An Association between Pancreatic and Cholestatic Biliary Disorders in Dogs.

Canine chronic biliary tree disease (CBTD) is a suspected risk factor for pancreatic injury. The aim of this study was to evaluate the frequency and features of pancreatic involvement in canine CBTD, and their relationship with hyperlipemia and its severity. CBTD was defined as the increase in at least two of ALP, GGT, total bilirubin, cholesterol, and a biliary tree abnormal abdominal ultrasound (graded mild to severe). Pancreatic ultrasound appearance was recorded and classified as acute/chronic. Dogs were divided into a PBD group (pancreatic and biliary disease) and BD group (only biliary tree disease). PBD group was subgraded into a "pancreatic injury" and "pancreatitis" group. Eighty-one dogs were retrospectively included: 56 in the PBD group and 25 in the BD group. Of the PBD group, 20 had pancreatitis (15 chronic and 5 dogs acute). US score was mild in 64 dogs and moderate in 17 dogs, and it was not associated with evidence of pancreopathy. Sixty-six dogs had hyperlipemia (mild = 27 dogs; moderate-to-severe = 39 dogs) and no association with pancreopathy was found. Pancreatic injury was more frequent than pancreatitis in CBTD dogs. Although both acute and chronic pancreatic injury may be present, chronic forms were more frequent. Pancreatic injury should be considered in CBTD patients due its possible clinical significance.

Utility of 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin)-ester-lipase for monitoring dogs with chronic pancreatitis.

BACKGROUND: The utility of 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin)-ester-(DGGR)-lipase activity (DLA) in monitoring clinical progression of chronic pancreatitis (CP) in dogs is unknown. OBJECTIVE: To examine the association of DLA with clinical signs of CP, as assessed by a CP clinical severity score (CPCSS). ANIMALS: Twenty-four dogs. METHODS: This is a retrospective study. Chronic pancreatitis was diagnosed based on clinical signs and DLA > 250 U/L and monitored using CPCSS and DLA. RESULTS: The study included 134 visits (median, 10 visits/dog; range, 2-11). Mild-moderate (CPCSS, 0-3) and severe (CPCSS, ≥4) disease were documented in 94 (70%) and 40 (30%) visits, respectively. In emergency visits (n = 44; 33%) CPCSS (median, 5; range, 0-15) and DLA (median, 534 U/L; range, 63-7133) were higher (P < .001 and P = .003, respectively) than in scheduled ones (n = 90; 67%; median, 1; range, 0-6 and median, 384 U/L; range, 49-3747, respectively). DGGR-lipase activity was associated (P = .009) with the CPCSS, with a lower activity documented in mild-moderate CPCSS (median 391 U/L; range, 49-3747), compared to severe score (median, 558 U/L; range, 63-7133). DGGR-lipase activity was significantly, but weakly, correlated with CPSS (r = 0.233, P = .007). DGGR-lipase activity inefficiently discriminated mild-moderate vs severe CP (area under the receiver operator characteristics curve, 0.64; 95% confidence interval, 0.53-0.75; P = .012), with DLA cutoff of 428 U/L corresponding to sensitivity of 65% and specificity of 63%. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased DLA is associated with emergency revisits in dogs with CP, possibly reflecting acute flare-ups. DGGR-lipase activity was associated with the CPCSS over the follow-ups but could not differentiate disease severity.

Progression of lipase activity and pancreatic lipase immunoreactivity in dogs hospitalized for acute pancreatitis and correlation with clinical features.

