Vet Radiology Ultrasound - 2022 - Villm - Prevalence of Gallbladder Sludge and Associated Abnormalities in Cats Undergoing
Vet Radiology Ultrasound - 2022 - Villm - Prevalence of Gallbladder Sludge and Associated Abnormalities in Cats Undergoing
See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Received: 29 July 2021          Revised: 6 January 2022            Accepted: 16 January 2022
DOI: 10.1111/vru.13091
O R I G I N A L I N V E S T I G AT I O N
                                                               KEYWORDS
                                                               biliary, feline, microlithiasis
Vet Radiol Ultrasound. 2022;63:601–608.                                     wileyonlinelibrary.com/journal/vru     © 2022 American College of Veterinary Radiology.    601
                                                                                                                                                             17408261, 2022, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vru.13091 by Cesar Sanchez Jimenez - <Shibboleth>[email protected] , Wiley Online Library on [10/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
602                                                                                                                                          VILLM ET AL .
irrespective of disease. Only one study provides data from cats pre-           or without GBS that were evaluated within 1 week of the ultrasound
senting for abdominal ultrasound.1                                             examination were used for analysis. Case identification was performed
    An association of GBS with hepatobiliary disease has been sug-             by an ACVIM-certified small animal internist (SD), and ACVR-certified
gested by finding sludge in about 40% of cats with hepatobiliary disease       veterinary radiologist (ML). Data recording was performed by the fol-
and 20–62% with extra-hepatic biliary obstruction.12–15 Cats with GBS          lowing: small animal internal medicine resident (JV), ACVIM-certified
were three times more likely to have bacteria cultured from bile and a         small animal internist (SD), and ACVR-certified veterinary radiologist
diagnosis of feline cholangitis than those without     GBS.2   The bile and    (ML).
pancreatic ducts share a common duodenal papilla and could make                   Abdominal ultrasound reports were used to record the presence or
cats more susceptible to gallbladder and pancreatic disease. Bacte-            absence of GBS (Figure 1) along with common bile duct (CBD) size, and
rial infection of the pancreas and hepatobiliary system can occur from         any GB, hepatic, pancreatic or intestinal abnormalities. Reports were
ascending bacteria from the gastrointestinal (GI) tract or transloca-          searched for the description of echogenic material within the gallblad-
tion and hematogenous seeding of bacteria.16–18 Triaditis has also been        der lumen or anechoic contents within the GB lumen to determine the
described in cats as concurrent inflammation within the pancreas, gas-         presence or absence of GBS, respectively. All images were retrospec-
trointestinal tract, and hepatobiliary system which suggests a potential       tively reviewed by one ACVR-certified veterinary radiologist (ML) to
link between these organ systems.19      In a recent prospective study, tri-   verify the reported findings of the GB, liver, and pancreas. All images
aditis was identified in 30% (8/27) of cats with non-specific GI signs.20      and reports were available for this observer, but they were not aware
It is possible that cats with hepatobiliary disease might also have evi-       of presenting complaints or final diagnoses. Cases were excluded if
dence of pancreatic or GI disease, suggesting that evaluation of hepa-         GB contents were not described and ultrasound images of the GB
tobiliary abnormalities should also include evaluation of the pancreas         were either unavailable or inconclusive. In patients with more than
and GI tract.                                                                  one abdominal ultrasound performed, data from the first ultrasound
    The objectives of this study were to determine the prevalence of           was used. Ultrasonographic changes consistent with hepatobiliary dis-
GBS in a population of cats that underwent abdominal ultrasound; to            ease on the report were described and evaluated as normal or abnor-
describe clinical signs, laboratory findings and abdominal ultrasound          mal which included analysis of the gallbladder (gallbladder wall (GBW)
abnormalities; and to compare these findings to cats without GBS.              thickness, CBD dilation, GBS, gallbladder contents, and other gallblad-
We hypothesized that the ultrasonographic finding of GBS in cats               der abnormalities), liver, pancreas, and gastrointestinal tract. Gallblad-
would be associated with hepatobiliary, gastrointestinal, and/or pan-          der sludge was defined as the presence of echogenic material with-
