CLINICAL AND PATHOLOGIC FINDINGS IN IGUANIDS WITH SODIUM URATE CHOLELITHIASIS.

Four green iguanas (Iguana iguana) and one blue iguana (Cyclura lewisi) from five facilities were diagnosed with sodium urate cholelithiasis. One case was diagnosed antemortem via ultrasonography, and the iguana underwent a choledochotomy for treatment. The other four cases were identified at necropsy. Pathologic hepatic and biliary changes were present in four of the five cases at necropsy. Histologically, four iguanas had hepatic fibrosis, three had bile duct hyperplasia, and one had cholangiohepatitis and pancreaticocholedochitis. Two iguanas had pathologic renal changes. This is the first report of sodium urate cholelithiasis in reptiles. This case series highlights the potential significant clinical disease caused by sodium urate cholelithiasis and the importance of biliary system evaluation. Further investigation is recommended to explore the pathogenesis of reptilian sodium urate cholelith formation.

Prevalence and clinical relevance of cholelithiasis in cats: A multicenter retrospective study of 98 cases.

BACKGROUND: Cholelithiasis is an uncommon and mainly incidental finding in dogs; current literature on this topic is scarce in cats. HYPOTHESIS: Report prevalence, clinical presentation, management, and outcome of cholelithiasis in cats. ANIMALS: Ninety-eight cats with cholelithiasis. METHODS: Retrospective multicenter case series. Electronic databases from 3 hospitals were searched for cats diagnosed with cholelithiasis by ultrasonography (US). Cholelithiasis was classified as incidental (IC) or symptomatic (SC) depending on clinicopathological signs, biliary tract US appearance, and presence of another disease potentially explaining the clinical presentation. Multivariate analysis was used to investigate factors associated with clinical expression of cholelithiasis and, within the SC group, survival. RESULTS: The observed prevalence of cholelithiasis was 0.99% (95% confidence interval [CI], 0.79%-1.19%) among cats that underwent abdominal US. Cholelithiasis was classified as IC in 41% and SC in 59%. Choleliths found in multiple locations within the biliary tract (odds ratio [OR], 8.11; 95% CI, 2.32-34.15; P = .001) or associated with US signs of obstruction (OR, 18.47; 95% CI, 2.13-2413.34; P = .004) were significantly associated with SC. Concurrent hepatobiliary diseases were suspected or confirmed in 83% of cases with SC. Forty-three cats (74%) with SC survived to discharge. Biliary tract obstruction (BTO) was negatively associated with survival (OR, 13.87; 95% CI, 1.54-124.76; P = .001). None of the cats with IC that had available follow-up (47%) developed clinicopathological signs related to cholelithiasis. CONCLUSIONS AND CLINICAL IMPORTANCE: Cholelithiasis is uncommon and can be asymptomatic in cats. Symptomatic cholelithiasis frequently is associated with another hepatobiliary disease or BTO or both. Biliary tract obstruction is associated with poorer outcome.

Intrahepatic cholelithiasis with gallbladder-like metaplasia of intrahepatic bile ducts associated with gallbladder agenesis in a wild boar.

An unknown-aged adult female wild boar (Sus scrofa) was brought to Kyungpook National University for postmortem examination. Gross examination revealed gallbladder agenesis. Histologically, the liver was cirrhotic and had intrahepatic cholelithiasis, the choleliths were yellow, brown, gray, and black, and had coffin-lid and pyramidal appearances. Fourier-transform infrared spectroscopy analysis revealed that the components were 80% struvite and 20% calcium oxalate monohydrate. Chronic inflammatory cell infiltration was observed, with hyperplastic hepatocellular nodules characterized by large nuclei, prominent nucleoli, and scant cytoplasm with frequent binucleation, surrounded by thick fibrous septa. The epithelium of intrahepatic bile ducts that contained choleliths had undergone gallbladder-like metaplasia, which might have been induced by chronic irritation from the stones or by the accompanying chronic bacterial infection that was observed in Gram stains.

