Hi. So welcome to this, talk on, feline gastrointestinal disease. So, I think this is definitely one of the most common, presentations I see in kind of referral population, but also doing advice calls for, primary practitioners as well.

It can be really common. And what I'm hoping to do is that we can work through kind of a logical approach to gastrointestinal disease and what the most common, things that we might see in our patients are. So we'll look at the different types of the disease, we'll look at the diagnostic approach, we'll look at treatment, we'll look at some new novel treatments, and we'll also look at a case study just to consolidate our knowledge as well.

So, gastrointestinal disease broadly can be, classified as inflammatory disease, neoplastic disease, parasitic bacterial or viral disease. We can get foreign bodies, whether they be, kind of like foreign objects or, even like massive ferals, so tricobazoas. And we can also get secondary, GI disease as well.

And it's important for us to, be able to, classify, what disease, is occurring where. With cats, what I absolutely love about them is that they tend to just be lethargic and a bit inappetent or hyperexic no matter what the underlying, condition is. So they definitely make it a little bit more challenging for us to try and determine what the underlying, diseases are.

Obviously, we would expect to see vomiting and diarrhoea, but actually, we don't see it in all of the cases of, GI disease. So if I have a cat, particularly with weight loss, lethargy, in appetence, then I will be thinking about gastrointestinal disease, even if this patient doesn't have any vomiting or diarrhoea. When we're thinking about gastrointestinal disease, the most common things we see is IBD or potentially small cell lymphoma.

And IBD is inflammatory bowel disease, and the most common thing we will see on, histology would be a lymphoplasmacytic, enteritis or gastritis. And that can be, associated with weight loss, and sometimes the animals actually have a normal or increased appetite, despite the weight loss. So we don't always see this reduced appetite.

We can see significant gastrointestinal disease without vomiting and diarrhoea occurring. So with cats with kind of GI disease, weight loss is being recognised as a presenting sign in up to 100% of cases, so around 82 to 100% of cases. Diarrhoea only in 25 to 60% of cases, and vomiting in only 25 to 73% of cases.

Whether they really don't have vomiting or diarrhoea, we don't know, or whether they're outside cats, and this is happening outside and we're just not seeing it. But it's really important to recognise that sometimes the only presenting sign we'll see is, weight loss. So, I'm very much an advocate of having, like, preventative medicine and having health checks every 6 months, particularly when cats are older, because owners don't always recognise a weight loss, particularly in our fluffy cats, you know, the long-haired ones, we might not notice it as, easily, but having kind of weight charts, we can, see, more readily if we have got the weight reducing.

We also need to think about, if this patient is actually vomiting, or is it regurgitating. So, what I usually do is lead with quite open questions to the owners and just say, I know it's not very nice, but can you describe to me what happens when he brings up this food or she brings up this food? And really what we're trying to see is, is there active rection or abdominal effort?

Are there prodromal signs, so like lip smacking or signs of nausea? What sort of time are they doing it in relation to eating and what's the description of the vomitous or the regurgitated food? So if we've got vomiting, then we usually have active wretching and abdominal effort.

We often have lip smacking and nausea, noted. It's can be a variable time after eating, and it's often partly digested, and bile or blood may also be present. And this is different to regurgitation, which is a passive event.

So we don't see this active wretching or abdominal efferent. We don't see the prodromal signs. It often happens shortly after eating, and it's often tubular in nature and undigested.

And the reason it's really important is regurgitation, that fits more with kind of an esophageal disease, whereas vomiting is more GI disease or extra systemic diseases. So, you know, renal disease, liver disease, hyperthyroidism, any of those can cause, vomiting. We also want to be able to differentiate diarrhoea as well.

So, if we've got small intestinal versus large intestinal disease. So, again, I start with very open questions and say, not nice, but how would you actually describe the, faeces, and then ask more questions. So, you know, is there pain associated with it?

Is there kind of incontinence? Is an urge to defecate. So if we're looking at small intestinal disease, and we often have an increase in faecal volume.

We rarely will have present, mucus, but we can have melena being present. We don't often have hematochezia. We may have stetera where we have these fatty faeces if there's malasorption.

We don't usually have urgency in defecating or suss, and often the frequency of defecation can be, 2 to 3 times a day or normal. We don't have dysgesia, but we may have flatulence and bugy, and we may have vomiting. Appetite is usually normal, but can be reduced.

Weight loss or an increased in some cases. Weight loss, usually occurs when the, the disease is more chronic. We rarely see faecal incontinence with small intestinal disease, and perianal irritation is often absent.

Whereas in large intestinal disease, we usually have a normal or decreased faecal volume, but it's common to have mucus, but not so much, Melina, which is usually absent. But we can get fresh blood with hematochezia. We can see urgency in defecating and tsins, and often defecation is 3 times normal.