BACKGROUND: Lipase activity and pancreatic lipase immunoreactivity (PLI) have not been compared in dogs hospitalized for acute pancreatitis (AP). OBJECTIVES: To describe the progression of lipase activity and PLI, and correlations with clinicopathologic features in dogs with AP. ANIMALS: Thirty-nine dogs with AP based on clinical signs and lipase activity >350 U/L (reference interval [RI], 24-108 U/L). METHODS: Retrospective study. Lipase activity (LIPC Roche), PLI (SpecPL), and clinical signs were recorded daily. Admission (d1) data (clinical, laboratory, and ultrasound [US] findings), and clinical signs during hospitalization (d2-d3) were assessed for correlation with lipases. RESULTS: Median (range) duration of clinical signs before presentation was 2 days (1-7 days). Median (range) lipase activity and PLI at d1 were 1070 U/L (range, 357-1500 U/L) and 1111 µg/L (range, 292-1500 µg/L). Strong correlation between assays at d1 (rs 0.96; P < .0001; n = 39), remained equally strong on d2 (rs 0.964; P < .0001; n = 39), and d3 (rs 0.966; P < .0001; n = 22). On d2, lipase activity and PLI were within RI in 13/39 (33%) and 18/39 (46%) of cases. Lipase activities were minimally increased (median, 124 U/L) in 5 dogs with d2 PLI <200 µg/L. On d3, 4 more dogs had normal lipase activity and PLI, and the nature and magnitude of change were always the same for both assays. Clinical signs were not associated with lipases. Only a hyperechoic mesentery, but not an US diagnosis of AP, correlated significantly with lipase activity and PLI. CONCLUSIONS AND CLINICAL IMPORTANCE: Lipase decreases rapidly to near or within RI within 2 days of treatment in the majority of dogs with AP. Both lipase assays yielded virtually identical results. Mesenteric echogenicity may be an early marker of AP in dogs.

Retrospective analysis of association between hepatopathy and serum DGGR lipase activity in dogs: a pilot study.

1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assays are used to measure lipase activity in the diagnosis of pancreatitis. The effect of hepatic lipases released from damaged hepatocytes on serum DGGR lipase activity has not been reported, to our knowledge. We identified dogs with histologically confirmed liver lesions and concurrent unremarkable pancreatic histology, and dogs with no histologic evidence of hepatic or pancreatic disease. Dogs with relevant comorbidities were excluded. The hepatopathy group (n = 7) included 4 dogs with inflammatory hepatopathies, 2 with hepatic neoplasia, and 1 with unspecified (non-inflammatory, non-neoplastic) hepatopathy. The control group (n = 5) included one dog each with enteritis, subcutaneous hemangiosarcoma, hydrocephalus, myelomalacia, and tetanus. A Mann-Whitney U test compared selected biochemical parameters including serum DGGR lipase, alkaline phosphatase, alanine aminotransferase, and amylase activities, with statistical significance defined as p ≤ 0.05. Data are presented as median and range. Serum DGGR lipase activity (RI: <44 IU/L) was not different between the hepatopathy (52 IU/L; range: 27-85 IU/L) and control (37 IU/L, 25-105 IU/L; p = 0.947) groups. Serum amylase activity (RI: 256-1,610 IU/L) was significantly higher in the hepatopathy group (830 IU/L; 711-1,210 IU/L) than the control group (541 IU/L, 336-695 IU/L; p = 0.028). No association or correlation between serum DGGR lipase activity and hepatic lesions (based on histologic or biochemical findings) was identified, suggesting that clinically relevant changes in serum DGGR lipase activity may not be expected secondary to hepatopathy alone.

Effects of medical history and clinical factors on serum lipase activity and ultrasonographic evidence of pancreatitis: Analysis of 234 dogs.

