Canine gallbladder disease is reported in association with choleliths, mucoceles, bacterial infection, neoplasia, and some hepatic diseases.1–4 The pathogenesis of canine gallbladder disease has been associated with disorders causing biliary stasis (eg, extrahepatic biliary obstruction or cholelithiasis) that may increase susceptibility to bacterial infection.1,5–8 Clinical signs associated with gallbladder disease in dogs are often vague and include nonspecific abdominal signs.1,2,5,7 Ultrasonographic imaging of the intraand extrahepatic biliary system can assist in the recognition of biliary obstruction as well as abnormal biliary contents in the gallbladder or bile duct (eg, gallbladder mucoceles, choleliths, and masses).5–7 Ultrasonographic identification of gallbladder rupture has been reported in dogs, but there is limited information on evaluation of ultrasonography for identification of gallbladder rupture, and to our knowledge, no attempt has been made to systematically identify imaging characteristics that can be used to predict rupture or the need for surgical intervention in a population of dogs with histologically confirmed gallbladder disease.
Histologic features of the healthy canine gallbladder include tall simple columnar epithelium that extends into sinus-like invaginations into the smooth muscle of the tunica muscularis, with a typical serosa.9 Dogs with gallbladder disease have various degrees and combinations of intramural hemorrhage, inflammation, fibrosis, cystic mucosal hyperplasia, and necrosis.2,5,10 Necrosis of the gallbladder, with or without associated gallbladder rupture, has been reported in dogs; however, the ultrasonographic image findings affiliated with this diagnosis have not been well established in veterinary medicine.1
The primary goal of the study reported here was to identify ultrasonographic findings associated with histologically confirmed gallbladder disease or surgically proven gallbladder rupture. We hypothesized that ultrasonographic characteristics can be used to predict either ruptured gallbladder or increased risk of gallbladder rupture caused by gallbladder disease. A secondary goal was to identify histologic, clinical, laboratory, and microbiologic variables that correlate with gallbladder rupture in dogs.
Materials and Methods
Criteria for selection of cases—A retrospective study of dogs with gallbladder disease at the University of Minnesota Veterinary Medical Center from July 1, 1997, through December 28, 2007, was performed. Dogs were identified from electronic medical record data as well as electronic billing codes as all dogs that received abdominal ultrasonography and abdominal surgery (cholecystectomy, cholecystotomy, or exploratory celiotomy) or necropsy. The criteria for inclusion in the study were an abdominal ultrasonographic examination performed by a board-certified radiologist within the 10 days preceding surgery or necropsy, surgical or necropsy confirmation of gallbladder status, and gallbladder histologic examination. If available, survey abdominal radiographs, CBC, serum biochemical profile, coagulation profile, and urine analysis within 5 days of the ultrasonographic examination as well as gallbladder bacterial culture results from surgical or necropsy specimens were evaluated.
Procedures—The medical record for each dog was reviewed for the reason for evaluation, previous history of nonspecific medical problems (previous unexplained vomiting, enteritis, or hepatic biochemical profile abnormalities), clinical signs (vomiting, anorexia, lethargy, jaundice, or diarrhea), duration of clinical signs, and physical examination findings (eg, fever, signs of abdominal pain, or lymphadenoapthy). Data on CBC, coagulation profile, urine analysis, aerobic and anaerobic bacteriologic culture of biliary samples, cytologic examination of bile for bacteria, type of surgical intervention or necropsy with specific attention to the gallbladder content and the integrity of the gallbladder, and gallbladder wall histologic findings were collected.
