfalls as well. So we'll go through each of those, one at a time. So with respect to the clinical signs, unfortunately, they're really quite non-specific for both acute and chronic pancreatitis in cats, with lethargy and anorexia being the most common clinical signs.

Now that's unfortunate because, you know, they really are non-specific and the kind of clinical signs we'd see with lots of different morbidities of our patients. So unfortunately, vomiting is actually not that frequent in cats, certainly when compared to dogs and or humans. And depending on the study you look at, the frequency has been as low as 35 out of 50% of feline pancreatitis patients presenting with with vomiting.

So that's, I suppose one of the the take home messages from this talk that, you know, we should have feline pancreatitis on our differential list. For many of our patients with these really quite non-specific vague presenting signs of of lethargy and anorexia, and I certainly wouldn't exclude the possibility of feline pancreatitis because of a lack of vomiting. And with respect to physical examination findings.

Again, there's, there's often not a huge amount there. So we do want to sort of look closely, but in the patients, with certainly acute pancreatitis, dehydration is, is, is not uncommon. That might be due to reduced water intake as a reduced as a result of reduced appetite, but also it might be because of loss of water through vomiting and or diarrhoea.

Hypothermia is sort of variable in its frequency in patients and sort of varies from 39 to 68%. Depending on, the study that you look at, and ultimately hypothermia has been identified as a poor prognostic indicator. So I think it's always very important, when we diagnose a patient with, with feline pancreatitis to sort of look at the different prognostic indicators that we've got, to help guide, owners' expectations about the likely outcome.

And concentrating on temperature can be quite useful for that. Hyperthermia and pyrexia is, is less frequently seen, in between 7 to 26% of patients. It is obviously associated, with the inflammatory nature of the disease in, in cats.

But, you know, as I've said, you know, bacterial involvement is really quite uncommon. So even having a febrile cat with pancreatitis, that wouldn't make me, particularly suspicious that there was necessarily bacterial involvement. Jaundice, icterus or hyperbilirubinemia, is also surprisingly infrequent.

It's only 6 to 37% of patients are clinically jaundiced at presentation. Now the jaundice occurs in these patients, of course, because of post-hepatic biliary duct obstruction. And often the sort of severity of the pancreatitis will dictate how likely they are to become hyperbilirubinemic with, you know, the most severe forms of the disease more likely to induce post-hepatic cholestasis.

Abdominal pain is a really interesting one in cats with pancreatitis because of course it's one of the cardinal signs of pancreatitis in dogs and certainly, you know, in humans, the level of discomfort can be really severe. However, when looking at the results of clinical signs in retrospective studies in cats with feline pancreatitis, only a very small number of cats have recognisable abdominal pain, so about 10 to 30% of these patients. And so that's really quite a low proportion of our cats that are reported to have abdominal pain.

Now that may be representative of the fact that abdominal pain is not common in pancreatitis, but I think logic dictates that probably it's more likely these cats are in fact painful but are really quite good at hiding the signs of abdominal pain and don't display them particularly well. So I think we have to be particularly aware of the possibility of abdominal pain in these cats and certainly consider the use of analgesia presumptively, even if we're not absolutely sure we've identified abdominal pain, but also potentially consider the use. Of published pain scoring systems, to help us more reliably identify abdominal pain in cats, and monitor response to appropriate analgesic therapy.

So just moving on to imaging, as I said, we want to combine compatible clinical signs, imaging findings, and lipase testing to try and reach a diagnosis of feline pancreatitis. So the things, the things that we've got to be aware of are that certainly radiography, is a very poor imaging modality. For the diagnosis of feline pancreatitis.

Whilst we can see, a loss of abdominal detail, on abdominal radiographs in the area of the pancreas, a loss of serosal detail, because of the localised, sterile peritonitis. It's really not a very sensitive way, to screen for feline pancreatitis. And likely really doesn't play a role in the diagnosis of these patients at all.

Ultrasound is much superior, and much more, likely to identify, pancreatitis, or the changes associated with it, and any of these comorbidities that we've discussed earlier on as well, such as, changes that you be consistent with, cholangitis within cats. And things to be aware of with abdominal ultrasonography are that it's a very operator dependent test. So the experience of the operator and the the quality really of the machine being used really makes a big difference in how likely you are to identify these pancreatitis specific changes.