We can see dysgesia. We don't often see flatulence, but we can see vomiting in about 30 to 35% of acute colitis cases. Appetite usually remains normal, and often they don't lose weight with large intestinal disease, but they may have faecal incontinence and they may have perianal irritation.

So, it's obviously quite a long list with this, and you wouldn't expect the owners just to turn out all this information, but try and get as much of the information without having kind of guided questions and then ask a bit more about kind of, for example, incontinence, flatulence, and, things like that as well. So, when we're looking at our diagnostic approach, we often want to do haematology and biochemistry, because we want to see is there a systemic disease, So, kidney disease, liver disease, etc. That could be a cause of our, GI signs.

We may also want to do a, bile acid stimulation test. To look at our liver function a bit closer. We often want to do FPLI's, folate and carbalamine.

We also may want to do TLI particularly if there's a lot of weight loss as well. And the degree of hypercarbulimia in IBD correlates with the degree of histological damage and a poor prognosis. So we want to know about, cabalamine, both for prognosis, but also for supplementation as well.

We also want to look at the albumin levels. That's why biochemistry is really important. So not just checking for, kidneys and liver.

In cats, it's rarer for them to develop hyalinemia, secondary to GI disease compared to dogs. And the prevalence bunemia ranges from about 5 to 24%. So in dogs, hyper-albumia, so an album less than 20 is associated with a poor outcome.

However, hyperalbumia is not a negative predictor of survival in cats, so it's something we need to be aware about, but it doesn't affect their, survival. Hypercabalinemia can be seen due to reduced intrinsic fat availability, so for example in EPI chronic pancreatitis or oopathic biliary disease, can see where we've got intestinal bacteria competition or ileal mucosal disease resulting in down regulation of intrinsic factor. Cabalamine receptors.

And in a previous study, hypercarillemia was, found in, 28.2% of cats with GI disease and was associated most commonly with alimentary lymphoma, and the most severe grade of histological intestine inflammation. And hypercarbolinemia has been shown to be a negative prognostic indicator in feline elementary lymphoma.

So, I just wanted to put up this, kind of study, which was looking at the relationship of, serum coallamine to methy mauric acid concentration, and clinical variables, in cats. And the reason for this is that, serum carbalamine concentration will obviously suggest carbalamine deficiency in cats, but serum methylmyonic acid, so we'll call that MMA, more accurately indicates carbalamine, deficiency. So, with this one, what's important is that your carbalamine, may not be reduced in all cases, even if you've got a cellular deficiency in the carbalamine.

So low levels of MMA. So now we're looking at, generally anything less than 400 is indicative of being poor, carbalamine, . Levels, so hypercabauminemia.

So, you'll often see on, lab results, so the reference range for carbalamine might be less than, say, 250, but we tend to supplement anything less than 400. When we're looking at our diagnostic approach, we also want to, if they've got diarrhoea, think about doing full faecal, analysis, including parasitology, culture, and GRD as well. And due to intermittent parasitic, shedding, then I tend to treat with fambendazole at 50 mg per gig, daily for 5 to 7 days in, my cases as well.

We also want to think about doing abdominal imaging with ideally ultrasound to further evaluate the GI tract, liver, and pancreas in particular. We also want to think about doing, PCR tests for feline diarrhoea samples, but what's important is that when we do these, diarrhoea PCR panels, some organisms can just be present as a normal commensal, and they can be found in normal animals. And having a positive PCR does not mean that that's the cause of the clinical signs.

It just means that it is present. So there was a previous study out of Edinburgh University by Doctor Paris, which looked that multiple coinfections were positive, sorry, were common. And at least 2 of the, 8 potential enteropathogens the authors tested for were detected in 62.5% of cats.

And they had increased carriage noted among pedigree and young cats in particular. But it's really important not to just broadly treat all of these, diseases because they may just be, found in healthy animals as well. So this is the, study that she, did.

So, they found an overall prevalence of, coronavirus in about 56.9%, panleukopenia in 22.1, Clostridium profiins in 56.6%, Salmonella in 0.8%, Giard in 20.6%, Tritrichomonas in 18.8%, Cryptosporidium in 24.4%, and toxoplasma in 1%.

And again, certain things like coronavirus, GRD, and tri trichomonas were more common in pedigree cats. So, I personally don't like a lot of these, panels of PCR testing cause I think we need to think about which infections are more likely to be causing disease and then test. For them.

So, for example, coronavirus very rarely causes GI disease and we don't treat it if we just find it in. So, you know, I wouldn't really test for a patient for coronavirus and say that that's the cause of its diarrhoea. And we know that a lot of cats, particularly pedigree, Pedigree and particularly younger cats will have coronavirus carriage.

