Surgical approaches to extrahepatic biliary tract obstruction in ......3.1 Anatomy of the biliary...

Surgical approaches to extrahepatic biliary

tract obstruction in cats

Word count: 11829

Esmeralda Komdeur Student number: 01301173

Supervisor: Prof. dr. Hilde de Rooster

Supervisor: Dr. Erika Bianchini

A dissertation submitted to Ghent University in partial fulfilment of the requirements for the degree of

Master of Veterinary Medicine

Academic year: 2018 - 2019

Ghent University, its employees and/or students, give no warranty that the information provided in

this thesis is accurate or exhaustive, nor that the content of this thesis will not constitute or result in

any infringement of third-party rights.

Ghent University, its employees and/or students do not accept any liability or responsibility for any

use which may be made of the content or information given in the thesis, nor for any reliance which

may be placed on any advice or information provided in this thesis.

Voorwoord

In de eerste plaats wil ik mijn promotor ontzettend bedanken voor alle adviezen en opbouwende commentaren zij mij gegeven heeft. Hier heb ik heel veel aan gehad. Ook wil ik mijn co-promotor bedanken. Als laatste wil ik dank brengen aan alle eigenaren, die zo vriendelijk zijn geweest om mij informatie te geven over hun huisdier, zodat ik van begin tot eind heb kunnen weergeven wat er met de patiënten is gebeurt.

Inhoudsopgave

Titel Pagina

1. Samenvatting 1

2. Lijst met afkortingen 2

3. Introduction 3

3.1 Anatomy of the biliary system of the cat 3

3.2 Physiology of bile 3

3.3 Extrahepatic biliary tract obstruction in cats 4

4. Case series 5

4.1 Materials and Methods 5

4.2 Results 5

4.2.1 Macroscopic anatomy of the biliary tract 5

4.2.2 Patient details 6

4.2.3 Clinical symptoms 6

4.2.4 Laboratory results 7

4.2.5 Abdominal ultrasound 8

4.2.5.1 Secondary changes caused by EHBO 8

4.2.5.2 Location and possible cause of obstruction 8

4.2.6 Microbiology and histopathology 9

4.2.7 Surgical approach 10

4.2.7.1 Complications 11

4.2.7.2 Hospitalisation 11

4.2.8 Postoperative morbidity and mortality 12

5. Discussion 14

6. Conclusion 19

7. References 20

1

1. Samenvatting

Galgangpathologie is niet veelvoorkomend bij de kat. In deze gevallenstudie worden 12 katten sinds

Januari 2014 opgevolgd vanaf het moment dat ze werden aangeboden op de faculteit tot april 2019,

waarin de laatste eigenaren gecontacteerd werden om te evalueren hoe het momenteel met hun

huisdier ging. Het diagnostisch proces, met daarin de verschillende testen die werden uitgevoerd,

wordt beschreven en de resultaten zijn in tabellen te zien. Na het stellen van de diagnose van

extrahepatische galgangobstructie werden alle katten geopereerd. Afhankelijk van de plaats van de

obstructie werden er verschillende operatietechnieken toegepast. Sommige katten werden een

tweede keer geopereerd in verband met het opnieuw optreden of aanwezig blijven van symptomen.

Tijdens en na de hospitalisatie periode traden er een tal van complicaties op. Niet alle katten hebben

de hospitalisatieperiode overleefd. De katten die de kliniek hebben verlaten, werden ingedeeld in een

korte termijn en een lange termijn groep om hierin de complicaties en mortaliteit te kunnen

beoordelen. De mortaliteitscijfers zijn hoog. De meeste katten zijn in de korte termijn tijdsperiode

overleden. De resultaten bij de 12 bestudeerde katten werden vergeleken met wat er in de literatuur

beschreven staat.

Summary

Biliary tract disease is uncommon in the cat. In this case series, 12 cats were followed up since January

2014 from the moment of admittance to the Faculty Clinic until April 2019, when the last owners were

contacted to evaluate the wellbeing of their pet. The diagnostic procedures are described and the

results are shown in tables. After the cats were diagnosed with extrahepatic biliary tract obstruction,

they were operated. Depending on the localisation of the obstruction, different types of surgery were

performed. Some cats were operated twice, due to remaining or reoccurring symptoms. During and

after the hospitalisation period a number of complications occurred. Not all the cats survived the

hospitalisation period. The cats that were discharged from the hospital were divided in a short-term

and a long-term group, to assess complications and mortality. The mortality rate is high. Most cats died

during the short-term time period. The findings in the 12 cats that were included were compared to

the literature.

2

2. Lijst met afkortingen:

ALP: alkalic phosphatase

ALT: alanine aminotransferase

aPTT: activated partial thromboplastin time

AST: aspartate aminotransferase

CKD: chronic kidney disease

E. coli: Escherichia coli

EHBO: extrahepatic biliary tract obstruction

Fr: French gauge

GGT: gamma-glutamyl transferase

HCT: haematocrit

IRIS: international renal interest society

μmol/L: micromole per litre

NA: not available

S. felis: Staphylococcus felis

PT: prothrombin time

U/L: units per litre

3

Fig. 1 Plastic model of the feline biliary tract 1. Gallbladder; 2. Cystic duct; 3. Common bile duct; 4. Hepatic ducts; 5. Lobar ducts

3. Introduction

3.1 Anatomy of the biliary system of the cat

The gallbladder is a pear-shaped organ, which lies in a fossa between liver lobes; on the medial side

there is the quadrate lobe, on the lateral side, the right medial lobe. The biliary tract consists of an

intra- and extrahepatic part (Fig 1). Bile is secreted by the hepatocytes into the canaliculi; these

capillaries are situated between the hepatocytes, but they don’t have epithelial lining. From there, the

bile flows through the interlobular and lobar ducts towards the extrahepatic tract. The bile leaves the

liver via the hepatic ducts and is drained into the gallbladder through the common bile duct and cystic

duct. The part of the extrahepatic biliary tract between the gallbladder and the first hepatic duct is

named the cystic duct; the part between the first hepatic duct and the duodenal papilla is the common

bile duct (König et al., 2004). In the gallbladder, bile is stored before being delivered to the duodenal

lumen (Center, 2009).

The sphincter of Oddi surrounds the duodenal papilla and

forms a natural barrier between the biliary tract and the

duodenum. It should prevent intestinal contents entering

the biliary tract. Normal bile is sterile and under normal

circumstances, the flow will only go in one direction (Sung

et al., 1992; Mayhew, 2002; Mehler, 2006; Center, 2009;

Mayhew and Weisse, 2012; Radlinsky, 2013). If the

sphincter doesn’t function properly, intestinal contents

can enter the biliary tract and ascend in the direction of

the gallbladder. In case of a mechanical obstruction in the

biliary tract, the bile can’t flow. As a result of this biliary

stasis, the bile will thicken and form sludge that might lead

to occlusion of the extrahepatic biliary tract (Center,

2009).

In 80 % of the cats, the pancreatic duct joins the common bile duct before entering the duodenum through the papilla (Etue et al., 2001). Because of this particular anatomic feature pathologies of the pancreas can have an effect on the biliary tract and vice versa (Mayhew et al., 2002; Jergens, 2012).

