Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis

Serum feline trypsinogen-like immunoreactivity (fTLI) concentrations and abdominal ultrasound have facilitated the noninvasive diagnosis of pancreatitis in cats, but low sensitivities (33% and 20–35%, respectively) have been reported. A radioimmunoassay has been validated to measure feline pancreatic lipase immunoreactivity (fPLI), but the assay's sensitivity and specificity have not been established. In human beings, the sensitivity of computed tomography (CT) is high (75–90%), but in a study of 10 cats, only 2 had CT changes suggestive of pancreatitis. We prospectively evaluated these diagnostic tests in cats with and without pancreatitis. In all cats, serum was obtained for fTLI and fPLI concentrations, and pancreatic ultrasound images and biopsies were acquired. Serum fPLI concentrations ( P <.0001) and ultrasound findings ( P = .0073) were significantly different between healthy cats and cats with pancreatitis. Serum fTLI concentrations ( P = .15) and CT measurements ( P = .18) were not significantly different between the groups. The sensitivity of fTLI in cats with moderate to severe pancreatitis was 80%, and the specificity in healthy cats was 75%. Feline PLI concentrations were both sensitive in cats with moderate to severe pancreatitis (100%) and specific in the healthy cats (100%). Abdominal ultrasound was both sensitive in cats with moderate to severe pancreatitis (80%) and specific in healthy cats (88%). The high sensitivities of fPLI and abdominal ultrasound suggest that these tests should play an important role in the noninvasive diagnosis of feline pancreatitis. As suggested by a previous study, pancreatic CT is not a useful diagnostic test for feline pancreatitis.     

Determination of serum fPLI concentrations in cats with diabetes mellitus

Diabetes mellitus (DM) is one of the most common feline endocrinopathies. Pancreatitis is a reported cause for poor control of DM in cats; however, its prevalence in diabetic cats is unknown. Measurement of serum feline pancreatic lipase immunoreactivity (fPLI) has been proposed as a sensitive and specific test for the detection of pancreatitis in cats. The aim of this study was to assess fPLI concentrations in diabetic cats and compare these with non-diabetic cats of similar age. Samples from 29 cats with DM and 23 non-diabetic cats were analysed. Serum fPLI concentrations were significantly higher in samples from diabetic cats (P<0.01). A weak association was found between serum fructosamine and fPLI concentrations (R(2)=0.355, P=0.015), but there was no association between fPLI concentrations and the degree of diabetic control. There were no significant differences in reported clinical signs between cats with or without DM regardless of serum fPLI concentration. This is the first study to demonstrate elevated serum fPLI concentrations in cats with DM, suggesting that pancreatitis could be a significant comorbidity in these cats.     

Laboratory tests for diagnosis of gastrointestinal and pancreatic diseases

The panel of laboratory tests available for diagnosis of gastrointestinal (GI) diseases in dogs and cats is wide, and, recently, several new tests have been developed. This article will focus on advances in laboratory tests that are available for the general practitioner for diagnosis of GI diseases. Laboratory tests for diagnosis of gastric and intestinal infectious diseases include fecal parasite screening tests, enzyme-linked immunosorbent assays for parvoviral enteritis, and some specific bacterial tests like fluorescent in situ hybridization for identification of specific bacteria attached to the intestinal epithelial cells. Serum concentrations of folate and cobalamin are markers of intestinal absorption, but are also changed in exocrine pancreatic insufficiency and intestinal bacterial overgrowth. Hypocobalaminemia is common in GI and pancreatic disease. Decreased serum trypsin-like immunoreactivity is a very sensitive and specific test for the diagnosis of exocrine pancreatic insufficiency in dogs and cats. Serum pancreatic lipase is currently the most sensitive and specific test to identify pancreatic cell damage and acute pancreatitis. However, serum canine pancreas-specific lipase is less sensitive in canine chronic pancreatitis. Increased serum trypsin-like immunoreactivity is also specific for pancreatic damage but is less sensitive. It is very likely that further studies will help to better specify the role of these new tests in the diagnosis of canine and feline pancreatic diseases.     

