Cholelithiasis in the Dog: Prevalence, Clinical Presentation, and Outcome
ABSTRACT
Canine cholelithiasis is considered to be an uncommon condition and is frequently cited as being an incidental finding. However, there is a paucity of contemporary literature to support these assertions. The aim of this retrospective cross-sectional study was to report the prevalence, clinical presentation, and long-term follow-up of cholelithiasis in dogs. The electronic database at the Small Animal Hospital, University of Glasgow was searched to identify dogs that were diagnosed with cholelithiasis on ultrasound between 2010 and 2018. Sixty-eight dogs were identified, giving an overall prevalence of cholelithiasis in our hospital of 0.97% (confidence interval 0.76–1.22%). Medical records of 61 dogs were available for review. Cholelithiasis was classified as an incidental finding in 53 (86.9%) dogs, with 8 (13.1%) dogs being classified as symptomatic, having complications of cholelithiasis that included biliary duct obstruction, biliary peritonitis, emphysematous cholecystitis, and acute cholecystitis. Follow-up was available for 39 dogs, with only 3 dogs (7.7%) developing complications attributed to cholelithiasis, including biliary duct obstruction and acute cholecystitis, within the subsequent 2 yr. Cholelithiasis is an uncommon but frequently incidental finding in dogs. Within the follow-up period, few of the dogs with incidental cholelithiasis went on to be become symptomatic.
Introduction
A cholelith or gallstone is a stone-like mass or calculus formed from bile precipitates in the gallbladder or, less frequently, in the intrahepatic or extrahepatic ductal system.1–3
In human medicine, cholelithiasis is reported to affect up to 25% of humans in the Western world.2,5 Despite this high prevalence, symptomatic cholelithiasis accounts for only a small proportion of cases of cholelithiasis in human patients, with up to 90% of people being asymptomatic at the time of diagnosis.4,5 More commonly, choleliths are identified as an incidental finding during screening for unrelated medical conditions, with ultrasonography being the primary imaging modality of choice in humans for detection of choleliths, with a sensitivity of 94%.5,6
The rate at which asymptomatic choleliths become symptomatic in people is low but significant. Follow-up epidemiological studies have revealed that approximately 20% of people with cholelithiasis develop biliary symptoms or complications requiring treatment.5,7 Symptomatic choleliths may trigger clinical signs such as biliary colic, nausea, and vomiting.4 Complications of cholelithiasis include acute cholecystitis/cholangitis, acute pancreatitis, biliary duct obstruction, gallbladder perforation, and gallstone ileus.2,5,7 Management of complicated choleliths requires surgery with a cholecystectomy, although medical treatment with ursodeoxycholic acid (UDCA) may be effective in dissolving cholesterol stones in select patients, by lowering biliary cholesterol supersaturation.2
In contrast, the overall prevalence of canine cholelithiasis has been estimated at between 0.03 and 15%, and although there are numerous reports of canine cholelithiasis in the veterinary literature, the frequency of incidental cholelithiasis is unknown.8–23 As in humans, complications of cholelithiasis described in dogs include extrahepatic biliary duct obstruction, cholangitis/cholecystitis, gallbladder perforation, and cholecystocutaneous fistula.10–13,15,17–23 Currently, the rate at which dogs with incidental cholelithiasis develop complications is also unknown. The optimal management of incidental canine cholelithiasis is also unknown.
The objective of this retrospective study was to describe the prevalence, clinical presentation, and long-term outcome based on follow-up of cholelithiasis in dogs presenting to an academic referral institution. We hypothesized that in the majority of dogs cholelithiasis would be an incidental finding and subsequently asymptomatic.
Materials and Methods
Case Selection
A retrospective case-controlled cross-sectional study was performed at the Small Animal Hospital, University of Glasgow, United Kingdom. The project was approved by the University of Glasgow Ethics Committee. Medical records of dogs with cholelithiasis that were presented to the Small Animal Hospital between January 1, 2010, and June 30, 2018, were retrospectively reviewed. Dogs were identified by searching the electronic patient data base for terms including “cholelith,” “cholelithiasis,” “gallstone,” “gall stone,” “GB stone,” and/or “gallbladder stone.” Dogs were included in the study if they underwent an abdominal ultrasonography as a component of their diagnostic investigation.
Ultrasonography was performed by a board-certified European College of Veterinary Diagnostic Imaging diagnostic imager, a European College of Veterinary Diagnostic Imaging resident under the direct supervision of a board-certified diagnostic imager, or a Royal College of Veterinary Surgeons Advanced Practitioner in Diagnostic Imaging.
