The Vet Education Webinar Series 2016

Biliary Mucocoeles

With

Dr Gemma BirnieBVSc MACVSc

Vet Education is Proudly Supported by Hill’s Pet Nutrition Australia

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Gallbladder MucocoelesGallbladder MucocoelesDr. Gemma Birnie

Resident in Small Animal Medicine

Brisbane Veterinary Specialist Centre

Australia

Gallbladder MucocoeleGallbladder Mucocoele

Distends the gall bladder

Can cause extra-hepaticbiliary obstruction

Necrosis and rupture of thegallbladder wall can occur

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Emergent diseaseEmergent disease

AnatomyAnatomy

• Gall bladder is located inbetween the quadrate andright medial liver lobes

• Fundus, body and neck

• Connected via short cysticduct to the common bile duct

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• Storage reservoir for bile

• Bile can be concentrated, acidified and modified(addition of mucin and immunoglobulins)

• Bile is then released into the gastrointestinal tract at themajor duodenal papilla

• Not essential• Cholecystectomy is well tolerated

FunctionFunction

• Middle aged dogs

• Cocker spaniels

• Shetland Sheepdogs

• Miniature schnauzers

SignalmentSignalment

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• Vomiting 69%

• Lethargy 44%

• Anorexia 42%

• Abdominal pain 19%

• Jaundice 16%

• Polydipsia and polyuria 7%

• Average duration of clinical signs 5 days

• Some dogs are asymptomatic (up to 23% has beenreported)

Clinical SignsClinical Signs

• Leukocytosis

• Elevated liver enzymes

• Hyperbilirubinaemia

• Elevated amylase and lipase

• Increased Cholesterol

• Lactate and PCV associated with outcome

Clinical PathologyClinical Pathology

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• Diagnosed via ultrasound usuallyduring an investigation for acuteabdominal pain, vomiting, suspectedliver or GIT disease.

• 5 different patterns have beenreported (Choi et al. Vet Radiol. 2014)with no significant differencebetween clinical signs

• Varies between echogenic bile sludgeto stellate and kiwifruit like pattern

UltrasoundUltrasound

Besso et al. Ultrasonographic appearance and clinical findings in 14 dogs with gallbladdermucocele. Veterinary Radiology and Ultrasound 2000;41:261-271

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Immobileechogenic

Incompletestellate

TypicalStellate

Kiwi fruit andstellatecombination

Kiwi fruit with residualcentral echogenic bile

Choi et al. Comparison between ultrasonographic and clinical findings in 43 dogs withgallbladder mucoceles. Veterinary radiology and ultrasound 2014;55:202-207

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Sensitivity of ultrasonography examination forgallbladder rupture is 78%, specificity 100%

Gall Bladder RuptureGall Bladder Rupture

Crews et al. Clinical, ultrasonographic and laboratory findings associated withgallbladder disease and rupture in dogs: 45 cases. JAVMA 2009;234:359-366

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• Peri-cholecystic reaction

• Echogenic peritoneal fluid

Gall Bladder RuptureGall Bladder Rupture

Crews et al. Clinical ultrasonographic andlaboratory findings associated with gallbladderdisease and rupture in dogs: 45 cases. JAVMA2009;234:359-366

• Rupture of the gallbladder can lead to an acute clinicalsigns and the need for emergency surgery

• Recent case series of 5 dogs; normal total bilirubindespite rupture

• Perform an abdominocentesis

Bile PeritonitisBile Peritonitis

Guess, Harken and Biller. Anicteric gallbladder rupture in dogs: 5 cases(2007-2013). JAVMA 2015; 257:1412-1414

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• Fluid:serum bile concentrations

• Abdominal fluid should have a higher bilirubinconcentration than plasma

Modified Wright stain Diff-Quick stain

AbdominocentesisAbdominocentesis

• Unknown??

• Recent studies have tried to determine anyhistological link to drugs, other underlingdiseases, infections etc.

CauseCause

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• Hyperlipidaemia

• Hyperadrenocorticism

• Possible hypothyroidism

Predisposing FactorsPredisposing Factors

• Odds of a mucocoele in dogs with Cushing’s were29 times that of dogs without Cushing’s

• Association with hypothyroidism reported to be 3times more likely – observational bias

Gall Bladder Mucocoeles and EndocrinopathiesGall Bladder Mucocoeles and Endocrinopathies

Mesich et al. Gall bladder mucoceles and their association withendocrinopathies in dogs: a retrospective case-control study JSAP 2008;50:630-

635

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• In a study to create a hyperadrenocorticism statethere was no greater incidence of GBM

• There was a change in the composition of bile tocytotoxic, hydrophobic, unconjugated bile acids

Lipid DisturbanceLipid Disturbance

Kook et al. Effect of twice daily oral administration of hydrocortisone on the bileacids composition of gallbladder bile in dogs. JAVMR 2011;191:1607-1612

• Focused on flea and tick preventative medications,heart worm prophylaxis, NSAIDs or other oralanalgesic drugs and xenobiotics for DJD. Newgeneration drugs

• Possible association between imidacloprid use inShetland sheepdogs and GBM formation.