creatic abnormalities detected by clinical, biochemical and ultrasound         out shadowing within the GB lumen. Gallbladder wall thickness was
assessment.                                                                    classified as abnormal with a measurement of greater than or equal
                                                                               to > 1 mm (Figure 2) and the CBD was abnormal with a measurement
                                                                               equal or greater than > 4 mm. The liver and pancreas were consid-
2       MATERIALS AND METHODS                                                  ered abnormal if there were changes in echogenicity, size, and shape
                                                                               or were noted to have focal lesions such as nodules or masses. Final
2.1       Experimental design and selection of subjects                        diagnosis was retrospectively recorded for each cat and placed in cat-
                                                                               egories including urologic, gastrointestinal, hepatobiliary, pancreatic,
Feline patients that had an abdominal ultrasound performed at the              infectious, neoplasia, cardiac, neurologic, other and unknown. Some
Virginia-Maryland Veterinary Teaching Hospital between October                 cats were diagnosed with multiple diseases thus were placed in mul-
2014-October 2015 were included in this observational, retrospec-              tiple categories if thought to be contributing to the presenting com-
tive study. Cat were excluded if ultrasound images of the liver, GB, or        plaint. When a definitive diagnosis could not be found in the medical
pancreas were unavailable. All decisions for subject inclusion or exclu-       record, a presumptive diagnosis was given. Cats with hepatobiliary dis-
sion were made by observer(s) with expertise in small animal internal          ease were given a presumptive diagnosis if histopathology or bile cul-
medicine and veterinary radiology (SD, ML). Approval for use of the            ture were unavailable. Cases were reviewed by a both a small animal
medical record data in this study was provided by both owners and the          resident (JV) and ACVIM-certified veterinary internist (SD) to confirm
veterinary teaching hospital director.                                         agreement in diagnoses independently.
Medical records of enrolled patients were searched retrospectively for         All analyses were performed by a statistician using SAS version 9.4
cats undergoing an AUS during the study period. Signalment, clinical           (SAS Institute Cary, North Carolina, USA). Risk factors associated with
signs, complete blood count, and biochemical findings were recorded.           the primary outcome of the presence of GBS were evaluated. Con-
Clinicopathologic abnormalities associated with hepatobiliary disease          tinuous risk factors included age, ALT, ALP, GGT, total bilirubin, albu-
including ALT, ALP, GGT, total bilirubin, albumin, cholesterol as well         min, cholesterol, WBC, neutrophils, and lymphocytes. Categorical risk
as white blood cells (WBC), neutrophils, and lymphocytes in cats with          factors included sex, breed, clinical signs (lethargy, vomiting, anorexia,
                                                                                                                                                               17408261, 2022, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vru.13091 by Cesar Sanchez Jimenez - <Shibboleth>[email protected] , Wiley Online Library on [10/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
VILLM ET AL .                                                                                                                                          603
F I G U R E 1 Ultrasonographic images (longitudinal and transverse) displaying gallbladder sludge (white arrows) within the gallbladder lumen of
cats (Phillips iU22 high-definition ultrasound, 8 mHz microconvex and 12 mHz linear probes, Phillips Medical Systems, Bothell, WA)
weight loss, and diarrhea), ultrasound abnormalities including GBW           ACVR-certified veterinary radiologist or a veterinary radiology resi-
thickening, CBD dilation, other GB abnormalities, liver abnormali-           dent under the supervision of an ACVR-certified veterinary radiologist
ties (including nodules, masses, change in echogenicity, and changes         using a high-definition ultrasound system (Philips iU22, Philips Medi-
seen in portal vasculature), and pancreatic abnormalities (including         cal Systems, Bothell, WA) equipped with preset broad bandwidth oper-
masses/nodules, change in pancreatic and peripancreatic echogenic-           ating frequency transducers (8 mHz microconvex and 12 MHz linear).
ity, size, dilations in pancreatic duct). Normal probability plots showed    Animals were positioned in dorsal or left lateral recumbency.