To estimate the overall prevalence, the imaging database was also searched for the total number of abdominal ultrasound scans performed during the same time period.
Review of Medical Records
Medical records of dogs with cholelithiasis were reviewed and the following information collected from the visit where the ultrasound diagnosis of cholelithiasis was made: signalment (age, breed, sex, and neuter status), the location and number of the cholelith(s), and the ultrasonographic appearance of the gallbladder and remainder of the biliary tract. Presenting clinical signs, clinical pathology, and final diagnosis were used to determine if choleliths were incidental or symptomatic findings.
Dogs were determined to be symptomatic for their choleliths if they had clinical signs associated with cholelithiasis (vomiting, abdominal pain, pyrexia, lethargy, anorexia, and/or jaundice), the gallbladder appeared abnormal on ultrasound (increased thickness to the gallbladder wall, hyperechogenicity of gallbladder wall, gallbladder wall edema, dilation of the cystic duct, and/or dilation of the common bile duct), or they had biochemical evidence of biliary disease (increase in bilirubin, alkaline phosphatase, gamma-glutamyltransferase, and/or cholesterol) and where there was no alternative explanation for the clinical presentation.17 Dogs were deemed to have incidental choleliths if there were either no clinical signs or biochemical evidence attributed to cholelithiasis or the clinical signs/biochemical changes could be attributed to another confirmed disease process (e.g., pyelonephritis causing abdominal pain) and where the biliary tract was otherwise reported as normal in appearance.
Radiographic and computed tomography (CT) images if performed within 28 days of initial ultrasound were reviewed by diagnostic imagers for the presence of cholelithiasis and findings recorded. If performed within 24 hours of the ultrasound diagnosis of cholelithiasis, routine hematological and serum biochemical data pertaining to biliary disease were recorded.
When available, follow-up information was also collected and recorded.
Statistical Analysis
Descriptive statistics were used for analysis of the epidemiologic data. Data were tested for normality using a Ryan-Joiner test, which is similar to the Shapiro-Wilk test. The means of continuous normally distributed variables were compared using a t test. Non‐normally distributed continuous data were reported as medians and were compared using the Mann-Whitney U test. Findings were considered significant if P < 0.05. Statistical analysis of the data was performed using a commercial software packagea.
The prevalence was calculated by dividing the number of cases by the total number of dogs that underwent abdominal ultrasonography over the time period of the study. The 95% confidence intervals around this prevalence estimate were calculated using a method specifically designed for low prevalence estimates.24
Results
Prevalence
Between January 1, 2010, and June 30, 2018, 7036 individual dogs underwent abdominal ultrasonography. A total of 68 dogs were identified to have cholelithiasis on abdominal ultrasound, giving a prevalence of 0.97% (confidence interval 0.76–1.22%).
Signalment
Of the 68 dogs, 34 were males (50%), 20 of which were neutered and 14 of which were intact, and 34 were females (50%), 26 of which were neutered and 8 of which were intact. Median age at the time of identification was 9 yr (range 3 mo to 17 yr).
Thirty-one breeds were represented. Breeds included mixed-breed dogs (n = 11), Labrador retrievers (n = 7), border collies (n = 5), Cavalier King Charles spaniels (n = 4), cocker spaniels (n = 4), Jack Russell terriers (n = 3), English springer spaniels (n = 3), basset hounds (n = 2), German shepherd dogs (n = 2), golden retrievers (n = 2), miniature schnauzers (n = 2), Rhodesian ridgebacks (n = 2), shar peis (n = 2), Siberian huskies (n = 2), and one each of Australian shepherd, bichon frise, British bulldog, dachshund, Dalmatian, Dogue de Bordeaux, English bull terrier, French bulldog, Irish water spaniel, Lhasa apso, Maltese terrier, miniature dachshund, Old English sheepdog, pug, Staffordshire bull terrier, standard poodle, and West Highland white terrier.
Diagnostic Imaging
Of the 68 dogs, 64 were reported to have cholecystoliths (stones identified in the gallbladder) identified on ultrasound evaluation of the abdomen. Three patients had choleliths identified in the intrahepatic bile ducts, one of whom had both intrahepatic mineralization and cholecystoliths. Three patients had a choledocolith (stone identified in the common bile duct), one of whom also had cholecystolith. Thirty-seven dogs were reported to have a single stone, and 30 dogs had multiple stones. In one dog it was not clear if there were multiple small stones close together or a large stone. In 24 cases concurrent gallbladder sludge/sediment was reported. A summary of the diagnostic imaging abnormalities in the symptomatic dogs is provided in Table 1.