Static ultrasonographic and radiographic images were jointly reviewed by 2 authors (LJC and DAF), and classification of data was based on agreement. Ultrasonographic images were evaluated for gallbladder contents (mucocele, mobile sludge [aggregated contents], mobile precipitate, or choleliths), thickened gallbladder wall (> 3 mm),11 maximum gallbladder wall thickness (millimeters) perpendicular to the angle of interrogation, lamination of the gallbladder wall, increased echogenicity or reaction in the gallbladder fossa, fluid in the gallbladder fossa, peritoneal fluid beyond the gallbladder fossa, dilated extrahepatic bile duct (> 3.0 mm), extrahepatic duct architecture (normal, segmentally dilated, or diffusely dilated), dilated intrahepatic bile ducts,12 gallbladder wall echogenicity relative to the liver (hyperechoic, isoechoic, or hypoechoic), liver echogenicity relative to the kidney cortex, liver echotexture (nodular, uniform, or mass), cystic duct lumen (normal, dilated, mass, miscellaneous plug, or stone), cystic duct architecture (normal, segmentally dilated, or diffusely dilated), pancreatic echotexture (normal, increased and as echogenic as the regionally increased mesenteric reaction, or decreased and less echogenic than the regional organs), adrenal gland status (normal, mass, or mild diffuse enlargement),13 renoliths or renal pelvic mineralization, and cystic calculi. For the purpose of this study, a gallbladder mucocele was defined as ultrasonographic findings of an echogenic, fine, granular, organized structure that was non–gravity dependant, resembling a stellate pattern with a more or less prominent hypoechoic rim adjacent to the gallbladder wall.5,10,14,15 At our institution, the ultrasonographic protocol is established and includes shaking of the gallbladder to determine whether contents are mobile. Additionally, patients may be imaged in a standing position at the end of the study to evaluate mobility versus immobility of gallbladder contents including mural masses, choleliths, and gallbladder mucoceles. Gallbladder mucoceles were diagnosed by use of ultrasonography rather than retrospective review of the surgery report because it was not clear how many dogs had specific visual inspection of gallbladder contents at surgery, compared with a diagnosis made on the basis of prior ultrasonographic evidence; all mucoceles noted in the surgery report were included among those identified ultrasonographically. Radiographic images were evaluated for serosal detail overall in the abdomen, serosal detail in the right cranial portion of the abdomen, excess intestinal gas in the right cranial portion of the abdomen (a continuous linear gas in the duodenal intestinal loop, colonic intestinal loop, or both or a gascontaining intestinal loop of a diameter in excess of the diameter of a lumbar vertebral body),16 mineralization or gas in the region of the gallbladder or biliary tree, and liver size estimated on the basis of the fundic-pyloric axis.17 Imaging findings were numerically scored as yes versus no (presence vs absence of a finding). When echogenicity was the variable evaluated, it was a range of values (0 = hypoechoic, 1 = isoechoic, and 2 = hyperechoic).
To provide insight on the relative severity of the hematologic and serum biochemical abnormalities, the numeric values were indexed as a function of the specified reference range. Only data from the University of Minnesota Veterinary Medical Center laboratories were included. The indexing process consisted of setting all individual animal values for each test to 1.0 if the value was within the specified reference range. If a value exceeded the upper limit of the reference range, the individual animal value was divided by the maximum reference value and expressed as a value > 1.0. Similarly, if a value was less than the lower limit of the reference range, the individual animal value was divided by the minimum reference value and expressed as a value < 1.0. The serum hematologic variables evaluated included total WBC count, neutrophil count, presence of neutrophil toxic changes, lymphocyte count, monocyte count, and platelet count. The serum biochemical variables evaluated included concentrations or activities of total bilirubin, alkaline phosphatase, GGT, ALT, AST, cholesterol, amylase, glucose, calcium, urea nitrogen, creatinine kinase, albumin, and globulin. The coagulation profile, when available, included prothrombin time, activated partial thromboplastin time, serum fibrinogen concentration, and the presence or absence of fibrin degradation products. If multiple blood tests were done in a single dog, the values obtained immediately prior to the ultrasonographic examination were used.
The gallbladder wall was histologically evaluated by a board-certified pathologist (IM) for evidence of necrosis, hemorrhage, inflammation (suppurative or lymphoplasmacytic), mucosal hyperplasia, and fibrosis. These histologic changes were considered present and of clinical importance if moderate to severe change was assessed by the pathologist; this was done to differentiate the predominant abnormality from mild and potentially secondary reactive change. Statistical comparisons were made between available nonhistologic data (imaging findings, laboratory findings, history and physical examination, and patient outcome) and the presence or absence of each of the evaluated histologic findings.
For the survival analyses, dogs that were euthanized because of financial constraints or for reasons of prognostic uncertainty were excluded. Dogs that lived for 2 weeks following surgical management were classified as having survived. Dogs that died of the disease or that were euthanized because of deteriorating clinical status despite treatment were classified as dying of the disease.
Demographic data (age, breed, sex, and weight) were summarized. Data were analyzed with a statistical package.a The F2 test of independence and Spearman correlation analyses were performed to determine any statistical association among the clinical, hematologic, serum biochemical, ultrasonographic, or radiographic variables and the presence or absence of gallbladder rupture, histopathologic findings in the gallbladder, or patient survival. Discriminant analysis with a forward stepwise regression procedure for variable inclusion (P < 0.05 for inclusion; P > 0.1 for exclusion) was used to determine whether any of the variables were useful in the preoperative prediction of gallbladder integrity, histopathologic findings, or the likelihood of patient survival. Similar analyses were performed on the presence or absence of ultrasonographically defined gallbladder mucoceles versus histopathologic findings, outcome of aerobic cultures, or presence or absence of gallbladder rupture. Significance for all analyses was defined as P < 0.05 (< 5% probability that there was no relationship or no difference).
