Volume 188, Issue 3 p. 109-110
Evaluating the Evidence
Free Access

Is the DGGR lipase test as reliable as the Spec cPL test for diagnosing acute pancreatitis in dogs?

Lisa Morrow

Lisa Morrow

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

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Peter Graham

Peter Graham

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

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First published: 07 February 2021

BOTTOM LINE

  • There is good evidence that the serum DGGR lipase test is as reliable as the Spec cPL test for diagnosing acute pancreatitis in dogs.

Clinical scenario

Benji is a 40 kg Labrador retriever with a body condition score of seven (on a nine-point scale). He went rummaging through the neighbour's rubbish two days ago, and he is now lethargic, inappetent and has been vomiting. On clinical examination, you find he is dehydrated, tachycardic and tachypnoeic. He is also guarding his abdomen and has a hunched posture.

You suspect acute pancreatitis but would like to do further testing before initiating treatment. You take a blood sample, and, when filling out the submission form, you notice that the lab offers two tests for canine pancreatitis. One of them, the serum 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) lipase test, you have never heard of before. You wonder whether the serum DGGR lipase test is as reliable as the Spec cPL test you usually use for diagnosing acute canine pancreatitis.

The question

In [dogs with acute pancreatitis], is [serum DGGR lipase compared with Spec cPL] as reliable for [diagnosing the disease]?

Search parameters

The search strategy can be viewed at https://bestbetsforvets.org/bet/572, and is also available as a supplement to this article on Vet Record's website at https://bvajournals.onlinelibrary.wiley.com/toc/20427670/2021/188/3

Search outcome

  • Two hundred and thirty-seven papers were found in the Medline search.

  • Two hundred and thirty-three were excluded because they did not answer the question.

  • One was excluded because it was a review article, in vitro research or conference proceeding.

  • In total, three relevant papers were obtained.

  • One hundred and eighty-one papers were found in the CAB search.

  • One hundred and seventy-six were excluded because they did not answer the question.

  • Two were excluded because they were review articles, in vitro research or conference proceedings.

  • In total, three relevant papers were obtained.

  • Overall, three relevant papers were identified.

Search last performed: 22 December 2020

Summary of evidence

Paper 1: Agreement of serum Spec cPL with the 1,2-o-dilauryl-rac-glycero glutaric acid-(6′-methylresorufin) ester (DGGR) lipase assay and with pancreatic ultrasonography in dogs with suspected pancreatitis1

Patient group: The study included 142 dogs with suspected pancreatitis (based on the presence of at least two clinical signs) that were presented at a referral centre between 2009 and 2013. To be eligible for inclusion, dogs must have had both lipase tests performed on the same blood sample and have undergone a complete ultrasonographic examination within 24 hours of blood sampling.

Study type: Diagnostic test comparison.

Outcomes: First, the precision of the DGGR lipase assay and the linearity of its measurement range were determined. Agreement between the DGGR lipase and Spec cPL assay results at various cut-offs was then evaluated using Cohen's κ coefficient. In addition, the level of agreement between pancreatic ultrasonography and each of the two lipase tests was investigated.

Key results: There was a strong positive correlation between the results of DGGR and Spec cPL tests (rho=0.899). Agreement between the two tests was substantial at both ‘suspect’ and ‘positive’ cut-off values.

Maximum agreement with Spec cPL at the ‘suspect’ cut-off value (200 μg/l) was achieved when the DGGR cut-off was set at 130 IU/l (κ=0.877). For the ‘positive’ Spec cPL cut-off (400 μg/l), maximum agreement with the DGGR results was achieved when the DGGR cut-off was set at 190 IU/l (4kP=0.816).

Study weaknesses: As this is a retrospective study, there is a higher risk of bias arising from inaccurate or incomplete data collection. Furthermore, although the reference range for the DGGR lipase test is given as 24–108 IU/l, the study from which this reference range was derived is neither cited nor described in sufficient detail. Both this and the lack of comparison with a gold standard mean that caution should be used when attempting to interpret the clinical relevance of the test results.

Paper 2: Evaluation of SNAP cPL, Spec cPL, VetScan cPL Rapid Test and Precision PSL assays for the diagnosis of clinical pancreatitis in dogs2

Patient group: Fifty client-owned dogs presented at an emergency clinic with clinical signs of gastrointestinal disease between January and June 2017 were prospectively enrolled in the study. All dogs underwent physical examination, serum biochemistry analysis and abdominal ultrasound examination, as well as having blood samples analysed using the four diagnostic assays for pancreatitis.

Study type: Diagnostic test comparison.

Outcomes: The sensitivity and specificity of the SNAP cPL, Spec cPL, VetScan cPL Rapid Test and Precision PSL assays were calculated using clinical suspicion score as the gold standard. Intraclass correlation coefficients were then used to determine the level of agreement between the four assays.