Canine and feline pancreatic lipase immunoreactivity

The diagnosis of pancreatitis in dogs and cats can be challenging. Several diagnostic tests have been evaluated over the years, but the majority have been shown to be of limited utility owing to poor performance or limited availability or because invasive procedures are required. Assays for the measurement of pancreatic lipase immunoreactivity (cPLI for dogs and fPLI for cats) were first developed over a decade ago and now include Spec cPL and SNAP cPL for dogs and Spec fPL and SNAP fPL for cats. Owing to their high sensitivity and specificity for pancreatitis compared with those of other serum tests, concentrations of cPLI and fPLI have been demonstrated to be the serum tests of choice for evaluation of dogs and cats, respectively, suspected of having pancreatitis. False-positive and false-negative results can occur, and recognition of the limitations of pancreatic lipase immunoreactivity assays is important. As there is currently no gold standard for antemortem diagnosis of pancreatitis in dogs and cats, the combination of a complete history and physical examination, measurement of pancreatic lipase immunoreactivity, and ultrasonographic examination of the pancreas is the best approach for an accurate noninvasive diagnosis of pancreatitis.     

Feline exocrine pancreatic disorders.

Despite the uncommon clinical diagnosis, cats frequently suffer from disorders of the exocrine pancreas. Pancreatitis is the most common feline exocrine pancreatic disorder. Pancreatitis can be acute or chronic and mild or severe. The etiology of most cases of feline pancreatitis is idiopathic. Some cases have been associated with severe abdominal trauma, infectious diseases, cholangiohepatitis, and organophosphate and other drug intoxication. The clinical presentation of cats with pancreatitis is nonspecific. Vomiting and signs of abdominal pain, which are the clinical signs most commonly observed in humans and dogs with pancreatitis, are only uncommonly observed in cats with pancreatitis. Routine laboratory findings are also nonspecific. Abdominal ultrasonography is a valuable diagnostic tool in feline patients with pancreatitis. Serum activities of lipase and amylase are rarely increased in cats with pancreatitis; however, these cats often have elevated serum fTLI concentrations. The goals of management are removal of the inciting cause, provision of supportive and symptomatic therapy, and careful monitoring for and aggressive treatment of systemic complications. Exocrine pancreatic insufficiency is a syndrome caused by insufficient synthesis of pancreatic digestive enzymes by the exocrine portion of the pancrease. The clinical signs most commonly reported are weight loss, loose and voluminous stools, and greasy soiling of the hair coat. Serum fTLI is subnormal in affected cats. Treatment of cats with EPI consists of enzyme supplementation with powdered pancreatic extracts or raw beef pancreas. Many cats with EPI have concurrent small intestinal disease. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require parenteral cobalamin supplementation. Pancreatic adenocarcinoma is the most common neoplastic condition of the exocrine pancreas in the cat. At the time of diagnosis, the tumor has already metastasized in most cases, and the prognosis is poor. Pancreatic pseudocyst, pancreatic abscess, pancreatic parasites, pancreatic bladder, and nodular hyperplasia are other exocrine pancreatic disorders, that are less commonly seen in cats.     

Development and analytical validation of a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity in serum

Pancreatitis is recognized as an important cause for morbidity and mortality in cats, but diagnosis remains difficult in many cases. As a first step in trying to identify a better diagnostic tool for feline pancreatitis the objective of this project was to develop and analytically validate a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity (fPLI). Feline pancreatic lipase (fPL) was purified from pancreatic tissue and antiserum against fPL was raised in rabbits. Tracer was produced by iodination of fPL using the chloramine T method. A radioimmunoassay was established and analytically validated by determination of sensitivity, dilutional parallelism, spiking recovery, intra-assay variability, and interassay variability. A control range for fPLI in cat serum was established from 30 healthy cats using the central 95th percentile. The sensitivity of the assay was 1.2 microg/L. Observed to expected ratios for serial dilutions ranged from 98.8% to 164.3% for 3 different serum samples. Observed to expected ratios for spiking recovery ranged from 76.9% to 147.6% for 3 different serum samples. Coefficients of variation for intra- and interassay variability for 4 different serum samples were 10.1%, 4.5%, 2.2%, and 3.9% and 24.4%, 15.8%, 16.6%, and 21.3%, respectively. A reference range for fPLI was established as 1.2 to 3.8 microg/L. We conclude that the assay described is sensitive, accurate, and precise with limited linearity in the lower and limited reproducibility in the lower and higher end of the working range. Further studies to evaluate the clinical usefulness of this assay are needed and in progress.     