Results
Forty-five dogs fulfilled the inclusion criteria of the study. The prevalent breeds were Cocker Spaniel (n = 4; 8.8%) and Shetland Sheepdog (n = 4; 8.8%). There were 27 (60.0%) spayed females, 1 (2.2%) sexually intact female, 13 (28.9%) neutered males, and 4 (8.9%) sexually intact males. Median body weight of dogs at initial evaluation was 11.25 kg (24.75 lb; range, 3.0 to 48.6 kg [6.6 to 106.9 lb]) and 70% of the dogs weighed < 20 kg (44 lb). The median age at diagnosis was 10.0 years (range, 3.5 to 15.0 years).
Forty of 45 dogs had an ultrasonographic scan within the 3 days prior to surgery or necropsy and included all dogs that had confirmed gallbladder rupture. Of the remaining 5 dogs, ultrasonographic examinations were within the 10 days prior to surgery. Within 5 days of the ultrasonographic examination, 22 dogs also had abdominal radiographs available for interpretation.
The most frequent clinical signs at initial evaluation were vomiting (35/45 [77.8%] dogs), lethargy (33/45 [73.3%]), anorexia (32/45 [71.1%]), jaundice (21/45 [46.7%]), abdominal pain (20/45 [44.4%]), diarrhea (13/45 [28.9%]), and fever (9/45 [20.0%]). Median duration of clinical signs was 3 days (range, 1 to 60 days) prior to evaluation. Fifteen (33.3%) dogs had a previous history of nonspecific medical problems, such as unexplained vomiting, lethargy, or increased serum liver-related enzyme activities. The most common serum biochemical abnormalities at evaluation were increased serum alkaline phosphatase activity (40/43 [93.0%] dogs), bilirubin concentration (38/43 [88.4%]), GGT activity (26/43 [60.5%]), ALT activity (36/43 [83.7%]), and AST activity (31/43 [72.1%]). Median magnitudes of the indexed mean abnormalities (within reference range = 1) were serum bilirubin (14.7), alkaline phosphatase (16.8), GGT (3.8), ALT (3.4), and AST (2.9). The most common hematologic abnormalities were leukocytosis (32/40 [80.0%] dogs) and neutrophilia (30/40 [75.0%]). Median magnitudes of the indexed mean abnormalities (within reference range = 1) were leukocytosis (1.58) and neutrophilia (1.39). Only 10 of 40 (25.0%) dogs had toxic change in the circulating neutrophils; all of these had histologic gallbladder necrosis (5 with gallbladder rupture).
Results of bacterial cultures were positive in 10 of 40 (25.0%) samples via aerobic culture and 1 of 20 samples via anaerobic culture (Table 1). The isolated aerobic species included nonhemolytic Escherichia coli (n = 6), Streptococcus sp (2), Enterococcus sp (2), Pseudomonas aeruginosa (1), Bacillus sp (1), gram-negative bacilli (1), and gram-positive cocci (1). Four dogs had more than 1 aerobic species isolated from bile. The only anaerobic bacterium cultured was Clostridium perfringens. Of the 11 dogs with positive culture results, 9 dogs had gallbladder wall necrosis and 5 had gallbladder rupture. Positive results of culture were most often found in dogs without a gallbladder mucocele; only 2 of 21 (9.5%) dogs with a mucocele had positive results of aerobic bacterial culture, and none had positive results of anaerobic culture.
Comparison of survival status, bile bacterial culture results, and gallbladder integrity at surgery (or necropsy) in 43 dogs with or without an ultrasonographically identifiable biliary mucocele.*
| Bile bacterial culture results | Survival status | Mucocele present | Mucocele absent | ||
|---|---|---|---|---|---|
| Gallbladder rupture | Gallbladder intact | Gallbladder rupture | Gallbladder intact | ||
| Positive | Lived | 1 | 0 | 3 | 4 |
| Positive | Died | 0 | 1 | 1 | 0 |
| Negative | Lived | 5 | 9 | 5 | 8 |
| Negative | Died | 1 | 1 | 0 | 2 |
| Not done | Lived | 1 | 1 | 0 | 0 |
| Not done | Died | 0 | 0 | 0 | 0 |
* Excludes 2 dogs that were euthanized because of the owner's unwillingness to permit surgery.