3.2 Physiology of bile

Bile consists among others of bile salts, bilirubin, electrolytes and water. The hepatocytes have

transporters that are involved in the formation of bile; bile acids are actively pumped to the canaliculi

by these transporters. In the cat, these bile acids are conjugated only to taurine (Center, 2009). The

hepatocytes also excrete bilirubin into the canaliculi (Mayhew and Weisse, 2008). Water and

electrolytes follow through osmosis. When the bile flows through the biliary tract, there is secretion

and absorption of water and electrolytes, modifying the bile (Center, 2009). The function of the

gallbladder is to store and concentrate bile (Center, 2009). If an animal is sober, the gallbladder is

relaxed and filled.

4

One of the functions of bile is to bind endotoxins (Mayhew and Weisse, 2008). When endotoxins are

bound to bile salts, there is less chance of absorption and endotoxemia. Another function of bile is to

emulsify fats. Emulsified fats are easier to digest and absorb. Bile also plays a role in the absorption of

fat-soluble vitamins A, D, E and K. When bile salts are not present in the intestine, these vitamins are

less absorbed.

When the animal eats, the gallbladder contracts and bile flows through the cystic duct and common

bile duct into the duodenum via the papilla (Center, 2009). There are several factors that can influence

the biliary flow. Cholecystokinin (CCK) and motilin are signals for the gallbladder to contract and for

the sphincter of Oddi to relax (Thune et al., 1990; Center, 2009).

Most bile acids and bilirubin are excreted through the feces, but a part is reabsorbed and transported

back to the liver (Mayhew and Weisse, 2008). When the concentration of reabsorbed bile acids reaches

a certain amount in the liver, it gives a negative feedback signal; as a result, the CCK release is inhibited

(Center, 2009).

3.3 Extrahepatic biliary tract obstruction in cats

Extrahepatic biliary tract obstruction (EHBO) has been described in cats of a wide age range (Martin et

al., 1986; Cornell et al., 1993; Fahie and Martin, 1995; Eich and Ludwig, 2002; Mayhew et al., 2002;

Bacon and white, 2003; Buote et al., 2006; Harvey et al., 2007; Mayhew and Weisse, 2008; Morrison

et al., 2008; Baker et al., 2010; Linton et al., 2015). Any pathology that results in mechanical obstruction

of any part of the extrahepatic biliary tract can cause EHBO (Kelly et al., 1975; Barsanti et al., 1976;

Martin et al., 1986; Matthiesen and Rosin, 1986; Fahie and Martin, 1995; Mayhew et al., 2002; Bacon

and White, 2003; Martin et al., 2003; Buote et al., 2006; Jergens, 2006; Mayhew, 2006; Center, 2009;

Mehler and Mayhew, 2013; Radlinsky, 2013; Basu and Charles, 2014; Linton et al., 2015). Extrahepatic

biliary tract obstruction is considered relatively uncommon in cats (Mayhew et al., 2002; Bacon and

White, 2003; Mayhew, 2006; Mayhew and Weisse, 2008). However, diagnostic tools and techniques

are constantly evolving, explaining why biliary tract disease is diagnosed more often nowadays (Mehler

and Mayhew, 2013). After diagnosing EHBO, there are several different treatment options depending

on the underlying pathology. Before deciding to perform surgery, medical treatment should be

considered; some underlying pathologies of EHBO can be resolved with medication only (Boothe et al.,

1992; Jergens, 2006; Mayhew, 2006; Center, 2009; Otte et al., 2017). In case surgery is indicated, there

are various approaches depending on where the obstruction is located (Mayhew 2006; Mehler and

Mayhew, 2013). Besides the underlying pathology, there are complications during and after surgery

that have a negative effect on the prognosis (Mayhew et al., 2002; Buote et al., 2006; Mehler, 2011).

The aim of this study is to report a case series of cats with EHBO, presented to the Small Animal Clinic,

Faculty of Veterinary Medicine of Ghent University. The diagnostic process will be reviewed and the

surgical approaches as well as the outcomes will be evaluated and discussed.

5

4. Case series

4.1 Materials and Methods

The medical records of feline patients with biliary tract disease that were admitted to the Small Animal

Clinic of the Faculty of Veterinary Medicine of Ghent University between January 2014 and January

2019 were searched for patients that had complaints compatible with EHBO. The terms ‘bile duct’,

‘biliary tract’, ‘biliary obstruction’, ‘biliary stenting’, ‘gallbladder’ and ‘biliary tract obstruction cat’

(both in Dutch and English) were used as search criteria. Cats that were euthanised without treatment

or patients that were treated with medication only were excluded. Patients needed to have had an

abdominal ultrasound and blood analysis before being eligible.

Patient data collected from the files included breed, gender, age, and chronicity of symptoms. The

anamnesis and clinical examination were scanned for symptoms as anorexia, icterus, lethargy,

vomiting and weight loss.

After additional examinations were done, patients were sent to surgery. During anaesthesia a combination protocol was used in all patients. All surgeries started with a ventral midline incision through the skin and linea alba. The length of the

incisions varied between patients. They all started at the same point: the xyphoid. The incisions ended

in the area between the umbilicus and the pubis. After routine opening of the abdomen a general

inspection of the organs was performed. In all the patients the patency of the biliary tract was assessed

by determining if bile evacuation was possible by gentle pressure on the gallbladder and by flushing

the biliary tract. This was done by either retrograde catheterisation, which was performed through an

antimesenterial duodenotomy, or by normograde catheterisation through an incision in the

gallbladder or ductus choledochus. If retrograde catheterisation was possible, but the papilla was

swollen, a stent was placed. Is catheterisation proved possible but the gallbladder showed

abnormalities, a cholecystectomy was performed. If catheterisation proved impossible, a

cholecystoduodenostomy was performed. Further description of the surgeries will be provided later

on.

Most complications occurred during the recovery period. Some developed during the rest of the

hospitalisation period. The duration of the hospitalisation and the given medication are summarised

in chapter 2.7.2 Hospitalisation. Morbidity and mortality were evaluated by details deduced from the

patient files and by contacting the owners and/or the referring veterinarians. The complications were

categorized into 3 groups; perioperative, short term (3 months from moment of discharge) and long-

term (after 3 months past discharge).

Apart from the retrospective case series, the macroscopic anatomy of the feline biliary tract was

studied. Several cast of the biliary tract of deceased cats without hepatobiliary complaints were made

at the Faculty of Veterinary Medicine of the University of Ghent.

4.2 Results

4.2.1 Macroscopic anatomy of the biliary tract

A common finding was a marked curve up to 180 degrees between the gallbladder neck and the

proximal part of the cystic duct. Another distinctive quality of the bile duct was its ability do dilate.

6

4.2.2 Patient Details

In total, the medical records of 20 cats were identified after first screening, but only 12 cats were in

line with all inclusion criteria. General data about these patients can be found in Table 1. Eight cats

were male; the remaining 4 were female. The cats had a median age of 87 months (range 26-177

months). The time between the occurrence of the first symptoms and hospital admittance varied from

1 day to 4 weeks (median 11 days). Four cats (cats N° 7, 8, 9 and 10) were medically treated by their

own veterinarian before being admitted to the faculty. These previous treatments included antibiotics

(n=3), anti-emetics (n=1), buprenorphine (n=1), corticosteroids (n=1), infusion therapy (n=1) and

NSAID’s (n=2)).