CHOLELITHIASIS IN CAPTIVE MOUNTAIN CHICKEN FROGS (LEPTODACTYLUS FALLAX): DIAGNOSTIC IMAGING AND HISTOPATHOLOGICAL FEATURES.

The mountain chicken frog (Leptodactylus fallax) is a critically endangered species highly reliant on ex situ conservation programs. In captivity, cholelithiasis has been reported during clinical examinations using diagnostic imaging and observed during postmortem examinations. Some individuals have presented with nonspecific clinical signs potentially associated with this condition, but little is known about its clinical relevance. A retrospective evaluation of ultrasonographic (n = 139) and radiographic (n = 156) images and histopathology samples (n = 32) obtained between 2014 and 2020 from 133 individuals was performed. An ultrasound scoring system was developed to evaluate changes in the gallbladder, with 38% (53/139) of the images showing abnormal contents. Gallbladder distension appeared associated with these findings (generalized estimating equation model, P < 0.001). In contrast, radiography proved to have low overall sensitivity (48%) when compared to ultrasonography for identifying abnormal gallbladder contents. A weak level of agreement (Cohen's kappa = 0.535) was observed between the imaging modalities. Histologically, cholecystitis was present in 86% (12/14) of the individuals, thickening of the gallbladder wall in 71% (10/14), and intrahepatic cholangitis in 90% (18/20). There was no evidence of cholestasis in any of the affected individuals. A significant difference was observed in the hepatic melanomacrophage density between animals with and without cholelithiasis (Welch two-sample t test, P < 0.001). This study provides an overview on the use of diagnostic imaging modalities to evaluate cholelithiasis and proposes a convenient ultrasound score to standardize monitoring of the condition in L. fallax. It is also the first systematic review of histopathological changes associated with cholelithiasis in this species.

Clinical features and outcomes in 38 dogs with cholelithiasis receiving conservative or surgical management.

BACKGROUND: Ursodeoxycholic acid is used in human medicine for litholytic management of choleliths, but the efficacy of medical management in dogs with cholelithiasis is unknown. OBJECTIVES: To describe the clinical features and outcomes of dogs with cholelithiasis, focusing on cases that received medical treatment, and to identify patient factors that influenced decision-making for surgical or medical management. ANIMALS: Thirty-eight dogs with cholelithiasis identified on abdominal ultrasonography (AUS). METHODS: Medical records of dogs with cholelithiasis on AUS between 2010 and 2019 were retrospectively reviewed. Cases were classified as symptomatic (n = 18) or incidental (n = 20) and divided into medically treated (n = 13), surgically treated (n = 10), and no treatment (n = 15) groups. Biochemical variables and cholelith location were compared between symptomatic and incidental groups using Mann-Whitney U and chi-squared tests, respectively. Survival times were compared using Kaplan-Meier survival analysis. RESULTS: Symptomatic cases had higher alkaline phosphatase (P = .03), gamma-glutamyl transferase (P = .03), and alanine transferase (P = .02) activities than did incidental cases. A higher proportion of symptomatic cases (44.4%) had choledocholithiasis than did incidental cases (0%; P = .003). Seventy percent of surgically managed dogs, 7.7% of medically managed dogs, and 0% of nontreated dogs had choledocholiths at presentation. Seventeen dogs had follow-up AUS: cholelithiasis completely resolved in 4/8 medically treated, 5/7 of surgically treated, and 1/2 nontreated dogs. Median survival time was 457.4 days, with no significant difference between incidental and symptomatic dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Medical treatment can be effective for management of cholelithiasis in dogs, with clinical presentation and cholelith location playing important roles in treatment decision-making.

Cholelithiasis in the Dog: Prevalence, Clinical Presentation, and Outcome.

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.

Changes in pre- and postoperative serum leptin concentrations in dogs with gallbladder mucocele and cholelithiasis.