Assessing the severity of canine pancreatitis

The objective of this study was to determine whether laboratory testing currently available is able to provide prognostic information in canine pancreatitis. A prospective study of dogs with naturally occurring pancreatitis was undertaken. Twenty-two cases with histologically confirmed pancreatic inflammation were included in the study. Each dog had routine haematology parameters, serum biochemistry (including lipase and amylase), serum trypsin-like immunoreactivity and trypsinogen activation peptides (TAP) in urine and plasma measured. Twelve of the dogs were classified as having severe disease. These dogs had statistically significant increases in urinary TAP-creatinine ratio (UTCR) measurement, serum lipase, serum phosphate and serum creatinine concentrations. Additionally dogs with severe pancreatitis had significantly decreased urine specific gravity levels. The most sensitive and specific test to assess the severity of pancreatitis was the measurement of UTCR.     

FEASIBILITY OF ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN HEALTHY CATS

Cats are predisposed to diseases of the biliary tract and the exocrine pancreas and these can be challenging to diagnose. In humans and dogs > 10 kg, endoscopic retrograde cholangiopancreatography (ERCP) has been successfully used to diagnose some of these disorders. The purpose of our study was to determine whether ERCP would also be feasible in cats using a pediatric duodenoscope. Four purpose‐bred, clinically healthy, castrated domestic shorthair cats participated in two studies. Study 1 compared standard white light endoscopy with chromoendoscopy for localizing the major duodenal papilla. In Study 2 ERCP was performed. Repeated clinical examinations and measurements of serum feline pancreatic lipase immunoreactivity (fPLI) were performed before and up to 18 hours after interventions on all cats. Chromoendoscopy was subjectively judged to be superior for localizing the major papilla. Insertion of the ERCP catheter was best accomplished when cats were in dorsal recumbency. Complete ERCP was successful in two cats. In the other cats, either retrograde cholangiography or pancreatography was possible. Serum fPLI concentrations increased temporarily in two cats during Study 2 when measured immediately, 2, 4, and 18 h after ERCP. Peak fPLI concentrations were detected either immediately after ERCP or 2 h later. No clinical signs of complications were observed within 18 h after the procedures. Findings indicated that ERCP is technically demanding but feasible in healthy cats. Future studies need to determine whether the temporary increases in serum fPLI concentrations are clinically important and to investigate the utility of ERCP in feline patients.     

Serum values of amylase and pancreatic lipase in healthy mature dogs and dogs with experimental pancreatitis

Serum values of amylase and pancreatic lipase were determined by the iodometric and the turbidimetric methods, respectively, in 44 mature healthy dogs and in 8 dogs with experimentally induced pancreatitis (plus 1 sham-operated control). Serum value of amylase in mature healthy dogs varied from 250 to 1,500 Caraway units/dl and that of pancreatic lipase varied from 0 to 50 IU/L. Maximal serum values of amylase and pancreatic lipase in the dogs with experimentally induced pancreatitis varied from 4,540 to 14,000 Caraway units/dl and 325 to 810 IU/L, respectively. Following pancreatic damage, serum values of amylase and pancreatic lipase increased rapidly in the 8 dogs and ran parallel to each other in 6 of the 8 dogs studied. However, the serum value of amylase returned to within normal range earlier than the serum value of pancreatic lipase in 2 dogs; the reverse was true in 2 other dogs.     