Table 1 Patient details of cats surgically treated for extrahepatic biliary tract disease

4.2.3 Clinical symptoms

The patients were presented to the Faculty of Veterinary Medicine with a variety of symptoms. The

most common symptoms have been summarised in Table 2. Vomiting (n= 9) and anorexia (n=8) were

seen most often, followed by icterus (n=7), lethargy (n=4) and weight loss (n=4). Two cats showed only

1 out of those 5 most common symptoms (vomiting), 2 showed 2/5 symptoms (icterus and vomiting

or weight loss), 6 showed 3/5 symptoms (several different combinations), and the remaining 2 showed

4/5 symptoms (anorexia, icterus, lethargy, vomiting).

Table 2 Symptoms shown by the cats presented to the Faculty clinic

Case Gender Breed Age (months) Chronicity of symptomes (days)

1 Male Main Coon 74 7

2 Male Scottisch fold 26 15

3 Male Ragdoll 85 2

4 Female Ragdoll 73 1

5 Male European Shorthair 98 1


7 Female European Shorthair 37 23



10 Female European Shorthair 126 24

11 Female British shorthair 88 7

12 Male Ragdoll 78 7

Case Anorexia Icterus Lethargy Vomiting Weight loss

1 - - - + -

2 + + - - +

3 - + - + -

4 + - - + +

5 + - + - +

6 + - + + -

7 + + + + -

8 + + - + -

9 + + - + -

10 + + + + -

11 - - - + -

12 - + - - +

7

4.2.4 Laboratory results

Pre-operative haematology results were available in 8 cats. Of these, 2 were normal. Mild lymphopenia

was present in 1 cat, severe lymphocytosis occurred in another one. Leucocytosis was seen in 1 cat,

and monocytosis in 2; once severe and once mild. Eosinopenia was present in 5 cats; 2 were severe

and 3 were mild. Two cats had a severe neutrophilia, and one cat showed a mild neutropenia. The

abnormal values are presented in Table 3. Cats N° 3 and 10 showed anaemia with haematocrit (HCT)

values of 28% and 25%, respectively.

Table 3 Abnormal haematology results from cats with extrahepatic biliary tract obstruction

Case Parameter Value Reference

2 Neutrophils Eosinophils

1.32 x 10^9/L 0.14 x 10^9/L

1.48 – 10.29 x 10^9/L 0.17 – 1.57 x 10^9/L

6 Lymphocytes Monocytes

30.43 x 10^9/L 9.97 x 10^9/L

0.92 - 6.88 x 10^9/L 0.05 – 0.67 x 10^9/L

7 Neutrophils Eosinophils

17.16 x 10^9/L 0.02 x 10^9/L

1.48 - 10.29 x 10^9/L 0.17 – 1.57 x 10^9/L

8 Lymphocytes Eosinophils

0.83 x 10^9/L 0.10 x 10^9/L

0.92 - 6.88 x 10^9/L 0.17 – 1.57 x 10^9/L

10 Leucocytes monocytes Neutrophils Eosinophils

22.97 x 10^9/L 2.4 x 10^9/L 18.20 x 10^9/L 0.04 x 10^9/L

2.87-17.02 x 10^9/L 0.05-0.67 x 10^9/L 1.48-10.29 x 10^9/L 0.17-1.57 x 10^9/L

12 Eosinophils 0.09 x 10^9/L 0.17-1.57 x 10^9/L

Coagulation times were measured in 9 cats; they were abnormal in 3 (N° 2, 5, 12). One had a mildly

increased prothrombin time (PT). Another one had a mildly increased activated partial thromboplastin

time (aPTT). The third cat had a mild increase in PT and a moderate increase in aPTT.

In all cats, biochemical results were available. Alkalic phosphatase (ALP), alanine aminotransferase

(ALT), and total serum bilirubin values were measured in all cats. Gamma-glutamyl transferase and

aspartate aminotransferase were only measured in a few cats (n=1 and n=3 respectively). The

abnormal results from blood samples that were taken pre-operatively are summarized in Table 4. Since

cat N° 1 showed no abnormalities, the values are not included in the table. Some cats (N° 3, 4, 9) were

admitted to the faculty more than once because of reoccurring problems; therefore, biochemistry has

been tested more than once. Only the results from the first analyses were taken into account. ALP was

increased in 7 out of 12 cats with a median value of 174 U/L (range 124-330). ALT values were increased

in 10 out of 12 cats with a median value of 497 U/L (range 270-834). Bilirubin was increased in 8 cats

with a median value of 117 μmol/L (range 43-148 μmol/L). The analysis of the blood sample of cat N°

11 was done at another laboratory than those of the other patients, therefore the reference value

differs from the others. These results were not taken in account when determining the median value.

Gamma-glutamyl transferase (GGT) vales were increased in 3 patients (N° 4, 10, 11) with a median

value of 12 U/L (6-20). AST was measured in only 1 cat and it was increased.

Table 4 Biochemical results in the individual cats with extrahepatic biliary tract obstruction

Case Values Reference

2 Bilirubin 95 μmol/L 0 - 15 μmol/L

3 ALP 127 U/L ALT 481 U/L

14-111 U/L 12-130 U/L

4 ALP 143 U/L ALT 834 U/L AST 246 U/L GGT 9 U/L

14-111 U/L 12-130 U/L < 42 U/L < 4 U/L

8

Bilirubin 128 μmol/L 0-15 μmol/L

5 ALT 270 U/L Bilirubin 85 μmol/L

12-130 U/L 0-15 μmol/L


14-111 U/L 12-130 U/L


14-111 U/L 12-130 U/L

8 ALP 124 U/L ALT 482 U/L Bilirubin 148 μmol/L

14-111 U/L 12-130 U/L 0-15 μmol/L


14-111 U/L 12-130 U/L 0-15 μmol/L

10 ALT 628 U/L GGT 20 U/L Bilirubin 208 μmol/L

12-130 U/L < 4 U/L 0-15 μmol/L

11 ALT 330 U/L GGT 6 U/L Bilirubin 8,6 μmol/L

< 73 U/L < 4 U/L < 1.7 μmol/L


14-111 U/L 12-130 U/L 0-15 μmol/L

4.2.5 Abdominal ultrasound

In 11 out of the 12 cats, the abdominal ultrasound was performed at the university clinic. In cat N° 7,

this was done at the referring veterinarian; an extensive report was provided and the exam was not

repeated at the time of presentation.

In 6 cats, the ultrasound was repeated at multiple occasions, either to monitor the progression of the

lesions (n=3; cat N° 3, 8, 12) or because the cat had recurrent clinical symptoms (n=4; cat N° 4, 6, 9,

12).

In most of the patients (n=9) the cause of the EHBO and the secondary changes to the biliary tract were

visualised, whereas in others (n=3), only these secondary changes were seen. A graphic representation

of the number of patients that showed certain sonographic findings is given below.

