´

Relatório Final de Estágio

Mestrado Integrado em Medicina Veterinária

SMALL ANIMAL MEDICINE AND SURGERY

Yvette Charlotte Klerx

Orientador

Dr. Miguel Augusto Soucasaux Marques Faria

Co-orientador

Dr. Alfred Legendre (John & Ann Tickle Small Animal Teaching Hospital, University of Tennessee)

Porto 2014

Relatório Final de Estágio

Mestrado Integrado em Medicina Veterinária

SMALL ANIMAL MEDICINE AND SURGERY

Yvette Charlotte Klerx

Orientador

Dr. Miguel Augusto Soucasaux Marques Faria

Co-orientador

Dr. Alfred Legendre (John & Ann Tickle Small Animal Teaching Hospital, University of Tennessee)

Porto 2014

III

Abstract

This report aims to conclude Integrated Master in Veterinary Medicine. It consists of a brief

description and discussion of five clinical cases that I have followed during my externship at the

John and Ann Tickle Small Animal Hospital of the University of Tennessee, for a total of 16

weeks, with a main focus on the area of Small Animal Medicine and Surgery.

During this period, I had the opportunity to join and participate in specialized areas, going

through different rotations, such as integrative medicine, cardiology, orthopedic rehabilitation,

internal medicine, soft tissue surgery, ophthalmology, oncology and dermatology. My

contribution consisted of performing appointments and physical examinations, presenting

diagnostic and therapeutic plans, assisting or participating in procedures, updating medical

records as well as communicating with clients. Alongside this, I presented clinical cases during

rounds, performed research, discussed recent articles and prepared various presentations.

The realization of this externship was of great relevance to expand and ameliorate my clinical

skills, autonomy as well as self-confidence in execution of duties. The main objectives were

fulfilled by employing maximum focus on all assigned responsibilities, being a team player,

learning how to manage bureaucratic aspect and by interacting with the patient’s owners.

Overall, this externship was an extremely educational and unique experience which has not

only been very significant for my development but will also have a positive impact on my future

career. I strongly recommend any veterinary student to go through such an experience.

IV

Acknowledgements

My sincerest thanks to my mentor, Dr. Miguel Faria, for the availability and useful

suggestions provided through this final stage and entire course. To Dr. Alfred Legendre for

endowing this unique opportunity for many years, for the 24/7 availability and the wonderful

conversations in the Dutch language that made me feel at home. It was a pleasure to meet you.

My mother and father, Anneke and Hans Klerx, to whom this is dedicated. Thank you for

making this possible and supporting me through all my decisions. For believing in me and

encouraging me. For being there and for giving strength when everything seems to be going

wrong. For teaching that hard workers achieve success and that optimism is an important key

for life.

To my one and only sister, Michèle Klerx, for being my role model and best friend. For being

proud of me and matching my level of craziness. For being there even when different countries

separate us from being together. For remaining the same silly sister and for caring about me,

even if we don’t see each other that often. You know I'm proud of you as well.

To the sweetest grandmother, Jet Klerx, my guardian angel.

To Riet Van Riel, my other lovely grandmother for receiving me for one entire month, we had

a fantastic time together.

To Donny and Peer for sharing the same passion for animals, for following me through all

those years and being such a great support.

To Annemiek Van Riel, for the honesty and constructive critic. I appreciate your dedication

and willingness to be involved.

To Joana Portugal for your friendship and all the never-ending conversations we had through

those years. For the adventures and hilarious stories. As I said before, we could write a book!

To Ana Salazar, for the funny emails we exchanged when an Atlantic Ocean was impeding

us from having our typical lunches. For being, just as Lara Neves, a wonderful friend.

V

To my Tennessee girls, Daniela Bento, Daniela Martins, Marta Gomes and Sara Dinis.

Thank you for being the best roomies in the world. For supporting through ups and downs and

for being my lovely American family during those 3 months. To Inês Palhinhas for

understanding that a life without cupcakes and Mexican food is not the same.

To Joana Soares, simply for your enormous support.

To Jessica Miner, the sweetest American girl I met. Thank you for being there for me. And to

all the other amazing people as well as patients, for making this experience unforgettable.

To Franky, for the 14 years of pure happiness. For growing up by my side and teaching me

to appreciate the simple things in life.

To Noa, the most extraordinary dog on earth, for guiding me through life…

VI

List of Abbreviations:

% – Percentage

ACTH – Adrenocorticotropic hormone

ALP – Alkaline Phosphatase

ALT – Alanine aminotransaminase

aPTT – Activated partial thromboplastin

time

AT – Adrenocortical tumor

ATH – Adrenocortical tumors causing

hyperadrenocoriticism

BAL – Bronchoalveolar lavage

bFGF – Basic fibroblast growth factor

BG – Blood glucose

BID – Twice daily

CBC – Complete Blood Count

CK – Creatine Kinase

Cm – Centimeters

COPD – Chronic obstructive pulmonary

disease

CO2 – Carbon dioxide

cPLI – Canine pancreatic lipase

immunoreactivity

CRI – Constant rate infusion

CT – Computerized tomography

cTLI – Canine trypsin-like immunoreactivity

DIC – Disseminated intravascular

coagulation

dL – Deciliter

ECG – Electrocardiography

EOD – Every other day

EPI – Exocrine pancreatic insufficiency

FAST – Focused Assessment with

Sonography for Trauma

fL – Femtoliters

flair – Fluid-attenuated inversion recovery

Fr – French scale

g – Gram

HDDST – High dose dexamethasone

suppression test

HSA – Hemangiosarcoma

ICU – Intensive care unit

IV – Intravenous

IM – Intramuscular

KCS – Keratoconjunctivitis sicca

Kg – Kilogram

L – Litter

VII

LDDST – Low dose dexamethasone

suppression test

MAHA – Microangiopathic hemolytic

anemia

m2 – Square meter

MDR1 – Multidrug resistance protein-1

mEq – Miliequivalents

mg/Kg – Milligram by kilogram

mg/m2 – Milligram by meter square

mL – Milliliter

mL/h – Milliliter per hour

mm – Millimeter

mmHg – Millimeter of mercury

mmol – Millimoles

MRI – Magnetic resonance imaging

ng – Nanogram

OS – Left eye

OU – Both eyes

P53 – Phosphoprotein p53

PCV – Packed cell volume

PO – Per os

Pg - Picogram

PT – Prothrombin time

QID – Four times daily

Ras – Rat sarcoma

SID – Once daily

T4 - thyroxine

TS – Total solids

Tsc2 – Tuberous sclerosis-2

TSH – Thyroid stimulating hormone

UTVMC – University of Tennessee

Veterinary medical center

UTI – Urinary tract infection

UV – Ultraviolet light

VEGF – Vascular endothelial growth factor

VPC – Ventricular premature complex

µg – Microgram

µL – Microliter

ºC – Celsius

® – Registered trademark symbol

VIII

Contents

Abstract…………………………………..………………………………………….............. III

Acknowledgements……………..……………………………….……………………….... IV

List of Abbreviations…………………………….………………………………………… VI

Contents …………………………………………………………………………………… VIII

Clinical case Nr. 1: Gastroenterology – Chronic pancreatitis………….………... 1

Clinical case Nr. 2: Pulmonology – Chronic bronchitis ………………………..… 7

Clinical case Nr. 3: Soft Tissue Surgery – Adrenalectomy ……………………. 13

Clinical case Nr. 4: Ophthalmology – Descemetocele …………………………. 19

Clinical case Nr. 5: Oncology – Splenic hemangiosarcoma …………………... 25

Appendixes

Appendix I ………………………………………………………………………...… 31

Appendix II ………………………………………………………………………….. 33

Appendix III ………………………………………………………………............... 34

Appendix IV ……………………………………………………………………….... 36

Appendix V …………………………………………………………………………. 38

1

Clinical case Nr. 1: Gastroenterology - Chronic pancreatitis

Characterization of patient and reason of appointment: Blackjack is a 9 year old, male

castrated, 35 Kg, Labrador Retriever, that was presented to the UTVMC Emergency service

with signs of acute lethargy and vomiting with the duration of one day.

Anamnesis: Blackjack had all vaccines up to date and was dewormed regularly. He lived

indoors with private/public outdoor access and had the tendency to go into trash, plants or toxic

agents. The diet was inconstant, ranging from a miscellaneous human diet to a low fat

veterinary prescription diet. According to medical history, three cases of pancreatitis had been

reported within the last year. Although the recurrence, he recovered successfully from all

episodes. During this period, he had three other episodes at home and the owners treated by

withholding food for one day and reintroducing it gradually (Royal Canin GI Low Fat® or a

homemade sweet potato with chicken), and by giving maropitant, tramadol and acepromazine.

This last episode, the vomiting initiated immediately after a walk through a park, and consisted

mainly of bile. In the morning, Blackjack was lethargic, unable to stand, had polydipsia, anorexia

and a mild cough. However, his stools and urination were normal. Physical exam: Blackjack

was presented in sternal recumbency, mildly dehydrated (7%) and had tacky mucous

membranes. Femoral pulse was weak but with a normal rate. The respiratory rate was normal.

No crackles or wheezes were ausculted. Additionally, he had occasional non-productive cough

and a rectal temperature of 38.9°C. Gastrointestinal examination: Superficial and deep

abdominal palpation did not reveal clear signs of pain or discomfort. Examination of head,

esophagus, abdomen and rectum did not evince significant changes. List of problems:

Lethargy, vomiting, cough, anorexia, polydipsia, dehydration, weak pulse. Differential

diagnosis: Dietary indiscretion, intolerance or allergy; IBD; lymphangiectasia; gastrointestinal

obstruction due foreign body, neoplasia or stricture; pancreatic abscess; EPI; acute/chronic

pancreatitis; aspiration pneumonia; infectious pneumonia (B. bronchiseptica, S. zooepidemicus,

P. multocida, P. aeruginosa or K. pneumoniae). Diagnostic tests: FAST (Focused assessment

with sonography for trauma) scan - Ascites. Abdominocentesis - Exsudate with moderate

neutrophilic inflammation (Appendix I, table 3). PCV and TS: 56% and 8.0 g/dL. Blood glucose -

114 mg/dL. Lactate - 1.9 mg/dL. Blood pressure - 85 mmHg. Complete blood count - Left shifted

neutrophilia, lymphopenia and mild thrombocytosis (Appendix I, Table 1). Chemistry panel -

Mildly elevated liver enzymes, elevated creatine kinase and hypercholesterolemia (Appendix I,

Table 2). PT / aPTT - 8.2 / 24.9 seconds. Abdominal ultrasound - Moderate abdominal effusion,

hypoechoic pancreas with irregular margins, hyperechoic fat surrounding pancreas and other

organs in cranial abdomen; two hyperechoic splenic nodules. Abdominal and Thoracic

radiographs - Appendix I, Fig. 1, 2 and 3. Ultrasound guided FNA of pancreas - Neutrophilic

2

inflammation and possible fibrosis; findings consistent with acute pancreatitis. Diagnosis:

Chronic pancreatitis with acute flare-up and aspiration pneumonia. Treatment and evolution:

Blackjack was hospitalized and remained in the ICU for 6 days. Day 1 - He received a poly-ionic

solution (Plasmalyte A®) at 288 mL/h IV, and later a 350 mL IV bolus to correct hypovolemia.

Fentanyl with lidocaine IV at CRI of 1.4-2.8 mL/h was provided as pain management. In order to

control the aspiration pneumonia and prevent from sepsis, 1050 mg of ampicillin/sulbactam

(Unasyn®) IV TID was provided as well. Additionally, 35 mg of maropitant and pantoprazole IV

SID was given to control nausea and hyperacidity, respectively. The primarily given fluid bolus

drastically improved his mentation and blood pressure (120 mmHg), allowing him to stand. He

had no vomiting or diarrhea while hospitalized. Day 2 - A 250 mL fresh frozen plasma

transfusion was provided during 4 to 6 hours to correct the hypoalbuminemia. He received 2

mg/kg IM SID of diphenhydramine (Bendadryl®) preceding the plasma transfusion as prevention

for possible anaphylactic reaction. In the afternoon, Blackjack began to have increased

respiratory rate and ptyalism, indicative of severe pain. The pain management was reassessed

and the fentanyl-lidocaine rate increased. Amylopectin (Vetstarch®), a synthetic colloid was

added at 20 mL/h as attempt to reduce fluid retention. Abdominal circumference was re-

evaluated on a daily basis (increased from 83.8 to 88.9 cm). Day 3 and 4 – The abdominal

circumference decreased to 61 cm and to 55.9 cm, respectively. At this point, the patient was

kept on the same medication, and an ultrasound guided FNA of the pancreas confirmed the

diagnosis of acute pancreatitis. As anorexia persisted, a nasogastric tube was placed and was

fed with 4 mL/h of a peptide-based nutrition for metabolic stess (Perative®). Day 5 - The

nasogastric tube came out after a sneezing episode but the appetite returned gradually. The

fluid therapy was reduced and the pain management adjusted accordingly. Day 6 - Blackjack's

blood work showed no abnormalities, so he was sent home with oral omeprazole (40 mg), a

broad spectrum antibiotic (amoxicillin and clavulanic acid 375 mg) and strict instructions for a

consistent low fat diet. Prognosis: Fair if strict low fat diet is followed and recurrences are

avoided.

