Bile duct obstruction associated with pancreatitis in 46 dogs

Abstract Background Pancreatitis is a common cause of extrahepatic bile duct obstruction (EHBDO) in dogs. Information describing the clinical course of dogs with pancreatitis associated bile duct obstruction (PABDO) is limited. Objectives To describe the clinical course of PABDO in dogs and determine if presumed markers of disease severity are predictors of survival. Animals Forty‐six client‐owned dogs with PABDO. Methods A retrospective review of medical records from dogs diagnosed with PABDO was performed. Data, including clinical signs and biochemical changes, were collected 6 times throughout the course of disease. Outcome was defined as either survival (discharge from the hospital) or death. Results Thirty‐three (79%) out of 42 dogs with PABDO survived. Thirty‐one (94%) of the 33 dogs that survived received medical management alone. Time from onset of clinical signs to initial documented increase in serum bilirubin concentration, peak bilirubin elevation, and initial decline in serum bilirubin concentration were 7 (median), 8, and 15 days, respectively. The median number of days from onset of clinical signs to outcome date was 13. Clinical signs of fever, vomiting, and anorexia were decreased in frequency from the onset of clinical signs to the time of peak bilirubin. Median bile duct dilatation at the time of ultrasonographic diagnosis of PABDO and peak bilirubin were not different between survivors (7.6 mm, 11.7 mg/dL) and nonsurvivors (6 mm, 10.6 mg/dL, P = .12, P = .8). Conclusions Dogs with PABDO often have a prolonged course of illness and improve clinically despite biochemical evidence of progression of EHBDO.

Bile duct obstruction can result in clinically important complications including derangements of hemostasis, 2,3 hepatic injury, 4 alterations in hepatic circulation, 5 reduced liver reticuloendothelial activity, 6 gallbladder wall necrosis, and gallbladder rupture. 7 Various treatments have been described for dogs with pancreatitis associated bile duct obstruction (PABDO), including biliary decompression procedures and supportive medical treatment. Biliary decompression can be achieved with percutaneous ultrasound-guided cholecystocentesis, endoscopic retrograde biliary stenting, or surgical intervention, such as cholecystoduodenostomy or choledocal stent placement. [8][9][10] Surgery of the biliary tract carries substantial risk in dogs with pancreatitis, with a case fatality rate of 50% in dogs. 11 Complications associated with cholecystocentesis are uncommon but can include bile peritonitis and cardiorespiratory arrest. 12 The authors' clinical impression is that most dogs recover without biliary decompression. Unfortunately, few reports describe the clinical course and outcome of dogs with PABDO. 8,13 The primary aim of our study was to describe the clinical course of PABDO and determine if presumed markers of disease severity, including degree of bile duct dilatation, serum concentrations of bilirubin, urea (BUN), creatinine, and albumin, serum activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP), white blood cell count (WBC) and platelet counts are predictors of survival to discharge from the hospital.

| Case selection
Medical records of dogs that were diagnosed with PABDO at the Virginia-Maryland College of Veterinary Medicine (VMCVM) were identified by review of medical records for cases presenting from February 1999 to January 2017. Terms used during the medical record search included "obstruction bile duct: biliary passage," "fibrosis bile duct: biliary passage," "disease bile duct due to unknown," "obst bile duct," and "pancreatitis." Dogs were diagnosed with pancreatitis based on a point scoring system (Table 1). Dogs with a pancreatitis score ≥ 10 were considered to have pancreatitis. A diagnosis of EHBDO was made if the patient had a plasma bilirubin concentration ≥ 2.0 mg/dL on at least 1 occasion and ultrasonographic evidence of bile duct dilatation (common bile duct diameter greater than 3 mm). Ultrasound images from each case were reviewed by a board-certified radiologist (M. M. L.).
Cases were excluded if another cause of hyperbilirubinemia (ie, hemolysis or primary hepatic disease) or concurrent gallbladder mucocele, biliary neoplasia, or obstructive cholelithiasis was identified. Note: Superscript letters that are the same within each row indicate significant differences between time points based on Bonferroni's procedure for multiple comparisons. The level of significance is set at P ≤ .05. See Table 2 for description of time points.