4.2.5.1 Secondary changes caused by EHBO

Six of the 12 cats showed signs of hepatomegaly. There were 9 cats with a distended gallbladder. The

gallbladder wall was thickened in 5 cats with a median thickness of 2.3 mm (range 1.5 mm to 3 mm).

Echogenic sludge was visible in 4 cats. Dilated hepatic ducts were seen in 9 cats (maximum 6 mm). A

dilated common bile duct was visible in 11 cats with a median diameter of 6.8 mm (range 3.8 to 11

mm) and the wall was thickened in 3. A mild amount of free abdominal fluid was seen in 6 cats.

4.2.5.2 Location and possible cause of obstruction

The duodenal papilla was enlarged in 9 cats (range 4.2 mm to 12 mm). Mineralised elements were

present in the gallbladder and common bile duct of 1 cat. The pancreas was involved in the disease

process of 2 cats. It was enlarged in both of them, and in one of them there also was some

mineralisation present.

9

Fig. 2 Abdominal ultrasound findings in cats with EHBO

4.2.6 Microbiology and histopathology

Bile was taken from all cats for bacterial culture and sensitivity testing. Aspiration of the gallbladder

content was performed either pre- or intra-operatively. Pre-operatively this was done ultrasound-

guided. In 7 cats, in-house cytology was performed on bile, abdominal fluid, liver, choledochal duct,

and papilla. The results and are shown in Table 5.

Histopathological samples of liver, gallbladder, duodenum, papilla, and pancreas were taken intra-

operatively in 9 out of the 12 cats. These results are shown in Table 6.

Table 5 Bacteriology and cytology results of bile aspirated from cats with extrahepatic biliary tract obstruction

Case Bacteriological culture Cytology

1 E. coli Cocci + rods

2 Negative Inconclusive

3 E. coli Depigmented bile

4 Negative Bile: depigmented bile with degenerated neutrophils, rod-shaped bacteria and phagocytosed bacteria Liver: neutrophilic, plasmocytic hepatitis with proliferation and inflammation of the intrahepatic biliary tract

5 E. coli NA

6 Negative NA

7 S. capitis NA

8 Negative Lymphoid cells, suggesting lymphoma

9 Negative Ductus choledochus: lymphoid cells, suggesting lymphoma Abdominal fluid: segmented neutrophils and phagocytic macrophages

10 S. felis NA

11 E. coli NA

12 Negative Papilla: epithelial clusters with a small amount of malignity signs; mild anisocytosis, multiple nucleoli, several cells in mitosis

0

2

4

6

8

10

12

Nu

mb

er

of

pat

ien

ts

Ultrasound findings

Abdominal ultrasound findings

10

Table 6 Histological results of tissue samples taken from cats with extrahepatic biliary tract obstruction

Histopathological diagnosis of the underlying cause of EHBO

1 Neutrophilic, necrotising cholangiocystitis

2 - Adenocarcinoma of the pancreas with metastases in the regional lymph nodes - Dilatation and inflammation of the intrahepatic biliary tract

3 - Chronic, neutrophilic and lymphoplasmacytic cholangiohepatitis - Chronic, purulent infection of the papilla - Neutrophilic enteritis

4 - Chronic, purulent cholangiohepatitis with dilatation and proliferation of the biliary tract - Ulcerative, neutrophilic and plasmocytic enteritis

5 NA

6 - Purulent, necrotising pancreatitis

- Chronic, neutrophilic periportal hepatitis and cholangiectasis - Biliary cystadenoma - Neutrophilic, lymphoplasmacytic enteritis of the duodenum and jejunum

7 NA

8 NA

9 - Chronic, lymphoplasmacytic cholangitis - Chronic pancreatitis

10 - Neutrophilic, lymphoplasmacytic cholangiohepatitis - Chronic pancreatitis - Neutrophilic, lymphoplasmacytic enteritis

11 - Chronic lymphoplasmacytic cholangiohepatitis - Neutrophilic enteritis

12 Adenocarcinoma of the papilla

4.2.7 Surgical approach

The underlying cause for extrahepatic biliary tract obstruction (EHBO) for each case and the type of

surgery performed are summarized in Table 7.

Table 7 Underlying causes of extrahepatic biliary tract obstruction and surgical approach

Case Diagnosis 1st Surgery 2nd Surgery

1 Chronic cholangitis Cholecystectomy NA

2 Pancreasadenocarcinoma Cholecystoduodenostomy NA

3 1st Papillitis 2nd Bile peritonitis

Retrograde catheterisation and flushing of the biliary tract

Exploratory celiotomy

4 1st Bacterial cholangiohepatitis 2nd Pancreascarcinoma

Cholecystoduodenostomy

Exploratory celiotomy

5 Pancreatitis and pancreaticoliths Cholecystectomy NA

6 Papillitis and necrotizing pancreatitis

Stent placement in common bile duct Hair removal from stent

7 Pancreatitis Stent placement in common bile duct NA

8 Gastrointestinal lymfoma Stent placement in common bile duct NA

9 Chronic cholangitis Retrograde catheterisation and flushing of the biliary tract

Cholecystoduodenostomy

10 Cholelithiasis and possible cholangitis

Choledochotomy with suction of present mucus and retrograde flushing of the biliary tract, then cholecystotomy with normograde flushing of the biliary tract

NA

11 Cholangitis/ cholangiohepatitis and mineralised elements in the gallbladder

Retrograde catheterisation and flushing of the biliary tract

NA

12 Adenocarcinoma of the papilla Retrograde flushing of the biliary tract and stent placement in common bile duct

NA

11

The combination protocols used for anaesthesia consisted of several different products, namely: CRI

epinephrine (n=1), CRI fentanyl (n=9), CRI remifentanil (n=3), dexmedetomidine (n=1), isoflurane

(n=13), methadone (n=11), propofol (n=12).

In 3 cats (N° 3, 10, 11), catheterisation and flushing of the biliary tract restored the patency of the

extrahepatic biliary tract. This was done retrograde in cat N° 3 and 11 and both retro- and normograde

in cat N° 10.

There were 2 cats in which a cholecystectomy was performed. N° 1 had a chronic cholangitis with

sludge formation. This caused chronic partial EHBO. There were also choleliths present. In N° 5 there

was a cystic mass attached to the gallbladder and the gallbladder wall was rather fragile. In both cases,

the gallbladder was bluntly dissected and the gallbladder neck ligated. In N° 1, the gallbladder was then

removed. In N° 5, the lobus quadratus of the liver was also ligated and removed en bloc with the

gallbladder because it had an abnormal appearance.

Three cats underwent a cholecystoduodenostomy. The gallbladder was bluntly dissected. Then an

incision of 2.5 to 3 cm was made in the gallbladder as well as in the duodenum. Both incision lines were

sutured together with 2 continued suture lines.

In 4 cats, a polyethylene stent was placed. Once a 6 Fr (cat N° 7) and three times an 8 Fr (cat N ° 6, 8,

12) was used. These stents were sutured to the duodenal mucosa with resorbable suturing material.