BACKGROUND: Leptin has been shown to have various physiological and pathological roles in the canine gallbladder. In this study, we performed pre- and postoperative short-term follow-up analyses to confirm changes in serum leptin levels before and after cholecystectomy due to gallbladder mucocele (GBM) or cholelithiasis in dogs. RESULTS: Twenty-six cholecystectomized dogs (GBM: n = 14; cholelithiasis: n = 12) for prophylactic or clinical symptom relief were enrolled in the present study. Dogs were subgrouped according to clinical symptoms and prognosis after surgery as follows: 1) asymptomatic group (n = 13), 2) recovery group (n = 8), and 3) death group (n = 5). Liver enzymes, total bilirubin, lipid profiles, and leptin concentrations were determined from sera on the pre-operative day and at 1, 3, and 7 days postoperation. Serum leptin concentrations were gradually but significantly decreased in the asymptomatic group (p = 0.008, 0.004, and 0.004 on days 1, 3, and 7, respectively, compared with that before surgery) and the recovery group (p = 0.048 and 0.048 on days 3 and 7, respectively, compared with that before surgery). However, in the death group, leptin concentrations did not differ significantly over time (p = 0.564). Additionally, serum leptin levels in the recovery group (p = 0.006) and death group (p = 0.021) were significantly higher than those in the asymptomatic group. Liver enzymes and total bilirubin (T-Bil) were significantly decreased only in the recovery group, particularly on day 7. In the asymptomatic group, liver enzymes and T-Bil were not changed significantly over time, and in the death group, only T-Bil was significantly decreased on day 7. Total cholesterol and triglyceride levels were not significantly decreased over time in all groups. CONCLUSIONS: These results indicate that leptin is a potential biomarker reflecting the severity and prognosis of GBM and cholelithiasis both before and after cholecystectomy in dogs.

Associations between serum leptin levels, hyperlipidemia, and cholelithiasis in dogs.

Leptin and its receptor play several physiological roles in the canine gallbladder, and the dysregulation of leptin might play a role in the pathogenesis of gallbladder diseases such as gallbladder mucocele. Previous studies revealed a positive association between hyperlipidemia and gallstones in humans. However, the latter is still unclear in dogs with cholelithiasis. In this study, we examined the differences in leptin, leptin receptor, total cholesterol, and triglyceride levels between healthy dogs and dogs with cholelithiasis, and evaluated the correlation between leptin and hyperlipidemia. Twenty-eight healthy dogs and 34 client-owned dogs with cholelithiasis were enrolled in the study. Leptin concentrations and lipid profiles were determined from sera, and leptin and leptin receptor expression levels were quantified in gallbladder tissue. In dogs with cholelithiasis, serum concentrations of leptin (p < 0.001), total cholesterol (p < 0.001), and triglycerides (p < 0.001) were significantly higher compared with those in healthy dogs. Positive correlations were observed between serum leptin and total cholesterol (95% confidence interval (CI) = 0.61-0.89, r = 0.725, p < 0.001), and between leptin and triglycerides (95% CI = 0.63-0.89, r = 0.782, p < 0.001) in the cholelithiasis group. Hypercholesterolemia (Odds Ratio (OR) = 9.720; 95% CI = 1.148-82.318) and hypertriglyceridemia (OR = 12.913; 95% CI = 1.548-107.722) were shown to be risk factors for gallstone disease. In cholelithiasis patients who underwent cholecystectomy, serum leptin levels were significantly higher than in patients that had not undergone surgery (p < 0.001). Leptin and leptin receptor expression was upregulated in the gallbladder tissues of cholelithiasis patients (p < 0.01 and p < 0.001, respectively). These results indicate that increased serum leptin concentrations and hyperlipidemia (hypercholesterolemia or hypertriglyceridemia) are associated with canine cholelithiasis and that homeostatic imbalance of these parameters might affect the pathogenesis of gallstones.

Intrahepatic cholelithiasis in dogs and cats: A case series.

A retrospective study of intrahepatic cholelithiasis (IC) in 9 dogs and 2 cats was conducted. Only 1 dog showed clinical signs related to hepatobiliary disease before referral and during the follow-up period. Intrahepatic cholelithiasis might be a subclinical finding in both dogs and cats.