Radiographs were available for 27 dogs that incorporated the cranial abdomen. Mineralized radiopacities were identified in the region of the hepatic silhouette, the anatomical location felt consistent with the biliary tree, consistent with cholelithiasis in 16 dogs (59%). A total of 9 dogs had a concurrent CT incorporating the cranial abdomen. Radiopaque structures within the gallbladder were identified in 8 dogs (89%). Radiographs and CT examinations were available for 3 dogs, with choleliths identified using both modalities.
Clinical Presentation
At the time of diagnosis, 7 of the 68 dogs with choleliths could not be designated as either symptomatic or incidental owing to insufficient clinical history and were excluded from further analysis. Of the remaining 61 dogs, 13% (8/61) had clinical signs and complications attributed to cholelithiasis. Cholelithiasis was deemed incidental in 87% (53/61).
Eight dogs were symptomatic for cholelithiasis. The median age for these dogs was 6 yr (range 2–9 yr). The clinical presentation of the symptomatic dogs is summarized in Table 1. Dog 1 presented with obstructive jaundice secondary to choledocholithiasis, which required emergency exploratory laparotomy and cholecystoduodenostomy. Enterococci and nonhemolytic Escherichia coli spp. were cultured from the cholelith. Chemical analysis of the cholelith was not performed. Dog 2 had a rupture and septic biliary peritonitis. A cholecystectomy was performed. Histopathology revealed a severe hemorrhagic necrotizing and suppurative cholangiohepatitis and cholecystitis. Clostridium spp. was cultured from bile. Analysis of the cholelith was not performed. Dog 3 was diagnosed with septic peritonitis suspected secondary to biliary tract rupture and was euthanized at the owner’s request without further investigations. Dog 4 was diagnosed with an emphysematous cholecystitis on ultrasound. The dog underwent a cholecystectomy, with histopathology revealing a severe suppurative, necrotizing cholecystitis. Gallstone analysis was not performed. E coli, Enterococcus, and Prevotella spp. were cultured from the bile. Three dogs (5, 6, and 7) had a suspect acute cholecystitis (based on presentation, diagnostic imaging, and clinicopathological findings) and were medically managed. Dog 8 presented with a chronic history of intermittent vomiting, decreased appetite, and lethargy, secondary to a partial biliary duct obstruction. The dog was scheduled for a cholecystectomy; however, following the development of marked abdominal pain, repeat ultrasound revealed spontaneous passage of the cholelith.
In the remaining 53 dogs, cholelithiasis was considered an incidental finding. The median age for these dogs was 9 yr (4 mo to 17 yr). Of these dogs, the final diagnoses included neoplasia (n = 22, which included hepatic mass, lymphoma, multiple myeloma, nasal carcinoma, pancreatic mass, thyroid carcinoma, pituitary neoplasia, soft tissue sarcoma, mammary carcinoma, mast cell tumor, plasmacytoma, and histiocytic sarcoma), immune-mediated diseases (n = 5, which included 4 dogs with immune-mediated hemolytic anemia and 1 dog with immune-mediated thrombocytopenia), intervertebral disc disease (n = 4), pancreatitis (n = 4), chronic hepatitis (n = 2), drug-induced gastrointestinal ulceration (n = 2), hyperadrenocorticism (n = 1), dietary responsive enteropathy (n = 1), extramedullary hematopoiesis (n = 1), hepatic amyloidosis (n = 1), histiocytic disease (n = 1), hyperparathyroidism (n = 1), idiopathic epilepsy (n = 1), idiopathic megaesophagus (n = 1), mitral valve disease (n = 1), otitis externa (n = 1), portosystemic shunt (n = 1), protein-losing nephropathy (n = 1), pyelonephritis (n = 1), and reflex dyssynergia (n = 1). Fourteen dogs had concurrent comorbidities, which included acute pancreatitis (n = 4), hyperadrenocorticism (n = 3), hypothyroidism (n = 2), diabetes insipidus (n = 1), fungal dermatitis (n = 1), steroid-responsive meningitis (n = 1), and mitral valve disease (n = 1).
Clinical Pathology
Clinicopathological data were available for 50/61 dogs (7/8 in the symptomatic group, 43/53 in the asymptomatic group) are summarized in Table 2. As anticipated based on our inclusion criteria, dogs symptomatic for cholelithiasis had significantly higher aspartate transaminase (P = 0.0385), alanine aminotransferase (P = 0.0396), gamma-glutamyltransferase (P = 0.0024), bilirubin (P = 0.0168), and cholesterol (P = 0.011) in comparison with dogs with incidental cholelithiasis. There were no other significant differences between the symptomatic and asymptomatic groups.