But that does not mean that that is a cause of any of their disease. So I think a lot of these we need to take with a pinch of salt, and we also need to be thinking about doing more, guided testing against the pathogens that are more, prevalent and gonna be more, expected to cause disease. So Giardia, we can, get infection by the feca or root, and we get these environmentally resistant cysts, which are shedding the faeces, when they contaminate drinking food or water and are then ingested by other cats.

So they are kind of surface toxins and cause surface infections, and they don't enter the interocytes. That they can, damage, the intestinal, lining through a number of mechanisms. So they produce toxins, they disrupt the normal microbiota, induce inflammatory responses, inhibit normal enterocytic enzymatic function, blunt microvilli, and can lead to motility disorders resulting in intestinal malabsorption and, hypersecion.

So clinical signs with GR it can range from just subclinical to acute or chronic, small or large intestinal diarrhoea. And more severe disease is often seen when we have other intestinal pathogens or, concurrent intestinal disease. Reaching a diagnosis can be difficult because the cyst can be shared, sporadically, and so pooled samples will be more, sensitive.

But, I would also potentially treat, if I just had a single faecal sample and it was negative, but I still had a high index of suspicion. Then I would still treat with 50 mg per kg of Vambendazole for 5 to 7 days. Repeat treatment may be needed and sometimes you need to combine it with metronidazole.

But what's really important is actually to clean the environment. So, also make sure that the animals, ideally kind of wash their, coats as well, so that they don't have any cysts, laying by their peri, anal region, clean the environment really well, and make sure that they're not kind of reinfecting themselves if you are getting recurrent Giardia infections in a particular animal. It's also zoonotic, so we need to have meticulous hygiene.

Particularly if you've got young children or any immunosuppressed individuals in the household. So another infection, which is definitely, important as well, is Tritrichomonas foetus, and this is found in the colon, and it sheds these flagated protozoa into the faeces. So we most commonly see this infection where we have, large groups of cats with more, low standards of hygiene, though any cat can be infected.

Studies have identified infections to be most prevalent in cats less than one year of age, if their pedigree and with Siamese and Bengals being overrepresented. The infection can be asymptomatic or result in chronic large bowel diarrhoea, and they often have this liquid malodious, faeces that often contains mucus and fresh blood. But despite this, the cats are often clinically well.

They still maintain their weight, they're still eating well, but they can develop quite severe signs and even faecal incontinence. They usually will clear it after 2 years, but do you want a cat with large bowel diarrhoea for 2 years? The answer is probably not.

So, as with, Diardia, tritrichomonas is intermittently shed, so we, improve the sensitivity, by doing a PCR test and also doing pooled samples as well. If, we have infections which are clinically significant, then we use, Renidazole. So, Renidazole is something which cause quite a lot of side effects if it's used at a higher dose.

So, we used to use it at about 30 mg per gig twice a day. We now recommend 10 to 30 mg per gig once a day for 14 days. And the side effects we see can be neurological, including twitching and seizures, but these side effects are usually dose dependent.

So the lower Doses we're now using. So if we've got any young animals or ones with liver disease, we use more than 10 mg per gig once a day, so much lower. And the signs typically resolve once the treatment, finishes.

The prognosis is good, but cats can sometimes sometimes continue to shed the organism for many months after resolution of clinical signs. And there has been some recent literature on the emergence of more resistant T foetus infections, where they need prolonged doses of Renidazole or much higher doses to achieve clinical resolution. We did a study, back in my residency and showed that probiotics have been useful in the treatment of T foetus infections.

So, I would definitely, always give probiotics in combination with Renidazole. We also have isospira species, so these are coccidia, coccidial agents, and up to about 2% of faecal feline faecal samples are infected, and it's usually by ingestion of the osis or parenteric host. And the mature stages live in the intestines of cats, and they shed osis into the environment.

And those sor related oosis can be directly ingested by other cats, but rodents harbour and cyst stages can act as transport, hosts as well. So infection and clinical disease is most common in kittens, kept in large unhygienic groups, and infection rarely causes clinical diseases in adult cats. So in kittens, infections can be subclinical through to severe diarrhoea.

So generally they will. Self clear it. But if we've got really severe diarrhoea in a young animal, I will treat.

And that's with TMPS as well as, sanitation as well. Or you could also potentially use to hold trousers, which has been used in both cats and in kittens. So, after we've done our faecal analysis and our blood work, we want to be looking at abdominal imaging.

And really, for me, radiographs are only really helpful if there's a foreign body is, gonna be a differential, because you're not getting enough about the intestinal layering or the, kind of the mucosal thickening or submucosa, or muscularis or anything. You can't tell that on an X-ray, and you can't evaluate the pancreas and kind of liver and things like that as well. So, abdominal ultrasound is gonna be the superior imaging modality.

And it can help to localise the disease area, which can then guide the next step of the investigation. An ultrasound's really useful because, you can look at wall layering, thickness of the intestine, look at lymph node involvement, and other organ involvement. So, for example, hepatic disease and pancreatitis involvement in cases of triitis.