Cholélithiase intrahépatique chez les chiens et chats : une série de cas. Nous avons réalisé une étude rétrospective de la cholélithiase intrahépatique (CI) chez 9 chiens et 2 chats. Seulement un chien manifestait des signes cliniques en lien avec la maladie hépatobiliaire avant la recommandation et durant la période de suivi. La cholélithiase intrahépatique pourrait être un résultat subclinique chez les chiens et les chats.(Traduit par Isabelle Vallières).

Cholelithiasis in adult bearded dragons: retrospective study of nine adult bearded dragons (Pogona vitticeps) with cholelithiasis between 2013 and 2015 in southern Germany.

With an increased number of pet reptiles, many diseases occur due to nutritional disorders. Between 2013 and 2015, irregular gallbladder contents (sludge/choleliths) in adult bearded dragons (Pogona vitticeps) were recorded in many of the routinely conducted necropsies at the reptile rescue station in Munich (Auffangstation für Reptilien, München e.V., Munich, Germany). Nine animals, six from the rescue station and three from an associated veterinary practice (Tierärztliche Praxis für Exoten, Augsburg, Germany), were studied. Gallbladder contents from all animals were analysed at the Institute for Clinical Chemistry in Zurich, Switzerland. In three of nine animals, one cholelith composed of 100% calcium carbonate (CaCO3 ) was detected and it precipitated either as pure calcite or as a calcite:vaterite combination. In the remaining six animals, analyses suggested a protein-based material. The detection of choleliths/sludge was not anticipated at necropsy or surgery in eight of nine animals. The diet of the six animals from the rescue station was retrospectively described as mainly insects, whereas the diet of the three animals from the veterinary practice also contained little plant matter. Fed insect species were mealworm larva (Tenebrio molitor), house cricket (Acheta domestica), migratory locust (Locusta migratoria) and zophobas larva (Zophobas morio), all high in protein and fat. In other species, a nidus must be present for CaCO3 to precipitate. As a protein-based sludge was detected in six gallbladders, it is possible that a high-protein diet could lead to such a nidus and subsequently to cholelith formation. Cholelithiasis seems to be a rising problem in adult bearded dragons and is likely underdiagnosed, as many choleliths were found at necropsy. This rise in cholelithiasis may correlate with an unnatural high-protein, high-fat insect-based diet instead of a balanced plant-based diet.

Life-threatening perianaesthetic complications in five cats undergoing biliary tract surgery: case series and literature review.

Case series summary The aim of this case series was to describe the intra- and early postanaesthetic complications occurring in five cats undergoing major surgeries involving the gallbladder and the biliary tree. The five cases of this series were admitted to the Queen Mother Hospital for Animals between June and December 2015, and were all overseen by the same senior anaesthesist. Pre-existing pancreatitis was a common finding. Observed life-threatening events were persistent, unresponsive hypotension in the absence of major blood loss, which occurred mainly during surgical manipulation of the biliary tract, and postoperative renal failure. Relevance and novel information Biliary surgery carries the potential for life-threatening complications in cats. The pathogenesis of such morbidities is likely to be multifactorial. The perianaesthetic use of haemoglobin-based oxygen-carrying solution may be considered as an alternative treatment option when hypotension is unresponsive to fluids and traditional positive inotropes and vasopressors.

Increased Leptin and Leptin Receptor Expression in Dogs With Gallbladder Mucocele.