Four cats needed a second surgery. Cat N° 3 had an exploratory celiotomy 6 days after the primary

surgery, because bile peritonitis was diagnosed after ultrasound-guided abdominocentesis. N° 4

underwent an exploratory celiotomy 10 months after the original surgery, because of reoccurring

symptoms. In cat N° 6, there was only a week between the surgeries. The patient had developed icteric

mucosae. The patency of the stent was disturbed by hairs stuck to the sutures that were keeping the

stent in place. The stent was removed and flushed. Patency of the common bile duct was assessed and

the stent was replaced. New sutures were placed, but this time the knots were tied more lateral and

the ends were cut shorter. For cat N° 9 there was an interoperative interval of 7 weeks. The first

operation was a retrograde catheterisation and flushing of the biliary tract, but symptoms remained

and the cat was later diagnosed with a sterile bile peritonitis. Then it was decided to perform a

cholecystoduodenostomy.

4.2.7.1 Complications

Complications occurred during the perioperative period in 8 out of 12 cats These complications were:

anaemia that required a blood transfusion (N° 2, 4, 5 and 9), anorexia (N° 6 and 7), bile peritonitis,

cardiac arrest (N° 7, 9), hypoglycaemia (N° 2), hypotension (N° 2, 5,9), hypothermia (N° 2, 5), Icterus

(N° 6), lethargy (N° 2), pancreatitis (N° 3), tachycardia (N° 1, 2), respiratory distress (N° 7, 9).

4.2.7.2 Hospitalisation

Hospitalisation time varied between 2 and 18 days with a median time of 6 days. During this

hospitalisation medical treatment was provided. This consisted of fluid therapy (n=12), amoxicillin

clavulanic acid (n=10), ephedrine (n=8), methadone (n=8), ursodeoxycholic acid (n=7), buprenorphine

(n=5), cefazolin (n=5), metoclopramide (n=5), S-adenosylmethionine (n=5), blood transfusion (n=4),

maropitant (n=4), vitamin K (n=4), omeprazole (n=3), prednisolone (n=2), butorphanol (n=1), cefalexin

(n=1), enrofloxacin (n=1), insulin (n=1), mirtazapine (n=1), and tramadol (n=1).

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4.2.8 Postoperative morbidity and mortality

One patient was lost to follow up. Some patients were hospitalised more than once. During the primary

hospitalisation period 2 cats died; 1 of them had cardiorespiratory arrest within 48 hours after surgery

(N° 7) and the other was euthanised within 24 hours after surgery, because of uncontrollable

hypotension and persistent hypoglycaemia (N° 5).

The other cats were discharged from the hospital. Of these, 3 died within 3 months after discharge.

One cat (N° 3) was discharged for 3 days before returning to the clinic with persisting symptoms. The

cat had a second surgery 6 days after the primary and was euthanised intraoperatively due to a poor

prognosis. Another (N° 8) was euthanised 2 months after surgery because of remaining symptoms

(vomiting) and a degrading quality of life. Cat N° 9 died 7 weeks after the primary surgery. He suffered

from a cardiorespiratory arrest during the recovery period of the second surgery.

Of the cats surviving longer that 3 months after discharge, 5 had recurrent clinical symptoms. These

symptoms included anorexia, vomiting and weight loss. The median disease-free interval was 8.25

months (range 0- 19 months).

Cat N° 1 has been doing very well since the moment of discharge. He has been symptom free for 19

months.

Cat N° 4 had a disease-free interval of almost 7 months, after which the anorexia, vomiting and weight

loss reoccurred. During the second surgery many abnormalities of the liver, biliary tract and pancreas

were found (Figure 3 and 4). Multiple liver masses were visible. An ulcer can be seen on figure 3 where

the tip of the instrument is pointing. The patient was euthanised intraoperatively. Histological samples

were taken and the masses in the liver turned out to be metastasis from a gastrinoma in the pancreas.

Fig. 3 Liver metastases from a gastrinoma of the pancreas Fig. 4 Hepatic masses and duodenal ulcer

In cat N° 6 the main reoccurring symptom was vomiting. This happened a couple of times during the

first 2 months after surgery. After this, he was symptom free for 15 months. Then the intermittent

vomiting started again and he got a bleeding in the left eye. He was diagnosed with hypertension,

dynamic left ventricular outflow tract obstruction and chronic kidney disease (CKD) IRIS stage 2. In the

next 3 months he also showed partial anorexia, lethargy and weight loss. On abdominal ultrasound the

common bile duct was dilated (10mm) and the papilla was enlarged (6mm). The medication he

received is: prednisolone, mirtazapine, maropitant, amoxicillin and amlodipine. He is given a renal diet.

Cat N° 10 suddenly died 6 months after surgery. During these 6 months she was symptom free. Then

she acutely started vomiting, got anorexia and became lethargic. On blood examination AST and ALT

were severely increased and she was lymphopenic and thrombocytopenic. She also had hypothermia.

She died 3 days after the first occurrence of symptoms.

13

Cat N° 11 has been doing very well. However, she does still occasionally vomit. Her blood values were

all normal at the first check-up 1 month after surgery.

Cat N° 12 was symptom free for 2.5 months after surgery, then he suddenly developed a big

ecchymosis on the abdomen. The blood work 3 months after surgery showed an increased ALT and

ALP when compared to the results from the day of the surgery. The cat is clinically doing well.

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5. Discussion

Extrahepatic biliary tract obstruction is considered to be relatively uncommon in cats (Mayhew et al.,

2002; Bacon and White, 2003; Mayhew, 2006; Mayhew and Weisse, 2008). This is indeed reflected by

the low number of feline cases that were presented to the university hospital for surgical correction of

biliary tract disease over the past 5 years. Based on the available literature describing cases of feline

EHBO, there doesn’t seem to be any age nor sex predisposition (Martin et al., 1986; Cornell et al., 1993;

Fahie and Martin, 1995; Eich and Ludwig, 2002; Mayhew et al., 2002; Bacon and white, 2003; Buote et

al., 2006; Harvey et al., 2007; Mayhew and Weisse, 2008; Morrison et al., 2008; Baker et al., 2010;

Linton et al., 2015). The lack of age predisposition is also reflected in the cases presented to the faculty

clinic; the age of the patients varied between 2.5 and almost 15 years. Although twice as many male

as female cats with EHBO were observed in this small study cohort, there is insufficient evidence to

conclude that male cats are really overrepresent, since the proportion in cats with EHBO was not

statistically different from the proportion in cats presented to the clinic (data not shown).

The most important finding on clinical examination was icterus. As additional examinations

haematology, biochemistry and abdominal ultrasound were performed. The most pronounced

abnormalities were increased liver enzymes on biochemistry and, on ultrasound, the secondary

changes due to the obstruction were visible. Depending on the localisation of the obstruction different

types of surgery were performed.

Extrahepatic biliary tract obstruction can be the sequela of various pathologies. As mentioned in the

anatomy introduction, in cats, the common bile duct and the pancreatic duct fuse before entering the

duodenum. This is similar to the situation in humans (Paulsen & Waschke, 2011) but different from the

anatomy in dogs (Center, 2009). In dogs, the ducts insert separately. Thus, the feline biliary tract is

more prone than the canine to be affected by pancreatic disease (Mayhew et al., 2002; Jergens, 2012;

Radlinsky,I2013).