So there's lots of different ultrasound changes that we may be able to see in animals with gastrointestinal, disease. So we can see change in thickness of the wall and potentially loss of layering. We can see loss of layering of the GI tract is most commonly associated with neoplasia, but it can occasionally be seen in cats with severe inflammatory disease.

So it's really important when we do ultrasound, we're not saying this is neoplastic. Or this is inflammatory. We can say what might be more likely, but the only way of knowing would be to do biopsies.

Lymphoma can present as either solitary or multiple intestinal, masses, most often transmural, hyperchoic, circumvential thickening of the GI wall associated with loss of normal wall layering, or as a diffuse thickening of the small intestinal muscularis layer with otherwise normal wall layering. A previous study identified a significant increased thickness of the intestinal wall and muscularis layer in the small intestine of cats with GI, small cell, T-cell lymphoma, and IBD. A muscularis to submucosa ratio of more than 1 was likely to be associated with GI lymphoma or, IBD.

So you can see that a lot of these indices that we might be measuring, we can see them, whether these cats have IBD or have lymphoma. Diffuse selective thickening of the muscularis layer is reported more commonly in cats with low grade lymphoma than IBD but none of these things are gonna say, yep, this is definitely neoplasia, or yep, this is definitely IBD. So, really, we need to think about doing intestinal biopsy for a definitive diagnosis, but we'll also come on to the kind of the treatment to know, do we actually need to biopsy in all of these.

So, endoscopy is, simple, and obviously, that's what I love doing as a medic, and you can see this is an endoscopy picture here. But the samples can be very superficial, and the whole gastrointestinal tract can't be evaluated. So, for example, the Giginum, we're not gonna be able to evaluate.

And the ilium, we can go through if we do a lower GI scope through the colon and through the ileosecocholic junction, we can get into the ileum and take some biopsies. But really, laparotomy may be required to get more full thickness biopsies and routine sampling of the ilium, because that's not gonna be possible for all, practitioners to be able to get into the ilium. It is more of an advanced, technique.

So, particularly because cats can get triitis, so where they get inflammation of both the gastrointestinal tract, the liver, and the pancreas, if we do a laparotomy, we can get biopsies of the liver and the pancreas as well. And we can also get full thickness transmural, biopsies, and we can also sample lymph nodes as well through our mesenteric lymph nodes if they were abnormal. So, endoscopy, as I said, it, it does depend on the skill of the practitioner, not just about whether you're getting into the ilium, but also whether you get good samples.

So, in a previous study comparing samples from any practitioner versus practitioners trained in taking, mounting, and submitting endoscopy samples, there's a vast difference in the quality of samples that were obtained. So for samples submitted by any practitioner, 9 to 24% were inadequate for diagnosis, 53 to 69% were questionable, and only 7 to 38% were adequate. So this is actually quite important when we're thinking we're actually anaesthetizing this animal and taking biopsies, and in a vast majority of these samples, they're actually inadequate or questionable.

Whereas when we had trained practitioners, only about 0.0 to 4% of these were inadequate, 18 to 28% were questionable, but 68 to 82% were adequate. So, I would strongly advise, if you're doing endoscopy, is to learn from, experienced, colleagues and make sure you're happy with your technique, before, considering it, for routine, diagnosis.

There's also been some, there's also been some concern about doing endoscopic biopsies, whether we can truly differentiate an IBD from a small cell lymphoma. So, in one study, endoscopy, biopsies were useful for diagnosis lymphoma, but were not for gastric lymphoma, but were not adequate for differentiating between IBD and lymphoma in the small intestine. And the other thing that we need to bear in mind is that the most common sites of alimentary lymphoma are the dunum and the ilium.

So the dunum is not something we can, reach via endoscopy, and the ilium is something that more experienced practitioners would be able to reach. And in this study, 4 cats were incorrectly diagnosed with IBD on the basis of endoscopic samples alone. In another study, found that there's a population of cats in which the diagnosis of small cell lymphoma could only be found on ileal biopsies, and therefore suggest that clinicians should consider performing both upper and lower GI endoscopy in cats with infiltrative small bowel disease.

So, if we're thinking of, cats, and if neoplasia is on our differential list, then really, we should be doing upper and lower, and, endoscopy so that we can get into the, ilium as well. So, obviously, it's a little bit more invasive, and we're not getting these full fitness biopsies like we would be doing, if we had, surgery. So, again, differentiating IBD in small cell lymphoma is problematic, but we'll also come on to it, is it really necessary?

So there's no correlation found between the two conditions on the basis of clinical signs, physical exam findings, or endoscopy or surgical observations. And ultrasound. Can be similar in both.