But also the severity as well can help with the most severe cases of acute pancreatitis having really quite dramatic changes on ultrasound. They're actually relatively easy to detect. Whereas patients with much milder acute pancreatitis and certainly chronic pancreatitis, the changes can be very, very subtle, if not completely absent.

I think we have to bear in mind as well that we can't really use abdominal ultrasonography to differentiate acute from chronic pancreatitis. That differentiation is really made based on some clinical presentation and ideally histopathology. Of the pancreas, and that sometimes, the appearance of a normal feline pancreas, can mimic some of those changes that we might see with chronic pancreatitis as well.

So we have to be sort of careful that we don't overinterpret, in fact, some changes in these individuals. And generally the pancreas lies sort of next to the liver, the left limb of the pancreas lies behind the greater curvature of the stomach and adjacent to the liver, and the right limb lies alongside the medial aspect of the duodenum, and it's normal appearance, it should be isochoic with respect to the liver. In cats, the left lobe, which I mentioned lies behind, the stomach, is generally more readily visible, than the right lobe, which is sort of the converse of, of what we tend to see, in dogs.

And in dogs, changes of the right lobe of the pancreas are more common than in the left, whereas in cats, the changes can be sort of seen in either lobe with, with reasonably similar frequency. So the sonographic changes that we're going to look out for with acute pancreatitis are enlargement of the pancreas with a surrounding hyperechoic mesentry. So the fat that's around the pancreas can become really quite bright, quite hyperchoic because of the localised peritonitis.

As a result of the enzyme release into that area, and that can actually almost highlight the borders of the pancreas itself and make it more readily identifiable. And within and around that hyperchoic mesentry, you often get small amounts of fluid as well. So this is normally anechoic fluid, so it's completely black, and if you're able to take a sample of this fluid and analyse it, it's consistent with .

A sterile, peritonitis, as a result of the pancreatic inflammation. We don't tend to see large volume effusions, in association with, with pancreatitis, but it's, it's not impossible. The sensitivity of ultrasonography for the diagnosis of pancreatitis really does vary between study as well, and, you know, certainly over time, with the older studies, you know, reporting a lower sensitivity.

But essentially it, it's ranged from 11, you know, to 67%, which is obviously not fantastic when we're looking, at the sensitivity of a test. So I think that's one of the reasons why pancreatic ultrasonography is not really the be all and end all and certainly should be, . Combined with pancreatic lipase testing.

And chronic pancreatitis is something that can be somewhat variable in its appearance, and sort of the descriptions of the sonographic appearance of chronic pancreatitis are not well established, but generally we think about things like the heterogeneous appearance to the pancreas, so it's really quite patchy. With these more hypoechoic or brighter areas dotted throughout the pancreas, which likely represent areas of fibrosis because of the chronic nature of the disease, and we're also perhaps more likely to see a dilated common bile duct because of chronic extrahepatic biliary duct obstruction. We may see enlargement of the pancreas as well, and the pancreatic margins, may become, irregular also.

But as I said earlier, you know, we can't use ultrasonography to help us, determine, the craicity. And not infrequent finding as well that we might see are high hypoechoic nodules within the pancreas of cats. So they're often really quite small, you know, in the order of a few millimetres in size, and they can be variably dispersed throughout the pancreas.

And quite often these are representative of areas of nodular hyperplasia, sort of not dissimilar from what we can see in the liver with old age change as well. So if we see those, certainly it can raise the index of suspicion about neoplastic change within the pancreas, but I think we should sort of feel reassured that these hypoechoic nodules are not uncommon in older animals, and that as we talk about in a couple of slides, if we're at all in doubt, we can always perform pancreatic aspirates, to help screen, for neoplasia. So here are a couple of images of typical changes that we might see in feline pancreatitis.

So on the slide on the left, we've got a dilated and tortuous. A common bile duct, which we'll often see in these cats with chronic extrahepatic biliary duct obstruction. When you measure the width of the common bile duct, once we're getting over 3 to 4 millimetres, we're looking at that being consistent with dilation, you know, and in some cats with really chronic extrapatic bili duct obstruction, we can see this duct going up towards a centimetre in width and it can be really quite Obvious, the dilation of this duct.