Clinical and pathologic changes in experimentally induced acute pancreatitis in cats

Acute pancreatitis was induced in 6 cats by infusion of oleic acid into the pancreatic duct. Clinical changes included fever, tachycardia, and variable degrees of abdominal pain; vomiting occurred rarely, and diarrhea was not noted. Serum lipase activities were significantly increased through the 4th day after the surgical operation, although amylase activities were significantly decreased during most of the acute phase. Serum calcium and phosphate concentrations were decreased significantly on the 4th day after surgical operation. Hematologic alterations included normocytic, normochromic, responsive anemias, but changes in WBC values were not statistically significant. Evidence of exocrine pancreatic insufficiency after induction of acute pancreatitis was not demonstrated in any cats during the study. The results of this study indicate that increases in serum lipase activity are the most consistent and earliest indicators of acute pancreatitis in cats, but that more sensitive methods of laboratory evaluation should be sought.     

Feline pancreatic ducts are consistently identified on CT and more likely to be dilated in the body of pancreas in cats with elevated feline pancreatic lipase immunoreactivity

Feline pancreatitis is a challenge to diagnose and no previously published study has described the CT characteristics of the pancreatic duct (PD) in cats. The current prospective analytical study was performed to identify and describe the CT characteristics of the PD in normal cats and to compare that to those cats with an elevated feline pancreatic lipase immunoreactivity (fPLI). Contrast‐enhanced CT was performed in 16 normal cats and 13 cats with an elevated fPLI. Two ACVR‐certified radiologists blinded to the fPLI status assessed whether or not the PD could be identified, contrast phase during which the PD was most conspicuous, and PD shape in the body, right and left lobes. A second‐year radiology resident blinded to the fPLI status measured maximum PD diameter and PD:parenchyma. The PD was identified in 84 of 87 pancreatic segments, which was most conspicuous in the portal phase in 28 of 29 cats. The PD shape was tubular (48/84), tapered (34/84), or beaded (2/84) with no significant difference (P = 1.0 to .1615) between groups. Mean maximal PD diameters of normal cats were 1.5‐1.7 mm, which was significantly larger in the body of the pancreas in cats with an elevated fPLI (2.4 mm, P = .0313). Mean PD:parenchyma was not significantly different between groups (P = .2001 to .949). In conclusion, the feline PD can be consistently identified on CT, for which the portal phase is preferred. Cats with an elevated fPLI are more likely to exhibit dilation of the PD in the body of the pancreas on CT.     

Pancreatitis in cats: diagnosis and management of a challenging disease

Feline pancreatitis can be a very difficult disease to diagnose and often requires a combination of clinical suspicion, appropriate physical examination findings, elevations in serum feline pancreatic lipase immunoreactivity, and changes on abdominal ultrasonography consistent with pancreatic disease. The diagnostic difficulties encountered are related to a lack of specific and readily attributable clinical signs in cats. The sensitivity and specificity of the diagnosis of pancreatitis are highest when a combination of tests is utilized; but even when such tests are employed, the diagnosis is still problematic, especially in cats with chronic pancreatitis. Therapy is symptomatic and focuses on maintaining fluid volume, controlling pain and vomiting, preventing infection, and adjusting to changes in the cat's condition as they occur.     

Measurement of feline lipase activity using a dry-chemistry assay with a triolein substrate and comparison with pancreas-specific lipase (Spec fPLTM)

Pancreatic lipase immunoreactivity (Spec fPL) is currently considered to be the most accurate blood test for the diagnosis of feline pancreatitis. In this study, we measured lipase activity in cats using a newer catalytic lipase assay of dry-chemistry system (FDC-v-LIP) to determine the reference range and compared the results with those for Spec fPL. Based on the results of healthy cats, the reference range of FDC-v-LIP was determined to be less than 30 U/l. FDC-v-lip did not show a strong correlation with Spec fPL in cats with various diseases, which resulted in the low sensitivity and positive predictive value. However, the relatively high (>90%) specificity and negative predictive value indicated that FDC-v-LIP could be a useful patient-side screening test for the exclusion of feline pancreatitis.     