Discussion: Pancreatitis may be classified as acute or chronic and is a condition that

consists of pancreatic hyperstimulation caused by premature enzyme activation, leading to

severe inflammation.1,2,3 It’s a very common but under-diagnosed disease, affecting any breed,

age or sex.2,3 The most frequently affected breeds are Miniature Schnauzer, Shetland

Sheepdog, Yorkshire Terrier, Boxer, Spaniels, Terriers and Collie, while the age range is

between 5 to 9 years old.1,2,3 The breed predisposition suggests the existence of a possible

underlying genetic predilection as well as an emerging association in some breeds with imune-

mediated diseases (Cocker Spaniel), especially correlated to keratoconjunctivitis sicca.1

Autoimmune chronic pancreatitis appears to have a higher prevalence in males and at least

3

50% develop diabetes mellitus, exocrine pancreatic insufficiency, or both.1 However,

approximately 90% of the cases are idiopathic with no evident cause, others than a possible

hereditary factor.1 A less frequent cause might be duct obstruction or bile reflux to pancreatic

duct.1 The idiopathic form seems to be particularly common in Spaniels, Collies and Boxers.1,2

According to some studies, many dogs with pancreatitis are obese or have subclinical

endocrinopathies associated, such as hyperadrenocorticism, hypothiroidism and diabetes

mellitus.3,8 Other studies propose a mild increased risk in female dogs and with the use of

certain medications such as, potassium bromide, phenobarbital, azathioprine, and L-

asparginase, as well as diet indiscretion.3,8 Although severe hypertriglyceridemia has not yet

been proven to be an exact cause in dogs, others than the Miniature Schnauzer, it is presumed

that it might have impact on the disease in dogs of all breeds.3

The main function of the exocrine pancreas is secreting digestive enzymes, bicarbonate and

intrinsic factor into the proximal duodenum.1 The function of those enzymes is to achieve

primary digestion of the larger food molecules which mostly requires an alkaline pH

environment.1 The pancreas itself, secretes several other enzymes, implicating α-amilase and

lipase as active molecules and proteases, phospholipases, ribonucleases and

deoxyribonucleases as inactive precursors, or also known as zymogens.1,2 However, tryspsin, a

serine protease, is the major inactive zymogen that is activated by zymogen trypsinogen

contained by the pancreatic acini.1 Consequently, trypsinogen is activated by the enzyme

enterokinase localized within the duodenum in response to intraluminal fat and amino acids.1,2

This causes peptide cleavage and results in activation of trypsin, which then leads to activation

of other zymogens within the intestinal lumen.1,4 In addition to this, other factors can contribute

to pancreatic secretion.1,2 Those involve the enteric nervous system, the vagus nerve and the

hormones secretin and cholecystokin.1,2 Pancreatitis is often a self-limiting process but may

progress to pancreatic necrosis due to reduced pancreatic blood flow, leukocyte and platelet

migration, leading to electrolyte and acidbase imbalance.4 While in chronic pancreatitis the most

common findings are low cellularity, lymphocytic or neutrophilic infiltration, with irreversible

fibrosis and atrophy, in the accute form of the disease it is more suggestive to find

hypercellularity, neutrophilic infiltration (intact and degenerated), degenerated pancreatic acinar

cells, pancreatic necrosis, peripancreatic fat necrosis and edema.2,3

The clinical signs may vary from anorexia, vomiting and diarrhea, abdominal pain, lethargy or

weakness but no pathognomonic signs exist for canine pancreatitis.3 A study concluded that the

signalment on presentation was similar in acute and chronic pancreatitis, of which the most

frequent were lethargy, inappetence, vomiting and diarrhea.9 However, other recent reports

proved that pancreatitis can be subclinical, occurring with lethargy and weakness as very mild

and non-specific, isolated clinical signs.3 A more severe form of the disease may include signs,

4

such as icterus, fever or hypothermia, dehydration, hemorrhage, diathesis, ascites or even

cardiovascular shock, DIC and multiorgan failure.3 Blackjack had evidence of anorexia, vomiting

and lethargy but no apparent abdominal pain or diarrhea.

In terms of diagnostics, a complete blood count, biochemical panel and urinalysis are not

specific but might give an indication of the disease and should always be included to rule out

other differentials.1,3 The clinicopathologic findings are often normal in mild cases, however

anemia or hemoconcentration, leukocytosis or leucopenia, as well as thrombocytopenia can be

some of the abnormalities.3,4 Other than this, electrolyte imbalance, elevated hepatic enzyme,

hyperbilirubinemia or azotemia due dehydration may be appreciated.3,4 Measurement of serum

amylase or lipase activity is often reported on routine biochemical panels. Anyway, there are

several typical pancreatic enzyme assays of which serum cPLI concentration is considered the

most sensitive (64-93%) and specific available, comparing to cTLI (36.4-46.7%), serum amylase

activity (18.2-73.3%), serum lipase activity (13.6-69%) and abdominal ultrasound (67-68%).3 For

Blackjack these testing was not essential regarding the obvious history and diagnostic findings.

Regarding the low sensitivity (24%), the diagnosis can not be based on abdominal radiographs

solely.3 Nonetheless, typical radiographic findings such as Blackjack’s, involve an increased soft

tissue opacity with decreased serosal detail, especially in the right cranial abdomen which is

indicative of localized peritonitis.3,4 Occasionally, it is possible to identify punctiform calcification

in longstanding diseases, which is mainly caused due saponification of mesenteric fat around

the pancreas.4 In case of acute disease, gaseous dilation of bowel loops or displacement of the

stomach and duodenum, abdominal effusion, as well as, intestinal obstruction and false

masslike appearance caused by surrounding fat necrosis may be identified.1,3 Ultrasonography

is considered the most sensitive (68%) technique to obtain accurate visualization of the

pancreas.3 Some of the characteristic ultrasonographic findings consist of hypoechoic and

enlarged pancreas, dilated pancreatic duct, swollen hypomotile duodenum, biliary dilation,

peritoneal fluid and cavitary lesions such as abscess or pseudocyst.4 Performing a correct

measurement of the pancreas might help diagnosing abnormal morphological changes in size,

which seems to be more subtle in chronic pancreatitis and EPI, than in acute pancreatitis.6

Other advanced imaging modalities have not been proven worth cost-effective results in

veterinary medicine, and beside that, have a high complexity level associated and limited

availability.3 Given that no single specific modality is totally reliable, abdominal ultrasonography

in combination with histopathology or cytology are vital for a truthful diagnosis.3,4 In any case of

pancreatitis, histology is highly from all, the gold standard and is ultimate to differentiate

inflammation from possible neoplasia.1,5 According to one study, some dogs with chronic

pancreatitis were erroneously diagnosed with chronic hepatitis on basis of increased serum

hepatic enzymes because of concurrent reactive hepatitis and by not confirming it

5

histologically.5 Chronic pancreatitis appears to be associated with reactive hepatitis but not

chronic hepatitis.5 For Blackjack, a biopsy or a fine needle aspirate were both suggested and

after explaining the advantages and disadvantages of both modalities, the last option was

chosen by the owners. The fine needle aspirate is clearly the less risk-associated method but

not the most diagnostic.3,4,5

Therapeutically, canine pancreatitis consists mainly of symptomatic treatment.3,4

Dehydration, hypovolemia and consequent tissue hypoperfusion with diminished pancreatic

microcirculation might have effect on the development of local and systemic complications and

are so, a reason to perform a proper fluid therapy.3 The treatment of choice is the replacement

with isotonic fluid solutions such as 0.9% NaCl or lactated Ringer’s solution, but it is unclear

which shows the best results.3,4 The fluid therapy consists of a 10 mL/kg bolus with 5

mL/kg/hour rate for the first 8 hours.10 According to response, the bolus can be discontinued

and the rate can be decreased to 2.5 mL/kg/h if responded adequately, or the same bolus and

rate can be repeated if the patient is refractory, monitoring carefully for fluid overload.10 More

severely affected animals may require initial shock rates (90 mL/kg/h for 30 to 60 minutes)

followed by synthetic colloids.1 Synthetic colloids and plasma administration may purpose

benefits due the proteinase inhibitors as component, which is responsible for the correction of

hypoalbuminemia, replacement of α-macroglobulins and coagulation factors, as well as

improvement of systemic inflammation.10 Electrolyte imbalance such as hypokalemia, should be

considered since most of the fluid solutions contain only 4 mEq/L of potassium when most

cases require at least 20mEq/L.1 The correction can be achieved with potassium chloride IV at a

rate of 0.15 to 0.5 mEq/kg/h.1

Analgesia is the next step of the treatment approach, as pancreatitis causes severe

abdominal pain and discomfort which should not be underestimated. Buprenorphine can be an

excellent option for mild to moderate pain, while morphine, hydromorphine, methadone or

fentanyl are best for severe pain.3 Blackjack was submitted to a multimodal pain management,

combining fentanyl with lidocaine, allowing not only to lower dosages, but also to diminish side

effects. Other options for combined pain management are ketamine or morphine.3 The

prophylactic use of antibiotics has no proven benefits and ins regarding to this, only

recommended in infectious complications, such as Blackjack’s aspiration pneumonia.3 Blackjack

received a broad spectrum antibiotic (ampicillin/sulbactam), but metronidazole, ciprofloxacin or

chloramphenicol are other alternatives that have the ability to achieve therapeutic levels in the

pancreas.3 As management of emesis and high susceptibility to gastroduodenal ulcers,

Blackjack received maropitant and pantoprazole, respectively. Other antiemetics as

metoclopramide seem to be very effective but not ideal, since it may increase pancreatic

enzyme release and aggravate pain caused by elevated gastric motility.1

6

Nutrition management is an essential step that has been changing along the years.1,2,3 While

initially food withholding was recommended, now the opposite is accomplished in practice.1,2,3 It

is recognized that patients should not be withhold of enteral nutritional support for longer than

24 hours, and that parenteral and enteral nutritional support are both better alternatives than

providing none.3,4 In case of absence of vomiting signs, the patient should be fed by mouth and

if anoretic, a feeding tube should be placed.3 A jejunostomy tube should only be considered in

animals with refractory vomiting or severe pancreatitis, enduring exploratory or therapeutic

laparotomy.1,3,4,10 The selection between parenteral or enteral is mainly made according to

toleration of the patient, since the application of the latter is more complex.3

Beside this, a continued fat restriction or a strict and balanced low fat diet is currently the

preferred option for dogs.3,4 Surgical intervention is rarely an indication but may be necessary

regarding the sequels that chronic or recurrent inflammation can cause, involving pancreatic

abscess or pseudocysts, necrotic masses and extrahepatic biliary tract obstruction.3,4

The prognosis for dogs with pancreatitis is difficult to foretell in order to the unpredictable

nature of the disease, depending mainly of the severity on presentation and complications

associated.1,3,4 This way, patients such as Blackjack, with acute flare-ups require exactly the

same intense treatment as those who present with the classical acute form, covering the

equivalent risk of mortality.1

References:

1- Nelson R.W, Couto C.G (2009) “The Exocrine Pancreas” in Small Animal Internal Medicine, 4th edition, Mosby Saunders,

579-596.

2- Steiner J. M (2010) “Canine Pancreatic Disease” in Ettinger S.J, Feldman E.C Textbook of Veterinary Internal Medicine, 7th

edition, Saunders Elsevier, vol 2, 1296-1315.

3- Washabau R.J (2012) “Diseases of Gastrointestinal Tract” in Washabau R.J, Day M.J Canine and Feline Gastroenterology,

1st edition, Saunders Elsevier, 799-811.