that all continuous variables were skewed. Accordingly, continuous             Gallbladder sludge was present in 44% of cats (n = 84; 46 females,
data were summarized as medians (range) while categorical variables          38 males). The mean age of cats presenting for abdominal ultra-
were summarized as counts and percentages. Bivariate associations            sound was 11 years (range 0.5-20.0 yrs), with no significant difference
between the primary outcome and risk factors were assessed using             (P = 0.24) between cats with GBS (11.5 yrs mean age, range 0.8-20.0
Fisher’s exact test (categorical variables) and the Wilcoxon rank sum        yrs) and without GBS (11.0 yrs mean age, range 0.5-19.0 yrs). Of 192
test (continuous variables). Significant variables were then used to         cats, 52% (n = 101) were spayed females, 1.6% intact females (n = 3),
select significantly associated variables. These constituted the predic-     and 45.8% (n = 88) castrated males. Fourteen breeds were represented
tors in the full multivariable logistic model (total bilirubin, CBD thick-   including domestic shorthair (n = 139), domestic longhair (n = 28),
ening, GBW thickening). Linearity between the log odds and each of the       Siamese (n = 6), Maine Coon (n = 4), Ragdoll (n = 3), Bengal (n = 2),
continuous variables was assessed using a generalized additive model.        Himalayan (n = 2), Scottish Fold (2), and one of each of the following
Fit of the model was assessed using the Hosmer and Lemeshow good-            breeds: Burmese, Exotic Shorthair, Oriental, Russian Blue, Sonoma, and
ness of fit test. Stepwise was used to select the final model. Statistical   Sphinx. There was no significant difference between the sex (P = 0.95)
significance was set to p < 0.05.                                            in cats with or without GBS. There was no significant difference in
                                                                             prevalence of clinical signs between the two groups (Table 1) nor were
                                                                             there significant differences regarding clinicopathologic data (Table 2).
3        RESULTS                                                             Hyperbilirubinemia was present in 16% (17/108) cats without GBS and
                                                                             17% (14/84) of cats with GBS.
This study included 193 cats that underwent abdominal ultrasound for           Initial statistical analysis identified total bilirubin as significantly dif-
suspicion of clinical disease. One cat was excluded during this time,        ferent among groups (p = 0.03). Common bile duct dilation and total
because there were no ultrasound images for review making a total            bilirubin were not significantly associated with GBS in the full model
of 192 evaluated in this study. All ultrasounds were performed by an         (p = 0.323, p = 0.560, respectively). Gallbladder wall thickening was
                                                                                                                                                       17408261, 2022, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vru.13091 by Cesar Sanchez Jimenez - <Shibboleth>[email protected] , Wiley Online Library on [10/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
604                                                                                                                                    VILLM ET AL .
F I G U R E 2 Ultrasound images (longitudinal and transverse) displaying gallbladder wall thickening (white crosses mark the inner and outer
wall) in cats (Phillips iU22 high-definition ultrasound, 8 mHz microconvex and 12 mHz linear probes, Phillips Medical Systems, Bothell, WA).
Gallbladder wall thickening is between 3–4 mm and 1–2 mm in the top two and bottom two images, respectively
significantly associated with GBS (p = 0.035). The final model found      4       DISCUSSION
GBW thickening as the only significant predictor for the presence of
GBS with an OR of 3.7 (95% CI 1.4-10.0, p = 0.001). Gallbladder wall      Gallbladder sludge was a common finding in our study and the preva-
thickening was seen in 11% (21/192) of cats presenting for ultrasound     lence of GBS in cats presenting for abdominal ultrasound was higher
and 71% (15/21) of those cats had gallbladder sludge (Table 3). GBW       than previously reported.1 The clinical significance of GBW thicken-
thickening was appreciated in 18% (15/84) of cats with GBS and 6%         ing on ultrasound as a predictor of GBS is unclear. Gallbladder wall
(6/108) of cats without gallbladder sludge. There was not a signifi-      thickening and GBS can both be present with bacterial cholecysti-
cant difference between other GB abnormalities, liver, pancreatic, and    tis and cholangiohepatitis but can also be present with a variety of
intestinal ultrasound abnormalities in cats with GBS compared to cats     other clinical diseases rendering these findings as non-specific for GB
without GBS (Table 3).                                                    disease.2,21 Gallbladder sludge was common in cats with a variety of
  Concurrent diseases of the cats in this study are listed and sum-       diseases other than hepatobiliary suggesting it can be nonspecific and
marized in Table 4. Infectious causes included histoplasmosis, toxo-      potentially insignificant in many cats.