On the image on the right here, we have a patient with acute pancreatitis. So we have the large, pancreas here. With an echo texture that's similar to the liver, and surrounding it, we've got this rim of quite hyperechoic or brighter peripancreatic fat representative of the localised peritonitis in this area.

There's not really any significant volumes of of of fluid surrounding the pancreas in this patient, but that that's not uncommon to see as well. Pancreatic aspirates, certainly not something that is going to be routinely performed, in primary care practise. But, you know, if you're confident with abdominal aspiration of, of viscera, it is something that that could be considered, in the investigation of these patients.

I think the things to be aware of is that pancreatic aspirates are actually very safe, to perform. There shouldn't be, significant concerns about, complications of the procedure. Previously, the idea of aspirating the pancreas, you know, might have been one that wouldn't have been considered frequently because of the, the worry about inducing or worsening pancreatitis, but that doesn't really seem to be the case.

Of course, there are some other important structures in that area, particularly some blood vessels that we need to be . You know, aware of, and we don't damage and cause bleeding, but otherwise pancreatic aspirates can be useful, for sampling the pancreas with ultrasound guidance and can actually have reasonably good recovery rates, with 67% of samples in one study, diagnostic, when taken from, particularly the pancreases of cats that have acute pancreatitis. The use of, aspirates really, is in the differentiation of, neoplastic change within the pancreas for an inflammatory change, and also in detecting the presence of bacterial involvement as well.

Now what we have to bear in mind, of course, is that bacterial involvement generally is, is very, very uncommon. And feline pancreatitis. So actually there's quite a low likelihood that we're going to detect bacteria in these samples.

And then also when we see a pancreas that concerns us that there could be a neoplastic change going on, and we sample it, we do have to be aware that it's not that easy cytologically, to differentiate pancreatitis from neoplasia, with associated inflammation due to the degree of sort of cellular atypia that it causes. So certainly they can be useful in screening for neoplasia, but if you're highly suspicious of pancreatic neoplasia and aspirates, you know, aren't consistent with that, I certainly wouldn't exclude the possibility of a carcinoma and, you know, perhaps would recommend proceeding to biopsy for histopathology. And to be more accurate.

As I said earlier, effusion samples are typically, sterile, exudates or they can be, modified transiates as well, and are generally really quite low volume, localised around the pancreas and duodenum. Moving on to the clinical pathology, so we're going to look at the blood changes and see what, how they can be in the diagnosis of feline pancreatitis, and unfortunately they're not that good. Certainly the biochem and CBC changes are really quite variable in feline pancreatitis.

Some patients may present with absolutely no abnormalities on their biochem or haematology, you know, and yet have feline pancreatitis. And generally I think the worse the acute pancreatitis, the more likely we are to see changes. So common ones would include liver enzyme elevations, so our cholestatic markers.

Of course, because of the degree of post hepatic cholestasis that's induced, so ALP for instance, but also we'll get elevation of the hepatocellular markers as well, because of a secondary hepatopathy, so elevations of the ALT as well, are not sort of uncommon in patients with more severe forms of of pancreatitis. Hyperbilirubinemia as well may be present in the most severe cases, because of, cholestasis. And azotemia as well in the more severe patients.

So elevations in the urea and creatinine may be representative of either. Pre-renal azotemia, in patients that are, hypovolemic, and have reduced GFR, and those patients are volume responsive azotemic, so we give them fluid therapy and correct their azotemia, whereas we may also see renal azotemia, which is essentially patients with acute kidney injuries. So acute kidney injury can be seen in the more.

Advanced forms of acute pancreatitis, and is associated with essentially multiple organ inflammation and dysfunction. Because of all the inflammatory mediators and digestive enzymes that are released into the bloodstream that then circulate around the body and damage various organs including the kidneys and the heart. So of course, a patient with a renal lasotemia or an acute kidney injury, is going to be one of those patients that will require particularly intensive medical management and will confer a poorer.