Other than variable amounts of echogenic mobile or organized content, 8 (17.8%) dogs had no ultrasonographic evidence of gallbladder abnormality (Figure 1). The most frequently noted ultrasonographic abnormalities in the 45 dogs with gallbladder disease included echogenic peritoneal fluid (24/45 [53.3%] dogs), thickened gallbladder wall (23/45 [51.1%]), and echogenic reaction in the gallbladder fossa (22/45 [48.9%]; Table 2; Figure 2). None of the 45 dogs had ultrasonographic or radiographic evidence of a cholelith or intrahepatic bile duct distension at the time of ultrasonographic imaging. Extrahepatic bile duct distension (> 3 mm) was identified in 12 of 13 dogs. The predominant radiographic abnormality was poor serosal detail in the right upper quadrant or diffusely throughout the abdomen (7/22 [31.8%] dogs), suggestive of peritoneal effusion.
Distribution (number of affected dogs) of imaging findings in 45 dogs with gallbladder disease and rupture.
| Variable | Gallbladder disease (n = 45) | Gallbladder rupture (n = 18) |
|---|---|---|
| Ultrasonographic findings | ||
| Gallbladder mucocele | 21 | 9 |
| Gallbladder mobile sludge | 19 | 8 |
| Gallbladder mobile precipitate | 5 | 1 |
| Choleliths | 0 | 0 |
| Thickened gallbladder wall (> 3.0 mm)* | 23 | 10 |
| Lamination of gallbladder wall | 14 | 7 |
| Echogenic reaction, gallbladder fossa | 22 | 13 |
| Peritoneal fluid, gallbladder fossa | 24 | 14 |
| Peritoneal fluid, beyond gallbladder fossa | 17 | 12 |
| Dilated extrahepatic bile duct (> 3.0 mm) | 12 | 2† |
| No definable gallbladder abnormalities‡ | 8 | 0 |
| Radiographic findings§ | ||
| Serosal detail, right cranial portion of the abdomen | 7 | 5 |
| Excess gas, right cranial portion of the abdomen | 3 | 2 |
| Serosal detail, overall abdomen | 7 | 5 |
* Mean gallbladder wall thickness was 4.7 mm in dogs with gallbladder disease and 5.4 mm in dogs with gallbladder rupture.
† An extrahepatic bile duct was specificajly identified in only 3 dogs with gallbladder rupture.
‡ No mucocele, no thickened or laminated wall, no peritoneal fluid within or beyond the gallbladder fossa, and no echogenic reaction of tissues bordering the gallbladder fossa.
§ Radiography was performed in 22 dogs with gallbladder disease and 9 dogs with gallbladder rupture.
Transabdominal ultrasonographic images of gallbladders from dogs with histologically confirmed gallbladder disease without gallbladder rupture. A—Mobile gallbladder precipitate. B—Mobile gallbladder sludge. C—Gallbladder mucocele.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Transabdominal ultrasonographic images of gallbladders from dogs with histologically confirmed gallbladder disease without gallbladder rupture. A—Mobile gallbladder precipitate. B—Mobile gallbladder sludge. C—Gallbladder mucocele.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Transabdominal ultrasonographic images of gallbladders from dogs with histologically confirmed gallbladder disease without gallbladder rupture. A—Mobile gallbladder precipitate. B—Mobile gallbladder sludge. C—Gallbladder mucocele.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Transabdominal ultrasonographic images of gallbladders in dogs with histologically confirmed gallbladder disease; white arrows indicate hyperechoic tissue of the gallbladder fossa. A—Gallbladder mucocele rupture through rent in gallbladder wall. B—Ruptured gallbladder, luminal mucocele, echogenic fluid in the gallbladder fossa, and hyperechoic reaction in the adjacent tissue. C—Thickened gallbladder wall with mobile sludge. D—Intact gallbladder with mobile sludge and lamination (black arrows) of the gallbladder wall.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Transabdominal ultrasonographic images of gallbladders in dogs with histologically confirmed gallbladder disease; white arrows indicate hyperechoic tissue of the gallbladder fossa. A—Gallbladder mucocele rupture through rent in gallbladder wall. B—Ruptured gallbladder, luminal mucocele, echogenic fluid in the gallbladder fossa, and hyperechoic reaction in the adjacent tissue. C—Thickened gallbladder wall with mobile sludge. D—Intact gallbladder with mobile sludge and lamination (black arrows) of the gallbladder wall.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Transabdominal ultrasonographic images of gallbladders in dogs with histologically confirmed gallbladder disease; white arrows indicate hyperechoic tissue of the gallbladder fossa. A—Gallbladder mucocele rupture through rent in gallbladder wall. B—Ruptured gallbladder, luminal mucocele, echogenic fluid in the gallbladder fossa, and hyperechoic reaction in the adjacent tissue. C—Thickened gallbladder wall with mobile sludge. D—Intact gallbladder with mobile sludge and lamination (black arrows) of the gallbladder wall.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
The most common histologic changes found in the gallbladder of all dogs included necrosis (n = 32), vascular thrombosis (24), hemorrhage (24), and mucosal hyperplasia (22; Table 3; Figures 3 and 4). Within the subset of 21 dogs with biliary mucoceles, the predominant histologic changes included necrosis (n = 17), thrombosis (13), granulation tissue (11), mucosal hyperplasia (9), hemorrhage (9), and suppurative inflammation (7). Within the subset of 11 dogs with bacteria cultured from their bile, the predominant histologic changes included necrosis (n = 10), thrombosis (7), hemorrhage (7), and suppurative inflammation (7).