4- Simpon K. W (2003) “Diseases of the Pancreas” in Tams T.R Handbook of Small Animal Gastroenterology, 2nd

edition,

Saunders Elsevier, 353-365.

5- Watson P.J, Roulois A.J, Scase T.J, Irvine R, Herrtage M.E (2010) “Prevalence of hepatic lesions at post-mortem examination

in dogs and association with pancreatitis” in Journal of Small Animal Practice, 51, 566-572.

6- Penninck D.G, Zeyen U, Taeymans O.N, Webster C.R (2012) “Ultrasonographic measurement of the pancreas and pancreatic

duct in clinically normal dogs” in American Journal Veterinary Research, Vol 74, No.3, 74, 433-437.

7- Watson P.J, Roulois A.J, Scase T.J, Holloway A, Herrtage M.E (2011) “Characterization of Chronic Pancreatitis in English

Cocker Spaniel” in Journal of Veterinary Internal Medicine, 25, 797-804.

8- Watson P.J, Roulois A.J, Scase T.J, Johnston E.J, Thompson H, Herrtage M.E (2007) “Prevalence and breed distribution of

chronic pancreatitis at post-mortem examination in first-opinion dogs” in Journal of Small Animal Practice, 48, 609-618.

9- Bostrom B.M, Xenoulis P.G, Newman S.J, Pool R.R, Fosgate G.T, Steiner J.M (2012) “Chronic pancreatitis in dogs: A

retrospective study of clinical, clinicopathological, and histopathological findings in 61 cases” in The Veterinary Journal, 195,

73-79

10- Mansfield C (2012) “Acute pancreatitis in dogs: Advances in Understanding, Diagnostics, and Treatment” in Topics in

Companion Animal Medicine, 27, 123-132.

7

Clinical case Nr. 2: Pulmonology - Chronic bronchitis

Characterization of patient and reason of appointment: Maximus was a 6 year old, male

castrated, 25 Kg, English Bulldog, that was presented to the UTVMC Emergency service with a

history of chronic coughing which initiated approximately one month ago.

Anamnesis: Maximus was an indoors dog that was walked in a public environment several

times a day. The diet was based on dry food (Purina Light & Healthy®). Recently, Maximus was

vaccinated for distemper, parvovirus, adenovirus type 1, parainfluenza, leptospirosis and rabies,

and was dewormed regularly. The cough initiated approximately one month ago and had

progressively worsened. One month prior to this, he was treated by the referring veterinarian

with trimetoprim/sulphadiazine (Tribrissen®) but did not seem to improve. After this first

treatment attempt, he boarded twice regarding the cough. Concerning to medication, he was

receiving prednisone 20 mg EOD, doxycycline 100 mg BID and milbemycinoxime with lufenuron

(Sentinel®) for heart worm prevention. Physical exam: The lung sounds were mildly decreased

on the left thorax. Thorough cardiovascular examination did not reveal any signs of cardiac

dysfunction and rectal temperature was 39.2 ºC. Respiratory exam: Decreased lung sounds,

more intense on the left side of the thorax with very mild crackles. Both nares were slightly

stenotic, frontal sinuses sounded normal on percussion, larynx and trachea were normal on

palpation. List of problems: Cough, decreased lung sounds, mild crackles. Differential

diagnosis: Brachycephalic airway syndrome, chronic or allergic bronchitis, aspiration

pneumonia, dirofiloriasis, carcinoma, lymphoma, granuloma, blastomycosis, histoplasmosis,

bacterial pneumonia or bronchitis caused by B. bronchiseptica, S. zooepidemicus, P. multocida,

P. aeruginosa, K. pneumonia, Mycoplasma spp. Diagnostic tests: Complete blood count - No

significant changes. Chemistry panel - Mild hyperglobulinemia (3.8 g/dL) and mild elevation in

bicarbonate (26mmol/L). Thoracic radiographs - Mild bronchial pattern and bronchial wall

mineralization (Appendix II, Fig. 4, 5 and 6).

Maximus remained in ICU for respiratory watch during the first hours and was released in the

afternoon. Maximus' state was not critical and so, he was discharged in the condition of

returning in the morning fasted. In order to perform a flexible bronchoscopy with

bronchoalveolar lavage for cytology and culture, which is considered the gold standard to

diagnose chronic bronchitis. An elongated soft palate, as well as, mildly thickened bronchial

mucosa, slightly thickened mucus accumulation in bronchioles and hyperemic trachea were

appreciated. During the bronchoscopy, coupage was used to release mucus and promote

coughing in contemplation of obtaining samples from the deeper airways. Bronchoalveolar

lavage - Low grade neutrophilic to mixed (few lymphocytes) inflammation and goblet cell

hyperplasia. Bronchoalveolar culture (mycoplasma and aerobics) - No organisms seen.

8

Diagnosis: Maximus was diagnosed with sterile chronic bronchitis. Treatment and evolution:

He was discharged the same day of the bronchoscopy, but no medication was prescribed.

However, an antihistamine, such as cetirizine hydrochloride (Zyrtec®) at 5 to 10 mg, was

suggested as trial in pursuance of evaluating, whether or not existed an allergic or seasonal

component to the disease. Any irritants within the household or environment were suggested to

be removed or minimized as prevention. Other recommendations were to continue the

prednisone but on a dose of 25 mg for 2 weeks, then decreasing it to the lowest effective dose,

with a 25 to 30% decrease every 2 weeks until reaching an effective maintenance dose.

Alternatively, inhaled corticosteroids were indicated, such as fluticasone at 125 µg BID

associated with a special inhaler for dogs. In addition, theophylline at 10mg/kg PO BID was also

suggested. For the worsening periods of the cough during night time, a cough suppressant was

indicated, as long as the cough continued to be non-productive (hydrocodone 5.5 mg QID-BID

as needed or diphenoxylate 5 to 12.5 mg BID until the cough was under control, and then, as

needed). Prognosis: Good to fair.

Discussion: Canine chronic bronchitis is a longstanding inflammation of the lower airways

that can present different etiologies. Those can enclose an infectious, toxic or alergic cause and

it usually emerges with evident signs of coughing of at least two months of duration in one

consecutive year.1,2,3,4 The etiology is often unknown, but the disease itself is a reflection of

repeated inflammatory sequences that leads to mucosal damage, mucus hypersecretion,

obstruction of the airways and thus, disturbed mucociliary clearance.2,4 Consequently,

predisposition to infections can occur due to reduced defense mechanisms.1,4 Other potential

etiologies for increased secretion in the bronchi are atmospheric pollution, such as chronic

exposure to sulfur dioxide, passive smoking in poorly ventilated and confined spaces,

respiratory tract infections, hypersensitivity to certain allergens and genetic or acquired defects

such as α1-antitrypsin deficiency, immunodeficiency and mucociliary defects.1 The breeds

affected are generally middle-aged to older small breed dogs, which can be related to the high

susceptibility to mitral valve insufficiency and tracheal collapse.1,3,4 However, Cocker Spaniels,

Poodles and Terriers appear to be the principal breeds involved.3,4 Several other diseases can

lead to coughing, giving especial emphasis to the cardiac diseases that arise isolated or

simultaneously with a coadjuvant pulmonary condition, such as bronchitis.3,4 The major heart

diseases that can accompany coughing are left atrial dilation due to valvular insufficiency or

generalized cardiomegaly, pulmonary hypertension and congestive heart failure.4 Nonetheless,

in presence of a heart murmur, the chronic cough is more likely to have pulmonary than cardiac

origin.3 Whereas in younger dogs it is important to search for an infectious disease, in older

dogs a neoplasic cause should be considered as well. The most common neoplasias that may

be found in the bronchi are bronchial adenocarcinomas.3 Thereby the definitive diagnosis of

9

sterile chronic bronchitis is mainly made by exclusion.2,3 It is of great relevance to obtain a

detailed history in order to determine a possible environmental or infectious cause, evaluating

the frequency, pattern and development of the cough and differentiating it from another possible

underlying or primary disease.1,2,3,4 Physical examination may reveal normal to increased lung

sounds, with occasional expiratory wheezes or pan-inspiratory crackles.2 Other signs are

expiratory dyspnea and if more severe, exercise intolerance and collapse.2,3 However, most of

the dogs with chronic bronchitis are geriatric and seem to be systemically healthy, presenting

with only one exclusive chief complaint, which is persistent and productive cough.3 This is

similar to Maximus, that was presented with one main clinical sign, chronic coughing, although,

non-productive. Additionally he had diminished lung sounds on the left side of the thorax which

could be due to thickening of the bronchial walls that causes mild obstruction of the airways.4 It

is recognized that longstanding inflammation can lead to bronchiectasy, which is usually

irreversible in this stage of the disease.1,4 Other complications that may occur are COPD

(chronic obstructive pulmonary disease), pulmonary hypertension, tracheobronchomalacia, and

mycoplasmal or other bacterial infections.4 In some way, the canine lower airways appear to

have extensive interconnections between alveoli and bronchioles, which permits collateral

ventilation.1 This means that the disease must be highly developed before the clinical signs and

COPD are evidenced.1

In case the patient is systemically affected, it is important to evaluate the blood parameters

by performing a CBC (complete blood count), a chemistry panel and possibly a urinalysis.1,4 On

Maximus a blood work was performed since he was a middle-aged dog that had no recent

references of testing available. The results were mostly unremarkable, evincing a very mild

hyperglobulinemia with elevated bicarbonate. The hyperglobulinemia was explained by the

chronic inflammation, while the elevation in bicarbonate could be due metabolic alkalosis

comparing to the slight decrease in chloride (107mEq/L). No obvious signs of allergy or parasitic

infection were detected, however, the latter could had been confirmed by performing fecal

examination, even though he was dewormed.

Whereas pulmonary function testing is common to perform in humans due to high specificity

for bronchitis, in veterinary medicine it has added difficulties to execute on a routinely basis

concerning the inaccessible equipment.3 These testing consist of analyzing arterial blood gas,

endtidal CO2, or pulse oximetry to evaluate gas exchange and breathing effort.3 More practical

tests, consist of collecting blood for arterial blood gas analysis which can detect hypoxemia or

increased alveolar-arterial gradient to confirm pulmonary dysfunction.3 Additionally, a 6-minute

walk test is based on measuring the distance a dog is capable to walk within 6 minutes.3 If the

result is less than 400 meter, the patient is considered to have respiratory disease.3 One study

showed that using barometric whole body plethysmography with bronchoreactivity testing and

10

pharmacological stimulation, could help characterizing pulmonary function and ventilatory

deficits in dogs with restrictive pulmonary disease, such as obesity.6 However, thoracic

radiography may also be supportive. To accomplish this appropriately, at least three views

should be obtained: left lateral, right lateral and ventrodorsal. This is applicable not only to

identify the lung affected but also to detect possible masses, cardiac disease or foreign bodies,

which is impracticable without a tridimensional view. Radiographs usually reveal bronchial or

interstitial infiltrates, even though they might be subtle.2 Controversially, a study showed that

dogs with bronchitis shared many radiographic findings with healthy dogs, linking interstitial

bronchial calcification or dilatation and interstitial infiltrates.2 The major divergence found was

thickening of the airway walls, revealing that radiography has low sensitivity (~50-65%) and

might as well be unreliable to detect pulmonary dysfunction, particularly in very obese

patients.2,4 Maximus’ radiographs were consistent with mild bronchial pattern and bronchial wall

mineralization which is indicative of chronic bronchitis. No signs of pneumonia were seen,

however, two accidental findings were evidenced: 1) a presumptive herniated and mineralized

intervertebral disc at T13-L1, as well as a 2) mild degenerative joint disease of right

scapulohumeral joint, both appeared to be asymptomatic, and were for this reason, no further

investigated (Appendix II, Fig. 6).