BACKGROUND: Lipase measurements and ultrasonographic (US) evidence of pancreatitis correlate poorly. OBJECTIVES: Identify explanations for discrepant lipase and pancreatic US results. ANIMALS: Two hundred and thirty-four dogs with gastrointestinal signs. METHODS: A retrospective study was conducted, in which lipase activity and US were performed within 30 hours. Medical history, clinical examination results, lipase activity, and US results were recorded. RESULTS: Lipase and US results were weakly correlated (rs  = .25, P < .001). At both evaluated time cut-offs, median lipase activities were significantly higher with shorter durations of clinical signs before presentation (≤2 days, 334 U/L; >2 days, 118 U/L; P = .03; ≤7 days, 334 U/L; >7 days, 99 U/L; P = .004), but US was not significantly more frequently positive. For both cut-offs (>216/≤216 U/L, >355/≤355 U/L; reference range, 24-108 U/L), median disease duration was significantly shorter (3 vs 4 days) with higher lipases. Previous pancreatitis episodes were significantly associated with an US diagnosis of pancreatitis (P = .04), but median lipase activities were not significantly higher (386 U/L vs 153 U/L; P = .06) in these dogs. Pancreatic US was significantly more often positive when the request contained "suspicion of pancreatitis" (P < .001) or "increased lipase" (P = .01). Only changes in pancreatic morphology, echogenicity, and peripancreatic mesentery were significantly associated with a positive US diagnosis, and also had significantly higher lipase activities. CONCLUSIONS AND CLINICAL IMPORTANCE: Duration of clinical signs before presentation differently affects laboratory and US evidence of pancreatitis. Previous pancreatitis episodes and information given to radiologists influence US results. These findings can be helpful for future studies on pancreatitis in dogs.

Advances in the diagnosis of acute pancreatitis in dogs.

In the last 20 years, the diagnosis of pancreatitis has become more frequent as a result of improved diagnostic modalities such as abdominal ultrasound examination, advanced imaging, and immunoassays for the measurement of pancreatic lipase. Our aim is to provide a state-of-the-art overview of the clinical diagnosis of acute pancreatitis (AP) in dogs with a particular focus on pancreatic lipase assay validation and clinical performance, in addition to advanced imaging modalities. We also discuss the potential indications for cytology and histopathology in dogs with suspected AP.

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.

Increased canine pancreatic lipase immunoreactivity (cPLI) and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase in dogs with evidence of portal hypertension and normal pancreatic histology: a pilot study.

The clinical presentations of both liver disease and pancreatitis are nonspecific and overlapping, which may cause difficulty in diagnosis. In our retrospective pilot study, we assessed whether dogs with evidence of portal hypertension and absence of pancreatitis on pancreatic histology have increases in canine pancreatic lipase immunoreactivity (cPLI) and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase. We included dogs that had been presented between 2008 and 2019 if they had normal pancreatic histology, histologically confirmed hepatopathy, and if canine pancreas-specific lipase (Spec cPL; Idexx) or DGGR lipase had been measured. Only dogs with portal hypertension were included. Six dogs fulfilled the inclusion criteria. Four of 6 and 2 of 6 dogs had Spec cPL and DGGR lipase exceeding the upper reference limit, respectively. From the 4 dogs with increased Spec cPL, 2 had concentrations of 200-400 µg/L and 2 had concentrations ≥ 400 µg/L. Our results suggest that canine portal hypertension might lead to increased Spec cPL and DGGR lipase values in the absence of pancreatitis on histology. Until more evidence in a larger number of dogs with portal hypertension is available, both tests should be interpreted cautiously in the presence of portal hypertension.

Hyperlipasemia in critically ill dogs with and without acute pancreatitis: Prevalence, underlying diseases, predictors, and outcome.

