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Serial serum pancreatic lipase immunoreactivity concentrations in a dog with histologically confirmed pancreatitis
A 15-year-old 15.1-lb (6.9-kg) castrated male Lhasa Apso was presented to the Veterinary Medical Teaching Hospital at Texas A&M University for evaluation of chronic vomiting of several months' duration.
A 15-year-old 15.1-lb (6.9-kg) castrated male Lhasa Apso was presented to the Veterinary Medical Teaching Hospital at Texas A&M University for evaluation of chronic vomiting of several months' duration. The owner reported that initially the dog had been vomiting twice a week, but that two weeks before presentation the vomiting had increased to daily episodes. Initially, the vomitus had been white and foamy, but as the frequency of the vomiting had increased, the vomitus had changed to a bile-tinged fluid.
INITIAL PRESENTATION AND DIAGNOSTIC TESTS
At presentation, the dog's vital signs were normal (temperature = 100.9 F [38 C]; pulse rate = 100 beats/min with a strong pulse; respiratory rate = 36 breaths/min). On physical examination, the dog was alert and responsive with no pain noted on abdominal palpation. A IV/VI systolic murmur was auscultated and was loudest at the left apex. The results of a cranial nerve examination were normal except for bilaterally absent menace responses that were attributed to mature cataracts identified during a comprehensive ophthalmologic examination. The results of a complete blood count, serum chemistry profile, and urinalysis were normal except for isosthenuria (urine specific gravity = 1.015).
Further diagnostic tests included radiography, abdominal ultrasonography, and gastroscopy.
A thoracic radiographic examination revealed mild enlargement of the left atrium, consistent with mitral insufficiency, but normal lung fields and pulmonary vessels. The results of an abdominal radiographic examination were unremarkable except for bilaterally small kidneys.
An abdominal ultrasonographic examination revealed a focally thickened pyloric antrum, but no obstruction was detected. Decreased corticomedullary differentiation of both kidneys was also noted. All other abdominal structures appeared to be normal. The pancreas was identified and was normal in size and echogenicity.
To further explore the cause of the vomiting, the dog was anesthetized, intravenous fluids were administered, and gastroscopy was performed, which revealed a large polyp-like growth in the pyloric antrum. This mass precluded the advancement of the endoscope into the duodenum. Multiple endoscopic biopsy samples were taken from the stomach wall, mass, and mucosa surrounding the pylorus. During the procedure, the dog had a brief period of hypotension but responded well to a continuous-rate infusion of dobutamine. The dog recovered well from anesthesia. Pending histologic examination results, the dog was discharged with no medications.
Histologic examination of the gastric mucosa and the associated pyloric growth revealed mild, diffuse lymphocytic-plasmacytic gastritis.
READMITTANCE AND ADDITIONAL DIAGNOSTIC TESTS
The owner reported that dog's vomiting episodes had increased in frequency after several days at home, so the dog was readmitted for an exploratory laparotomy. At admittance, the patient appeared to have no historical or physical signs of abdominal pain. The results of the preoperative blood work (complete blood count, serum chemistry profile) were normal.
During surgery, a distinct nodular mass was identified within the pylorus. The pancreas appeared nodular but otherwise normal. A Billroth I procedure was performed to resect the pyloric mass. Despite gentle dissection, the pancreas was manipulated while performing the gastric and duodenal anastomosis.
The dog had no intraoperative complications and recovered well after surgery. Fluid therapy was continued overnight along with scheduled doses of hydromorphone for pain. Despite receiving nothing by mouth, the patient vomited large volumes of a light-brown fluid throughout the night.
Histopathologic examination results confirmed the pyloric mass to be a polyp associated with mild lymphocytic-plasmacytic gastritis.
Repeat abdominal ultrasonography
After the exploratory laparotomy, the dog continued to vomit at least six times a day. Four days after surgery, the dog also developed signs of acute abdominal pain. However, the dog's vital parameters remained normal (temperature = 101.3 F [38.5 C]; pulse rate = 120 beats/min with a strong pulse; respiratory rate = 36 breaths/min). A repeat abdominal ultrasonographic examination revealed a fluid-filled hypomotile stomach, an enlarged and hypoechoic pancreas, and hyperechoic peripancreatic fat (Figure 1). The enlarged hypoechoic pancreas and the hyperechoic peripancreatic fat were consistent with pancreatitis.1,2
Figure 1. An abdominal ultrasonogram of the dog's pancreas four days after the Billroth I procedure. The pancreas is enlarged and hypoechoic, with surrounding hyperechoic fat.