Diagnostic approaches to acute pancreatitis

Acute pancreatitis is a challenging medical condition, with the potential for high mortality and comorbidity in companion animal patients. The anatomic position and relationships of the pancreas make direct observation of pancreatic pathology difficult, so the diagnosis of pancreatic disease is typically based on the measurement of biochemical markers in serum and imaging studies of the abdomen. The digestive enzymes typically used in the diagnosis of pancreatitis, amylase and lipase, have poor sensitivity and specificity. Recently, pancreas specific lipases have been purified from dogs and cats, leading to the availability of specific immunoassays for these proteins that show great promise in the diagnosis of acute pancreatitis. After the diagnosis of acute pancreatitis is established, there is a need to assess the severity of the disease to give an accurate prognosis for the patient. This article will review currently available methods used to diagnose acute pancreatitis and the ability of these methods to assess accurately the severity of the disease.     

Serum amylase and lipase activities in the diagnosis of pancreatitis in dogs

To determine the usefulness of information provided by measurement of serum amylase activity in the evaluation of dogs for pancreatitis, the relationship of amylase activity to lipase activity in 713 paired serum samples was investigated by statistical analysis. Little change in mean amylase concentration was found until lipase values exceeded 800 U/L. The ranges of amylase activity (mean +/- 2 SD) were essentially the same for dogs with no pancreatitis (0 to 100 U of lipase activity/L) as for dogs with a high probability for the disease (700 to 799 U of lipase activity/L), 0 to 4,029 U/L and 857 to 4,869 U/L, respectively. Pathologic findings from biopsy and necropsy reports from 92 dogs for which serum lipase determinations were done indicated that serum lipase increased not only with pancreatitis, but also with other medical problems, such as renal and hepatic disease. It was concluded that determination of serum amylase activity without knowledge of serum lipase activity was of little value to diagnose pancreatitis. High amylase activity was not specific for pancreatitis and low amylase activity could not rule out the disease. The results of this study also showed that low serum lipase values almost always eliminated the possibility of pancreatitis and that high values were often, but not always, diagnostic for pancreatitis.     

Comparison of the sensitivity of different diagnostic tests for pancreatitis in cats

The objective of this study was to compare the sensitivity of different diagnostic tests for pancreatitis in cats. Twenty-one cats with confirmed pancreatitis were evaluated at the Small Animal Clinic of the School of Veterinary Medicine in Hannover, Germany, between September 1997 and January 1999. Clinical signs of affected cats were nonspecific, with 95% of the cats showing anorexia and 86% lethargy. Also, hematologic and biochemical abnormalities of affected cats were nonspecific. Serum feline trypsin-like immunoreactivity (fTLI) in these 21 cats with pancreatitis was 127.5 +/- 109.5 microg/L (mean +/- SD; range, 24-500 microg/L). Fourteen of the 21 cats with pancreatitis had complicating conditions. Their serum fTLI was 153.9 +/- 124.3 microg/L (mean +/- SD; range, 29 500 microg/L). In this study, abdominal ultrasound showed a sensitivity for pancreatitis of 24%, and abdominal computed tomography had a sensitivity of 20%. Serum fTLI had a sensitivity between 86% when a cut-off value of 49 microg/L was used (upper limit of the control range) and 33% when a cut-off value of 100 microg/L was used. We conclude that in this group of cats with pancreatitis, measurement of serum fTLI was the most sensitive diagnostic test of those evaluated. Abdominal ultrasound, however, may be a valuable diagnostic tool in some cats with pancreatitis.     

Sensitivity and specificity of canine serum total amylase and isoamylase activity determinations.

Serum isoamylases were determined prospectively in dogs with pancreatic and extrapancreatic diseases. Mean serum isoamylase determinations were significantly different (p less than 0.05) between normal dogs and dogs with pancreatitis and exocrine pancreatic insufficiency. The sensitivity of serum isoamylase determination exceeded that of total amylase activity for the diagnosis of pancreatitis. Serum isoamylase determinations were less influenced by extrapancreatic diseases compared to total amylase activity when used in the diagnosis of pancreatic disease. Neither serum isoamylase determination nor total amylase activity had adequate sensitivity to support their use in the diagnosis of exocrine pancreatic insufficiency. There were significant (p less than 0.05) linear correlations between isoamylase determinations, total amylase activity, and trypsin-like immunoreactivity concentration.     