Follow-Up
Of the 61 dogs, follow-up was available in 39 cases for over a median period of 174 days (range 10–1688 days).
Of the eight symptomatic dogs, one dog was euthanized and the remaining dogs were discharged from hospital, with one dog lost to follow-up. Therefore, six dogs were available for follow-up over a period of 37–1404 days (median 773). All six dogs had follow-up ultrasound examination and serum biochemistry performed at various time points. At the time of initial diagnosis, five of the six cases had been prescribed UDCAb as part of their management at median dosage of 13.5 mg/kg (range 9.4–14.4 mg/kg) q 24 hr. The median duration of treatment was 244 days (range 56–793). Three cases were prescribed antioxidant therapyc,d,e. In the two dogs that underwent surgery for management of complications relating to cholelithiasis (Dogs 1 and 2), no new choleliths were identified on follow-up ultrasonography. In one dog (Dog 8), the cholelith passed spontaneously and no new choleliths were detected on follow-up ultrasound. Choleliths remained in three dogs (Dogs 4, 5, and 7), and two went on to develop complications attributed to cholelithiasis; Dog 5 re-presented with a suspect flare up of cholecystitis on day 655, and Dog 7 re-presented on day 653 and again on day 793 with cholecystitis. Both dogs were treated medically with antibiotics, UDCAb, antioxidant therapyc,d, and supportive care with successful outcome. Dog 4 was followed up for 766 days and had no further complication attributed to cholelithiasis.
Of the 53 dogs with incidental cholelithiasis, follow-up was available in 33 cases over 10–1688 days (median 145). Serum biochemical analysis was performed during the follow-up period in 31 cases, and 20 cases had re-evaluation of the biliary tract by ultrasound. Choleliths did not spontaneously resolve in any case. Five cases were prescribed UDCAb at a median dosage of 12.4 mg/kg (10–15 mg/kg) q 24 hr. The median duration of treatment was 66 days (range 10–303). One of these dogs had been prescribed UDCAb 10 mo prior to the development of cholelithiasis. Six cases were prescribed antioxidant therapyc,d,e. Follow-up ultrasounds performed in all dogs prescribed UDCAb revealed persistence of cholelithiasis. One dog had complications potentially related to their cholelithiasis. This dog, which was treated for acute pancreatitis at the time of identification of cholelithiasis, re-presented on day 678 with jaundice and anorexia. Biliary obstruction secondary to pancreatitis and suspected cholecystitis was diagnosed based on the ultrasonographic appearance of the gallbladder and clinicopathological abnormalities. The exact etiology of the biliary obstruction was not confirmed; exploratory laparotomy was declined by the owners, who requested euthanasia.
Overall, 2/6 (33%) symptomatic dogs and 1/33 (3%) dogs with incidental cholelithiasis went on to develop clinical signs attributable to cholelithiasis.
Discussion
In this retrospective study, the overall prevalence of cholelithiasis was 0.97%, and in the majority of cases, cholelithiasis was concluded to be an incidental finding. Moreover, dogs with incidental choleliths infrequently went on to develop clinical signs of cholelithiasis.
Our results are not dissimilar to previous estimates of the prevalence of cholelithiasis in the dog. Previous prevalence studies were based on postmortem observations, with rates of between 0.03 and 13% being reported, with the higher prevalence rate being based on inclusion of small concretions measuring less than 1 mm in size.8,9 Ultrasonography, which was used to identify cases of cholelithiasis in the current study, is highly sensitive for the detection of gallstones, although smaller, clinically insignificant concretions may have been reported as sludge and this may account for the differences between the studies.6 On the basis of our results, we conclude that in comparison with other incidental abnormalities of the gallbladder such as the presence of gallbladder sludge, which has a reported prevalence of 35–53%, cholelithiasis appears to be a relatively uncommon ultrasonographic finding in the dog.25,26
As previously reported, the prevalence of cholelithiasis observed in the canine population is much lower than that observed in humans, where prevalence rates of up to 25% are reported.2,5 This observation is likely to reflect species differences in the pathogenesis of cholelithiasis, including the lower concentration of cholesterol in canine bile.25,27 Cholesterol choleliths account for 80–90% of human choleliths, whereas pigment choleliths are reported to be more common in dogs.4,8,10–12,17,20
In our study population, cholelithiasis was considered to be an incidental finding in the majority of dogs (87%), providing evidence to support what has long been a common perception in the veterinary field.1 This observation is similar to the situation in humans, in which up to 90% of patients have no clinical symptoms attributable to cholelithiasis at the time of identification.2 With the increasing use of ultrasound as a routine diagnostic tool in veterinary medicine, the frequency of detection of incidental choleliths is likely to increase.28 Previous studies, in which radiography was the primary imaging modality, report rates of detection in the region of 50%.17 Similarly, in our study we observed radiographic evidence of choleliths in only 59% of cases, and as such, up to 40% of choleliths may previously have gone undetected. Choleliths may not be visible on survey abdominal radiographs if they contain insufficient calcium, are of small size, or with superimposition of the gastrointestinal tract.29