Cytology and serum cPLI assay
Aspirates of the pancreatic region were obtained, and a cytologic examination revealed marked suppurative inflammation with no etiologic agents identified. A blood sample for a serum canine pancreatic lipase immunoreactivity (cPLI) assay was collected.3 Serial serum chemistry profiles and complete blood counts revealed a rising serum alkaline phosphatase (ALP) activity and marked mature neutrophilia but no other abnormalities. The serum cPLI concentration was 388 µg/L (reference range = 2 to 102 µg/L; concentrations greater than 200 µg/L are considered diagnostic for pancreatic inflammation).4
The day after the ultrasonographic examination, the dog was anesthetized again for a gastroduodenoscopy to assess gastric emptying and a laparotomy to place a jejunostomy tube for nutritional support. Gastroscopy revealed fluid in the stomach but a normal-appearing gastric mucosa. The pyloric antrum appeared swollen, but an 8.5-mm endoscope was easily passed into the duodenum, indicating that the pyloric obstruction had been successfully relieved. The entire pancreas appeared swollen and firm (Figure 2), and multiple adhesions were noted between the small intestine and the greater omentum. The previous Billroth I surgery site appeared to be healing appropriately. An 8-F jejunostomy tube was placed in the proximal jejunum, and the site was sutured to the body wall.
Figure 2. The pancreas during a laparotomy five days after the Billroth I procedure. Note that the body and right limb of the pancreas appear red and swollen.
To calculate the resting energy requirement (RER), we used the formula: RER (kcal/day) = 70 (BWkg)0.75 . We initially fed the dog 25% of its RER and planned to increase the amount gradually over the next three or four days until the RER was met. A constant-rate infusion of liquid elemental nutrition—a mixture of Vivonex T.E.N. (Novartis Medical Nutrition), 8.5% Aminosyn II (Abbott Laboratories) solution, B vitamins, and water—was administered. We administered crystalloid fluids supplemented with potassium chloride to maintain venous access and to meet maintenance fluid requirements until enteral feeding reached the RER.
CONTINUED CARE AND MONITORING
The dog continued to vomit several times a day, despite receiving ondansetron (0.5 mg/kg intravenously b.i.d.), and also developed profound diarrhea. To allow the dog's gastrointestinal tract more time to adjust, we did not increase the enteral nutrition amount to the RER. We instituted peripheral partial parenteral nutrition to help meet the dog's caloric requirements.
The diarrhea resolved by Day 8, but the vomiting persisted. The dog showed persistent restlessness and aggressiveness, especially when we tried to pick it up, which was interpreted as evidence of abdominal pain. Icterus of the sclera and pinna developed along with marked increases in the total serum bilirubin concentration (5.1 mg/dl, reference range = 0 to 0.8 mg/dl) and serum ALP activity (2,039 U/L, reference range = 24 to 147 U/L) and a decrease in the serum albumin concentration (1.6 g/dl, reference range = 2.4 to 3.6 g/dl). However, the patient's vital parameters remained normal. A repeat abdominal ultrasonographic examination revealed no major changes in the echogenicity of the pancreas, but the gallbladder was markedly distended, and the common bile duct (5.5-mm diameter) and duodenal walls were thickened (6 to 7 mm). Repeat serum cPLI concentration results were 416 µg/L, indicating ongoing pancreatic inflammation.
After several days of continued aggressive supportive care, including administration of nutritional support, antiemetics (ondansetron), analgesics (fentanyl constant-rate infusion at 3 µg/kg/hr), gastrointestinal protectants (ranitidine 2 mg/kg intravenously t.i.d.), and antibiotics (ampicillin 22 mg/kg intravenously t.i.d.), the dog finally began to improve; the vomiting and abdominal pain resolved. The results of a repeat abdominal ultrasonographic examination showed normalization of the size and appearance of the pancreas. And a repeat serum cPLI assay revealed a concentration of 226 µg/L, which is suggestive of pancreatic inflammation but compared with previous results was greatly decreased, paralleling the overall improvement in clinical signs and abdominal ultrasonographic findings.