Serum Phospholipase A2 in Canine Acute Pancreatitis

During 3 years 28 cases of acute pancreatitis were diagnosed in dogs. In 26 of these dogs, the disease was fatal. The most frequent symptoms were vomiting, anorexia and lethargy. Two thirds showed tenderness upon abdominal palpation. Ascites was found in 3 cases. Of the blood, parameters, serum amylase level was elevated in 86 % and lipase in 89 % of the cases. Sixteen dogs were uremic and half of the dogs were hyperglycemic. Two thirds of the dogs had leukocytosis. Using stepwise multiple regression the best blood parameters explaining acute pancreatitis were leukocytes together with lipase and glucose.In an attempt to find a more specific serum test for dogs to diagnose acute pancreatitis serum phospholipase A2 (PLA₂) activity was measured. In sixteen out of the 28 dogs with acute pancreatitis, serum PLA₂ activity was increased. The ascites fluids were rich in PLA2. Serum PLA₂ is more often increased in the severe necrotizing pancreatitis (80 %) than in the milder forms of acute pancreatitis (44 %). All dogs with increased serum PLA₂ had also increased serum amylase and lipase activities. The dogs with an increased serum PLA₂ and dogs with ascites had fat necrosis in the vicinity of the pancreas. Experimental pancreatitis was induced in 4 dogs by injecting Na-taurocholate and trypsin into the pancreas. In these cases, very high PLA₂ activities in the serum and ascites fluids were detected, but none seemed to be present in the urine samples.Key words: dog, acute pancreatitis, phospholipase A2     

Effects of dexamethasone on pancreatic tissue and on serum amylase and lipase activities in dogs

The effects of dexamethasone on the pancreas and on pancreatic amylase and lipase activities were determined in clinically normal dogs and in dogs with neurologic disease. Dexamethasone increased serum lipase activity without any histologic damage to the pancreas in either group of dogs. It decreased serum amylase activity in the normal dogs and had a variable effect in dogs with neurologic disease, with or without confirmed pancreatitis. It was suggested that high serum lipase activity in dexamethasone-treated dogs may not be attributable to pancreatitis and that the reasons are still unknown. It was concluded that high serum lipase activity is an unreliable basis for diagnosis of pancreatitis in dogs treated with dexamethasone. The data allowed no conclusion about an additive effect of dexamethasone and neurologic disease causing pancreatitis.     

Evaluation of 1,2-O-dilauryl-rac-glycero glutaric acid-(6′-methylresorufin) ester (DGGR) and 1,2-diglyceride lipase assays in dogs with naturally occurring hypercortisolism

1,2-O-dilauryl-rac-glycero glutaric acid-(6′-methylresorufin) ester (DGGR) lipase activity has been proposed as a faster and less expensive test used in the diagnosis of acute pancreatitis (AP) compared to canine pancreatic lipase immunoreactivity (cPLI), which is considered the most sensitive and specific serum test available for dogs. Elevations in lipase activity have been observed in dogs with naturally occurring hypercortisolism (HC) and in those treated with exogenous steroids, which complicates the diagnosis of AP in dogs with HC. We compared lipase activity measured by DGGR and 1,2-diglyceride (1,2-DiG) assays in 22 dogs with HC, 22 with AP, and 22 healthy dogs. The dogs with HC had no clinical signs or ultrasonographic findings consistent with AP. DGGR lipase activity was elevated in 64% and 73% of the dogs with HC and AP, respectively, and in 18% of healthy dogs. 1,2-DiG lipase activity was high in 23% and 36% of the dogs with HC and AP, respectively, and in 5% of the healthy dogs. Both DGGR and 1,2-DiG lipase activities were significantly different between the healthy dogs and the other 2 groups, whereas no differences were detected between the dogs with HC and those with AP. Our results support a lack of specificity for both DGGR and 1,2-DiG lipase activity assays in aiding the diagnosis of AP in dogs with HC.