Pancreatitis: More common than you think (Proceedings)

The incidence of exocrine pancreatic disorders is quite large in both dogs and cats. In a large retrospective study of necropsy findings 1.5% of 9,342 canine and 1.3% of 6,504 feline pancreata showed significant pathological lesions. However, recently, it has been suggested that the true prevalence of pancreatitis is by far greater. In one study 208 dogs undergoing necropsy at the Animal Medical Center in New York City were enrolled and more than 21% had macroscopic lesions suggesting pancreatitis. Pancreata from all dogs were sectioned every 2 cm and a total of 64% had histological lesions of acute and/or chronic pancreatitis. In another study 25.6% of 200 un-selected dogs submitted to necropsy through a group of first-opinion practices in the UK showed evidence of chronic pancreatitis and 2% showed evidence of acute pancreatitis. These data suggest that pancreatitis is far more common in dogs than previously suspected. However, the data also suggest that infiltration of the pancreas with inflammatory cells is not necessarily clinically significant and more research is needed to better characterize clinically significant disease. Similar data have recently been reported for cats. In a study of 115 cats submitted for necropsy at the University of California in Davis that had 3 biopsies collected (i.e., one from the left limb, one from the right limb, and one from the body of the pancreas), 75.7% showed lesions suggestive of acute and/or chronic pancreatitis. This would suggest that, similarly to dogs, feline pancreatitis is far more common than previously expected, but also that more work is needed to clearly characterize clinically significant disease. Approximately 50% of all canine and feline patients with exocrine pancreatic disorders have pancreatitis. According to the current classification system of human pancreatitis acute pancreatitis is an inflammatory condition of the pancreas that is completely reversible after removal of the inciting cause. Chronic pancreatitis is characterized by irreversible histopathologic changes of the exocrine pancreatic tissue, such as atrophy or fibrosis. Both forms can be mild or severe. Mild forms of pancreatitis are associated with no or little pancreatic necrosis and systemic effects and often allow recuperation of the patient. In contrast, severe forms of pancreatitis are associated with extensive pancreatic necrosis, multiple organ involvement, and often a poor prognosis.

Etiology

Several diseases and risk factors have been associated with pancreatitis. Traumatic pancreatitis (due to road traffic accidents in both dogs and cats or falling from heights in cats) has been reported. Surgical trauma can also cause pancreatitis, but many human patients that undergo surgery of organs distant from the pancreas have also been shown to be at an increased risk for pancreatitis, suggesting that hypoperfusion of the exocrine pancreas during anesthesia may be of bigger concern than surgical handling of the organ itself. Infectious agents have been shown to cause feline pancreatitis, with the strongest causal relationship for Toxoplasma gondii, and rare cases of Amphimerus pseudofelineus infestation in cats. Babesia canis has been reported to be associated with pancreatitis in dogs. Weaker evidence has been presented for feline panleukopenia virus infections in kittens and infections with feline herpesvirus I and feline infectious peritonitis virus. Two cases of feline pancreatitis after topical use of fenthion, an organophosphate cholinesterase inhibitor, have been reported. Many other pharmaceutical compounds have been implicated in causing pancreatitis in human beings and dogs. Chronic hepatitis in dogs and cholangitis in cats coexist in patients with pancreatitis, but there is no evidence that they play a causative role. Hypertriglyceridemia and hypercalcemia can also cause pancreatitis. Finally, more than 90% of all cases of canine or feline pancreatitis are idiopathic.

Pathogenesis

According to a generally accepted pathogenic principle, pancreatic acinar cells ultimately respond in a common fashion to a variety of harmful stimuli, leading to inappropriate intracellular activation of trypsin, and subsequently activation of other digestive zymogens. These activated digestive enzymes cause local changes, such as inflammation, hemorrhage, acinar cell necrosis, and peripancreatic fat necrosis. Pancreatitis, when severe, is also associated with a variety of systemic complications, such as systemic inflammatory changes, systemic vasodilatation leading to hypotension, pulmonary edema, disseminated intravascular coagulation, central neurologic deficits, respiratory failure, renal failure, and multiorgan failure. Traditionally, it was hypothesized that these changes, similarly to local changes are caused by prematurely activated pancreatic enzymes. However, more recently, cytokines are believed to play a more important role in the progression of pancreatitis and the development of these systemic complications.

Clinical picture

Clinical signs in dogs with pancreatitis depend on the severity of the disease. Mild cases may remain subclinical. More severe cases may present with anorexia (91%; data from a study of 70 dogs with fatal pancreatitis), vomiting (90%), weakness (79%), abdominal pain (58%), dehydration (46%), and diarrhea (33%). Severe cases can present with systemic clinical signs such as fever or even cardiovascular shock. Cats, even with severe pancreatitis, present with even less specific clinical signs than do dogs. In one study of 40 cats with severe pancreatitis the following clinical signs were reported: lethargy (100%), anorexia (97%), dehydration (92%), hypothermia (68%), vomiting (35%), abdominal pain (25%), a palpable abdominal mass (23%), dyspnea (20%), ataxia (15%), and diarrhea (15%). Especially remarkable in feline pancreatitis patients is the low incidence of vomiting and abdominal pain, both of which are common clinical signs in human and canine pancreatitis patients. Clinical signs in patients with pancreatitis are due to pancreatic inflammation or systemic effects of the pancreatic inflammation.