BACKGROUND: Leptin and its receptor play a role in several disease processes such as pancreatitis and heart disease. However, their association with gallbladder mucocele (GBM) in dogs has not been reported. HYPOTHESIS/OBJECTIVES: To evaluate differences in the expression of leptin and leptin receptor between dogs with and without GBM. ANIMALS: Twenty-five healthy dogs, including 9 laboratory beagle dogs, and 22 client-owned dogs with GBM. METHODS: Serum leptin concentration was determined in blood samples of all dogs by ELISA. Canine gallbladder samples were collected from 9 dogs with GBM that underwent surgery for therapeutic purposes and from 9 healthy laboratory beagle dogs as a normal control group. Samples were analyzed for leptin and leptin receptor mRNA by real-time polymerase chain reaction. RESULTS: Serum leptin concentration was significantly higher in dogs with GBM than in healthy dogs (medians of 7.03 and 2.18 ng/mL, respectively; P < .001). Patients with GBM that had undergone surgery had significantly higher serum leptin concentrations than those that had not (medians of 12.2 and 4.09 ng/mL, respectively; P = .001). However, no difference in serum leptin concentration was found between dogs with GBM with or without endocrinopathies. The mRNA expression levels of leptin and its receptor were significantly increased in the gallbladder tissues of dogs with GBM. CONCLUSIONS AND CLINICAL IMPORTANCE: Dysregulation of leptin might be involved in the pathophysiology of GBM, and leptin concentrations might be associated with GBM severity.

Spontaneous Cholelithiasis in a Squirrel Monkey (Saimiri sciureus).

A mature female squirrel monkey was noted during routine semiannual examinations to have moderate progressive weight loss. Serum chemistry panels revealed marked increases in hepatic enzyme, bilirubin, and bile salt concentrations and hypoalbuminemia. Abdominal ultrasonography revealed echogenic, shadowing debris in the gallbladder, consistent with cholelithiasis. At necropsy, marked thickening and distension of the gallbladder, cystic duct, and common bile duct was noted, and more than 50 irregularly shaped, black gallstones were removed from the biliary tract. Gallbladder tissue, bile, and gallstones cultured positive for Escherichia coli and Proteus spp., suggesting a brown-pigment gallstone type secondary to a bacterial nidus. Histopathology revealed severe chronic-active diffuse cholecystitis and severe chronic-active hepatic degeneration and necrosis with severe cholestasis. To our knowledge, this report is the first description of spontaneous choleilthiasis in a squirrel monkey.

Obstructive cholelithiasis and cholecystitis in a kinkajou (Potos flavus).

A 14.5-yr-old female kinkajou (Potos flavus) was diagnosed with cholelithiasis after an episode of vomiting; diagnostics included biochemical analysis and abdominal ultrasound exam. Despite antimicrobial treatment, cholelithiasis led to cholecystitis. A cholecystotomy was performed to remove choleliths and inspissated bile. Morphological and spectroscopic properties of the choleliths were similar to those of gallstones from the brown pigment family and Streptococcus sp. and Escherichia coli were isolated from the bile. Biliary tract infection is directly related to pathogenesis of brown pigment gallstones. Serial ultrasound exams revealed that cholecystitis developed secondary to the presence of gallstones in the biliary tree. Despite full recovery postsurgery, the patient died 15 mo later from gallbladder necrosis. Based on the progression of this case, a cholecystectomy would be preferred over a cholecystotomy in similar cases, and the efficacy of long-acting antibiotics may not be adequate in nontarget species. Gallstones and biliary tract infection are rarely described in small domestic carnivores, and this is the first reported case in a kinkajou.

Congenital duplex gallbladder and biliary mucocele associated with partial hepatic cholestasis and cholelithiasis in a cat.

A 6-year-old neutered male domestic shorthair cat was presented for acute onset of vomiting. Exploratory laparotomy identified a duplex gallbladder and left cholecystectomy was performed. Histopathology confirmed biliary mucocele and hepatic cholestasis. While rare, biliary mucoceles should be considered as a differential diagnosis for feline extrahepatic bile duct obstruction.

Cholestasis and cholelithiasis in a domestic ferret (Mustela putorius furo).

A 3-year-old female spayed domestic ferret (Mustela putorius furo) was presented for evaluation of severely increased liver enzyme activities noted prior to anesthesia. The ferret showed no clinical signs of liver or gall bladder disease. Serum biochemical profile confirmed elevations in alanine aminotransferase and alkaline phosphatase activity and total bilirubin concentration. Abdominal ultrasound revealed a distended and convoluted common bile duct although no obstruction was seen. Upon exploratory laparotomy, a large amount of sediment was found within the bile duct that appeared to be obstructing it, but no other cause for the obstruction was found. A choledochoduodenostomy was performed, and the ferret recovered uneventfully from surgery. Liver enzyme activities returned to normal by 5 days post-operatively. Biopsy and culture results yielded no definitive cause of the bile duct obstruction. Cholestasis is a rarely reported disease in ferrets and generally has been described in connection with neoplasia or parasitism, neither of which was found in the current case.