Water was slowly reintroduced orally, and after several days, the patient began to drink readily with no vomiting or signs of abdominal pain. The dog was fed a canned low-fat diet (Royal Canin Veterinary Diet canine Low Fat LF) and boiled chicken and rice in small amounts several times a day with no vomiting or signs of abdominal discomfort. The serum cPLI concentration was 118 µg/L, which coincided with the resolution of the dog's clinical signs.
Unfortunately, the day the dog was to be discharged, it developed an acute onset of right-sided hemiparesis, decreased facial sensation, and ventral strabismus, most consistent with an intracranial embolic or ischemic event. The owner elected to have the dog euthanized. Necropsy revealed a pancreas that was white, firm, nodular, and thickened and had lobes shortened to about half of their normal size. A histopathologic evaluation of the pancreas revealed severe chronic interlobular fibrosis (multifocal) with mild interstitial inflammation. The intestinal lumen of the proximal duodenum was patent but had a restricted diameter because of the fibrosis. On cross section of the brain, an area of focal hemorrhagic necrosis was noted, suggestive of embolic cerebral necrosis.
Pancreatitis is one of the most challenging diseases to diagnose in veterinary medicine (see "Is it pancreatitis?" in this issue). This may be due, in part, to the vague clinical signs of pancreatitis; the wide variation of disease severity, ranging from subclinical to severe disease; or the lack of diagnostic tests that are both sensitive and specific for pancreatitis.1 For example, abdominal radiography, complete blood counts, serum chemistry profiles, and urinalyses only reveal nonspecific changes and cannot be used to determine a definitive diagnosis.1
Serum amylase and lipase activities have traditionally been used to diagnose pancreatitis in dogs. However, it has been suggested that about 50% of dogs with pancreatic inflammation have normal serum amylase and lipase activities and that about 50% of dogs with elevated activities of one or both of these enzymes do not have pancreatitis.5 This lack of specificity is due to the fact that the synthesis and secretion of both amylase and lipase is not limited to the exocrine pancreas. Thus, false increases in serum lipase activity have been described in dogs with hepatic, renal, or neoplastic diseases in the absence of pancreatic inflammation.6,7 So measuring serum amylase and lipase activities to diagnose acute pancreatitis is only useful when the measuring can occur in-house and only if the diagnosis is later solidified with more specific diagnostic tests.
Other minimally invasive tests that have been used to diagnose pancreatitis include assays for serum trypsin-like immunoreactivity (TLI) concentrations; serum, plasma, or urine trypsinogen activation peptide (TAP) concentrations; serum alpha-1 proteinase inhibitor-trypsin complex concentrations; or serum alpha-macroglobulin concentrations. However, none of these tests have been shown to be both sensitive and specific for pancreatitis in dogs.4,8,9 Serum TLI and TAP concentrations peak shortly after initiation of the disease and decline rapidly thereafter.10 So TLI or TAP concentrations may be normal by the time the patient is presented to a veterinary clinic.10
When stringent diagnostic criteria are applied, abdominal ultrasonography is highly specific for identifying pancreatitis and can be a valuable tool for diagnosing canine pancreatitis.1 However, the sensitivity of abdominal ultrasonography for pancreatitis is low. In a recent retrospective study of 34 dogs with pancreatitis, only 23 dogs (68%) had ultrasonographic examination findings suggestive of pancreatitis.1 Also, the use of abdominal ultrasonography requires special equipment and a high level of technical expertise. The reported 68% sensitivity was found when experienced ultrasonographers conducted the ultrasonographic examinations. To diagnose pancreatitis, stringent criteria must be met, and the presence of an enlarged pancreas or peripancreatic effusion is not sufficient for a diagnosis.11 In cats, computed tomography has been shown to be inferior to ultrasonographic examinations in diagnosing pancreatitis, and in dogs, only preliminary data are available.12,13 Furthermore, computed tomography's cost, anesthetic risks, and lack of availability preclude its usefulness in clinical practice.