So one study found that ultrasonographic thickening of the muscularis, propria of the small intestine was significantly associated with small cell, lymphoma, in cats, and lymphadenopathy has been associated with both IBD and lymphoma. immunohistochemistry, or PA, so, can help to distinguish IBD from lymphoma, but they're not perfect results. So immunohistochemistry looks at B cell and T cell markers, or we do PAR, which is polymerase chain reaction for clonal expansion and lymphocytes, may help to distinguish and they can both be done on histopathology, but we can see both false positive and false negative results.

And a recent study of 20 healthy client-owned cats found that when they did integrated results from histo, immuno histochemistry and clonality testing, they would have classed 12 of these cats as small cell lymphoma. One is emerging small cell lymphoma. 6 is lymphocytic enteritis, and one is pseudoclonality.

So they're not perfect tests by any means. We need to think, though, about the difference between treating IBD and small cell lymphoma. And is it really necessary for us to get a diagnosis?

So, when we're thinking about IBD, then I tend to do a diet trial first, and use things like Purina HA, Hill ZD, or Deck could do a hydrolyzed salmon. Antibiotic trials, I personally don't do. And the reason that I don't do them is that getting antibiotic responsive diarrhoea is not common in cats.

And it's not really very good for, antibiotic, stewardship. So I don't like having these patients on stuff like metronidazole for long term. I personally don't do that.

Also, trying to administer metronidazole to a cat is very difficult. So, they, I tend not to. Not to do antibiotic trials because it's not common to get.

An antibiotic responsive diarrhoea, it's not good for antibiotic stewardship. But also, it's, having, it really affects your microbiome as well, and you can get quite a marked intestinal dysbiosis. So I usually start with, if the diet trial has failed, the diet trial, you do need to give.

I usually give it for about 4 weeks, but usually you're seeing a response within the first week or two. It can be more difficult in cats that are going outdoors, and therefore they might be scavenging or eating little mice or other things as well. But I still do do it both for indoor and outdoor cats.

If they fail the diet trial, then I'd go on to steroids and prednisolone, I tend to give it about 1 mg per kg twice a day. Or 2 makes for cake once a day, whatever's easier for the owners. And if there's a good response, then I taper the dose, by 25% every 2 to 4 weeks.

Cats generally tolerate, steroids well, but we can get side effects, so we need to monitor them for diabetes, iatrogenic cushions, immune suppression, so particularly UTIs and things like gastric ulcerations. If Hypercarbulimia is present, then carbalamine supplementation is required. And in cats that are refractory to a treatment, then either increase the dose of Pred up to about 3 to 4 mg per kg per day, or adding chlorambacil.

And clombacil I usually use at 2 mg per kg per cat every second day if the cat is 4 kg or more, or every third day if the cat is less than 4 kg. So the reason why I was saying, do we really need to know the difference between IBD or small cell lymphoma is a small cell lymphoma will be treated with Pred and IBD. And they have, you know, medium survival time of about 2 years, so that's still quite a good survival.

When we're looking at the diet trials, there's kind of 3 different main types of exclusion diets we can have. So we can have a hydrolyzed diet, we can have a novel diet, or we can have a home cooked diet. And I tend to like to use a hydrolyzed diet because I know it's completely balanced.

It's gonna be, suitable for, for them long term, and I know that it's got all the right, ingredients. And the hydrolytic process reduces the native protein into polypeptides of a size that's unlikely to stimulate the immune system. So we have Purina HA which is hydrolysed soya, Hills ZD which is hydrolysed chicken, Roy cannon allergenic hydrolysed feather protein, Royal Cannon hypoallergenic, which is hydrolyzed soya, and Dequipec specific food allergy Management, which is hydrolysed salmon.

Alternatively, we could give a novel, carbohydrate and protein diet trial. So, for example, Hill's DD, which was duck and peas. But finding a commercial, completely novel protein and carbohydrate source can be difficult, as commercial diets often have a mix of proteins, and cats may also be fed a home cooked, human food as well.

And the final exfusion diet is a home-cooked diet, but I would always consult a veterinary nutritionist, for that to make sure it's fully balanced. When performing an elimination diet, the cats must only be fed this diet. So this can be problematic in outdoor cats who hunt.

So, the diet is usually continued exclusively for 2 to 4 weeks, but there was a previous study which showed that the duration actually didn't even need to exceed 4 days. And that's different as opposed to if we're looking for skin changes when veterinary dermatologists would have a, elimination diet for a minimum of 8 weeks. So, knowing what your elimination diet is for, we can see what The duration is.

And although that study showed only 4 days, I would still give it 4 weeks before I say the diet hasn't failed, because really, the diet is gonna be the best option for this patient, because that's gonna be no side effects or, you know, no drug interactions or anything that if we can get the patient managed on a diet, that's kind of a win-win, situation. So, a recent study, suggested that there may be merit in trialling a hydrolyzed diet first as a soul therapy in cats with chronic vomiting and or diarrhoea when investigations do not reveal a cause, before resorting to antibiotic or steroid, therapy. In this study, cats greater than 6 years of age had significantly higher odds of a poor response to diet compared with cats less than 6 years of age.