Distribution (number of dogs) of histologic findings and positive results of bacterial culture in 45 dogs with gallbladder disease.
| Histologic findings* | Ruptured gallbladder (n = 18) | Intact gallbladder (n = 27) | Aerobic culture† | Anaerobic culture† |
|---|---|---|---|---|
| Mucosal hyperplasia | 6 | 16 | 3 | 1 |
| Lymphoplasmacytic inflammation | 2 | 5 | 3 | 0 |
| Suppurative inflammation | 9 | 5 | 7 | 0 |
| Fibrosis | 1 | 1 | 1 | 0 |
| Hemorrhage | 12 | 12 | 7 | 0 |
| Necrosis | 17 | 15 | 9 | 0 |
| Thrombosis | 10 | 14 | 7 | 0 |
| Granulation tissue | 7 | 11 | 4 | 0 |
| Mucin in the lumen | 9 | 2 | 1 | 1 |
* Lesions were recorded only if the particular finding was moderate to marked in severity. Several concurrent changes were frequently present in the same gallbladder section (eg, necrosis, granulation tissue, and hemorrhage).
† †Bacteria isolated included Clostridium perfringens (1 dog), nonhemolytic Escherichia coli (6), Streptococcus spp (2), Enterococcus spp (2), Pseudomonas aeruginosa (1), Bacillus spp (1), gram-negative bacilli (1), and gram-positive cocci (1).
Photomicrograph of a section of gallbladder wall from a dog with gallbladder disease. Notice the marked mucosal hyperplasia, abundant mucinous fluid in the lumen, diffuse transmural necrosis, and granulation tissue between the gallbladder wall and liver. H&E stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Photomicrograph of a section of gallbladder wall from a dog with gallbladder disease. Notice the marked mucosal hyperplasia, abundant mucinous fluid in the lumen, diffuse transmural necrosis, and granulation tissue between the gallbladder wall and liver. H&E stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Photomicrograph of a section of gallbladder wall from a dog with gallbladder disease. Notice the marked mucosal hyperplasia, abundant mucinous fluid in the lumen, diffuse transmural necrosis, and granulation tissue between the gallbladder wall and liver. H&E stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Photomicrograph of a section of gallbladder wall from a dog with gallbladder disease. Notice the diffuse transmural necrosis and granulation tissue. Hyperplastic mucosal folds are covered by markedly vacuolated epithelial cells. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Photomicrograph of a section of gallbladder wall from a dog with gallbladder disease. Notice the diffuse transmural necrosis and granulation tissue. Hyperplastic mucosal folds are covered by markedly vacuolated epithelial cells. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Photomicrograph of a section of gallbladder wall from a dog with gallbladder disease. Notice the diffuse transmural necrosis and granulation tissue. Hyperplastic mucosal folds are covered by markedly vacuolated epithelial cells. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 234, 3; 10.2460/javma.234.3.359
Gallbladder rupture—Twenty-seven dogs had an intact gallbladder, and 18 dogs had confirmed gallbladder rupture (Table 2). Nine of the dogs with rupture had a mucocele; those 9 dogs represent 42.9% of the 21 dogs with a gallbladder mucocele. Gallbladder rupture was associated with the ultrasonographic findings of echogenic peritoneal fluid in the gallbladder fossa (r = 0.400; P = 0.006; Figure 2), echogenic reaction in the gallbladder fossa (r = 0.381; P = 0.010), and echogenic peritoneal fluid beyond the gallbladder fossa (r = 0.487; P = 0.001) and with the radiographic findings of decreased serosal detail in the right cranial portion of the abdomen (r = 0.424; P = 0.049) and decreased serosal detail overall (r = 0.424; P = 0.049). One or more of these imaging findings were found in 17 of 18 dogs with confirmed gallbladder rupture but were also found in 15 of 27 (55.5%) dogs without rupture. There was a positive correlation between gallbladder rupture and increased total WBC count (r = 0.425; P = 0.006) and increased absolute neutrophil count (r = 0.465; P = 0.002). There was a negative correlation between gallbladder rupture and a normal coagulation profile (r = −0.569; P = 0.001) and the indexed serum concentration for calcium (r = −0.323; P = 0.045).