Besides pancreatic disease, EHBO can be caused by other pathologies, similar to the causes in dogs. A

few examples of these underlying disease are: inflammation of the biliary tract (Mayhew et al., 2002;

Jergens, 2006), neoplasia (Barsanti et al., 1976), cholelithiasis (Radlinsky, 2013), diaphragmatic hernia

(Cornell et al., 1993), infection, parasites (Center, 2009; Basu and Charles, 2014) and even a foreign

body (Linton et al., 2015). Of all these, both inflammation and neoplasia of the biliary tract, liver,

pancreas, and duodenum are most common (Fahie and Martin, 1995; Mayhew et al., 2002).

Diagnosing EHBO can be difficult. Occasionally, clinical symptoms can be suggestive for biliary tract disease; however, they are most often vague and not specific (Jergens, 2006; Mehler, 2011; Mehler and Mayhew, 2013). This might lead to a belated diagnosis and treatment and, therefore, potentially to a worse prognosis (Mehler, 2011). Symptoms that are seen most often include: icterus, anorexia, lethargy, vomiting, and dehydration (Eich and Ludwig, 2002; Mayhew et al. 2002; Bacon and White, 2003; Buote et al., 2006; Mayhew and Weisse, 2008; Morrison et al., 2008; Center, 2009; Aguirre, 2010; Baker et al., 2010). Apart from the dehydration, all other symptoms were seen in the clinical cases included in the current study in varying combinations. Some patients had a worse general condition and showed more symptoms than others.

Haematology and biochemistry do not differentiate between EHBO and other abdominal conditions. Common findings in haematology are leucocytosis and non-regenerative anaemia (Bacon and white, 2003; Buote et al., 2006; Jergens, 2006; Center, 2009; Mehler and Mayhew, 2013; Kummeling, 2016). Haematology results were not available in all the cats from this study. Abnormalities that were present included: eosinopenia, lymphocytosis, lymphopenia, monocytosis, and neutrophilia. Two cats showed a pre-operative anaemia which was non-regenerative.

15

On biochemistry, hyperbilirubinemia and an elevation in liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) can be present (Center et al., 1983; Lawrence et al., 1992; Eich and Ludwig, 2002; Mayhew et al., 2002; Jergens, 2006; Mayhew, 2006; Morrison et al., 2008; Center, 2009; Baker et al., 2011; Mehler and Mayhew, 2013; Otte et al., 2017). According to an experimental study by Center et al. (1982) where the feline bile duct was ligated (creating a model of EHBO), ALT had a marked increase where ALP only had a mild increase. The increase in ALT was already significant during the first measurement 7 days postoperatively, whereas ALP did not significantly increase until the fifth measurement 35 days postoperatively. Case reports by Martin et al. (1986), Eich and Ludwig (2002), Bacon and White (2003), Harvey et al. (2007), Morrison et al. (2008), Baker et al. (2011), Linton et al. (2015) give the same presentation. However, there are also cases where the increase in ALP was more pronounced than the increase in ALT (Fahie and Martin, 1995; Mayhew et al., 2002; Buote et al., 2006; Mayhew and Weisse, 2008). In these cases, the increase in ALP was equally or more pronounced than the increase in ALT. In a retrospective study by Center et al, (1986) the usefulness of GGT and ALP in diagnosing hepatobiliary disease was investigated. It was concluded that GGT had a better sensitivity but a lower specificity that ALP in diagnosing hepatobiliary disease, and therefore it is recommended to test both in suspected patients. The biochemical results from the cats in this case series showed that they did not all have the same increased enzymes and the increases themselves also differed in severity. Not all the different enzymes were tested routinely. AST and GGT were only measured in some cases while ALT and ALP were measured in all the cats. In agreement with the study by Center et al. (1982) the increase of ALT occurred more often and was more pronounced than the increase in ALP.

A valuable medical imaging tool to diagnose EHBO is ultrasound (Mayhew and Weisse, 2008; Center, 2009; Radlinsky, 2013). The gallbladder and the bile duct can be visualised during ultrasound through longitudinal and transverse liver scans (Nyland and Hager, 1985). In several case reports, the normal and abnormal anatomy of the gallbladder have been studied (Léveillé et al., 1996; Etue et al., 2001; Hittmair et al., 2001; Gaillot et al., 2007). The tortuous aspect that was seen on the casts made for this study is also mentioned on ultrasound in normal cats by Léveillé and colleagues (1996) and in cats with EHBO by the group of Gaillot (2007). So, even though there are anatomical variations in the extrahepatic biliary tract, there is no evidence that they are the cause of obstruction. In cats with EHBO, gallbladder distention and wall thickening are not constant findings on ultrasound. Dilation of the gallbladder itself is not the most reliable indication of EHBO. In a retrospective study by Gaillot et al. (2007) less than half of the cats with EHBO had a dilated gallbladder; so a gallbladder of normal size did not rule out disease. However, in that study, dilation of the gallbladder was determined subjectively. Hittmair et al. (2001) evaluated the thickness of the gallbladder wall as a parameter in the diagnosis of EHBO in cats. A gallbladder wall thicker than 1 mm was considered an indication of EHBO. A thickness of the gallbladder wall less than 1 mm, on the other hand, did not rule out disease. Dilation of the common bile duct can also be used as an indication. According to Nyland and Hager (1985) enlargement of the common bile duct can be observed within 48 hours after obstruction. In a study by Léveillé and colleagues (1996) it was concluded that the normal diameter of the bile duct is maximally 4 mm. When dilated, it can reach a far larger size. The same study mentioned diameters up to 11 mm in diseased cats. One of the patients from this case series (N° 9) even reached a diameter of 27 mm. Using 4 mm as a cut-off value to determine whether a cat has an obstruction or not, is not reliable in cats with a previous history of EHBO. These cats may have persistent biliary tract dilation because of a lack of elasticity (Rosenthal et al., 1990; Léveillé et al., 1996; Mayhew, 2006). In such cases it is hard to accurately diagnose a relapse. This should be kept in mind when performing an ultrasound in cats with remaining or reoccurring symptoms after treatment.

In the studied cases, a few cats (N° 3, 4, 6, 9) had more than 1 ultrasound performed at the faculty clinic. These additional ultrasounds were needed, because these cats had persistent or recurring problems after the primary surgical intervention. The results from the preoperative ultrasound have been discussed earlier. Common findings during these ultrasounds were free abdominal fluid (n=3)

16

and dilation of the biliary tract (n=4). The free fluid was normal exudate in 2 cats and it was septic in 1 cat (presence of E. coli). This fluid may be produced as a result of a bile- or sterile peritonitis.

Another diagnostic tool, however not used routinely, is hepatobiliary scintigraphy. In cases where ultrasound is inconclusive, it is a valuable tool to determine the patency of the bile duct, detect abnormal biliary flow and differ between intrahepatic and extrahepatic obstruction (Boothe et al., 1992; Head and Daniel, 2005). The prolonged clearance t1/2 of the radioactive substance (Tc 99m) is the most obvious indicator of an abnormal flow. When radioactivity is detected in the gastrointestinal tract within 3 hours after IV administration of Tc 99m, the biliary tract is considered patent. If it takes more than 3 hours, or doesn’t appear at all, it is considered partially or fully obstructed respectively

(Head and Daniel, 2005).