CT scanning seems to be promising since the airway detail is superior comparing to

radiographs, but it is expensive and requires general anesthesia and is so, not commonly

employed.3 Beside this, bronchoalveolar lavage (BAL) is convenient to obtain samples for

cytology and microbiology.3 Cytology typically discloses neutrophilic or mixed inflammation,

mucus, hyperplastic bronchial epithelial cells, ciliated cells, macrophages and goblet cells.1,4

The presence of degenerative neutrophils may indicate bacterial infection, while eosinophilia is

suggestive of allergic component or parasitic disease.1,4 Isolation of Bordetella bronchiseptica,

Streptococcus spp., Pasteurella spp., Escherichia coli, Pseudomonas spp., Klebsiella spp., or

Mycoplasma spp. are strongly recommended and even aerobic bacteria can be isolated, since

the respiratory tract is not totally sterile.1,2 A significant growth and a positive bacterial infection

is considered when greater than 1.7 x 103 colony-forming units/mL is achieved in combination

with a suppurative inflammation on cytology.2 Bronchoscopy combined with BAL is the ideal and

preferred procedure to evaluate the severity of the disease and exclude other differentials.1,2,3,4

This technique has the potential to observe minutely within the deepest airways, and obtaining

this way, representative samples.1 Characteristically, the airways evidence excessive mucus,

irregular and thickened mucosa with hyperemia, fibrosis, epithelial hyperplasia, glandular

hypertrophy, and inflammatory infiltrates.1,2,3,4 According to one study, older dogs (>8 years),

seem to have more irregular bronchial mucosa, prominent mucosal vessels and bronchiectasis,

while younger dogs (10 months) have a higher percentage of neutrophils in BAL of all, as well

11

as a higher percentage of lymphocytes comparatively to middle-aged dogs (5-8 years).7

Patients that during this procedure experience bronchial collapse as regards to passive

expiration seem to have a worse prognosis.1,3

The treatment is generally managed symptomatically, starting by eliminating possible

environmental factors, such as tobacco, cleaning products, humidity and by replacing air filters,

as well as controlling obesity or anything that is recognized to have influence on the disease.3,4

However, obesity is the most significant factor and should be adequately managed, promoting

exercise according to the ability of the patient and by increasing it gradually.1,3,4 Due the

increased tracheal sensitivity for cough, it is recommended to use a harness instead of the

regular collars.1,3 As soon as bronchopulmonary infection is excluded, a treatment with

glucocorticoids should be initiated in order to reduce inflammation and secretion of mucus,

improving the cough.1,2 More specifically, prednisone (0.5 to 1 mg/kg) as oral medication is very

effective.2,3 It should be tapered as soon as improvement is seen (~10-14 days), reducing 25%

every 2 to 3 weeks until the lowest dose effective is achieved.2,3 According to a study, patients

that experience excessive side effects from glucocorticoids or those with coexisting medical

conditions, seem to respond positively to inhalation therapy with fluticasone proprionate (125 µg

BID).2,3 The medication should be inhaled approximately 6 to 8 times, however the ideal dosage

is uncertain because of undefined quantity that achieves the lungs.2,3 An adequate starting dose

is approximately 10 to 20 µg/kg twice daily.3 Controversially, endocrine effects evaluated by a

study, revealed cortisol suppression particularly by oral prednisolone and inhaled fluticasone,

considering inhaled budesonide a safer choice.5 Other medications that can contribute to the

treatment plan are bronchodilators, of which theophylline, a methylxanthine, is the most

commonly used. Theophylline has unproved and unspecific potential to decrease diaphragmatic

fatigue and increase mucociliary clearance, making this a preferred option.3,4 A long-acting form

of theophyline at a dose of 10 mg/kg BID or 15mg/kg SID, might also improve the expiratory

airflow and enclose synergic effects with glucocorticoids.3,4 However, most of the dogs with

chronic bronchitis don’t cover reversible bronchodilation which makes the use of this medication

controversial or unideal.1 Other bronchodilators used are aminophyline and oxtriphyline.4

Comparatively, sympathomimetics such as terbutaline or albuterol, do not achieve the same

efficiency and may cause anxiety and restlessness.3,4 Antibiotherapy is limited to patients with a

positive culture.3 In high suspicion of a non-confirmed bacterial infection, doxycycline or

azithromycin may be initiated since both have satisfying anti-inflammatory and antimicrobial

effects.3 On presentation, Maximus was on doxycycline and did not improve. Afterwards, the

results of cytology and culture confirmed the absence of an infectious cause. Other antibiotics

as fluorquinolones have elevated risk of bacterial resistance as well as theophylline toxicity, and

should be reserved for serious infections.3,4

12

In association with the treatment, nebulization followed by coupage should be recommended

to fluidize the secretions and to promote clearance of the airways.2 Chronic bronchitis is

generally an irreversible condition that is managed by reducing inflammation and ameliorating

quality of life, not only because the disease itself attends to be incurable, but also due to the

uncertain outcome.3 Concerning to this, before a therapeutic plan is stipulated, it is best to

initiate one medication at a time, in order to determine the ideal pharmacological combination

and adapting it over time, because relapse of the coughing may occur.3,4

References:

1- Kuehn N. F (2003) “Chronic Bronchitis in dogs” in King L.G Textbook of Respiratory Diseases in Cats and Dogs, Saunders

Elsevier, 1st edition, 379-387.

2- Johnson L. R, Mckiernan B. C (2010) “Canine tracheobronchial disease” in Fuentes V.L, Johnson L.R, Dennis S Bsava

Canine and Feline Cardiorespiratory Medicine, BSAVA British Small Animal Veterinary Association, 2nd edition, 274-

279.

3- Rozanski E (2014) “Canine Chronic Bronchitis” in Veterinary Clinics of North America: Small Animal Practice, 44, 107-116.

4- Nelson R.W, Couto C.G (2009) “Disorder of the Trachea and Bronchi” in Small Animal Internal Medicine, 4th edition, Mosby

Saunders, 285-291.

5- Melamies M, et al. (2012) “Endocrine effect of inhaled budosenide compared with inhaled fluticasone propionate and oral

prednisolone in healthy Beagle dogs” in The Veterinary Journal, 194, 349-353.

6- Manens J, et al. (2011) “Effects of obesity on lung function and airway reactivity in healthy dogs” in The Veterinary Journal,

193, 217-221.

7- Mercier E, et al. (2009) “Influence of age on bronchoscopic findings in healthy beagle dogs” in The Veterinary Journal, 187,

225-228.

13

Clinical case Nr.3: Soft Tissue Surgery – Adrenalectomy

Characterization of patient and reason of appointment: Katie was a 7 to 9 year old,

female spayed, 21 Kg, Australian Shepherd, that was presented to the UTVMC Soft Tissue

Surgery service for a right adrenalectomy.

Anamnesis: Katie was adopted one year ago, had vaccinations as well as deworming up to

date, and was fed with a dry Premium quality diet. She had a history of controlled discoid lupus

erythematosus, however, Katie's main problem was the recurrent UTI that she had been

experiencing every month, for 11 consecutive months. Ultrasound confirmed the diagnosis of

emphysematous cystitis as well as right adrenomegaly (0.90 cm). Amoxicillin was added to

enrofloxacin, which was extended to 4-6 weeks. Due to the slow hair growth and marked

lethargy, hypothyroidism was suspected which was confirmed later with a TSH/T4 level test.

Physical exam: The skin changes (alopecia, seborrhea, crustae and erythema) were related to

the previous diagnosis of calcinosis cutis. No murmurs or crackles were ausculted and the rate

was normal. Abdominal palpation revealed a mild hepatomegaly and the rectal temperature was

38.8ºC. Diagnostic tests: Crossmatch test- receptive to all blood donors. Chemistry panel -

mild decrease in BUN, moderate elevation in ALP and ALT (Appendix III, table 5). CT scan -

confirmed increased size of right adrenal mass of 1.63 cm (Appendix III, Fig. 7). PCV/TS – 57%

/ 8.0 mg/L. On re-evaluation, an ultrasound revealed an increase in size of the right adrenal

gland with invasion of the vena cava. Beside this, thrombus formation in caudal vena cava with

mineralization and a mild hepatomegaly were also appreciated, while a skin biopsy returned as

calcinosis cutis. Katie was experiencing exacerbated lethargy, polyphagia as well as polyuria

and polydipsia. An ACTH stimulation test was inconclusive, nonetheless, a LDDS (Low Dose

Dexamethasone Suppression) test, as well as a HDDS (High Dose Dexamethasone

Suppression) test made it possible to confirm the presence of adrenal-dependent Cushing's

disease. Pre-operative treatment: Prednisone 1 mg/kg PO SID, administered one day

previous to surgery and received last dose on the morning of surgery. Fluid therapy with

lactated Ringer’s solution at 100 mL/h. Anesthesia: Pre-medication – Fentanyl 5 µg/kg IV and

lidocaine 2mg/kg IV; Induction – Ketamine 5 mg/kg IV, midazolam 0.5 mg/kg IV, propofol 2

mg/kg IV; Maintenance – Propofol 2 mg/kg IV given twice, ephedrine sulfate 0.1 mg/kg after

induction due hypotension, dopamine 1 mL/h at CRI, ketamine 2 mg/kg IV, sevoflurane 2% with

oxygen, fentanyl-lidocaine at CRI; dexamethasone diluted at CRI during surgery; synthetic

colloid 120 mL IV and fluid bolus of isotonic solution 10 mg/kg during surgery; Antibiotic –

Cefazolin 20 mg/kg IV at anesthetic induction. Surgery: After trichotomy and antisepsis, Katie

was placed in dorsal recumbency. The midline incision was made from the xyphoid to just

cranial to the pubis. During the incision, hemostasis was performed with bipolar cautery. The

14

subcutaneous tissues were cut with Metzenbaum scissors and thebodywall was cut a with

curved Mayo scissor. The falciform fat was broken down digitally and tied off with 2-0

Monocryl®, and was then removed. A Balfour retractor was placed in the cranial abdomen and

the abdominal cavity was explored. After this, the mesoduodenum was retracted carefully,

without damaging the pancreas, to allow visualization of the right adrenal gland. During the

exploratory laparotomy, it was noticed that the right kidney's surface looked irregular. A red

rubber catheter (18 Fr) was cut in four pieces to create a Rumel tourniquet. The retroperitoneum

was bluntly dissected using curved hemostats for placement of the umbilical tape with the

Rumel tourniquets. The caudal torniquet was placed around the caudal vena cava and renal

vein (the left phrenicoabdominal vein was not included to allow blood flow). Cranial Rumel

tourniquet was placed over the vena cava cranial to the right adrenal gland. The tourniquets

were just placed but not actually tightened down. The right adrenal gland was dissected from

right kidney using curved hemostats and hemostasis was maintained with bipolar. The right

adrenal gland had a round egg shaped tumor with a stalk. Two malleable retractors were placed

to allow more visualization of the abdomen. A third malleable retractor was placed, as blunt

dissection of the fascia of the vena cava from the tumor continued. Medium hemoclips were

placed across the phrenicoabdominal vein and the vessel was transected with Metzenbaum

scissors. Fat was stripped next to the tumor using cotton tipped applications. A lymphatic

branch was transected in dissection. Dissection from vena cava continued carefully and

thrombus was manipulated out of the vena cava and into the phrenicoabdominal vein. Three

large hemoclips were placed across the stalk of the tumor. The tumor stalk (phrenicoabdominal

vein) was transected using curved Metzenbaum scissors. No hemorrhage was seen. Finally the

body wall was closed using 0 PDS® in a simple continuous pattern, 2-0 Monocryl® in

subcutaneous tissue in a simple continuous pattern and 3-0 in skin with a ford interlocking

suture. Post-operative complementary tests: PCV/TS – 45% / 5.1 mg/L. Blood Glucose – 137

mg/dL. Histopathology – confirmed adrenocortical carcinoma with vena cava and multifocal

vascular invasion. Complete blood count – moderate neutrophilia, monocytosis (Appendix III,

table 4). Chemistry panel – mild hypoalbuminemia, mild hyperglycemia, mild hypocalcemia, mild

hypophosphatemia, moderate elevation of ALP, mild hypernatremia and mild hyperchloremia

(Appendix III, table 5). Post-operative treatment: Katie recovered from surgery in the ICU,

where she remained during the night having received a poly-ionic and isotonic solution

(Plasmalyte A®) at 54 mL/h IV, and fentanyl + lidocaine IV at CRI of 1.6-6.5 mL/h. The

temperature, pulse and respiratory rate were re-evaluated every 6 hours. PCV, TS and blood

pressure were repeated twice daily. Katie was also on Soloxine® 0.3 mg PO daily and

amoxicillin 400 mg every 8 hours. During surgery Katie received 1.1 mg of dexamethasone IV

which was continued over 12 hours. The next day the dexamethasone was replaced by

15

prednisone on a dose of 10mg PO BID, and 50 mg of tramadol and 200 mg of gabapentin were

administered orally, every 8 hours. During physical examination, a corneal ulcer was noted on

the right eye so adequate treatment was provided. The following day, she was transferred to the

regular wards since her medical condition was not considered critical anymore. At this point,

blood work was repeated, as well as an ACTH stimulation test, in order to obtain a baseline of

cortisol levels posterior to surgery (even while on exogenous steroids). Previously to the ACTH

stimulation, cortisol levels were 31.5 ng/L and post stimulation, cortisol levels decreased to 29.6

ng/L (Appendix III, table 6). Katie stayed stable and was sent home the next day with 50 mg of

tramadol, 100 mg of gabapentin, 20 mg of prednisone, 0.2 mg of Soloxine®. Prognosis: Fair

regarding metastatic disease.