In our study there were few dogs presenting with symptomatic cholelithiasis. The complications we observed were similar to previous publications and included extrahepatic biliary duct obstruction, gallbladder rupture, emphysematous cholecystitis, and acute cholecystitis.8,11,17,19 These patients displayed symptoms of cholelithiasis, which included vomiting, jaundice, pyrexia, abdominal pain, and praying position, and had compatible biochemical and ultrasonographic changes of biliary tract pathology. In human medicine, more subtle clinical signs of cholelithiasis might include transient localized abdominal pain, known as “biliary colic,” which may be difficult to fully appreciate in veterinary patients.2 There were a number of dogs in our study that we were unable to categorize as symptomatic or incidental as they did not fulfill all the predetermined criteria of symptomatic cholelithiasis. Although they may have had appropriate clinical signs, there was either no biochemical evidence of biliary disease or no compatible ultrasonographic changes, and this may have led to a slight underestimation of symptomatic dogs.
A key finding in our study is that in addition to being an incidental finding, few (3%) of the dogs went on to develop clinical signs in the follow-up period. Long-term epidemiological studies in humans with asymptomatic choleliths report that the majority of people will remain asymptomatic throughout their life. Fewer than 25% of people will become symptomatic within 20 years of diagnosis, with significant complications reported in less than 10% of patients.5 The reason a subgroup of individuals will ultimately develop symptoms remains unknown.
By contrast, in people presenting with symptomatic cholelithiasis, recurrent clinical signs are frequent and progression to gallstone-related complications is common.30 As a consequence, laparoscopic cholecystectomy is recommended for symptomatic cholelithiasis in people.2,30 Interestingly, although we observed recurrence of cholelithiasis-related complications in 2/6 (33%) symptomatic dogs, in contrast to a previous report, both dogs underwent successful medical management, with neither requiring surgical intervention.17
There is no current consensus on the management of incidental cholelithiasis in dogs. UDCA is often prescribed because of the perception that it may lead to dissolution of choleliths. By acting as a choleretic, UCDA may ameliorate some of the factors that lead to the formation of brown pigment choleliths, namely, precipitation of insoluble calcium bilirubinate, inflammation-associated mucin formation, gallbladder hypomotility, and bile stasis.3,25 In humans, by lowering biliary cholesterol supersaturation, UDCA can be effective in dissolving cholesterol stones in select patients.2 In our study, all dogs prescribed UDCAb had follow-up ultrasound performed, and although there is insufficient data to draw meaningful conclusions, it is interesting to note that no choleliths dissolved over the follow-up period. Further prospective studies on the benefits of UDCA in the management of canine cholelithiasis are warranted.
Limitations of this study, as with all retrospective studies, include incomplete medical records and clinical workup. The same ultrasound protocol was not used for evaluation, and the probe and machine variables would be set as per the operators’ preferences. This is a common situation and is part of the operator dependency of this imaging modality. As mentioned, mild clinical signs of cholelithiasis may not be appreciated in veterinary patients, and this may have resulted in an underestimation of the number of symptomatic choleliths. In addition, by only including dogs in the study if they had undergone abdominal ultrasound examination, and therefore by definition dogs that were under veterinary care, we may have over- or underestimated the true prevalence in the general dog population. An estimation of the true prevalence of cholelithiasis would require screening of healthy dogs alongside a hospital-based population. Further limitations of this retrospective study include the lack of standardization of the follow-up assessment and the absence of life-long follow-up, both of which may have resulted in an underestimation of the number of cases that go on to develop complications or clinical signs of their cholelithiasis.
Conclusion
This retrospective study found that cholelithiasis was an uncommon finding in dogs on abdominal ultrasound examination. In the majority of cases, dogs were asymptomatic and cholelithiasis was an incidental finding. Within the follow-up period, the majority of dogs in our case series appeared to remain asymptomatic. However, a prospective long-term study with a standardized follow-up is required to verify this observation.
Contributor Notes
CT (computed tomography); UDCA (ursodeoxycholic acid)