A significant relationship was found between the histologic identification of gallbladder necrosis and gallbladder rupture (r = 0.420; P = 0.004). All 18 dogs with gallbladder rupture had moderate to severe histologic gallbladder necrosis (Figure 3). Of the 27 dogs with an intact gallbladder, 15 (55.6%) also had histologic evidence of wall necrosis. None of the individual or combined histologic criteria (necrosis, mucosal hyperplasia, hemorrhage, lymphoplasmacytic inflammation, and suppurative inflammation) were significantly associated with any of the imaging findings. There was, however, a positive correlation between gallbladder wall necrosis and total WBC count (r = 0.446; P = 0.004) and neutrophil count (r = 0.404; P = 0.009).
Survival—Two of the 45 dogs were euthanized because of owner unwillingness to pursue further treatment. Fortythree of the 45 dogs had surgical intervention (40 cholecystectomy, 1 partial cholecystectomy, 1 cholecystotomy, and 1 abdominal exploratory surgery). The dog with an abdominal exploratory surgery was euthanized prior to recovery from anesthesia because of extensive adhesions involving the gallbladder, liver, pancreas, and descending duodenum that were deemed inoperable. This dog was classified as dying because of disease. Another 5 dogs died following surgery: 2 of 45 (4.7%) dogs died of diffuse intravascular coagulopathy within 24 hours of surgery, 2 of 45 (4.7%) dogs died as a result of surgical site dehiscence 4 days after the surgery (cholecystectomy in 1 and partial cholecytectomy in the other dog), and 1 dog was euthanized 1 week following surgery for progressive lethargy, vomiting, and diffuse intravascular coagulopathy at the time of return to the hospital. One of 18 dogs with a preoperative diagnosis of biliary rupture followed by surgical management died. Overall survival rate was 86.0%. Survival rate for dogs with gallbladder rupture and bile leakage prior to surgery was 94.4%, for dogs with bacterial bile infection was 82.0%, and for dogs with gallbladder mucoceles was 81.0%, none of which were significantly different from overall survival rate.
Greater total lymphocyte count was the only hematologic variable that was associated with survival; greater total lymphocyte counts (r = 0.349; P = 0.034) were found among the group of dogs that lived. There was no significant difference among any of the indexed serum biochemical concentrations or any of the imaging variables between dogs that lived or died.
The discriminant analyses of the hematologic and biochemical variables, the ultrasonographic and radiographic findings, as well as the defined clinical signs were performed in an effort to determine whether there were any clinically useful variables that would predict gallbladder rupture, the type of gallbladder infiltrate, or survival. The only significant association was between diffuse echogenic peritoneal fluid identified via ultrasonography and the presence or absence of gallbladder rupture. This was 75.6% accurate (12/18 correct for rupture; 22/27 correct for no rupture) within this narrowly defined group of dogs. There were 5 of 27 false-positive and 6 of 18 false-negative predictions of gallbladder rupture.