Liver flukes promote cholelithiasis in sheep.

The main objective of this study was to investigate whether cholelithiasis in sheep is related to parasitism or other commonly observed disorders such as liver abscesses. Additionally, the features of the observed biliary calculi are described. The livers of 254 randomly selected clinically healthy adult dairy sheep were used. All visible concretions in the bile were considered as stones. Based on the macroscopical examination, 60 livers were normal, 40 were parasitized with Fasciola hepatica, 42 were parasitized with Dicrocoelium dendriticum, 28 were parasitized with both D. dendriticum and F. hepatica, 40 livers had abscesses and 44 had hydatid cysts. Biliary calculi were detected in 40 livers. Twenty livers had pigment stones and 20 livers had cholesterol stones. The percentage of cholelithiasis was significantly higher in livers parasitized with flukes compared with the others (P<0.05) and the parasitoses with F. hepatica and D. dendriticum were proven to be significant risk factors (P<0.05) for the presence of cholelithiasis in sheep.

[Regulation of calculus bovis on the function of mice oral fibroblasts].

To explore the influence of calculus bovis on the function of primary cultured mice oral fibroblasts, we determined the effects of calculus bovis on the fibroblast proliferation, collagen production, matrix metalloproteinases-2, -9 activities and tissue inhibitor of metalloproteinase-1 production by MTT assay, chloramine T method, gelatin zymography and enzyme-linked immunosorbent assays respectively. The results showed that calculus bovis could significantly inhibit the proliferation of fibroblasts and collagen synthesis in a concentration dependent manner, could significantly (P<0.05) suppress matrix metalloproteinases-2 activity and very significantly (P<0.01) inhibit the production of tissue inhibitor of metalloproteinase-1. In conclusion, the major function of calculus bovis in the process of ulcer healing is not to promote tissue regeneration, the mechanism that calculus bovis inhibits collagen synthesis may be partly due to its ability to very significantly (P<0.01) suppress the production of tissue inhibitor of metalloproteinase-1.

Bilirubin cholelithiasis and haemosiderosis in an anaemic pyruvate kinase-deficient Somali cat.

A Somali cat was presented with recurrent anorexia, lethargy, vomiting and icterus. A macrocytic-hypochromic, regenerative haemolytic anaemia was identified and hereditary pyruvate kinase deficiency was confirmed by means of breed-specific DNA mutation analysis. The case was complicated by the presence of markedly elevated serum liver enzyme activities, hyperbilirubinaemia, coagulopathy and ultrasonographic evidence of gall bladder choleliths and extrahepatic bile duct obstruction. The choleliths consisted of 100 per cent bilirubin, likely because of chronic haemolysis and haeme degradation. In conclusion, haemosiderosis and bilirubin cholelithiasis can be a consequence of chronic haemolysis in pyruvate kinase-deficient cats, as seen in human beings with a variety of chronic haemolytic disorders.

Solitary biliary hamartoma with cholelithiasis in a domestic rabbit (Oryctolagus cuniculus).

Hamartomas of the liver and biliary system are extremely rare entities in both animals and humans. Biliary hamartomas in humans are usually multiple and constitute the von Meyenburg complexes. This report describes the presence of a large solitary mass arising from the edge of the right medial liver lobe of a domestic rabbit. Histologically, the mass was composed of an extensive network of large varying sized cystic structures lined by simple cuboidal to columnar epithelium within an abundant fibrous stroma. Within many of the cyst lumina were varying sized, pale white to greenish hard concretions identified as choleliths and were analyzed and found to be composed of calcium carbonate. This is the first known report of biliary hamartoma with cholelithiasis in rabbits.