Discussion: Adrenocortical tumors (AT) occur in approximately 15 to 20% of dogs with

hyperadrenocorticism, which corresponds to less than 1% of all canine neoplasms.4,5 The most

commonly affected patients are middle-aged to older dogs without evident sex predilection,

although, a slight greater risk in females has been reported.3 The adrenal tumors that are most

frequently seen are mainly adenoma and carcinoma that account with equal incidence.4

Concerning to localization, the medullary tumors secrete catecholamines that tend to origin

severe hypertension, the adrenocortical secrete excessive glucocorticoids causing Cushing’s

syndrome. Nevertheless, in carcinomas, multiple hormone secretions, such as glucocorticoids,

mineralocorticoids and sex hormones, have been reported, even if very unusual.3,5 One study

reported that, approximately 50% of the dogs with adrenocortical tumors causing

hyperadrenocortisim (ATH), weigh more than 20 kg.4

Histopathology seems to be the only modality to distinguish the type of AT, however, it is

acknowledged that carcinomas tend to be larger in size, are more likely to invade other

structures and metastasize specially to liver, spleen, lungs and tricuspid valve.4,5 Thus, imaging

modalities likewise to abdominal ultrasound, radiography and CT scan might support

differentiation of ATs, and according to presence or absence of metastatic disease, the

malignancy might be predicted as well.3 Even though metastatic lesions represent no more than

26.7% of the canine adrenal tumors, it should always be considered.5 The exact pathogenesis

remains uncertain, but in humans, it is recognized that abnormal biosynthetic pathways result in

lack of adrenal steroidogenic enzymes (21β-hydroxilase and 11β-hydroxilase), leading to

hypersecretion of precursor steroids.3 Another factor for increased steroid precursors might be

invasion of the adrenal cortex by malignant cells that could possibly interfere with the normal

enzymatic trial.3 Some steroid intermediates, such as progestins, might disconnect cortisol from

its serum-binding protein, achieving increased concentrations of cortisol in the active form,

which will enhance the typical hyperadrenocorticism signs.3 Those progestins might as well act

as glucocorticoid agonists, resulting in increased glucocorticoid activity.3 Hence, excessive

16

cortisol is produced by the adrenal tumor which causes pituitary suppression, with consequent

decrease in ACTH concentration and atrophy of contralateral adrenal gland.4

The characteristic clinical signs consist of polyuria, polydipsia, polyphagia, panting,

pendulous abdomen, skin atrophy, symmetric alopecia, bruising, muscle atrophy and lethargy.3

Diagnostic wise, increased serum alkaline phosphatase activity, hypercholesterolemia and

hyposthenuric urine might suggest hyperadrenocorticism, making clinical pathology as well as

urianalysis with culture of enormous relevance.4 Approximately 85% of dogs with

hyperadrenocorticism have ALP activity higher than 150 IU/L.4

Katie’s recurrent UTI’s were explained by the endogenous glucocorticoid-induced

immunosuppression, as well as polydipsia, that turned not only the urine diluted, but made Katie

more predisposed to infection, causing interference with the identification of the infection.4

However, the definitive diagnosis can only be made by combining abdominal ultrasound with

respective measurement of the adrenal glands and a LDDS/ HDDS/ Endogenous ACTH tests.4

Radiographs are not efficient to identify adrenal glands or adrenal tumors, but might identify

calcification, hepatomegaly, distension of the urinary bladder and create suspicion of Cushing’s

disease.3,4 Approximately 50% of ATH are calcified, which is equally distributed between

adenoma and carcinoma.4 On ultrasound, adrenomegaly is considered when the maximum

width is greater than 0.8 cm, and adrenal atrophy at maximum width less than 0.3 cm.4

Nevertheless, AT can occur bilaterally and even if uncommon, it should not be confused with

bilateral macronodular hyperplasia, which consist of multiple nodules of different sizes within the

adrenal cortex and is mainly thought to be a variant of pituitary-dependent hyperadrenocorticism

(PDH).4 CT or MRI should be considered to evaluate size and extension of the tumor prior to

adrenalectomy.2,4

Therapeutically, ATH’s treatment of choice is adrenalectomy, as long as no severe

metastatic disease is appreciated.1 To minimize the high risks associated post-operatively,

especially during the following 72 hours, it is vital to manage a preoperatively plan to guarantee

the patient is stabilized. It is recognized that the larger the size of the tumor, the greater the

complications which makes the diagnostic testing previous to surgery crucial as well.4 Despite

other underlying diseases, Katie was considered a good candidate for surgery, given that the

right adrenal mass presented a size of approximately 1.63 cm. Many times those tumors can

extend from 6 to 8 cm of diameter which escalates the surgery complexity.4

The removal of the adrenal gland leads to abrupt decrease of glucocorticoids and to

signalment such as depression, inappetence, lethargy and collapse.1,2 Along mineralocorticoid

suppression, other electrolyte and acidbase imbalance may be induced, involving

hyponatremia, hyperkalemia, acidosis and azotemia.1 As prevention, essentially in surgery,

supplementation with glucocorticoids is required and fluid therapy might be as well.1 However,

17

Katie initiated the supplementation prior and during surgery regarding the fact that some

animals seem to have a delayed response to exogenous steroids.1 The healing process of the

suture line might be slower due catabolism and often protein depletion, requiring special care.1,2

The most worrying complications are hypertension with consequent cardiovascular disease and

pulmonary thromboembolism.1,2,4 To anticipate it, measurement of blood pressure is necessary

and a low-dose of aspirin can be provided along suspected hypercoabulability.1,4 For patients

that experience respiratory distress, oxygen as well as anticoagulant and thrombolytic agents

should be considered.1 Regarding to this Katie was maintained in cage rest, constant

respiratory watch and her position was changed every 4 hours, post-operatively.

The surgical approach can be performed by a ventral midline, as Katie, or paracostal

incision.1,2 The ventral midline incision allowed to execute a complete exploration of the

abdomen to detect possible metastasis and could had been a more useful choice in cases with

bilateral adrenalectomy.1,2 The second surgical approach gives better access to the adrenal

gland, although just unilaterally and does not cover the benefit to able a complete evaluation of

the abdomen.1,2 However, on ventral midline approach it is possible to extend the incision

paracostally on the side of the affected adrenal gland in case additional exposure is necessary.1

For Katie this was not required since the use of a Balfour retractor and three self-retaining

malleable retractors were efficient to obtain accurate visualization of the operating field.

Moistened sponges could had been used to cover the retractors, minimizing trauma to

surrounding organs and absorbing possible bleeding, although, its adequate removal from the

abdominal cavity must be certified.1 After dissection, an exploratory laparotomy was performed,

revealing irregular kidney surface of the right kidney and very mild hepatomegaly. Renal

damage could be consequence of chronic and recurrent UTI while hepatomegaly is explained

by hyperadrenocorticism. For temporary occlusion of the vena cava, a Rumel tourniquet was

created cutting a red rubber catheter and by using two parts of it for introduction of the umbilical

tape. In Katie, a double ligation was required due to invasion of the tumor within the vena

cava.1,2 The creation of a temporary occlusion of the major vein was crucial and critical at the

same time, since it avoids severe blood loss but also compromises blood supply, encourages

clotting and increases the risk of potential thromboembolism. However, the methodology with

these materials creates a better control on clamping since it tightens and unfastens easily, and

causes as well, a milder trauma to the vessels. The methods of hemostasis were achieved with

bipolar electrocautery for smaller vessels and hemoclips for phrenicoabdominal vein and tumor

stalk. Hand ligatures are difficult to perform around this area because vessels are small and

space area is limited.1,2 The hemoclips were used in larger vessels due to the rich blood supply

to the adrenal gland, as well as to assist with the removal of the tumor, for the reason that it

prevents disruption and avoids the possibility of leaving neoplastic tissue within the abdominal

18

cavity. Adequate dissection can be challenging since the adrenal capsule must remain intact.1,2

In aggressive invasions, vascular surgery might be required.1,2 Around 25% of adrenal

neoplasms seem to invade the vena cava, phrenicoabdominal veins or renal veins,

nevertheless, it appears more frequently in pheochromocytomas.1

Regarding the delayed healing process, those patients require a tough suture with adequate

tensile strength.1,2 For Katie, polydioxanone was used, a slowly absorbable suture for the body

wall and Monocryl®, absorbable as well, for subcutaneous tissue and skin.

Postoperatively, the patient requires monitoring for dehydration, electrolyte imbalance,

thromboembolism, hemorrhage, infection and hypoadrenocortical collapse.1 An unilateral

adrenalectomy causes temporary adrenal insufficiency which means the patient requires

temporary glucocorticoid supplementation until the remaining adrenal gland responds, produces

sufficient endogenous steroids and homeostasis is achieved.1,2,4 This occurs progressively,

particularly because the function of the contralateral adrenal gland was suppressed by the AT.1

The main difficulty is prognosticating the exact moment when homeostasis is achieved to

perform ACTH stimulation test and decrease glucocorticoid supplementation. Along bilateral

adrenalectomy, a life-long glucocorticoid and/or mineralocorticoid replacement is imperative.1

Katie’s treatment plan consisted of initiating dexamethasone post and operatively, and by

changing it for prednisolone the following day. This dose was continued for one week and then

tapered down gradually in 10 weeks. However, the medication adjustment could had been

made the same day, following surgery.1

According to one study, dogs with an adrenal gland tumor with maximum width of 5 cm, that

reported metastatic disease or vasculature invasion had poorer prognosis.6 Metastatic disease

seemed to be more frequent in dogs with adenocarcinoma and vein thrombosis.6 The median

survival time was 492 days as reported by a different study, which makes the prognosis for

Katie fair.7

References:

1- Fossum T.W (2012) “Adrenalectomy” in Small Animal Surgery, 4th edition, Mosby Elsevier, 633-646.

2- Adin C. A, Nelson R. W (2011) “Adrenal Glands” in Tobias K, Johnston S. Veterinary surgery Small Animal, 1st edition,

Elsevier Saunders, 2033-2041.

3- Hill K. (2013) “Primary Functioning Adrenal Tumors Producing Signs Similar to Hyperadrenocorticism Including Atypical

Syndromes in Dogs” in Rand J, Behrend E, Gunn-Moore D, Campbell-Ward M. Clinical Endocrinology of Companion

Animals, 1st edition, Wiley-Blackwell, 65-69.

4- Nelson R.W, Couto C.G (2009) “Disorders of the Adrenal Gland” in Small Animal Internal Medicine, 4th edition, Mosby

Saunders, 810-846.

5- Frankot J. L, Behrend E. N, Sebestyen P, Powers B. E (2012) “Adrenocortical Carcinoma in a Dog with Incomplete Excision

Managed Long-term with Metastasectomy Alone” in Journal of the American Animal Hospital Association, 48, 417-423.

6- Massari F, Nicoli S, Romanelli G, Buracco P, Zini E (2011) “Adrenalectomy in dogs with adrenal gland tumors: 52 cases

(2002–2008)” in Journal of the American Veterinary Medical Association, 239, 216-221.

7- Lang J. M, Schertel E, Kennedy S, Wilson D; Barnhart M, Danielson B (2011) “Elective and Emergency Surgical Management

of Adrenal Gland Tumors: 60 Cases (1999–2006)” in Journal of the American Animal Hospital Association, 47, 428-435.

19

Clinical case Nr. 4: Ophthalmology – Descemetocele

Characterization of patient and reason of appointment: Buster was a 5 year old, male

castrated, 9 Kg, Pug Carlin, that was presented to the UTVMC Ophthalmology service for an

evaluation regarding a deep corneal ulcer in the left eye.