Prognosis than those that aren't azotemic. Hypoglycemia, as well can be seen with acute necrotizing or superative pancreatitis, and we'll get onto these two forms a little bit later on in more detail. But obviously the identification of hypoglycemia should warrant immediate therapy, with a glucose bolus, and then often a follow-up glucose CRI and close monitoring of the blood glucose level, .

And other patients with acute pancreatitis may actually present with a hyperglycemia, because of a lack of, of, appropriate levels of, of insulin secretion. . We might see various electrolyte arrangements as well, including primarily loss of electrolytes, you know, through vomiting, and the need to supplement those parenterally.

And then with respect to the CBC, we may well see an acute pancreatitis, an inflammatory leukogram. Because of the inflammatory nature of the disease, with a left shift, neutrophilia or even a neutropenia if there is consumption of large numbers of neutrophils because of the severity of the inflammatory focus. DIC may be seen in the most severe cases.

And whilst these patients are initially hypercoagulable, once they use up all their clotting factors, they may well become hypocoagulable, and the testing for that with clotting times, platelet counts, and or viscoelastic testing, you know, may be useful in the diagnosis of DIC in those most severely unwell patients. So moving on to pancreatic lipase testing, so it's something that we need to know a reasonable amount about because, you know, this is one of the sort of three pillars of the diagnosis of feline pancreatitis. So lipase is an enzyme which is produced in the pancreas and should be released into the duodenum where it acts to aid digestion of fats.

With very, very small amounts of this lipase being present in the normal patient within the bloodstream. However, with feline pancreatitis, inflammation and damage of the pancreas allows larger amounts of pancreatic lipase to enter the bloodstream, and therefore we can test for lipase to see if there are elevated levels and therefore if that is consistent. With, pancreatic inflammation.

When we're thinking about the different types of lipase, traditionally, lipase hasn't been particularly sensitive as a test for pancreatitis because it is not specific to the pancreas itself, and other parts of the body can produce various liases as well and therefore diseases in other regions of the body can affect our ability to interpret our lipase levels. But what we will talk about is the DGGR lipase. And the, SE, FPLI lipase by IDEX as well, which can be more useful, markers of pancreatic inflammation.

So DGGR lipase, is basically, an ester, which is used for lipase reactivity assays, and this is, also produced in other tissues in the body, but it is a lipase that is a lot more specific to the pancreas, than most others. So a DGGR lipase is generally a blood test that is submitted to an external reference lab. And essentially, we look at the, the level of the DGGR lipase and compare it to reference intervals and if significantly elevated, that is, you know, often consistent with the diagnosis of pancreatitis.

Now the DGGR lipase has been looked at. Compared to the spec FPLI, which we'll get on to next slide to see sort of how reliable it is and what sort of cutoffs we should use, and essentially because of the relative non-specific nature of DGGR lipase, external reference labs are now using a relatively high cut off for the normal reference interval. For this, lipase, to help increase, the specificity of the test, whilst at the same time, unfortunately, losing a degree of sensitivity of the tests.

So of course that will always happen, . When you increase the cutoff of the test, you will increase specificity, you know, whilst reducing sensitivity. So I think the DGGR lipase is a blood test that can certainly be considered as a tool for the diagnosis of feline feline pancreatitis, because it's relatively cheap, and often quite a bit cheaper than the spec FPLI, and also the external reference labs often have quite a quick turnaround on this sample.

With the results sometimes being available, the next day. So again that can be quite useful. So it's a good test for the diagnosis of pancreatitis if the level is particularly high, whereas a normal DGGR lipase essentially couldn't be used to exclude feline.

Pancreatitis, because of current sort of cutoffs that we're, we're using. So moving on to the pancreatic lipase test, we have the feline pancreatic lipase immuno reactivity test, the SEC FPL, which is a commercially available elizer through IDEX Labs, which is a sample that can be sent out externally, and serum or serum gel tubes, and has been studied and found to have a high specificity. But variable sensitivity for the diagnosis of feline pancreatitis.