After diagnosing EHBO, there are several different treatment options depending on the underlying

pathology. Before deciding to perform surgery, medical treatment should be attempted. Underlying

pathologies such as inflammation or infection of the biliary tract might be resolved with medication

only. Treatment with anti-inflammatory drugs, antibiotics and diet alterations might be sufficient to

restore the patency of the common bile duct (Boothe et al., 1992; Jergens, 2006; Mayhew, 2006;

Center, 2009; Otte et al., 2017).

When medical therapy alone is insufficient, surgery should be performed. In all patients, it is important to check beforehand if there are any abnormalities on haematology and biochemistry, so anaesthetic precautions can be taken. Electrolyte and fluid therapy should be administered as needed to correct abnormalities. Electrolyte imbalance and dehydration can be expected in animals that have been vomiting. Coagulation can be disturbed since a vitamin K deficiency might co-exist with EHBO (Mayhew and Weisse, 2012; Radlinsky, 2013). Prolonged coagulation times can be measured by testing the prothrombin time (PT) and the activated partial tromboplastin time (aPTT) (Mehler and Mayhew, 2013, Radlinsky, 2013). When surgery is performed without knowledge of the coagulation status, unexpected haemorrhage can complicate the intervention. Therefore, it is advisable to perform the tests in all cats with EHBO. In one third of the cats from this case series in which the coagulation times were measured, they were abnormal. The chronicity of the symptoms didn’t seem to be correlated with the presence of increased PT and aPTT in the cats from this study. One cat showed symptoms for 15 days, another for 7 days and the last one only showed symptoms for 1 day and still had prolonged coagulations times. A hypothesis to explain these findings is that the obstruction could have been only partial in the beginning. This would not have been severe enough for the cat to show symptoms, but there could already have been an impact on the liver function and therefore an effect on the coagulation factors. However, there is no scientific evidence to support this hypothesis. The abnormalities in the cats were not severe enough to require immediate therapy, but they alerted anaesthetists and surgeons. If coagulation times are significantly prolonged, preoperative administration of vitamin K or a transfusion with fresh whole blood can be necessary (Center, 2009; Radlinsky, 2013). Center et al. (2000) showed in their experimental study of bile duct ligation that the administration of vitamin K normalized the observed prolonged coagulation times. Fresh whole blood transfusion is a better option for critical patients in which surgery cannot be postponed, since coagulopathies are reversed faster than with vitamin K therapy (Mayhew and Weisse, 2012; Radlinsky, 2013). If vitamin K is administered, this should be initiated 24 to 48 hours before the surgery with a dosage of 0.5-2.0 mg/kg subcutaneously (Radlinsky, 2013). It must be given every 8 to 12 hours, because it takes this long before coagulation times normalize (Edwards et al., 1987; Mayhew and Weisse, 2012; Couto, 2014). In this study only 1 patient (N° 11) was supplemented with oral vitamin K therapy before surgery, although this patient didn’t have prolonged coagulation times to start with. Since there is an absorption problem, oral therapy might be less efficient than subcutaneous administration (Edwards et al., 1987). As long as there is no scientific evidence that proves that vitamin K supplementation is not effective in

17

cats with EHBO, it seems advisable to administer subcutaneous preoperative vitamin K therapy in cases with coagulation disorders. An important complication of EHBO that is mentioned in literature but wasn’t seen in the patients from

this study is renal failure. This is a consequence of endotoxemia (Wardle and Wright, 1970; Bailey

1976; Cahill et al., 1987; Mayhew and Weisse, 2008, Mehler, 2011). As explained in the introduction,

endotoxins are bound by bile salts and therefore less absorbed by the intestines. In an experimental

study with rats it was shown that with a lack of bile salts, endotoxins can be absorbed easier, leading

to endotoxemia (Bailey, 1976). Endotoxemia is also considered one of the causes of hypotension

during anaesthesia (Buote et al., 2006). As a result, the anaesthetic strategy has to be adapted and

vasopressors and fluid replacements, such as hypertonic solutions or blood transfusions, should be

administered (Mayhew et al., 2002; Buote et al., 2006). Regarding the negative consequences of

endotoxemia, it is important to prevent this. The experimental study with rats by Bailey (1976) showed

that, when given sodium taurocholate orally, the animals didn’t develop endotoxemia. In a human

study by Cahill et al. (1987) endotoxemia was prevented by using oral sodium deoxycholate. Besides

administering oral bile acids, Pain and Bailey (1986) suggested after an experimental study in rats that,

giving lactulose can also be used to prevent endotoxemia. Similar studies have not been conducted in

the cat.

To treat the obstruction there are various types of surgery depending on where the obstruction is located. For example, if the proximal part of the biliary tract is blocked, a cholecystectomy can be performed. In cases of EHBO in which the common bile duct is not completely obstructed, when the obstruction is reversible or when the obstruction is caused by temporary swelling of the papilla, biliary stenting might be a treatment option (Mayhew 2006; Mehler and Mayhew, 2013). During surgery the localisation and severity of the obstruction can be determined. Then a final decision can be made for the type of biliary tract surgery that is going to be performed. In this study 3 different types of surgery were performed; cholecystectomy, cholecystoduodenostomy and biliary stenting.

In case of cholelithiasis a cholecystectomy or cholecystotomy is the surgery of choice, depending on the surgeon’s preference (Neer, 1992; Martin et al., 2003; Doran and Moore 2007, Center, 2009; Mayhew and Weisse, 2012; Mehler and Mayhew, 2013; Radlinsky, 2013). A cholecystotomy should only be performed if the gallbladder wall is still healthy (Doran and Moore, 2007). The advantage of a cholecystotomy is that, in case of a future obstruction, you have more surgical options than after a cholecystectomy since a cholecystoenterostomy can still be performed. The patient with choleliths (N° 10) that got a cholecystectomy already had a compromised gallbladder wall, therefore a cholecystotomy was not an option. A cholecystoduodenostomy is the type of a biliary diversion that is used most frequently. This gives the most physiological situation, since bile enters the intestine at approximately the same location as it normally does (Morrison et al., 2008; Mayhew and Weisse, 2012). The size of the stoma should be between 2.5 and 4 cm. Mehler and Mayhew (2013) recommended that the stoma should be as large as possible and the incision should start at the fundus of the gallbladder and end at the beginning of the cystic duct. During the healing process the stoma size might decrease to 50% of the original size (Tanger, 1990; Martin et al., 2003; Mayhew and Weisse, 2012; Mehler and Mayhew, 2013; Radlinsky, 2013). According to the data collected from the patient files, the stoma sizes from the patients with a cholecystoduodenostomy varied between 2 and 3 cm. Even though 2 cm is smaller than what is recommended, the patency of the stoma remained sufficient. Biliary stenting is the least invasive treatment option of EHBO, but can only be performed in selected cases with reversible causes of obstruction (Mayhew 2006; Mehler and Mayhew, 2013). There are complications that are specifically associated with biliary tract surgery. For example, after a cholecystectomy bile leakage can occur if the cystic duct isn’t properly ligated. This can lead to bile