Assays for measuring PLI in dogs have recently been developed and validated.14,15 A cPLI concentration reference range of 2.2 to 102 µg/L was established in 74 healthy dogs, and a serum cPLI concentration of 200 µg/L has been suggested as a cut-off value for diagnosing pancreatic inflammation.16 This report details the clinical course of a dog with presumptive pancreatitis, based on clinical signs and ultrasonographic changes, in which serum cPLI concentrations paralleled the disease's clinical progression. In this case, we were able to compare the clinical, surgical, and abdominal ultrasonographic findings and serum cPLI concentrations in a dog with presumptive pancreatitis. The serum cPLI results supported the diagnosis of pancreatitis and coincided with the clinical signs, the visual assessment of the pancreas during surgery, and the abdominal ultrasonographic findings. Serum concentrations of cPLI were higher when the dog's clinical signs were severe and normalized as the clinical signs resolved.
The serum cPLI concentration appears promising for monitoring the progression of pancreatitis in dogs. However, more clinical data as well as clinical experience with the assay are needed to conclusively determine the clinical usefulness of this assay.
Editors' note: Dr. Steiner is a paid consultant for Idexx Laboratories and is director of the Gastrointestinal Laboratory at Texas A&M University College of Veterinary Medicine.
Brandy Porterpan, DVM
Debra L. Zoran, DVM, MS, PhD, DACVIM
Jörg M. Steiner, med.vet., dr.med.vet., PhD, DACVIM, DECVIM-CA
Department of Small Animal Clinical Sciences
College of Veterinary Medicine and Biomedical Sciences
Texas A&M University
College Station, TX 77843
1. Hess RS, Saunders HM, Van Winkle TJ, et al. Clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in dogs with fatal acute pancreatitis: 70 cases (1986-1995). J Am Vet Med Assoc 1998;213:665-670.
2. Saunders HM. Ultrasonography of the pancreas. Probl Vet Med 1991;3:583-603.
3. Steiner JM, Teague SR, Williams DA. Development and analytic validation of an enzyme-linked immunosorbent assay for the measurement of canine pancreatic lipase immunoreactivity in serum. Can J Vet Res 2003;67:175-182.
4. Steiner JM, Broussard J, Mansfield CS, et al. Serum canine pancreatic lipase immunoreactivity (cPLI) concentrations in dogs with spontaneous pancreatitis (abst). J Vet Intern Med 2001;15:274.
5. Williams DA, Steiner JM. Canine pancreatic disease. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 6th ed. Philadelphia, Pa: WB Saunders Co, 2005;1482-1488.
6. Strombeck DR, Farver T, Kaneko JJ. Serum amylase and lipase activities in the diagnosis of pancreatitis in dogs. Am J Vet Res 1981;42:1966-1970.
7. Polzin DJ, Osborne CA, Stevens JB, et al. Serum amylase and lipase activities in dogs with chronic primary renal failure. Am J Vet Res 1983;44:404-410.
8. Mansfield CS, Jones BR. Plasma and urinary trypsinogen activation peptide in healthy dogs, dogs with pancreatitis and dogs with other systemic diseases. Aust Vet J 2000;78:416-422.
9. Ruaux CG, Atwell RB. Levels of total alphamacroglobulin and trypsin-like immunoreactivity are poor indicators of clinical severity in spontaneous canine acute pancreatitis. Res Vet Sci 1999;67:83-87.
10. Williams DA, Melgarejo T, Henderson J, et al. Serum trypsin-like immunoreactivity (TLI), trypsinogen activation peptides (TAP), amylase and lipase in canine experimental pancreatitis (abst). J Vet Intern Med 1996;10:159.
11. Lamb CR. Pancreatic edema in dogs with hypoalbuminemia or portal hypertension. J Vet Intern Med 1999;13:498-500.
12. Gerhardt A, Steiner JM, Williams DA, et al. Comparison of the sensitivity of different diagnostic tests for pancreatitis in cats. J Vet Intern Med 2001;15:329-333.
13. Forman MA, Marks SL, De Cock HE, et al. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis. J Vet Intern Med 2004;18:807-815.
14. Steiner JM, Teague SR, Williams DA. Development and analytic validation of an enzyme-linked immunosorbent assay for the measurement of canine pancreatic lipase immunoreactivity in serum. Can J Vet Res 2003;67:175-182.
15. Steiner JM, Williams DA. Development and validation of a radioimmunoassay for the measurement of canine pancreatic lipase immunoreactivity in serum of dogs. Am J Vet Res 2003;64:1237-1241.
16. Steiner JM. Diagnosis of pancreatitis. Vet Clin North Am Small Anim Pract 2003;33:1181-1195.