And that was likely. Because older cats are more likely to have neoplasia and we're less likely to have a food responsive enteropathy. So this was a really nice study, which was, done from, the RVC.

And they had anonymized records of over half a million cats, under veterinary, care. So this is from Vet Compass data, which is, producing a lot of really useful, research. So they had records of, 5000, 90% of cats which were receiving a hydroly diet were randomly reviewed for GI indication, prior and concurrent medication, and response after hydrolysed dietary intervention.

A poor response was defined as evidence of receiving antibiotic. Or steroid treatment at visits after the onset of the diet, or death from GI signs for at least, 6 months follow-up. And they found that 71% of the cats were first prescribed diet without concurrent antibiotics or steroids, while 29% 1st received the diet with these medications.

And as I said, cats older than 6 years, and cats prescribed antibiotic and or steroid therapy, had a higher odds of poor response. But that may be because vets will reach in to kind of try everything in the cases which were more severely, effective. But this study definitely showed that there's merit in trial in a hydrolyzed diet as a sole therapy in cats with vomiting or diarrhoea when their investigations don't reveal a cause before resorting to other, cases that then poorly respond.

So probiotics, I think, is kind of, still quite a, a buzzword, and we're still, using it. But do we really know what a probiotic is? And the International Scientific Association for Probiotics and Prebiotics in 2014 stated that probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.

And there are limited studies looking at the efficacy of probiotics in cats with diarrhoea, but there is, as I said before, there is some evidence of it in T foetus, and there may be, so that's tri-trichomonas, and there may also be a role for its use in cats with IBD. So, as I said with, antibiotic trials, you know, we, we need to really carefully consider this when we've got the age of antimicrobial stewardship. We have off-license metronidazole, which is most commonly given in practise.

I personally don't use it at all. Metronidazole will have some immunomodulation. Effects on some mediated immunity, but antibiotic administration can be really problematic due to compliance, and antibiotic responsive ventoropathy is really quite rare in a cat.

So, for all of these factors, I personally don't perform antibiotic trials, and for ones that fail elimination diets, I would use immunosuppression instead. So, as I said, we do immunosuppression with steroids to start at 1 mg per gig, twice a day. And if there's a good response, and I taper that dose every 2 to 4 weeks by 25%, and really my aim is to find the lowest effective dose or to stop it and just have dietary therapy in the longer term.

In cases that are refractory, then I increase the dose up to about 3 to 4 mg per kg per day. Or add an additional immunosuppression with clorambacil. So, if the cat's 4 kg or more, they get 2 mgs, of, that's total dose, so 2 migs per cat every second day.

And if the cat's less than 4 kg, then it's every 3rd day. We need to remember that chlorambucil is really well tolerated, but it is a, chemotherapy agent, so it needs to be worn with gloves and the tablets never split. We also know that bone marrow suppression can occur, so it can affect your red blood cells and white blood cells and platelets.

So I do a haematology at baseline, then I do it every month for 3 months, and then every month, 3 months thereafter if it's well tolerated. And owners always need to wear gloves to handle the tablets and handle the, excreta from their cats with, care. So, carbalamine supplementation, is needed in cats with small intestinal disease, and severe hypercardlinemia is associated with improvements in clinical, findings.

So, as we said, before, we need to supplement when carbalamine concentration is even in the low normal range. So less than 400. As studies have shown that these cats may have elevated MMA, which indicates a deficiency in carbalamine at the cellular level.

And carbalamine. Be supplemented in two ways. So it's either given at 250 mcg per cat, sub-Q weekly for 6 weeks, then one dose a month later, and then carbalamine tested, 1 month after the final dose to see if further supplementation is required.

Or we can give carbalamine supplementation orally, and that's given at 250 mcg or once a day for a total of 12 weeks. And carbalamines then tested 1 week after finishing oral supplementation. So then we need to come on to the treatment of small cell lymphoma, and these cats can do remarkably well.

So, I would give, prednisolone in combination with cloramacil at exactly the same doses, and always think about haematology and, you know, obviously warn the owners that it is, carcinogenic as well. I would always, I have a full discussion with the owners if my differentials are either IBD or small cell lymphoma, then if this animal is kind of severely affected, then I'm probably going in with steroids straight away. And if they're not improving, then I'd give them clorabil.

And the reported response rates are excellent, with 59 to 76% of cats receiving, achieving complete remission. And reported survival times range from about 20 to 30 months for those cats responding to therapy. So, really, they can have a good survival and the same treatment as a cat with severe IBD.