Anamnesis: Buster had an up to date vaccination and deworming plan, and lived in a

confined compartment of the house in order to guarantee cage rest due to cervical pain. He was

walked regularly, contacting with a private and public outdoor environment. In the past days,

Buster was experiencing increased blefarospasm and very mild epiphora, especially from the

left eye that after a visit to the regular veterinarian, was confirmed with the diagnosis of deep

corneal ulcer. His medication consisted of 20 mg of oral prednisone to control cervical pain.

Physical exam: Buster was alert and responsive during examination. The ulcer was visible and

situated more internally to the epicanthus on the lateral dorsal cornea. All other parameters of

physical examination were unremarkable. Ophthalmic exam: Menace reflex - present OU.

Pupillary reflex - direct and consensual, present OU. Eyelids - normal cilia with no evidence of

distichiasis, trichiasis or ectopic cilia. Position of eyeball and visual axes - normal OU.

Muscling and submandibular lymph nodes – normal. Lacrimal system - normal OU.

Schirmer tear test – 20 mm/minute OD and 23 mm/minute OS. Intraocular pressure - 12

mmHg OD, 10 mmHg OS. Conjunctiva – moderate conjunctival hyperemia OS. Cornea –

positive fluorescein test OS, characteristic ring appearance with Descemet’s membrane

uncovered and unstained on the base of the ulcer, consistent with descemetocele. Pigmentation

was noted ventrolaterally to ulcer. Cristaline - normal OU. Anterior chamber, pupil and iris –

mild flare OS. Vitreous and back of the eye - normal OU. List of problems: Deep corneal

ulcer, ocular pain and conjunctivitis. Differential diagnosis: Distichiasis, ectopic cilia,

entropion, trauma, deep corneal ulcer, KCS. Diagnostic tests: Cytology - epithelial cells,

neutrophils and no bacteria. Culture - negative. Diagnosis: Descemetocele. Treatment and

evolution: After discussing the available options, the owner decided to perform primarily a

restricted medical treatment. So, Buster was sent home with fresh serum (1 gtt OS every 2

hours during day and every 4 hours during night time), ciprofloxacin (1 gtt OS every 4 hours),

hypromellose (Genteal® one strip OS every 4 hours), atropine sulfate 1% (Atropine Ophthalmic

Solution® 1 gtt OS SID), and Elizabethan collar. Follow up: Buster was re-evaluated 3 days

later, however, the ulcer remained very deep and in high risk of perforation. There was no

evident stain up take, and thus no ulceration, since the corneal epithelium had grown over the

ulcer margins. In order to prevent perforation, the placement of a conjunctival hood graft, that

was previously discussed, was now strongly recommended. A complete blood count and

chemistry panel revealed mild anemia, elevated white blood cell count, moderate left shifted

20

neutrophila, mild lymphopenia, mild monocytosis, mild hypoalbuminemia, hypocalcemia, severly

elevated hepatic enzymes, mild hyperphophatemia, mild hypochloremia and mild

hypercholesterolemia (Appendix IV, table 7 and 8). The urine specific gravity was very low

(1.008) so a urine culture was performed. According to these findings, Buster's surgery was

delayed and he was sent home. The dose of prednisone was tapered down to ensure the long-

term prednisone administration was not masking a source of infection or inflammation. After 4

days, his blood values improved in response to a lower prednisone dose (Appendix IV, table 8).

Nonetheless, Buster's hepatic enzymes remained elevated which was not unexpected since the

prednisone therapy had been long-standing. This day, a conjunctival graft was performed.

Buster was re-evaluated 4 days post-operatively, revealing healthy healing process of the

cornea (Appendix IV, Fig. 8, 9 and 10). The topical treatment with ciprofloxacin (1 gtt OS every

4 hours) was continued to prevent from possible infection, as well as hypromellose (1 strip OS

every 4 hours) to maintain the lubrication of the eye. Prognosis: Good.

Discussion: Corneal ulcer, also recognized as ulcerative keratitis, is a commonly occurring

disease that consists of loss of epithelium layers and exposure of stroma as result of imbalance

between decreased epithelial protection and increased epithelial loss.1,2 From an anatomic

point, the protection of the cornea is provided by surrounding structures, essentially third eyelid,

upper and lower eyelid.1 However, the tear film located on the surface of the cornea, guarantees

protection by preventing from desiccation and providing oxygen as well as nutrients to the

corneal epithelium and anterior stroma.2 The cornea consists of a stratified epithelium that is

combined with a basal membrane, a thick collagenous stroma, a Descemet’s membrane and

more internally, a endothelium, corresponding in total to a thickness of 0.5 to 0.8 mm.1,2,3 The

Descemet’s membrane is continuously secreted by the endothelial cells and is recognized to

thicken with age.1,2,3 The central area of the cornea is thinner than the rest and appears to be,

for this reason, more affected by ulcerations.3 The etiology can cover anatomic (eyelid

abnormalities), traumatic (foreign body, entropion, distichiasis, trichiasis, ectopic cilia) or

infectious factors.1 Even though there is no explicit breed, sex or age predilection, secondary

corneal disease seems to arise particularly in Boxers and other brachycephalic breeds, as well

as patients with keratoconjunctivis sicca.2,3 Interestingly, on base on one study, the blinking rate

of dogs tends to be of approximately 14.5 to 12.99 blinks per minute, which is relevant for

adequate tear film distribution and to avoid corneal desiccation.2,4

Clinical signs are generally defined by photophobia, blepharospasm, epiphora and ocular

pain that can vary from mild to severe.1,2, Superficial corneal ulcers are usually more painful

than the deeper and more chronic lesions.1,2,3 In brachycephalic breeds, the grade of corneal

sensitivity seems to be reduced, presenting additional predilection to corneal damage.3

21

The diagnosis is based on accurate history, clinical signs and reaction to fluorescein test.1

Typically the fluoresceine dye remains on the area of corneal damage and by shinning the blue

light from the ophthalmoscope, green staining is visualized. In Buster’s left eye, the center of the

ulcer was clear and the walls were fluorescein positive, presenting a characteristic “donut” of

stain retention, indicative of descemetocele.1,2 Contrary to the walls that were corresponding to

stroma, the depth of the base was equivalent to Descemet’s membrane which is usually, unable

to take up stain, resulting in a negative fluorescein test.1,2 Occasionally the Descemet’s

membrane can present forced outward as consequence of the intraocular pressure.1

With the aim of avoiding recurrence, it is important to eliminate the primary cause and so,

further diagnostic testing is necessary.1,2 A Schirmer tear test is supportive to rule out primary

tear film disorders, while swabs should be obtained for cytology, aerobic bacterial culture and

sensitivity testing.1,3 Frequently isolated bacteria are mainly Streptococcus spp. as well as

Staphylococcus spp. that origin from the conjunctival surfaces or less common, Pseudomonas

spp.3 A thorough examination of eyelids, cilia, third eyelid and conjunctiva with assessment of

corneal or palpebral reflex should be considered during ophthalmic exam.1 Additionally, a rose

Bengal test can indicate increased rate of cell degeneration by stain retention on central corneal

epithelia.3 Regarding the high risk of corneal perforation with escape of aqueous and iris

prolapse, descemetocele is considered a medical emergency.1,2

When the superficial epithelium regenerates within 4 to 7 days, the stroma is replaced

gradually by stromal keratocytes that synthesize collagen, glycosaminoglycanes and

mucoproteins, taking weeks or months to renew.1,3 According to this, corneal ulcers should be

classified on feature of duration and depth.1 Simple ulcers tend to heal in approximately 7 days,

are acute, more superficial and do not involve stroma. Buster’s descemetocele is incorporated

in the group of complicated ulcers that tend to persist for longer than 7 days, have involvement

of stroma and are so, deeper and chronic.1 However, on Buster’s reassessment, a re-

epithelialization of the wall was noticed which was consistent with a negative fluorescein test.

Even with positive response to treatment and the absence of an active ulcer, the thin

Descemet’s membrane continued exposed so Buster persisted in risk of corneal perforation.

Regarding to this, a conjunctival hood graft was planned to obtain a greater change of

maintaining vision and achieve least corneal scarring before resulting in a possible perforation.3

Beside surgery, primary suture of the descemetocele can be performed, although, the suture

must be placed in viable corneal stroma and the risk of astigmatism turns this an inexpensive

but poor alternative.1,3 Other cases that present a healthy surrounding stroma, may benefit from

a simple ophthalmic cyanoacrylate adhesive, also known as tissue glue.1 This should be

performed under general anesthesia because the glue needs to be instilled and dried properly

with entire immobility of the eye.1 With antimicrobial properties and by stimulating vascular

22

ingrowth this can be a safe and reasonably priced alternative for deep ulcers.1 The use of a third

eyelid flap may be considered inappropriate for severe corneal disease, due to the fact that it

impedes topical medications from reaching the cornea and by not delivering adequate blood

suply.5

To maximize the success of surgical ophthalmic procedures, prevention of possible

complications should be considered previously.3 For Buster, topical ciprofloxacin was indicated

which is efficient against Pseudomonas spp and the ideal choice for his severe stromal defect.1

Though, a combination of antibiotics could had been considered to increase efficacy against

possible Gram positive organisms, since the results from the culture were pending at this point.1

Those include, combined polymyxin B, neomycin and bacitracin with broad spectrum activity

and bactericidal effect or a cefazolin ophthalmic formulation. Other alternatives such as

tobramycin have less activity against Gram positive organisms, while gentamicin has increased

risk of epitheliotoxic effect.1,3 The frequency of those applications should be defined according

to the severity of each case.1 Buster’s antibiotherapy was instilled every 4 hours, although, for

infected ulcers a loading dose is recommended and consists of instilling 1 drop every 5 minutes

for 6 to 12 doses.1 Systemic antibiotics such as amoxicillin and cephalexin are administered in

advanced cases when the integrity of the globe is in danger.3 For pain management as well as

prevention for posterior sinechiae and cataract development, topical atropine should be

considered.1,3 But, since the tear production can be affected by cycloplegic agents, the

frequency of administration should not exceed 1 to 3 times daily.1 Due the expandability of the

corneal ulcer, proteases and collagenases liberated by degenerated corneal cells and bacteria

can degrade collagen fibrils and glycosaminoglycans, potentiating the progression of the

disease.1,6 To combat those enzymes, autologous serum, a potent protease inhibitor with

growth factors is of extreme benefit.3,6 The serum can be easily obtained and shared between

species or patients as long as the donor is free from disease transmitted through blood.1,6

Buster’s severe corneal wound revealed negative culture, although it could had suffered from

severe infection regarding the long-standing administration of oral prednisone.1 Topical

corticosteroids and NSAIDs should be avoided because they represent a recognized delay to

corneal vascularization which is an important factor to encourage cicatrization.3 Administration

of medications in form of ointment should be avoided as well, especially in patients with

increased risk of corneal perforation, for the reason that the petrolatum present in it is able to

cause severe granulomatous uveitis if it penetrates the eye.1 Beside this, it is suggested to

lubricate the eyes regularly, as blink reflex, an essential factor for tear distribution, appears to

be decreased in patients with corneal defects.4

The treatment of choice for complicated and deep wounds such as from Buster, is a

conjunctival graft.1,3,6 This not only provides mechanical support and protection, but also

23

maintains supply of anticollagenases and growth factors, subconjunctival fibroblasts, with

consequent collagen formation and stromal regeneration.1,3 The five broad types of conjunctival

grafts include the island, complete, hood, bridge and rotational pedicle graft.1,3 Conjunctival

autografts can consist of bulbar or palpebral conjunctival mucosa, essentially with epithelium

and connective tissue.3 However, porcine small intestinal submucosa, bladder submucosa,

amniotic membrane, pericardium and equine renal capsule transplants have reported satisfying

results as well.3,5 The type of procedure should be selected according to the extension and

location of the ulcer.1,3 Buster’s procedure consisted of a conjunctival hood graft that seems to

be easy to harvest and place, especially because the descemetocele was located in the lateral

dorsal cornea. For example, a more centered ulcer would be easier reached with a rotational

pedicle graft.3

The technique used for Buster, consisted of proceeding a small incision in the lateral

conjunctiva near the limbus, dissecting and extending it gradually until covering the desired

area. Primarily to this, the epithelium that formed against the wall and bottom of the

descemetocele was carefully removed and fluorescein stain was applied to ensure the defect

was completely free of epithelium. The graft was fixed to the cornea with 8-0 Vicryl® and a

simple interrupted suture. The free margins of the conjunctiva were fixed to the limbus to limit

retraction.1 The conjunctival graft is considered thin enough when a tenotomy scissor can be

readily visualized through the conjunctiva and the Tenon’s capsule or bulbar fascia are not

included.1,3 Inclusion of those structures can increase traction and result in surgical failure.3