| Data collection
Data were collected at 6 time points during the course of illness (

| Statistical analysis
Normal probability plots were performed to determine whether con-
Three dogs that did not have time 5 data died shortly after discharge Clinical signs of fever, vomiting, and anorexia were significantly less prevalent by time 4 (Table 3). Abdominal pain was less prevalent between time 3 and 5 (  (Table 5). At time 4, ALT was significantly higher in survivors compared to nonsurvivors and albumin was significantly lower in nonsurvivors ( Table 5).

| DISCUSSION
Although pancreatitis is a common cause of EHBDO in dogs, 1 there is minimal information available to date describing the clinical course of this illness. Findings of our study provide further evidence that pancreatitis can cause sustained inflammation adjacent to the common bile duct that leads to a functional or physical obstruction over time.
In our population of dogs, the highest recorded bilirubin, which likely represents the peak of bile duct obstruction, occurred a median of 9 days after the onset of clinical signs. A prolonged period of recovery should be expected in dogs with PABDO since initial decline in bilirubin did not occur until a median of 15 days from onset of signs. A previous description of PABDO described an onset of icterus similar to our study. However, dogs in the previous study had mass lesions in their pancreas and evidence of chronic active fibrosing pancreatitis on histopathology. 8 Interestingly, many of the clinical signs resulting from pancreatitis, including anorexia, vomiting, and fever, had decreased by the time peak bilirubin occurred in our population. We suspect the initial inflammatory response associated with acute pancreatitis, which usually includes acinar cell damage and necrosis, leukocyte migration, and cytokine release, is resolving as the EHBDO develops. 14 It seems the clinical signs observed in dogs with PABDO might primarily be a result of pancreatitis rather than bile duct obstruction. Additionally, hyperbilirubinemia might persist despite resolution of biliary obstruction since conjugated bilirubin binds covalently to albumin and delays the clearance of bilirubin. 15 Overall survival for dogs with PABDO was 79% in our population, with only 7 dogs treated with medical management alone not surviving.
Two of the 4 dogs that had percutaneous or surgical decompression of the gallbladder died. The case fatality rate of dogs undergoing surgery in to assess for chronicity of biliary obstruction, was also not measured.
Supportive medical treatment was not standardized and could include IV fluid treatment, antibiotic treatment, analgesics, antiemetics, gastroprotectants, and fresh frozen plasma. Whether particular therapies, such as fresh frozen plasma, improved outcome in dogs that did not receive biliary decompression is unknown. All dogs that died were euthanized, which could have affected interpretation of survival.
Since pancreatitis can be challenging to definitively diagnose, we attempted to minimize ambiguity by creating a pancreatitis scoring system. Histopathology is usually required to obtain a definitive diagnosis.
Unfortunately, histopathology is impractical in a clinical setting and has its own limitations because pancreatitis often has a patchy distribution and the clinical relevance of inflammatory lesions is often difficult to determine. 18 Although various assays for pancreatic lipase are often highly sensitive, they have variable specificity. 19 The scoring system was designed to assign points for clinical signs, clinicopathologic changes, and ultrasonographic abnormalities that are typically associated with pancreatitis in dogs. 20,21 In addition to their variable specificity, assays for pancreatic lipase were not included in our scoring system because they were not consistently assessed in our population of dogs. Scoring systems are frequently used in humans with acute pancreatitis for diagnosis and assessing disease severity but there is not currently a universally accepted pancreatitis scoring system in dogs. 22 For example, some authors might use a combination of clinical signs, serum pancreatic lipase concentration, and abdominal ultrasound to make the diagnosis of acute pancreatitis, 23 while others depend heavily upon expert opinion. 19

CONFLICT OF INTEREST DECLARATION
Authors declare no conflict of interest.

OFF-LABEL ANTIMICROBIAL DECLARATION
Authors declare no off-label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION
Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION
Authors declare human ethics approval was not needed for this study.