So they found that the sensitivity, as well is really dependent on the severity of the disease, so severe forms of pancreatitis are more likely to test positive, than the milder forms. Now as a result of the high specificity but variable sensitivity, one study found that the test had a positive predictive value of 90% and a negative predictive value of 76%. So essentially, of patients that have a positive test result, 90% of them will have pancreatitis, so obviously it's really quite a specific test.

However, of patients that get a negative test result, 24% of those will unfortunately have pancreatitis, and it will have gone undiagnosed. So I think this highlights really that the SEC FPLI, certainly in a patient that we believe is likely to have feline pancreatitis. If we get a positive result on that, we can be quite reassured that it is likely a true positive.

We do have pancreatitis and where a negative result perhaps shouldn't be used to categorically exclude feline pancreatitis if suspected because of various other reasons. So it is, you know, generally a pretty specific test, but there are other diseases, of abdominal organs that that may falsely increase, the FPLI in these patients as well. IDEX have also produced an in-house snap FPLI as well.

The good news is that this generally correlates pretty well with the external reference lab spec FPLI. And what we mean by that is that, normal, test results, in cats that, we're screening for pancreatitis, you know, likely indicate the patient doesn't have feline pancreatitis, whereas abnormal results, likely do have pancreatitis, or could have an FPLI in, in the equivocal sort of grey range. There is generally good agreement between the DGGR lipase and the SEC FPLI when we use the higher cutoff for the DGGR lipase, which is good.

But unfortunately, studies have found that there is relatively poor agreement between the ultrasound changes. And DGGR lipase and SE FPLI. And so again it sort of highlights the importance of putting together several different aspects of the case, the imaging findings, the ClinPath, and the clinical history to try and help us with the diagnosis of feline pancreatitis because no one of these tests is completely reliable.

Interestingly, as well, there's evidence that there is not brilliant agreement between the results of the DGGR lipase and SE FPLI and histopathology as well. And what we bear in mind is that generally histopathology is considered the gold standard for diagnosis of feline pancreatitis, but as we'll get to in a few slides' time, there are certain pitfalls to consider with histopath as well. Looking at other markers, we can perform amylase measurement, however, it really serves no purpose in these cases, because it is really not specific or sensitive to feline pancreatitis.

So please don't overinterpret elevated amylase levels in any of our patients. It really is not specific to pancreatitis in cats or dogs. .

The TLI as well, has previously aided us in the diagnosis of feline pancreatitis prior to the availability of the SEC FPL and certainly TLI can be elevated in cases of feline pancreatitis, but it really isn't very sensitive as a marker for feline pancreatitis, so we should really use lipase testing. Instead, and consider the use of TLI really, instead for screening, chronic pancreatitis patients for the presence of exocrine pancreatic insufficiency, as we mentioned a little bit earlier on. So pancreatic biopsy is certainly not something that's commonly performed in primary care practise and it's really quite infrequently performed even at referral level.

For a variety of reasons, but I suppose primarily because, a presumptive diagnosis is often made with a combination of imaging, blood test results, and clinical findings, and then patients are treated and response to therapy helps reinforce the diagnosis. It's, it's not very common histopath is performed, and perhaps it is most frequently performed in patients when, either we are, Concerns regarding the presence of neoplasia, and we want to take a biopsy to screen for that, or in patients that are undergoing laparotomy for sampling of other organs. So the cat, for instance, that we believe has triaditis, we may be performing surgery to biopsy the liver and all the intestines, and perform cholecystocentesis, and at the same time it's often pretty sensible and reasonable to perform pancreatic biopsies as well in these patients.

So it is considered the gold standard for diagnosis, but, you know, really very, very rarely performed. I think one of the pitfalls we've got to be aware of is that even with biopsies we can miss pancreatitis because of its patchy distribution throughout the pancreas. So really we should sample all regions of the pancreas with multiple biopsies, to increase the likelihood of, of getting a positive results, on the histopath.

And therefore, you know, negative histopath really shouldn't be used to exclude pancreatitis in our patients. When we're looking at, histopathology results, and the various forms of pancreatitis, . There is a nice panel classification system, that was proposed in the ACVIM feline pancreatitis consensus of 2021, that broke patients down essentially into three groups.