plasmosis, feline infectious peritonitis (FIP), and mycoplasma haemofe-       Ultrasound is used in the diagnosis of feline hepatobiliary disease.
lis. The diseases included in the “other” category included respiratory   Ultrasound abnormalities in cats with cholangiohepatitis and cholecys-
cases, hematologic disease, bone marrow disease, and traumatic/bite       titis include GB wall thickening, choleliths, BD thickening, BD dilation,
wounds. Twenty of the 35 cats with hepatobiliary disease were diag-       enlarged pancreas, and GBS.2,13,21–23 In the current study, cats with
nosed with cholangiohepatitis, 5 of which were confirmed with hepatic     GBW thickening were at increased odds of having GBS present on
biopsy. The other cats were given a presumptive diagnosis of cholan-      ultrasound. Gallbladder wall thickening can be found with cholecysti-
giohepatitis. Other hepatobiliary diseases included hepatic lipidosis     tis, cholangitis, oedema, cystic mucinous hyperplasia, pericholecystic
(n = 9), hepatobiliary neoplasia (n = 5), and one congenital extrahep-    free fluid, and systemic disease unrelated to the GB.21 Sensitivity and
atic portosystemic shunt.                                                 specificity of GBW thickening on ultrasound for bacterial cholecystitis
                                                                                                                                                               17408261, 2022, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vru.13091 by Cesar Sanchez Jimenez - <Shibboleth>[email protected] , Wiley Online Library on [10/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
VILLM ET AL .                                                                                                                                            605
    Clinical Signs                    GBS                        n                 GBS (−) n (%)†                  GBS (+) n(%)†                  P value*
    Lethargy                          Absent                     72                43 (40)                         29 (35)                        0.5480
                                      Present                    120               65 (60)                         55 (66)
    Vomiting                          Absent                     122               67 (62)                         55 (66)                        0.6527
                                      Present                    70                41 (38)                         29 (35)
    Anorexia                          Absent                     75                46 (43)                         29 (35)                        0.2975
                                      Present                    117               62 (57)                         55 (66)
    Weight loss                       Absent                     74                46 (43)                         28 (33)                        0.2321
                                      Present                    118               62 (57)                         56 (67)
    Diarrhea                          Absent                     163               95 (89)                         67 (80)                        0.1047
                                      Present                    29                12 (11)                         17 (20)
†
 Within each column for each baseline variable, percentages sum to 100%.
*Significance set at.
P < 0.05, (−) = absent, (+) = present.
RI – reference interval.
*Significance P < 0.05.
was reported to be 87% - 96% and 49% - 90%, respectively.2,22 Gall-               Based on these findings from previous and the current study, GBW
bladder wall thickening and GBS detected on ultrasound increased the              thickening and GBS on ultrasound might suggest the presence of
likelihood of a positive bacterial culture in cats with suspected hepa-           cholecystitis and cholangiohepatitis. The lack of liver histology and bile
tobiliary disease.2 Echogenic contents (sludge) in the GB were found              cultures limited our ability to assess GB abnormalities on ultrasound in
to be associated with histologically confirmed          cholangiohepatitis.13     relation to clinical disease. Therefore, this study is unable to determine
                                                                                                                                                             17408261, 2022, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vru.13091 by Cesar Sanchez Jimenez - <Shibboleth>[email protected] , Wiley Online Library on [10/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
606                                                                                                                                          VILLM ET AL .
    Abnormality                       Status                 n (%)                  GBS (−) n (%)                 GBS (+) n (%)                P value*
    GBW thickening                    Absent                 171 (89)               102 (94)                      69 (82)                      0.009
                                      Present                21 (11)                6 (6)                         15 (18)
    CBD dilation                      Absent                 184 (96)               107 (99)                      77 (92)                      0.323
                                      Present                8 (4)                  1 (1)                         7 (88)
    Other GB findings†                Absent                 182 (95)               101 (94)                      81 (96)                      0.520
                                      Present                10 (5)                 7 (6)                         3 (4)
    Liver                             Absent                 132 (69)               78 (72)                       54 (64)                      0.270
                                      Present                60 (31)                30 (28)                       30 (36)
    Pancreas                          Absent                 155 (81)               91 (84)                       64 (76)                      0.200
                                      Present                37 (19)                17 (16)                       20 (24)
†
 Other GB findings include choleliths, septated GB, inspissated bile, peritoneopericardial diaphragmatic hernia, duplicate GB, GB polyp, hyperechoic GBW,
and GB distension.