BACKGROUND: Hyperlipasemia is frequent in critically ill people without evidence of acute pancreatitis (AP), and has been associated with increased morbidity and mortality. OBJECTIVE: To evaluate the prevalence of hyperlipasemia at admission and development of hyperlipasemia during hospitalization in critically ill dogs, explore factors associated with hyperlipasemia, and evaluate association with outcome. ANIMALS: Critically ill, client owned dogs (n = 1360), presented on emergency and admitted to the intensive care unit, that had 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase activity measured within 24 hours of admission. METHODS: Retrospective cross-sectional study of clinical and laboratory records. RESULTS: The DGGR lipase activity was increased >3× the upper reference limit at admission in 216/1360 (16%) dogs, of which 70/216 (32%) had a clinical diagnosis of AP. Other primary conditions associated with hyperlipasemia were renal, endocrine, and immune-mediated diseases, and upper airway obstruction. Predictors of hyperlipasemia at admission were prior glucocorticoid administration, vomiting and abdominal pain, increased age, plasma bilirubin and creatinine concentrations, and decreased hematocrit. Of dogs with repeat measurements, 78/345 (23%) had significantly increased lipase during hospitalization, of which 13/78 (17%) had a clinical diagnosis of AP. Other primary conditions associated with in-hospital hyperlipasemia were renal and immune-mediated disorders. Predictors of developing hyperlipasemia during hospitalization were hemodialysis events, increased plasma bilirubin and creatinine concentrations, and decreased hematocrit. Hyperlipasemia both at admission and during hospitalization was associated with longer hospitalization and higher mortality. CONCLUSIONS AND CLINICAL IMPORTANCE: Significant DGGR-hyperlipasemia is frequent in critically ill dogs and associated with a variety of nonpancreatic conditions and negative outcome.

Clinical and Pathological Data of 17 Non-Epithelial Pancreatic Tumors in Cats.

Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical data, histopathology, and immunohistochemistry. Seventeen feline pancreatic tissue samples were investigated histopathologically and immunohistochemically. Selected pancreatic and inflammatory serum parameters, e.g., feline pancreatic lipase immunoreactivity (fPLI), 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase and serum amyloid A (SAA), were recorded, when available. The neoplasms were characterized as round (n = 13) or spindle (n = 4) cell tumors. Round cell tumors included 12 lymphomas and one mast cell tumor in ectopic splenic tissue within the pancreas. Lymphomas were of T-cell (n = 9) or B-cell (n = 3) origin. These cats showed leukocytosis (3/3) and increased fPLI (5/5), DGGR lipase (3/5) and SAA (4/5) values. Spindle cell tumors included two hemangiosarcomas, one pleomorphic sarcoma and one fibrosarcoma. The cat with pleomorphic sarcoma showed increased SAA value. Overall survival time was two weeks to seven months. These are the first descriptions of a pancreatic pleomorphic sarcoma and a mast cell tumor in accessory spleens within feline pancreas. Although rare, pancreatic tumors should be considered in cats presenting with clinical signs and clinical pathology changes of pancreatitis. Only histopathology can certainly distinguish solitary pancreatitis from a neoplasm with inflammation.

Evaluation of SNAP cPL, Spec cPL, VetScan cPL Rapid Test, and Precision PSL Assays for the Diagnosis of Clinical Pancreatitis in Dogs.

BACKGROUND: The sensitivity, specificity, and agreement of 4 diagnostic assays (SNAP canine pancreatic lipase (cPL), specific cPL (Spec cPL), VetScan cPL Rapid Test, and Precision PSL) for pancreatitis in dogs have not been directly compared. HYPOTHESIS/OBJECTIVES: To determine the level of agreement among each of the 4 assays and a clinical suspicion score, level of agreement among the assays, and sensitivity and specificity of each assay in a clinically relevant patient group. ANIMALS: Fifty client-owned dogs with clinical signs of gastrointestinal disease. METHODS: Prospective study. History, physical examination, complete blood count, serum biochemistry, abdominal ultrasound examination, and the 4 diagnostic assays for pancreatitis were performed. Intraclass correlation coefficients (ICC) were used to determine the level of agreement between each assay and a clinical suspicion score determined by a panel of 5 board-certified veterinary internists. RESULTS: The ICC between the clinical suspicion score and the 4 assays were SNAP cPL, 0.61; Spec cPL, 0.68; VetScan cPL Rapid Test, 0.68; and Precision PSL, 0.60. The sensitivities of the assays ranged from 73.9 to 100.0%, whereas the specificities were SNAP cPL, 71.1-77.8%; Spec cPL, 74.1-81.1%; VetScan cPL Rapid Test, 76.9-83.8%; and Precision PSL, 64.0-74.3%. CONCLUSIONS AND CLINICAL IMPORTANCE: A good to excellent level of agreement was demonstrated among the 4 assays. The previously unreported sensitivity and specificity of the VetScan cPL Rapid Test were 73.9-83.3% and 76.9-83.8%, respectively. Results of any of the 4 diagnostic assays alone, in the absence of supporting clinical findings, are insufficient to establish a diagnosis of clinical pancreatitis in dogs.