Discussion
Dogs in the present study had similar demographic,4,10,14,15,18 historical, and clinical findings1,4,5,7,14,15,18 to those reported for dogs with gallbladder disease. The previous history of nonspecific medical problems such as unexplained vomiting or lethargy, increased serum liver-related enzyme activities, and tentative diagnoses of gastritis or enteritis in our population of dogs with gallbladder disease may represent previous indolent biliary disease. Similar unexplained transient clinical signs in dogs with a subsequent diagnosis of gallbladder disease have been reported.2,7
Although the etiology of canine gallbladder disease has not been established, the predominant histologic abnormality of necrosis in the absence of inflammatory cell infiltrate found in the present study has also been reported in a group of 23 dogs1; therefore, this condition cannot appropriately be referred to as cholecystitis. Our findings of 1 or more combinations of necrosis, thrombosis, hemorrhage, and mucosal hyperplasia of the gallbladder wall may reflect the primary pathologic features of canine gallbladder disease or may in part be a reflection of a later stage or severe form of disease that these dogs had, which warranted surgical management. Within this subset of dogs, the abnormal ultrasonographic findings of echogenic peritoneal fluid, thickened gallbladder wall, and echogenic reaction in the gallbladder fossa were the most common imaging findings and therefore should raise suspicion for gallbladder disease. Although gallbladder mucocele or positive results of bacterial bile cultures were the most common concurrent finding, we found no evidence to suggest that either of these was a primary versus secondary event; presumably, there is more than 1 pathophysiologic mechanism involved. Although a significant relationship was not found between bile culture results and the histologic gallbladder wall abnormalities, among the dogs that had bile cultures, bacteria were found in 70.0% of dogs with histologic evidence of gallbladder wall necrosis but no other concurrent gallbladder abnormality (ie, no mucocele, no apparent extrahepatic biliary duct obstruction, and no cholelithiasis). These results are similar to another report1 in which 81.3% of dogs with gallbladder wall necrosis also had concurrent positive results of gallbladder bacterial cultures. This suggests that there may be a relationship between bacteria in the gallbladder and necrosis of the gallbladder and that presurgical identification of bacteria is a negative indicator because of the potential of rupture among dogs with necrosis of the gallbladder. There is limited information available on the prevalence of concurrent bacterial bile infection and gallbladder mucoceles. From reports5,14,15 of dogs with mucoceles that had bacteriologic bile cultures, concurrent bacterial infection was found in 2 of 22 dogs, 1 of 8 dogs, and 7 of 9 dogs. In the present study, only 2 of 18 mucoceles yielded aerobic bacteria. In contrast, 8 of 23 dogs with nonmucocele gallbladder disease had bacterial infections. Most of the cultures revealed polymicrobial aerobic infections similar to previous reports5,14 and included bacterial species typically associated with the intestinal tract. Further complicating this issue is the fact that about equal numbers of the ruptured and nonruptured diseased gallbladders had identifiable infection.
Gallbladder mucoceles are characterized by ultrasonographic findings of an echogenic, fine, granular, organized structure that is non–gravity dependant, often resembling a stellate pattern with a more or less prominent hypoechoic rim attributed to mucin between the gallbladder wall and the organized structure, leading some to postulate that mucoceles may form secondary to mucosal hyperplasia.5,10,14,15 Gallbladder mucosal hyperplasia as a histologic finding was only found in 39.1% of dogs in the present study; the more frequently seen histologic abnormalities of necrosis, thrombosis, and granulation tissue as well as suppurative inflammation among some dogs with gallbladder mucoceles suggests a more complex etiology. This study provided no insight as to the likelihood or outcome of dogs with clinically inapparent mucoceles because of the selection criteria. This aspect of mucoceles merits further investigation.
The gold standard for gallbladder assessment and evaluation of gallbladder rupture in humans is ultrasonography or computed tomography, and identification of a rent in the gallbladder wall is quite common.19 Ultrasonographic identification of a gallbladder wall rent was reported in 2 of 3 dogs with a mucocele and confirmed gallbladder rupture.5 The sensitivity of abdominal ultrasonography for canine gallbladder rupture in a study15 of 30 dogs (12 with confirmed rupture) with a mucocele is reported to be 85.7%, with a specificity of 100% and a positive predictive value of 100% based on gallbladder wall discontinuity, hyperechoic cranial abdominal fat, free peritoneal fluid, or a free striated-stellate echogenic structure within the peritoneal cavity. The sensitivity of these findings in dogs with non–mucocele-related gallbladder rupture has not been previously reported. The present study population included 45 dogs, 18 of which had gallbladder rupture. Concurrent mucocele and gallbladder rupture was diagnosed in 9 dogs. The imaging findings of pericholecystic echogenic reaction, pericholecystic fluid, generalized echogenic peritoneal effusion, or localized or decreased radiographic serosal detail had a sensitivity of 94.4% and a specificity of 44.4% for gallbladder rupture. In only 1 dog with gallbladder rupture was a gallbladder rent observed ultrasonographically, and it had a protruding mucocele (Figure 2). The challenge of identification of a gallbladder wall rent in the absence of an extruding mucocele and the absence of a mucocele free in the peritoneum may contribute to the lower specificity of imaging characteristics for gallbladder rupture and bile leakage in non–mucocele-related gallbladder rupture.