So the chronic pancreatitis patients, in which inflammation was present and it was primary, lymphocytic. With variable amounts of fibrosis and cystic degeneration, so obviously the fibrosis there really representative of the chronic nature of the disease, and we then have the acute pancreatitis patients who were subdivided into two categories, the acute suprative. Pancreatitis patients, in which, of course, there's a lot of inflammation, and it was very, neutrophilic in nature, and then the acute necrotizing pancreatitis patients in which large amounts of edoema and necrosis, was present in these patients.

So, certainly, pancreatic histopathology has its role. It's particularly, I think, useful in, in the diagnosis of chronic pancreatitis, which can be really quite challenging, . To diagnose in other ways, we've already said how non-specific the imaging findings are with chronic pancreatitis.

The clinical signs as well, simply anorexia and variable appetite, sorry, potentially weight loss or hyperorexia variable appetite, and certainly chronic pancreatitis patients may not have persistently elevated. Lipase levels, so really quite hard to detect in some of these patients other than non- histopath. So we've talked a lot about how we diagnose pancreatitis, now on to the management of these guys.

So we said that most cases are idiopathic, and that there is no one specific treatment that we can use to target, the pancreatic inflammation in these patients. So essentially it's a combination of supportive and and symptomatic therapy. And giving patients time for the, pancreatic inflammation to subside.

We have to be aware that complications can occur, so we've sort of already discussed some of the complications including, acute kidney injuries. And, extraopathic biliary duct obstruction, and we have to be aware as well of the comorbidities and how aggressively we need to treat those or how some of the treatments for our pancreatitis could potentially even worsen some of those comorbidities. So fluid therapy is gonna be important in the patients with dehydration or hypovolemia, and it's something that we're gonna consider in those sort of more severely unwell, acute pancreatitis patients.

Antiemetics certainly have their role. We've typically, you know, selecting these drugs, to help with reduction of emesis, but also to help reduce nausea in these patients as well, which might help promote, their appetite and get them eating again, . So of course Marropotent is licenced in the UK, in the form of Cerenia, and that's an NK1 antagonist, which acts both peripherally and centrally within the vomiting centre and chemoreceptor trigger zone to help as an antiemetic, but also reduce nausea in these patients.

That can be started parentally in the hospital and then continued orally as an outpatient. For those patients that despite Neropotins are still vomiting and or we're worried about nausea, we can consider the additional use of Ondansetron. So this is a drug that's traditionally been used in human medicine as an antiemetic, anti-nausea medication for human chemo patients, but it's been used more and more in the veterinary profession.

Because of its increased potency when compared to neropotent, but also its ability to use it alongside neropotent in those particularly severe cases. And so this is a 5 HD3 antagonist that help reduces serotonin-based activation of the vagal nerve, which can help reduce vomiting and nausea in patients as well. So again, this can be given parently.

And then given orally once the patient is able to tolerate the medication, and it is generally very well tolerated, although it must be made aware that, it is, a particularly expensive drug, as well, certainly when compared to Neropotent. With regards to prokinetics, we often see in patients that have severe pancreatitis, a functional ileus of the stomach and, the proximal small intestine because of the inflammation. Perhaps also in association with the lack of food, entering the GI tract to stimulate, gut motility because of their, anorexia.

So patients who have, vomiting or who on ultrasound have evidence. Of ileus because of, a lack of peristaltic movement or large residual volumes of fluid, particularly within the stomach, and they may benefit from some prokinetic support as well. So the drugs that we might consider would be metoclopramide, so that can be given as boluss but is often more effective as a prokinetic if given through a CRI, or we could consider the use, of, of cisapride, as well, which is, an oral medication that's available.

From certain compounding pharmacies, veterinary compounding pharmacies in the UK, as a, as a pro-kinetic agent, once the patient is able to tolerate that, to tolerate oral medication. Erythromycin as well can act as a prokinetic, but I think perhaps should be, reserved for those cases that fail to respond to metoclopramide and cisapride, simply because it is an antibiotic and we have to be aware of our antibiotic stewardship. Pain is a really important component of feline pancreatitis, and we need to consider pain scoring very regularly to sort of be able to appropriately diagnose, treat and monitor response to therapy in our patients.