Drug AssociationDrug Association

Gookin et al. Association of gallbladder mucocele histologic diagnosis with selected druguse in dogs: A matched case-control study. JVIM 2015;29:1464-1472

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• In 2010 there was a reported association between GBM formationand ABCB4 mutation

• In 2014 this has been disproven – larger case numbers, gold standardcase numbers

• What we know now – there may be a multifactorial cause forgallbladder dysfunction which ABCB4 mutation is associated with.

ABCB4ABCB4

Cullen et al. Lack of association of ABCB4 insertion mutation with gallbladdermucoceles in dogs. Journal of Veterinary Diagnostic Investigation 2014; 26: 434-436

• Infection of the gallbladder is an inconsistentfinding

• The use of perioperative antimicrobials maycause false negative culture

BacteriaBacteria

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• Epithelium of the GB acquires a mucin secretoryphenotype – not due to cystic mucinous hyperplasia aspreviously thought

• Mucins in GBM are highly glycosylated

• Muc5a predominant mucin in GBM compared to Muc5b

New Research: Mucin PropertiesNew Research: Mucin Properties

Kesimer et al. Excess secretion of gel-forming mucins and associated innate defense proteins withdefective mucin un-packing underpin gallbladder mucocele formation in dogs. Plos one. 2015

• Cholecystectomy – patency of the common bileduct must be confirmed

• Histology of the gallbladders commonly findstransmural necrosis

TreatmentTreatment

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• Perioperative mortality rate of 21-40%

• Most mortalities in the first 2 weeks

• Hypotension after surgery negative prognosis

• No reported difference between those with rupture ornot

• Prognosis after discharge is great

Survival StatisticsSurvival Statistics

• Liver biopsies are often performedat the time of surgical resection

• Malek et al study found• Cholangiohepatitis 29%

• Biliary hyperplasia 29%

• Cholestasis 29%

• Pike et al• Lymphocytic plasmacytic infiltration

• Vacuolar hepatopathy

Concurrent Liver DiseaseConcurrent Liver Disease

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• There are no large studies documenting medicalmanagement

• Occasional case reports document its use

• May consider in asymptomatic cases which ownersdecline surgery – monitoring required

• Can result in acute emergency if there is GBM rupture

Medical ManagementMedical Management

• Ursodeoxycholic acid• Naturally occurring hydrophilic

bile acid

• Choleretic and hepato-protectant

• S-adenosylmethionine• Naturally occurring precursor

of cysteine which is used in theproduction of the antioxidantglutathione

“Hepato-Protectants”“Hepato-Protectants”

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•Shetland sheepdogs, miniature schnauzersand cocker spaniels

•Consider as a differential for vomiting,abdominal pain, elevated liver enzymeactivity

•Recommend Surgery

•Investigate for underlying endocrinopathywhen clinically well

Key PointsKey Points

Thank You!Thank You!

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ReferencesReferences

• Malek et al. Clinical findings and prognostic factors for dogs undergoing choleocystectomy for Gall BladderMucocele. Veterinary Surgery 2013;42:418-426

• Cullen et al. Lack of association of ABCB4 insertion mutation with gallbladder mucoceles in dogs. Journal ofVeterinary Diagnostic Investigation 2014; 26: 434-436

• Gookin et al. Association of gallbladder mucocele histologic diagnosis with selected drug use in dogs: A matchedcase-control study. JVIM 2015;29:1464-1472

• Walter et al, Nonsurgical resolution of gallbadder mucocele in two dogs. JAVMA 2008;232:1688-1693• Guess, Harken and Biller. Anicteric gallbladder rupture in dogs: 5 cases (2007-2013). JAVMA 2015; 257:1412-1414• Kesimer et al. Excess secretion of gel-forming mucins and associated innate defense proteins with defective mucin

un-packing underpin gallbladder mucocele formation in dogs. Plos one. 2015• Mesich et al. Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-

control study JSAP 2008;50:630-635• Smalle, Cahalane, Koster. Gallbladder mucocele: A review. Journal of the South African Veterinary Association

2015;86• Crews et al. Clinical ultrasonographic and laboratory findings associated with gallbladder disease and rupture in

dogs: 45 cases. JAVMA 2009;234:359-366• Choi et al. Comparison between ultrasonographic and clinical findings in 43 dogs with gallbladder mucoceles.

Veterinary radiology and ultrasound 2014;55:202-207• Kook et al. Effect of twice daily oral administration of hydrocortisone on the bile acids composition of gallbladder

bile in dogs. JAVMR 2011;191:1607-1612• Besso et al. Ultrasonographic appearance and clinical findings in 14 dogs with gallbladder mucocele. Veterinary

Radiology and Ultrasound 2000;41:261-271• Pike et al. Gallbladder mucoceles in dogs: 30 cases (2000-2002). JAVMA 2004;224:1615-1622