Bile peritonitis is reported secondary to gallbladder necrosis, extrahepatic biliary obstruction secondary to cholelithiasis, and traumatic bile leakage.1,18 In the present study, there was no evidence to indicate that septic or aseptic bile leakage from gallbladder rupture at initial surgical intervention was a negative predictor of survival. The mortality rate attributable to preoperative bile leakage in this study (5.5%) was considerably lower, compared with previous studies1,14,15 that have a range of 28% to 39% mortality rate following surgery for bile peritonitis. We prefer to use the term bile leakage from gallbladder rupture rather than bile peritonitis because we did not have histologic criteria of bile crystals within the serosa. Septic bile peritonitis has been associated with an increased risk of mortality, as compared to aseptic bile peritonitis in 1 group of 11 dogs and a second group of 26 dogs.18,20 Our data did not support a worse prognosis for dogs with leakage of septic versus aseptic bile.
Although reported elsewhere,18 increased serum creatinine concentration, increased activated partial thromboplastin time, increased circulating band neutrophils, leukocytosis, and bacteria in the biliary effusion among nonsurvivors, compared with dogs that lived, were not detected in the present study. Greater total WBC count and greater neutrophil counts have been reported in dogs that died of gallbladder disease, compared with those that survived.10 In the present study, with the exception of total lymphocyte count, hematologic and serum biochemical values were not significantly different between dogs that lived and died, which has also been reported.14 It is apparent that hematologic and serum biochemical variables are not useful in predicting survival among dogs with gallbladder disease.
Death within 1 week after surgery was attributed to sepsis, diffuse intravascular coagulopathy, and surgical site dehiscence. This was consistent with causes of death among dogs after surgery for mucoceles.14 Pancreatitis that developed after surgery has also been reported among 6 of 22 dogs.14 Pancreatitis was not identified in our population. It should be noted that few of the dogs in the present study died following surgery, which may suggest a role for aggressive surgical intervention.
Discriminate analyses failed to yield hematologic, biochemical, or radiographic variables that could be useful for prediction for survival, gallbladder rupture, or the histologic changes associated with gallbladder rupture. There was a relationship between ultrasonographically defined echogenic diffuse peritoneal fluid and gallbladder rupture that had a nominal sensitivity (66.6%) but a moderately high specificity (81.5%). Sensitivity of ultrasonography for detection of gallbladder rupture was increased (91.4%) by use of the combination of localized echogenic peritoneal fluid, echogenic reaction in the gallbladder fossa, and echogenic diffuse peritoneal fluid at the expense of a lower specificity (44.4%).
By use of all available variables, discriminant analysis resulted in both false-positive and false-negative predictions of gallbladder rupture and provided no insight into the likelihood of patient survival. The false-positive results of the analysis in 5 of 27 (18.5%) cases resulted from finding diffuse echogenic peritoneal fluid that could lead to a recommendation for surgery when the gallbladder is actually intact. However, it is not known whether echogenic diffuse peritoneal fluid is associated with eventual rupture or other complications. More research will be necessary to provide this insight. From another perspective, the false-negative results of the analysis in 6 of 18 cases are a more worrisome situation in that potentially serious disease may be underestimated. This must be recognized in clinical interpretation. If a large prospective study were conducted with greater control of variables, these outcomes may improve. It is worth noting that the maximum delay between ultrasonographic imaging and surgery or necropsy on the dogs with false-negative results was ≤ 3 days. Whether there was disease progression during that delay is not known.
There were several shortcomings to this study. Dogs had to be sufficiently ill to justify something other than conservative medical management on the part of the attending clinician. Therefore, the study did not provide insight regarding mild to moderate gallbladder disease or the outcome of medically managed cases. It did, however, provide perspective on which clinical, laboratory, and imaging findings were associated with confirmed severe gallbladder disease and gallbladder rupture. Also, because of the retrospective nature of the study, there were uncontrolled delays between any of the laboratory and imaging variables and the surgical or necropsy confirmation of the gallbladder status. The possibility exists, therefore, that the disease worsened between the time the values were obtained and the surgical or necropsy intervention.
The most frequent imaging findings in dogs with gallbladder rupture were echogenic fluid around the gallbladder, diffuse echogenic peritoneal fluid, and radiographically decreased peritoneal detail; therefore, these findings should raise the index of suspicion for gallbladder rupture. Ultrasonography provides a means for monitoring gallbladder disease and may provide some insight into which patients have, or are at increased risk for, gallbladder rupture. Survival rate among dogs with surgically managed gallbladder disease was approximately 86% and did not appear to be influenced by factors such as gallbladder rupture and bile leakage prior to surgical intervention, concurrent bacterial infection in bile, or concurrent gallbladder mucocele.
ABBREVIATIONS
| ALT | Alanine transaminase |
| AST | Aspartate aminotransferase |
| GGT | J-Glutamyl transpeptidase |
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SPSS, version 13.0, SPSS Inc, Chicago, Ill.