When we're looking at analgesia for acute pancreatitis, we really want to be reaching for the opioids and in the milder forms of disease buprenorphine. May well be appropriate, but certainly in the more severe forms of the disease, methadone or fentanyl is a CRI, may be more appropriate, for, for continuous analgesia, for these patients whilst they're in hospital. If the patient is well enough to be treated as an outpatient.

Then buprenorphine sublingually, you know, may, may be successful as an analgesic in these patients, and that can be combined with other oral analgesics such as gabapentin, perhaps tramadol. And of course there's there's also sort of reports as well about the ability of neurropotent to provide some form of visceral analgesia alongside its antiemetic and anti-nausea properties, which, which might be of some use as well. And our patients are regularly hyporeexic or anorexic.

And if they are, we want to really. You know, treat the pain as aggressively as possible because it's often the pain and the nausea, that are inhibiting the patient's appetite. But if despite appropriate therapy our patient still isn't eating, we may consider the use of appetite stimulants.

With drugs such as mirtazapine, or, the ghrelin, agonist Caro Mollin, but. In a patient in which protracted hypoorexia or anorexia has been documented, those with the most severe forms of pancreatitis and those that are likely needing hospitalisation for several days, I would probably, you know, not bank on appetite stimulants being that successful and jump straight into early assisted enteral nutrition with a feeding tube. So early initiation of nutrition in pancreatitis patients, is the way to go these days.

We really don't recommend withholding food at all in these patients unless they have intractable vomiting, that we are sort of trying to, medically manage. We really want to start, nutrition, into the GI tract as early as possible, . To help us with entercyte nutrition, and making sure there isn't a calorie deficit for these patients.

So with regards to feeding tubes, often the most appropriate one, might be the placement of a nasogastric feeding tube. They're very easy to place. In conscious patients without the need for sedation, just just some local anaesthetic down the nostril.

They're generally very well tolerated, and they don't have particularly high complication rates and often allow us to give assisted dental nutrition for a few days in hospital whilst we are. Medically managing their pancreatitis, you know, and they'll have these tubes in place and we'll keep offering them food by mouth as well. And once they start to accept food by mouth, these tubes can, can easily be removed and the patient, you know, sent home.

And if we're more worried about protracted hypoorexia, . Because for instance, the patient has severe chronic pancreatitis, or significant comorbidities, or, you know, are undergoing other surgical procedures such as gallbladder surgery, for instance, because they've got complete, obstructive disease as well as their. Pancreatitis, or if the patient has hepatic lipiddosis, these patients are often going to need quite protracted periods of tube feeding more than just several days in hospital, perhaps even several, several weeks at home in the case of feline lipiddosis.

Maybe in those patients we might be better. Placing esophagostomy feeding tubes, which again are very easy to place under a light general anaesthetic in the primary care setting, generally are very well tolerated with very low complication rates, you know, and can allow assisted denial nutrition for days to weeks in these individuals. And when we are feeding down these tubes or we're offering food orally to our patients, what we want to look at is the use of a highly palatable and highly digestible diet.

So generally the prescription gastrointestinal diets such as Royal Canyon gastrointestinal or Hill's ID are often the most appropriate. Note here that this is very different from canine pancreatitis, in which we recommend the use of ultra low fat diets because of the role of fat in in in as one of the causes of canine pancreatitis. Fat content.

Of diets does not seem to be an important factor in the cause or or the treatment of feline pancreatitis. So we don't have to use ultra low fat diets in in cats. One thing to bear in mind as, as well with, with diet and we'll sort of get this a bit more on the chronic pancreatitis patients is that, because of other comorbidities such as chronic kidney disease, inflammatory bowel disease, diabetes mellitis, .

We may have to use a diet that actually, you know, isn't one of these gastrointestinal diets and one that's more appropriate for the treatment of, of one of those other morbidities, depending on what that morbidity is and how severe it is in our patients. So just get to that in another slide or two. So moving on to antibiotics, these are really not necessary for the vast majority of our acute pancreatitis cases, as it is a sterile disease process without the involvement of bacteria.