18

peritonitis (Mehler, 2011). Sterile bile leakage will cause chemical peritonitis, since bile salts are causing the inflammation. This can transform into a septic bile peritonitis when bacteria are present, since the inflammation facilitates bacterial growth (Ludwig et al., 1997; Mehler, 2011; Mayhew and Weisse, 2012). Bacteria can end up in the peritoneal cavity by leakage of bile contaminated by an ascending infection, or by hematogenous spread. Chronic ascending cholangiohepatitis is a known complication after cholecystoduodenostomy. It is suggested that a stoma that is too narrow may inhibit a quick drainage of biliary-enteric reflux, allowing ascending infection to take place. This can lead to chronic inflammation (Johnson and Stevens, 1969; Tanger, 1982; Mehler, 2011; Mayhew and Weisse, 2012). Another complication is anastomotic dehiscence (Mehler, 2011). The problem with biliary stenting is that the biliary tract in the cat is very narrow (Léveillé et al., 1996). Therefore, only small stent sizes can be used. The limited diameter gives a serious risk of early clogging of the stent and recurrent obstruction and clinical symptoms (Mayhew, 2006; Mayhew and Weisse, 2008; Mehler, 2011). Stent occlusion has been described as early as 12 hours after surgery (Murphy et al., 2007). In retrospective human studies, 8 French gauge polyethylene stents were compared to 10 French stents. Both average clogging time and occurrence of cholangitis have been used as parameters. It was suggested that the cause for cholangitis was biliary stasis, which formed a base for bacterial overgrowth. The average time before clogging of the stent was 12-16 weeks versus 31-32 weeks respectively (Speer et al., 1985; Speer et al., 1988). It was also noticed that there was less early cholangitis in the 10 French. These are arguments to believe that larger stents are beneficial. Mehler (2011) suggested that in cats the largest stent size that doesn’t completely fill the lumen of the common bile duct should be used. By entering through the major duodenal papilla, it is tested if the diameter of the common bile duct is sufficient for the stent size. The 3.5 and the 5 French polyethylene catheters, corresponding to an outer diameter of 1.17 to 1.67 mm, are commonly used. These stents sizes have been reported in 6 clinical cases (Mayhew and Weisse, 2008). Two of these cats re-obstructed within a week. There have been no studies in cats so far that did investigate which size or which material would be optimal to stent the extrahepatic biliary tract. In the patients from this case series, stent seizes of 6 and 8 Fr have been used. No internal stent clogging has been reported. More data about stent seizes in cats should be recorded to investigate whether the usage of larger stent sizes is possible. Besides the size of the stent, bacterial biofilm forming plays an important role in stent clogging (Speer et al., 1986, Leung et al., 1988). When bacteria get in the stent lumen, they can adhere to the surface and form a biofilm, which can lead to stent clogging. Normally the sphincter of Oddi serves as a natural barrier for intestinal reflux into the biliary tract (Sung et al., 1990; Center, 2009). Therefore, it can prevent bacteria from getting in the biliary tract. Since most stents are placed with the distal tip through the sphincter of Oddi and in the duodenum, the natural barrier is no longer functional and bacteria can get in the lumen of the stent. An experimental study has been performed in cats, with the objective of investigating the role of the sphincter of Oddi in ascending infections (Sung et al., 1992). They found no biofilm material when the stent didn’t pass the sphincter of Oddi. However, if the obstruction is located in the distal part of the common bile duct or at the level of the sphincter of Oddi, the stent has to be placed with the distal tip in the duodenum, otherwise the obstruction would not be dissolved. The stents that have been placed in the cats in this study all had their tip in the duodenum. Early mechanical obstruction of the distal opening of the stent occurred in 1 patient. This was due to hairs that were attached to the stiches outside the stent. Another factor that influences the moment of bacterial colonisation is the material of the stent. A prospective human study showed that a metal stent had a longer duration of patency when compared to a plastic stent. Additionally, there was less obstruction in general in the metal stent, both in short term and long term (Kaassis et al., 2003). In cats the material which is used most often is red rubber (Mayhew and Weisse, 2008; Mehler and Mayhew, 2013). This choice seems somehow contra-intuitive since it is in an experimental study that red rubber is far from an inert material (Apalakis, 1976). Leung et al. (2000) did an experimental study in cats to see if prophylactic use of ciprofloxacin can prevent stent clogging. They noticed that the median time before clogging was significantly longer in

19

the cats treated with ciprofloxacin than the ones that didn’t get this antibiotic. The bacterial culture was also different between the treated and untreated group. In the treated group no gram-negative bacteria were present. They concluded that ciprofloxacin may have a beneficial benefit in delaying stent blockage. High morbidity and mortality rates have been associated with surgical intervention to resolve EHBO in

cats and the overall prognosis is guarded to poor (Mayhew et al., 2002; Bacon and White, 2003; Buote

et al., 2006; Mayhew and Weisse, 2008; Morrison et al., 2008). On the other hand, several cases with

good survival rates have been reported (Eich and Ludwig, 2002; Harvey et al., 2007; Baker et al., 2011;

Linton et al., 2015). The observed mortality rate in the cats in this case series is high. One cat was lost

to follow up but of the remaining 11 cats, 7 died due to biliary tract related problems. Three died of

natural causes, 4 were euthanised. The highest mortality rate occurred in the first 3 months after

surgery (n=5). Only 2 cats died after the 3 month time limit. Almost all the patients that survived more

than 3 months had reoccurring symptoms. The main reoccurring symptom was vomiting.

A possible indicator for the prognosis might be the underlying condition. There seems to be a

correlation between these two; as expected, neoplasia has a worse prognosis than inflammation and

mortality can be as high as 100% (Mayhew et al., 2002; Buote et al., 2006; Mayhew et al., 2006). The

type of surgery on the other hand, does not seem to have an influence on the prognosis. Mehler et al.

(2004) concluded after a retrospective study of 60 dogs, that there was no correlation between the

type of surgery and mortality rates. There are retrospective human studies that have investigated

which risk factors influence the post-operative morbidity and mortality rates (Pitt et al., 1980; Dixon

et al., 1983). These risk factors include: anaemia, increased bilirubin, malignancy of obstruction, age of

the patient and fever. The number of risk factors present in a single patient was also of influence of

the prognosis. Besides underlying condition, such risk factors have not been demonstrated yet in the

cat. Further investigation might be useful in order to prevent the high mortality rates.

6. Conclusion

In order to diagnose EHBO it is important to perform several tests. Haematology and biochemistry are

basic necessities. Standard biochemistry should include ALP, ALT and bilirubin; GGT and AST are not

necessary to diagnose biliary tract disease. Measurement of coagulation times is recommended in all

patients to assess whether pre-operative vitamin K supplementation or a blood transfusion is

advisable. Abdominal ultrasound can show the severity of the secondary effects and might show the

location of the obstruction. Despite the fact that there are advanced techniques to treat biliary tract

obstruction, the mortality rate in EHBO cats is still high. Therefore, more research should be done

about prognostic factors and additional treatment options to improve the prognosis.

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