Diagnosis

Complete blood count and serum chemistry profile often show mild and nonspecific changes. More severe changes can be observed in patients with severe forms of pancreatitis. Serum amylase and lipase activities are of no clinical value in the cat and are of limited clinical utility in the dog. The specificity of both of these parameters is only approximately 50%, even when stringent criteria are applied. Radiographic changes seen in some cases include a decreased contrast in the cranial abdomen and displacement of abdominal organs. However, these changes are rather subjective and abdominal radiography is non-specific for canine or feline pancreatitis. Abdominal ultrasound is useful in the diagnosis of pancreatitis in dogs and cats. The sensitivity of abdominal ultrasonography is up to 68% in dogs and up to 35% in cats. However, these numbers are largely operator-dependant. Changes identified include pancreatic swelling, changes in echogenicity of the pancreas (hypoechogenicity in cases of pancreatic necrosis and hyperechogenicity in cases of pancreatic fibrosis) and of peripancreatic fat (hyperechogenicity in cases of peripancreatic fat necrosis), fluid accumulation around the pancreas, and less frequently a mass effect in the area of the pancreas. Other findings that have been described are a dilated pancreatic duct or an enlarged duodenal papilla. Abdominal computed tomography is a routine procedure in humans suspected of having pancreatitis, but appears to be very insensitive for the diagnosis of pancreatitis in dogs and cats.

Trypsin-like immunoreactivity is specific for exocrine pancreatic function. However, the sensitivity of serum TLI concentration for pancreatitis in dogs and cats is only approximately 30-60% making it a suboptimal diagnostic test for pancreatitis in both species. However, serum TLI concentration remains the diagnostic test of choice for the diagnosis of EPI.

Recently, assays for measurement of pancreatic lipase immunoreactivity in dogs and cats have been developed and validated. Many different cell types in the body synthesize and secrete lipases. In contrast to catalytic assays for the measurement of lipase activity, use of immunoassays does allow for the specific measurement of lipase originated from the exocrine pancreas. Serum cPLI was measured in a group of dogs with exocrine pancreatic insufficiency and the median serum cPLI concentration was significantly decreased compared to clinically healthy dogs. In addition serum cPLI concentration was non-detectable in most of the dogs and minimal serum cPLI concentrations were observed in the rest of the dogs, indicating that serum cPLI concentration originates from the exocrine pancreas and is specific for exocrine pancreatic function. In another study serum cPLI was evaluated in dogs with experimentally induced chronic renal failure. While serum cPLI was significantly higher in dogs with experimentally induced chronic renal failure than in clinically healthy dogs, most dogs had serum cPLI concentrations within the reference range and none of the dogs had serum cPLI concentrations that were above the currently recommended cut-off value for pancreatitis. These data would suggest that serum cPLI concentration can be used as a diagnostic test for pancreatitis even in dogs with renal failure. Also, long-term oral administration of prednisone did not have any effect on serum cPLI concentration. Finally, the sensitivity of different minimally-invasive diagnostic tests was compared in dogs with biopsy-proven pancreatitis. The sensitivity of serum TLI concentration was below 35% and that of serum lipase activity was less than 55%. In contrast, the sensitivity for serum cPLI concentration for pancreatitis was above 80%. Clinical studies in cats have shown similar results. In a group of cats with experimentally induced pancreatitis both serum fTLI and fPLI concentrations did increase initially but serum fPLI stayed elevated much longer than did serum fTLI concentration suggesting that, as in the dog, serum PLI concentration is much more sensitive for pancreatitis than serum TLI concentration. In another study of cats with spontaneous pancreatitis serum fPLI concentration was more sensitive and more specific than serum fTLI concentration or abdominal ultrasonography. Thus, in both dogs and cats serum PLI concentration is the most sensitive and specific diagnostic test for pancreatitis currently available. Serum cPLI and fPLI concentrations are now being measured by commercially available ELISAs, Spec cPL™ and Spec fPL® . Also, a patient-side SNAP test for the semi quantitative assessment of canine pancreatic lipase is now available. The SNAP cPL assay is useful to rule out pancreatitis in dogs with suggestive clinical signs when the test is negative. Also, a positive test result suggests the presence of pancreatitis. However, a serum sample should also be sent to the laboratory for measurement of Spec cPL to confirm the diagnosis and to get a baseline value that can then be used to monitor the progression of the disease.

Traditionally, a pancreatic biopsy has been viewed as the most definitive diagnostic tool for pancreatitis. Pancreatic biopsies can be collected during abdominal exploratory or by laparoscopy. The presence of pancreatitis is easily diagnosed by gross appearance of the pancreas in many cases. However, the absence of pancreatitis can be difficult to prove and even if multiple biopsies are being collected, pancreatic inflammation, especially in cases of chronic pancreatitis, may easily be missed. It should also be noted that while a pancreatic biopsy in itself is not associated with many complications many patients with pancreatitis are poor anesthetic risks.

Pancreatic cytology is very helpful in confirming pancreatitis. However, fine-needle aspiration of the pancreas requires great operator experience. The presence of acinar cells in the cytological preparation confirms that the pancreas has been successfully aspirated, while the presence of inflammatory cells confirms the presence of pancreatic inflammation (i.e., pancreatitis). However, a lack of inflammatory cells does not rule out pancreatitis as pancreatitis can be highly localized.