Development of the anterior visual input pathway to the Drosophila central complex.

The anterior visual pathway (AVP) conducts visual information from the medulla of the optic lobe via the anterior optic tubercle (AOTU) and bulb (BU) to the ellipsoid body (EB) of the central complex. The anatomically defined neuron classes connecting the AOTU, BU, and EB represent discrete lineages, genetically and developmentally specified sets of cells derived from common progenitors (Omoto et al., Current Biology, 27, 1098-1110, 2017). In this article, we have analyzed the formation of the AVP from early larval to adult stages. The immature fiber tracts of the AVP, formed by secondary neurons of lineages DALcl1/2 and DALv2, assemble into structurally distinct primordia of the AOTU, BU, and EB within the late larval brain. During the early pupal period (P6-P48) these primordia grow in size and differentiate into the definitive subcompartments of the AOTU, BU, and EB. The primordium of the EB has a complex composition. DALv2 neurons form the anterior EB primordium, which starts out as a bilateral structure, then crosses the midline between P6 and P12, and subsequently bends to adopt the ring shape of the mature EB. Columnar neurons of the central complex, generated by the type II lineages DM1-4, form the posterior EB primordium. Starting out as an integral part of the fan-shaped body primordium, the posterior EB primordium moves forward and merges with the anterior EB primordium. We document the extension of neuropil glia around the nascent EB and BU, and analyze the relationship of primary and secondary neurons of the AVP lineages.

Longitudinal evaluation of serum pancreatic enzymes and ultrasonographic findings in diabetic cats without clinically relevant pancreatitis at diagnosis.

BACKGROUND: Cats with diabetes mellitus can have subclinical pancreatitis but prospective studies to confirm this are lacking. Metabolic control of diabetic cats with pancreatitis is difficult. HYPOTHESIS: Subclinical pancreatitis occurs in diabetic cats at the time diabetes is diagnosed or might develop during the follow-up period, hampering diabetic remission. ANIMALS: Thirty cats with newly diagnosed diabetes without clinical signs of pancreatitis on admission. METHODS: Prospective study. On admission and 2 and 6 months later, serum Spec fPL and DGGR-lipase were measured and the pancreas underwent ultrasonographic examination. Pancreatitis was suspected if serum markers were increased or ≥2 ultrasonographic abnormalities were detected. Cats were treated with insulin glargine and diabetic remission was defined as euglycemia ≥4 weeks after discontinuation of insulin. Nonparametric statistical tests were used for analysis. RESULTS: Subclinical pancreatitis at the time of diagnosis was suspected in 33, 50, and 31% of cats based on Spec fPL, DGGR-lipase and ultrasonography, respectively; and in 60% when diagnostic criteria were combined. During the follow-up period, suspected pancreatitis developed in additional 17-30% cats. Only 1 cat had transient clinical signs compatible with pancreatitis. Seventeen of the 30 cats (57%) achieved remission. Frequency of abnormal Spec fPL and DGGR-lipase and abnormal ultrasonographic findings did not differ in cats achieving remission and those who did not. Cats achieving remission had significantly lower Spec fPL at 2 months (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Based on laboratory and ultrasonographic measurements, many cats with diabetes might have pancreatitis, although without clinical signs. Cats with high Spec fPL might have a reduced chance of diabetic remission; however, this topic needs further studies in large cohorts of diabetic cats.