So that's why it's not always necessary to get a definitive answer, as long as the owner's aware that, you know, if they don't respond to treatment, we're treating them as if they've got severe IBD or a small cell lymphoma, but they're on the same treatment anyway. Concurrent hypercabalinemia is common, and supplementation needs to be given for the cats to respond optimally to immunosuppression. So this is a Kaplan Meyer curve looking at survival of 41 cats with, low grade, lymphoma.

And the overall median survival time was 704 days, but as you can see, some cats did really well. So even going at 2000, days are still surviving. So, we also need to think about other medications that we might need to give to our cats with gastrointestinal disease, and we might need to give, for example, appetite stimulants.

So, improving appetite is really essential, particularly in these cats that have lost a significant amount of weights. And the most common is, one that we would use would be mirtazapine, and that all It also has an antiemetic effect. And the licence route is transdermal, and there's also off licence oral as well.

It's also been found to be effective in cats with stable, chronic kidney disease, iris stage 2 and 3. And cats were found to have a significant increase in appetite and weight and significant reduction in vomiting. So, mirtazapine works by, pre-synaptic alpha 2 antagonism, which enhances serotonin and noradrenaline release.

It leads to antagonism of serotonin and histamine receptors, and the inhibition of these, 5HT2C and H1 receptors may account for the appetite stimulation effects. It also leads to reduction in nausea and vomiting, and that's theorised due to antagonism of the 5 HT3 receptor. Amiratas is the only licenced product and it's a transdermal ointment application.

So this was, a study that was, done. So a double blind, placebo-controlled, randomised study to evaluate the weight gain drug mirtazapine transdermally in cats with unintended weight loss. And they found that it, resulted in significant weight gain in, cats and was well tolerated, in this, population of, patients.

We also need to think about antiemetics. So, I think of antiemetics, not just for animals that are vomiting, but also ones with poor appetite, because we don't know if they're feeling nauseous. So, neuroppotent citrate is the most popular antiemetic for cats, and that's an NK1 receptor antagonist.

So substance P is a neurotransmitter, which plays an important role in this eliciting emesis. And it binds to the neuroynin receptors and has been detected in high concentrations in areas of the brain reported, important for emesis. And the recommended dose is about 1 to 2 Migs per gig pero or sub-Q every 24 hours.

Cerenia, is licenced as an injectable in cats, but the oral tablets are only licenced in dogs, so we use it in cats off licence. For cats that remain nauseous or vomiting, despite Roppotin, then I give on Dansetron, which can be considered, which is off licence. But it's a 5HT3 antagonist, and it acts both centrally and locally in the GI tract.

And it can be given at a dose rate of 0.5 to 1 mg per kg peros or IB either once or twice a day. So on to more novel treatments, we're thinking more about now, there's been some studies about faecal microbiota transplantation.

And that's a term used to describe the transplantation of a faecal microbiota from a healthy individual into a disease individual as a therapeutic tool. And really, what FMT is thought to do is to restore the normal GI flora, and it repopulates the gut with intact complex community of microorganism. And it may also play a role in competitive exclusion or inhibition of the GI pathogens, whereby beneficial microbes outcompete pathogens for adhesion, attachment, and nutrient utilisation.

And in human medicine, it's really, useful for recurrent Clostridium difficile infection. And has been shown promise for other conditions, including inflammatory bowel disease. So, this is, not the nicest pictures you want to be seen with a blender, but, this is where the faeces are being, made up.

And these, beautiful images are courtesy of Yvonne McGotti. So she's Doing a faecal, transplantation where she's, transplanting them, via, retention, enema into this, cat. You can also, there have been some studies looking at, providing it via orally, via, capsules as well.

So, in 2013, there was a case report which documented successful, FMT therapy in a cat with chronic vomiting and diarrhoea that had not resolved with traditional therapy. And within 24 hours, so really, really rapidly, the cat had clinical resolution and maintained a healthy clinical gut status for at least 3 months post-treatment. Similarly, in 2017, there was a case report of an Abyssinian cat with ulcerative colitis, which was unresponsive to conventional therapy, and that underwent FMT.

And they did a rectal enema, and that was described as a last, a therapeutic option before euthanasia. And in this Abyssinian cat, there was rapid improvement after the procedure in regards to faecal texture, odour, and, colour. After the initial successful response, the cat developed a relapse and a second FMT was performed.

And gradually over 3 months period, the cat started passing normal stools, and at follow up 11 months after procedure, prolonged clinical remission of the diarrhoea had been achieved with the cat passing normal faeces. So, FMT, although it's a novel treatment, it's definitely something I'm thinking about earlier in the disease course, because it's no real side effects noted. It can have a really rapid, response, and it could stop us from having to give, steroids and other treatment to, our patients.

So, I just wanted to end with, a case report. So this is Maxi's absolutely lush, 10 year old, mal neutered Siamese with outdoor access. And he was up to date with his vaccinations and flea and worm treatment.