*Significance P < 0.05, (−) = absent, (+) = present.
TA B L E 4       Numbers of cats with GB sludge in each disease category       study showed no relationship between any specific clinical sign and
                     *                                                         GBS. Healthy dogs with GBS have been evaluated prospectively and
    Disease category                                          n (%)
                                                                               have remained free of clinical signs over time.3 Because cats in the cur-
    Urologic                                                  11/30 (36)
                                                                               rent study had an abdominal ultrasound performed to evaluate clinical
    Hepatobiliary                                             14/35 (40)
                                                                               abnormalities, a prospective study of healthy cats would be necessary
    GI                                                        28/61 (46)
                                                                               to similarly determine the prevalence of GBS in asymptomatic cats.
    Pancreatic                                                6/8 (75)            Cats with GBS in our study did not have significantly increased liver
    Endocrine                                                 6/18 (33)        enzymes or total bilirubin. These findings are in contrast with a pre-
    Neoplasia                                                 34/58 (59)       vious report where GBS in cats was associated with increased liver
    Cardiac                                                   1/5 (20)         enzyme activities and hyperbilirubinemia.1 Our retrospective case
    Unknown                                                   3/10 (30)        control study included all cats without GBS that underwent ultrasound
                                                                               during the study period. In a retrospective study, Harran et. al. included
    Neurologic                                                3/7 (43)
                                                                               152 cats with ultrasonographically identified GBS compared to 32 ran-
    Infectious                                                4/6 (67)
                                                                               domly selected control cats without and found that cats with GBS had
    Other                                                     2/8 (25)
                                                                               significantly higher ALT, ALP, and total bilirubin.1 The use of 32 ran-
*137 diseases confirmed, 55 were presumptive.                                  domly selected cats as the control population could have led to selec-
                                                                               tion bias of cats with GBS.
                                                                                  The limitations of this study are a result of the retrospective design.
the association of GBS with hepatobiliary disease in cats. Our study           The study population was limited to cats presenting for clinical suspi-
does corroborate with other studies that GBS is associated with other          cion of disease or presence of clinical signs that received an abdom-
hepatobiliary abnormalities on ultrasound.                                     inal ultrasound. Other limitations in this retrospective study include
     A previous study found a prevalence of 14% in cats undergoing             the lack of liver and GB sampling in most of the patients so the rela-
abdominal ultrasound.1 This differed from our findings where GBS had           tionship of GBS to liver disease or bacterial cholecystitis could not be
a higher prevalence in cats undergoing abdominal ultrasound. Some              established. Clinicopathologic data was available for most but not all
differences between the studies include sample size, region, and tim-          cats within a week of abdominal ultrasound which could have affected
ing of the study. Whether concurrent diseases differed between the             our ability to detect significant differences between groups. Gallblad-
two studies is unknown as this was unavailable in the previous study.          der volume was not measured or analyzed in this study given the limi-
Lastly, the incidence of GBS could have increased during the time frame        tations of determining GB volume retrospectively. The still ultrasound
between both studies.                                                          images might not be representative of maximum GB length, width, and
     There was no significant difference in clinical signs in cats with GBS    high to accurately calculate GB volume.
when compared to those without GBS. Another study reported that                   In conclusion, findings from the current study indicated that gall-
the most common signs associated with GBS were non-specific such               bladder sludge is a common finding in cats undergoing abdominal ultra-
as hyporexia, lethargy, weight loss, dehydration and vomiting.1 How-           sound and appears to be non-specific. Cats with GBW thickening are
ever, non-specific clinical signs such as these are common reasons that        more likely to have GBS present on ultrasound, but the clinical signif-
abdominal ultrasound is performed in cats, and results of the present          icance of these findings are currently unclear. Further investigation of
                                                                                                                                                                 17408261, 2022, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vru.13091 by Cesar Sanchez Jimenez - <Shibboleth>[email protected] , Wiley Online Library on [10/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
VILLM ET AL .                                                                                                                                            607
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