Closing the rent in the bulbar conjunctiva with a simple continuous suture can help reduce pain

but might not be required.1 During general anesthesia, the absence of protective blink reflection

and loss of tear production implicate regular hydration with lactated Ringer’s solution or

balanced saline solution.3 According to one study, the use of more perioperative medications

and prolonged procedures were risk factors for the development of corneal ulcers under

anesthesia.4 Most of the ulcers were diagnosed one day after a non-ophthalmic surgery, while

those that developed later seemed to have worse prognosis.4 The advantages of the

conjunctival autografts are the prevention of staphyloma formation, and when harvested from

limbus, stem cells produce additional corneal epithelium.3 Beside this, the blood and lymphatic

vessels from the graft offer antiproteases, anticollagenases that prevent the extension of the

defect and impede infection due to antibacterial, antiviral and antifungical properties.3 This route

allows systemic antibiotics to achieve high concentration levels in the cornea.1,3 Concerning to

disadvantages, scar tissue can remain visible and create an opaque and a sometimes,

undesirable aspect to the cornea.3 Beside this, the owners should be alerted of possible rupture

and corneal perforation during surgery. Approximately 6 to 8 weeks post-operative, the cornea

24

is healed and the graft might need to be trimmed.1 Vascular nutrition and support will so be

interrupted, however, for very thin and subtle grafts as Buster’s, this is not necessary.1

If required, the conjunctival grafts can be easily augmented with a thin layer of porcine small

intestinal submucosa transplant, as additional constitutional support over which fibroblastic

ingrowth and collagen might be hastened.1,3,5 With conjunctival transplants, leukocytes,

antibodies, and α2-macroglobulin are integrated into the corneal defect discontinuing the

extension of the lesion.3 One study considered this an effective alternative for corneal

reconstruction by resulting in corneal transparency and preserving vision in most of the cases.5

However, dogs with pigmentary keratitis syndrome may be predisposed to worsening of the

pigmentation after grafting surgery, especially in brachycephalic breeds with severe corneal

lesions.5

References:

1- Maggs, D. (2012) “Cornea and Sclera” in Maggs D. J, Miller P. E & Ofri R, Slatter’s Fundamentals of

Veterinary Ophthalmology, 5th edition, Elsevier Saunders, 195-202.

2- Dubielzig R, Ketring K. L, McLellan G. J, Albert D. M (2010) “Diseases of the cornea and sclera” in Veterinary

Ocular Pathology: A Comparative Review, 1st edition, Saunders Elsevier, 201-203; 219-226.

3- Gelatt K. N, Brooks D. E (2011) “Surgery of the cornea and sclera” in Gelatt K.N, Gelatt J.P Veterinary

Ophthalmic Surgery, 1st edition, Saunders Elsevier, 191-209.

4- Park. Y, Son W, Jeong, M, Seo K, Lee L. Y, Lee I. (2013) “Evaluation of risk factors for development of corneal

ulcer after nonocular surgery in dogs: 14 cases (2009–2011)” in Journal of the American Veterinary Medical

Association, 242, 1544-1548.

5- Goulle F. (2012) “Use of porcine small intestinal submucosa for corneal reconstruction in dogs and cats: 106

cases” in Journal of Small Animal Practice, 53, 34-43.

6- Pot S. A, Gallhoffer N. S, Matheis F. L, Voelter-Ratson K, Hafezi F, Spiess B. M (2013) “Corneal collagen cross-

linking as treatment for infectious and noninfectious corneal melting in cats and dogs: results of a prospective,

nonrandomized, controlled trial” in American College of Veterinary Ophthalmologists, 1-11.

25

Clinical case Nr. 5: Oncology - Splenic hemangiosarcoma

Characterization of patient and reason of appointment: Jo was an 8 year old, female

spayed, 24 Kg, Springer Spaniel that was presented to the UTVMC Oncology to discuss

chemotherapy options.

Anamnesis: Jo was diagnosed with splenic hemangiosarcoma approximately 10 days

before she was presented through the emergency service. At that time she was very lethargic,

had a tense and painful abdomen on palpation, that by further diagnostics revealed to be a

severe hemoabdomen. During this period she experienced persistent VPC's, a moderate

thrombocytopenia, while ultrasound evinced a splenic mass. No cardiac mass or pericardial

effusion was detected. The coagulation profile was within the normal limits and no indication of

pulmonary metastasis was found. Immediate surgery was required and during splenectomy, a

red to black colored mass was detected on the head of the spleen. The liver was biopsied and

the results confirmed primary splenic hemangiosarcoma with hepatic metastasis. Jo’s

medication consisted of acetaminophen (30 mg 1/2 tablet PO BID), gabapentin (300 mg 1

capsule PO TID) and sotalol (80 mg 1/2 tablet PO BID). Jo lived outdoors during day time,

indoors at night and had an actualized vaccination and deworming plan. Physical exam (after

surgery): Jo had a heart rate of 160 beats per minute with no evince of arrhythmias or

murmurs. The respiratory rate was 36 breaths per minute and no wheezes or crackles were

noted during auscultation. All the lymph nodes were normal in size, shape and consistency.

Abdominal palpation was normal but on evaluation of the incision sites, the caudal aspect

appeared erythematous, swollen and purulent, indicative of infection. Remainder physical exam

was unremarkable. Diagnostic tests: Complete blood count - very mild neutrophila

(10.97x103/µL) and mild lymphopenia (0.9x103/µL). Chemistry panel - elevated ALP (187 µ/L)

and mild hypernatremia (151 mEq/L). ECG - no ventricular arrhythmias noted. MDR1 mutation

gene - negative. Treatment and development/evolution: Jo's blood work improved, evincing

resolution of thrombocytopenia. The liver values continued elevated but markedly improved

from previous chemistry panel. The echocardiography proved as well, that Jo was a good

candidate for the doxorubicin protocol. Beside this, a negative result to MDR1 mutation gene

test resulted in another point in favor, since this mutation is common in certain dogs and

impedes doxorubicin to be eliminated from the body, leading to severe toxicity. Amoxicillin (500

mg) and clavulanic acid (125 mg) was provided to treat the infected incision sites and sotalol

was discontinued. Follow up: One week later, Jo came back for a re-evaluation and initiation of

chemotherapy with doxorubicin. Radiographs and abdominal ultrasound revealed no obvious

evidence of metastasis (Appendix V, Fig. 11 and 12). The complete blood cell count remained

within the normal limits, presenting enough white blood cells (11.1x103/µL) and platelets

26

(>150x103/µL) to initiate the treatment safely. First diphenhydramine (Benadryl® 2mg/kg) was

administered subcutaneously as prevention for possible anaphylactic reaction, and later

doxorubicin (Adriamycin® 30 mg/m2) intravenously. Jo was discharged this same day and sent

home with maropitant (Cerenia® 60 mg PO SID) and metronidazole (250 mg PO SID), both as

necessary for possible side effects to chemotherapy. Approximately 3 weeks after the first

chemotherapy, Jo was re-evaluated by the UT and received the second dose of doxorubicin. So

far, the patient has been responding positively to this treatment plan. Prognosis: Guarded.

Discussion: Hemangiosarcoma (HSA), also recognized as hemangioendothelioma or

angiosarcoma, is a malignant neoplasm with vascular endothelial origin.1,2,3 The dog is the most

affected specie and the site of occurrence is primarily the spleen (50%).1,3 Other common

locations are right atrium (25%), cutaneous or subcutaneous tissue (13%), and liver (5%).1,3

HSA represents approximately 5% of all noncutaneous primary malignant neoplasms and about

12 to 21% of all mesenchymal neoplasms in dogs.1,3 However, HSA may be multifocal

achieving other organs, such as lung, kidney, muscle, urinary bladder and tongue.1,3 The most

affected breeds seem to be German Shepherds, Golden and Labrador Retrievers, particularly

older aged, male dogs.1,2,3 The cutaneous form of HSA has higher incidence in breeds with

minimal pigmentation and thin hair coat as possible relation to UV light exposure.1 Although this

form is less frequent, any subcutaneous HSA should not be undervalued since it can achieve

equal aggressiveness as splenic HSA.5

The etiology is unknown but evidence confirms the existence of dysregulation of angiongenic

growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor

(bFGF) and angiopoietins-1 and 2, resulting in angiogenesis with uncontrolled proliferation of

cells.1 A mutation in tumor suppressor genes (p53, Ras and Tsc2) are equally implicated in the

pathogenesis, although, recent studies suggest that some of those mutations are infrequent in

canine HSA. According to the double two-thirds rule, dogs presenting with splenomegaly have

two thirds chance to have a malignant splenic neoplasia and two thirds of those will be HSA.1,2

HSA is recognized to be a very aggressive disease, leading to rapid and wide metastasis to

brain, lungs, liver, omentum, mesentery and other organs.1,3 On Jo’s first presentation the

cardiology service intervened for a profound evaluation because one study reported that about

25% of the splenic HSA will have right atrial involvement.1,2

The clinical signs can be variable and unspecific, depending of the origin of primary tumor

and are usually related to tumor rupture, coagulopathies or cardiac arrhythmias.1,3 Common

signalment includes abdominal distension, lethargy, inappetence, weight loss, weakness and

collapse with sudden death.1,2,3 Occasionally the primary signs can be associated to secondary

right-sided congestive heart failure, cardiac arrhythmias, anemia or thrombocytopenia.3

27

A thorough physical examination can reveal pale mucous membranes, increased capillary

refill time, tachycardia, weak pulse, positive fluid wave test or even, a palpable mass.1

Staging as well as diagnosing of HSA is performed on basis of hematology, serum

biochemistry, urinalysis, coagulation testing, thoracoabdominal imaging and echocardiography.1

While in many cases anemia is seen, Jo’s most concerning disarrange was the moderate

thrombocytopenia. This latter is observed in about 75 to 97% of cases, ranging from mild to

severe and can be a result of disseminated intravascular coagulation (DIC) or secondary to

microangiopathic hemolysis (MAHA).1,3 The hematologic abnormalities are usually

characterized by red blood cell fragments (schistocytes associated with MAHA), acanthocytes,

leukocytosis with neutrophilia and monocytosis.1,3 The underlying anemia can be a cause of

spontaneous intracavitary bleeding or MAHA.3 Approximately 50% of cases have coagulation

abnormalities corresponding to DIC that make the performance of a coagulogram of great

relevance.1 Although, serum biochemistry is often vague, a very mild increase in ALP or other

hepatic enzymes may occur, as well as hypoalbuminemia and hypoglobulinemia.1 Additionally,

HSA effusions can be analyzed but are usually not more than a serosanguineous and non-

clotted sample that rarely include significant number of tumor cells required for diagnosis (less

than 25% of probability).1,3 Beside this, the sample can also present mesothelial cells that may

appear like neoplastic cells and lead to a false-positive result.3 Likewise to needle aspirations,

the cytologies have low diagnostic utility due the hemodilution.1,3 In any way, the definitive

diagnosis should be obtained or confirmed by surgical histopathology.1,3

Thoracic radiographs are very important to evaluate the metastatic status of the disease and

should always include three different views to reduce incidence of false negatives.1,3 When

evident pericardial effusion is present, the cardiac silhouette may appear enlarged and caudal

vena cava might be distended.2 To evaluate the abdomen, ultrasonography is a superior

modality.1 The neoplastic lesion generally have a heterechoic appearance varying between

anechoic to hyperechoic or targetoid.1,3 Echocardiography is used to measure the baseline

fractional shortening prior to a doxorubicin chemotherapy and to identify possible cardiac

masses.1,2,3 However, the absence of a mass does not rule out HSA and the presence of one is

not considered pathognomonic.1 For cutaneous or subcutaneous lesions, a needle core biopsy

can be useful, although, it is not implied in visceral lesions due the elevate risk of hemorrhage

and consequent dispersion to peritoneum.1 Multiple additional diagnostic testing’s have been

explored in order to obtain an accurate diagnosis without needing surgery. Concerning to some

studies, difference between cardiac HSA and idiopathic pericardial effusions was observed on

basis of distinctive concentrations in troponin I, an indicator of myocardial damage.1 In patients

with HSA, plasma concentrations of VEGF and urine concentrations of bFGF seem to be

elevated comparing to a normal control group.1 The disadvantage is the fact that none of those