Key results: The intraclass correlation coefficient between the Spec cPL assay and the Precision PSL assay (a DGGR test) was 0.89, indicating good agreement. When classifying equivocal clinical suspicion scores and assay results as ‘negative’, the Spec cPL assay's sensitivity was 90.9 per cent its specificity was 81.1 per cent. The sensitivity and specificity of the Precision PSL assay under the same assumptions were 90.9 per cent and 74.3 per cent, respectively.

When classifying equivocal clinical suspicion scores and assay results as ‘positive’, the Spec cPL assay's sensitivity and specificity were 81 per cent and 74.1 per cent, respectively. The sensitivity and specificity of the Precision PSL at this cut-off were 85.7 per cent and 64 per cent, respectively.

Study weaknesses: Although the findings indicate that there is good agreement between the Spec cPL and DGGR tests, the small sample size means that the study may be insufficiently powered to detect differences. Another possible limitation is the use of an unvalidated measure – clinical suspicion score – as the gold standard.

Overall, the lack of comparison to a validated gold standard and the small sample size make the sensitivity and specificity estimates unreliable. The lack of reported confidence intervals further compounds this.

Paper 3: Validation of a commercial 1,2-o-dilauryl-rac-glycero glutaric acid-(6′-methylresorufin) ester lipase assay for diagnosis of canine pancreatitis3

Patient group: Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) were selected from the pathology database of a referral hospital. Normal cases were selected based on the documentation of clinical signs for which pancreatitis was a differential diagnosis (eg, vomiting, diarrhoea, abdominal pain).

To calculate the DGGR reference interval, the DGGR lipase activity of 37 dogs with no clinical history of pancreatitis, gastrointestinal disease, thromboembolic disease, abnormal cardiac auscultation, congestive heart failure, azotaemia or concurrent corticosteroid treatment was retrospectively evaluated.

Study type: Diagnostic test comparison.

Outcomes: The precision, reproducibility and linearity of the DGGR lipase test, and the effect of sample haemolysis and freezing, were assessed. The reference interval of the DGGR lipase test was also determined, and the diagnostic sensitivity and specificity of the DGGR lipase and Spec cPL tests were calculated. The level of agreement between the two tests was then evaluated using Cohen's κ coefficient.

Key results: There was a strong positive correlation between the results of DGGR and Spec cPL tests (rho=0.925). Agreement between the two tests was substantial at high cut-off values, with maximum agreement achieved when the DGGR cut-off was set at 245 IU/l and the Spec cPL cut-off was set at 400 μg/l (κ=0.679).

Both tests showed poor sensitivity for pancreatitis, with DGGR having a sensitivity of 0 per cent (95 per cent confidence interval [CI]: 0–69 per cent) and Spec cPL having a sensitivity of 33 per cent (95 per cent CI: 18–87 per cent). However, both tests showed 100 per cent specificity (95 per cent CI: 56–100 per cent).

Study weaknesses: As this is a retrospective study, there is a higher risk of bias arising from inaccurate or incomplete data collection. Both acute and chronic pancreatitis cases were included in the study, but there were too few acute cases (n=3) for them to be evaluated separately. Overall, the sample size was very small, and the study is likely to be underpowered.

A long time elapsed between blood sampling and histopathology in some cases, limiting the extent to which the blood test results will correlate with the histopathological findings. Furthermore, some blood samples were taken after the biopsy was performed, and the surgery may have influenced the lipase assay results.

The DGGR test cut-off was derived from an inadequate reference interval study with less than the recommended minimum of 40 subjects. A performance comparison method that was independent of assigned cut-offs (eg, receiver operating characteristic curves) would have allowed for comparison without reliance on the data from the reference interval study.

Comments

The DGGR results are in high agreement with the Spec cPL results in all three studies, but ideal cut-offs still need to be determined. To do this, larger-scale studies comparing the test results with the histopathology gold standard are required.

Both tests have been reported with an ‘equivocal’ range for the diagnosis of pancreatitis. For both tests, there is a cut-off value below which pancreatitis is considered unlikely and an additional cut-off value above which pancreatitis is considered likely, leaving a range of values in between where interpretation is ambiguous. Further studies are needed to clarify this ambiguity.

Compared with Spec cPL, the DGGR assay is considerably less expensive and has a quicker turnaround. As such, the DGGR assay may be preferable to Spec cPL for use in emergency cases or those where the owner is concerned about costs.

The ‘Evaluating The Evidence’ section of Vet Record aims to answer specific clinical questions using a systematic approach to identify and succinctly summarise the relevant evidence from the scientific literature. The shortcomings of this evidence are also taken into account, thereby enabling vets to incorporate the best available evidence from the literature when making clinical decisions. Please contact us at [email protected] if you have an article you would like us to consider for publication in this section.