So they should only be considered in cases that have suspected bacterial involvement or cases in which it's been confirmed on a culture. Or on cytology on or histopathology, . So cases that may be suspected of having bacterial involvement might be those that are febrile, have a profound neutropenia and or band neutrophilia and certainly evidence of perhaps, Well sonographic evidence of disease that might be consistent with bacterial involvement, so changes that could be consistent with the pancreatic abscess, or perhaps in a patient that we suspect has concurrent neutrophilic cholangitis, which is, you know, a disease of bacterial colonisation of the biliary tract.

So generally, antibiotics not needed in the, hospital or outpatient setting. And corticosteroids have emerging evidence for their use in canine and human human pancreatitis. So there was a recent study looking at canine pancreatitis patients in Japan, acute, pancreatitis patients, and actually the use of an anti-inflammatory dose of prednisolone seems to improve outcome in these patients versus the patients that didn't receive that drug.

There is also really very weak evidence that glucocorticoids induce pancreatitis, even though it's sort of commonly, you know, mentioned in primary care practise about the association between glucocorticoids and pancreatitis. So I think it's. An area of interest in which we don't really know the role of glucocorticoids in the treatment of feline pancreatitis, but certainly we know that autoimmune forms of pancreatitis exist in cats, dogs, and humans, and in some patients steroids can be the cornerstone of treatment.

We also are aware that of course steroids may be beneficial with certain comorbidities, and so of course if we have a cat with pancreatitis and inflammatory bowel disease, the patient may well already be on or require prednisolone for the treatment of their IBD, so it sort of maybe at least beneficial in treating the comorbidities, if not certain, immune, mediated forms of pancreatitis. We do have to be aware, of course, that the steroids can have a detrimental effect, and particularly. And the concerns regarding the induction of diabetes mellitus in patients that already have reduced pancreatic, endocrine function, and I think, you know, the sort of summary would be that there is maybe a role for glucocorticoids in these patients, but we just don't know enough about it.

It's they're using in the acute setting yet to sort of recommend them. With regards to prognosis, in acute pancreatitis, the mortality rates can really vary depending on the study and severity of disease, and have been reported as low as 9% and as high as 41% in the literature. And in those patients, that succumb to the disease, ionised hypocalcemia, hypoglycemia and azotemia were all identified as poor prognostic indicators.

So just finishing up on chronic pancreatitis, this disease is more often associated with comorbidities than acute pancreatitis. So particularly we're thinking about inflammatory bowel disease, cholangitis, which, you know, make up trionitis. And the general consensus is that the treatment of those comorbidities, should be prioritised, and that the treatment of the chronic pancreatitis is essentially more symptomatic, and supportive.

There's unfortunately a very limited evidence base about the treatment options for feline chronic pancreatitis. But you know, along the lines of acute pancreatitis, we need to treat each problem as it occurs. So pain can be treated with analgesics, bupredorphine, tramadol, gabapentin, for instance.

Antibiotics again are are not necessary in these patients, unless, bacterial involvement has been confirmed. And nutritional support really depends on the individual case, but there certainly again is no need to fat restrict these patients. A gastrointestinal prescription diet would seem the most appropriate thing.

Although again, bear in mind, the potential importance of nutritional support in some of the treatment of the comorbidities. So for instance, a cat that's got pancreatitis. And inflammatory bowel disease actually may be better on a hydrolysed prescription diet as part of a targeted treatment for their IBD than they would be on a gastrointestinal prescription diet.

Again, immunosuppressive, anti-inflammatory, therapies can be considered, in patients with chronic pancreatitis. Certainly if we're happy that we've ruled out any significant comorbidities that might contraindicate the use of these drugs. And if we have a, a chronic pancreatitis patient that seems to be failing all of the therapies, it might be that as part of, the therapeutic trials of these patients, we put them on, glucocorticoids or even cyclosporin, as immunosuppressive medication, you know, to treat them for, immune-mediated forms of of feline pancreatitis.

So hopefully there's been a few top tips for you there to take away, regarding the diagnosis and treatment of these patients, as there's certainly not the most straightforward cases that we see, but ultimately can be very, very rewarding to successfully, to successfully diagnose and manage, in primary care practise. So many thanks for listening and I hope to see you again next time. Take care, bye bye.