He had a one month history of intermittent vomiting, lethargy and a one-week history of anorexia, and he had no response to short courses of Sinnulox or, Metacam. So, we did some blood work on him and he had a mild neutrophilia. So that could be an infection, inflammation, or just a stress response.

He had a mild anaemia with, chronic disease deemed most likely. He had mildly raised ALT, ALP, and bile acids, which could be primary hepatic disease or secondary due to GI disease. And he had a hyperalbumia, with, which was 22, so that's a negative in acute phase protein, and that could be lost by the gut, kidneys, or reduced production in the liver.

So we suspected hepatic and or GI disease and we couldn't rule out a secondary hepatopathy and we couldn't rule out a pancreatitis. So we did FPLI folate and balamine, and we also did urinalysis to rule out proteinuria as a cause of the hyperalbumia. So the FPLI was raised, so that could be primary or secondary pancreatitis.balamine was reduced, the folate was normal, and the urinalysis was unremarkable.

So the UPC was 0.2, so there was no indication of proteinuria being a cause for the hyperalbumia. So he had an abdominal ultrasound, and he had an enlarged hyperchoic pancreas with a hypo, hypoechoic pancreas with hypoechoic mesenteric and pancreatic, fat.

So, he had a normal appearance of the liver and the biliary tree, and thickening of the muscularis layer in the small intestine, mainly in the ilium and the dunum. So, in this scenario, we discussed with the owners, do we just do trial treatment? So our main preventions will be IBD or small cell lymphoma.

Do we do orroiditis? Do we do endoscopy and ultrasound guided FNA of the liver and the bile aspirate? Or do we do exploratory laparotomy so we can get full thickness biopsies and we can, try and get, liver biopsies and potentially pancreatic biopsies?

The owners went for an exploratory laparotomy. He had a coagulation profile done first, and that was normal because we wanted to do liver biopsies. And he had biopsies of the stomach, duodenum, ilium, duinum, liver, pancreas, and a bias.

So we had a full MOT. The biopsies were submitted. Histo and bioculture for bile aspirate for culture and sensitivity.

And the reason we do that is the liver, culture, well, positive culture from the, is more likely from a bile aspirate than it is from a liver. So I would always do the bile for culture. And we also placed an Otu because he wasn't eating very well.

Post-op, he had IVT, obviously had some pain relief, had some oppotent, and we started feeding convalescences about a third RER on day one, up to, full RER on day 3. He had potentiated amoxicillin pending results in case of an infectious, cholangitis, B12 supplementation. And Sammy and UDCA.

So his results revealed that he had a lymphocytic, plasmacytic gastritis and enteritis. He had a chronic pancreatitis, a neutrophilic cholangitis, and E. Coli cultured from the bowel.

So he had a triitis, so inflammation in all of these organs, but he was having an infection in the liver. So, inflammatory bowel disease, chronic pancreatitis, and infectious neutrophilic cholangitis. So that's all leading to a diagnosis of triitis.

So, he continued to enteral feeding until his appetite returned. Once the appetite was back to normal, we put him on a highrise diet for at HA, and we continued potentiation amoxicillin for 6 to 8 weeks because it needs to be quite a long time for liver, infection. And we continued Say and UDCA.

The O tube was removed after 3 weeks. He was exclusively fed prea HA and he had a resolution of vomiting and his weight gain at revisit 8 weeks later, and he was continued solely on dietary therapy. 6 months later, he had vomiting and small bowel diarrhoea.

He was still on the prena HA and he had full blood work, faecal analysis, and abdominal ultrasound performed. So blood work was unremarkable, but his folate, was normal, but balamine was reduced again and FPLI was increased. Faecal analysis was unremarkable.

And a dominant ultrasound revealed that the liver looked normal, but there was thickening of the muscularis and normal pancreatic parenchyma. So, in this scenario, we did do ethno, the liver and bile aspirate, and really what we wanted to do is rule out that there wasn't an infectious, cholangio hepatitis, and that was all unremarkable. So we had inflammatory bowel disease was the most likely with possible pancreatitis, but no evidence for return of a bacterial cholangitis.

And that's important because we were deciding, do we want antibiotics or do we want steroids. So we had, preno HA continued, and he was started on steroids at 2 migs per gig per day, and the vomiting and diarrhoea improved over a month, and the prednisolone was tapered by 25% every 4 weeks and then stopped, and he was continued on long-term dietary therapy and did really well. So hopefully, we can see that, as summary, gastrointestinal disease is common, and clinical signs can be vague, and we don't need to see vomiting and diarrhoea in all patients.

We can see concurrent diseases like we did with Max, so particularly hepatic and pancreatic disease, and investigations often involve blood work, imaging, and maybe biopsy of the gastrointestinal tract. And the prognosis for small cell lymphoma can be good and as good as, severe inflammatory bowel disease, so it's not always necessary to get biopsies. So I hope you enjoyed that and thank you for listening.

Bye.