28

alternatives is able to link to stage, remission status or outcome of the disease.1 However,

advanced imaging techniques involve contrast-enhanced computed tomography, contrast-

enhanced ultrasound and magnetic resonance imaging. Those modalities have been able to

differentiate malignant from benign.1

Following the clinical staging system of canine HSA, Jo’s disease was considered a stage III

(T2/T3, N0 and M1) because the splenic neoplasm was 5 cm, had no regional lymph node

involvement but evidence of metastasis to liver (Appendix V, table 9).1

Subsequent to a stabilized patient, the treatment of choice for HSA is surgery.1,2

Nevertheless, splenectomy is designed to remove macroscopic disease and prevent from life-

threatening hemorrhage, and is so, purely palliative.1,3 Prior to this, a patient likewise to Jo,

requires shock therapy, correction of hematologic abnormalities and constant monitoring of

cardiac arrhythmias. An open thoracoscopic pericardiectomy can be executed for primary

cardiac HSA, as a palliative procedure and discontinue the restriction of function caused by the

excessive pericardial fluid.1,2 In Jo’s, a splenectomy was performed and biopsies of the liver

were obtained. It is vital to perform this carefully without rupturing the neoplasm or causing

excessive hemorrhage.1,3 Anyway, cross match testing should be determined prior to surgery in

order to prepare blood transfusion if the patient’s status turns critical.1,3 When finalizing, biopsies

can be sampled, a thorough cavitary lavage is mandatory and the instruments must be changed

before abdominal closure.1 A continuous electrocardiogram permits monitoring possible

ventricular arrhythmias during this period, particularly within de 24 to 48 hours post-operative.1,3

Jo suffered from frequent VPC’s that required pharmacological intervention by administering

lidocaine. In one study of 59 dogs, about 24% developed arrhythmias, a cause of poor

myocardial pericardial perfusion in response to anemia, hypovolemia or anemia.1

Regarding the aggressive metastatic rate of canine HSA, additional chemotherapy has the

function of treating microscopic metastatic disease that surgery is unable to perform.1,2,3,4

Postoperative adjuvant chemotherapy with doxorubicin, doxorubicin and cyclophosphamide (AC

protocol) or vincristine, doxorubicin and cyclophosphamide (VAC protocol) demonstrated better

results than surgery alone.1,2,3 Nonetheless, the prognosis appears to be better if a three-drug

combination is used, than a two-drug combination or monochemotherapy.3 The VAC protocol

consists of a 22 days cycle, initiating with 30 mg/m2 of doxorubicin as well as 100 to 150 mg/m2

of cyclosphosphamide both administered intravenously.1 However, the latter can also be divided

over 3 to 4 days when administered orally.1 On day 8 and 15, one dose of 0.75 mg/m2 of

vincristine is provided intravenously and on the last day (day 22), the cycle can be repeated for

a total of 4 to 6 times.1 In any case, a complete blood cell count is a requisite prior to each

chemotherapy treatment.1 The treatment must be delayed one week if the neutrophils are less

than 2000/uL and platelets less than 75.000/uL.1 Common occurring side effects associated are

29

myelosuppression, gastroenteritis and alopecia, as with any chemotherapy, and cardiotoxicity

particularly as a result from doxorubicin.3 In order to this, electrocardiogram and

echocardiography have to be re-evaluated regularly.1,3

Other additional treatments suggested to Jo was a low-dose continuous metronomic

chemotherapy given orally, likewise to rapamycin that has no evidence of real benefits. As aim

of prolonging the survival time, other combinations exist and several studies are currently

focusing on the outcome of doxorubicin protocols followed by low-dose metronomic

chemotherapy or VEGF receptor kinase inhibitors.1

Conforming to a study that evaluated the treatment of HSA with dasatinib, notable sensitivity

was revealed as well as potent mediating cytotoxic effects.6 It also seems to inhibit

phosphorylation of the shared PDGFR-β target but at a lower concentration than required by

imatinib, the other medication present in this investigation.6 Nevertheless, both augmented the

response to doxorubicin suggesting that clinical responses can be improved using both drugs in

combination.6 Other studies compared the AC protocol in association to immunotherapy with

liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) revealing a

long-term survival time in 40% of the dogs.1,3 Unfortunately, liposomal MTP is not readily

available making this an inaccessible alternative, for so far.1,3 Radiation therapy is rarely

indicated, excepting dermal HSA that might benefit from palliative therapy.1

The most recent studies seem to be focused on combined therapy to control angiogenesis,

involving splenectomy with NSAID, as well as low-dose metronomic chemotherapy with

alternating courses of cyclophosphamide and etoposide.1,2 Unfortunately, the outcome was

similar to other doxorubicin injectable protocols.1,2 One similar study evaluated the effect of

deracoxib to an intensified-dose doxorubicin protocol resulting in an overall surviving time of

150 days, which was greater in stage III than stage II of the disease.4. It could be that the anti-

angiogenic effects of deracoxib are more important in dogs with more aggressive form of HSA,

although, further studies are warranted to truly confirm its efficacy as coadjuvant treatment.4

The prognosis of HSA with surgery alone is around 19 to 86 days, and so, very minimal.1,2,3

An improved prognosis can be obtained by instituting an additional low-dose continuous

chemotherapy, VAC or AC protocol, corresponding to approximately 178, 145 and 160 days of

medium survival time, respectively.1 The most promising median survival time was of 273 days

and achieved by combining splenectomy, AC protocol and liposomal MTP-PE.1 The detection of

cardiac metastasis, pericardial effusion, collapse and ascites are additional factors that can

define a worse outcome.1,2

On basis on a report, no significant advantages were seen by using VAC protocol over other

doxorubicin protocols in dogs with stage I and II.5 The major benefit was seen in dogs with the

most advanced stage (III), showing high response and prolonged median survival time.5 The

30

VAC protocol was well tolerated and no mortality occurred due to adverse events.5 Therefore,

dogs with advanced HSA should not be denied treatment and a chemotherapy protocol should

be considered.5 Despite the opposing and sometimes controversy information obtained by

innumerous studies and reports, the ideal protocol for canine HSA remains mysterious.

However, since any of the doxorubicin-based protocols have proven fair results, the decision

should be made, balancing between experience of clinician and concordance of owner.

References:

1- Thamm, D. H (2013) “Miscellaneous Tumors” in Withrow S.J, Vail M.D, Withrow & MacEwen’s Small Animal

Clinical Oncology, 5th edition, Saunders Elsevier, 679-684.

2- Johnson, K. D (2010) “Splenic Tumors” in Henry C. J, Higginbotham M. L Cancer Management in Small

Animal Practice, 1st edition, Saunders Elsevier, 246; 264-268.

3- Nelson R.W, Couto C. G (2009) “Selected Neoplasms in Dogs and Cats” in Small Animal Internal Medicine, 4th

edition, Mosby Saunders, 1195-1197.

4- Kahn, S. A, Mullin C. M, Lorimier L. P, Burgess K. E, Risbon R. E, Fred R. M, Drobatz K, Clifford C. A (2013)

“Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: A pilot study” in The

Canadian Veterinary Journal, 54, 237–242.

5- Alvarez F. J, Hosova K, Lara-Garcia A, Kisseberth W, Couto, G (2013) “VAC Protocol for Treatment of Dogs with

Stage III Hemangiosarcoma” in Journal of the American Animal Hospital Association, 49, 370-377.

6- Dickerson E. B, Marley K, Edris W, Tyner J. W, Schalk V, MacDonald V, Loriaux M, Druker B. J, Helfand S. C

(2013) “Imatinib and Dasatinib Inhibit Hemangiosarcoma and Implicate PDGFR-β and Src in Tumor Growth” in

Translational Oncology, 6, 158–168.

31

APPENDIX I – GASTROENTEROLOGY

CBC Parameters

Reference ranges Day 1 Day 4 Day 6 8:30 AM

Day 6 12:00 PM

RBC 5.6-8.7 (x106/µL) 7.09 4.68 5.65 6.36

HGB 14.7-21.6 g/dL 16.5 10.4 13.3 14.9

HCT 41-60 % 47.1 30.7 36.9 42.0

MCHC

34.5-36.3 g/dL 35.1 34.0 36.1 35.4

Segmented neutrophils

2.65-9.8 (x103/µL) 7.8 8.33 5.69 6.51

Band neutrophils

0-0.3 (103/µL) 2.15 - 0.08 -

Lymphocytes 1.1-4.6 (x103/µL) 0.68 1.62 0.86 1.46

Monocytes 0.165-085 (x103/µL) 0.68 0.97 0.55 0.72

Platelets 147-423 (x103/µL) 500 117 157 182

Chemistry Parameters

Reference ranges

Day 1 Day 2 Day 4 Day 6 8:30 AM

Day 6 12:00 PM

BUN 8-32 mg/dL 16 5 7 6 9

Total Proteins

5.4-6.8 g/dL 6.3 4.5 5.5 5.6 6.2

Albumin 3.2-4.1 g/dL 3.4 1.5 2.5 2.8 3.0

Calcium 10-11.9 mg/dL 10.6 8.6 10.2 10.8 11.1

ALP 15-164 u/L 177 124 104 105 113

AST 15-51 u/L 75 66 51 36 26

Sodium 142-149 mEq/L 144 140 149 148 148

Bicarbonate 14-22 mmol/L 18.0 17.0 25.0 24.0 23.0

Total Bilirubin

0.2-0.5 mg/dL 0.2 0.2 0.1 0.1 0.1

Creatine Kinase

49-324 u/L 632 332 143 376 76

Cholesterol 148-337 mg/dL 439 269 241 238 262

Fluid analysis

Parameter Result

Gross Light red and cloudy

Total nucleated cell count

12,090/µL

RBC 50,000/µL

Protein 5,5 g/dL

Blood glucose 226 mg/dL

Table 1 – Summary of Blackjack’s CBC along hospital admission.

Table 2 – Blackjack’s chemistry panel. Note the hypalbuminemia and decreased BUN evidenced in

the beginning and how it normalized within the last days. Originally his blood work showed no

significant abnormalities which changed drastically during the period of hospitalization.

Table 3 – Fluid obtained by abdominocentesis,

suggestive of exsudate with moderate

neutrophilic inflammation.

32

APPENDIX I - GASTROENTEROLOGY

Fig. 1 and 2 – Lateral views of the thorax. There is a focus of interstitial to alveolar pattern in the left caudal

subsegment of the left cranial lung lobe overlying the cardiac silhouette on the right lateral view. The right lung

lobes are normal. Suggestive of mild aspiration pneumonia. The ventrodorsal view is not included in the

appendixes.

Fig. 3 – Lateral view of the abdomen. There is a

moderate volume of intra-abdominal effusion with

subsequent loss of serosal detail. This is most severe

within the right cranial abdomen. The serosal margins

of many small intestinal segments are obscured by the

effusion. Suggestive of pancreatitis.

33

APPENDIX II – PULMONOLOGY

Fig. 4 and 5 – Lateral views of Maximus’ thorax. There is a visible diffuse and mild bronchial pattern throughout

the lungs. Mineralization of the mainstem bronchi is noted as well. This is compatible with chronic lower airway

inflammatory disease. There is no evidence of pneumonia.

Fig. 6 – Ventrodorsal view of the thorax. The

cardiac silhouette and pulmonary vasculature

are normal. There is an oval mineral opacity

within the plane of the T13-L1 intervertebral

foramen, and an oval osseous body cranial to

the right scapulohumeral joint, measuring

approximately 1.3 cm in length. Suspicion of

herniated intervertebral disc and degenerative

joint disease.

34

APPENDIX III – SOFT TISSUE SURGERY

CBC parameters Reference ranges Second day post-operative

WBC 5.1-14 (x103/µL) 17.5

RBC 5.6-8.7 (x106/µL) 6.81

HGB 14.7-21.6 (g/dL) 16.9

HCT 41-60 % 51.3

MCV 62-74 fL 75.4

MCH 22-26.1 pg 24.9

MCHC 34.5-36.3 g/dL 33.0

Segmented neutrophils 2.65-9.8 (x103/µL) 14.67

Lymphocytes 1.1-4.6 (x103/µL) 1.50

Monocytes 0.165-0.85 (x103/µL) 1.25

Eosinophils 0-0.85 (x103/µL) 0.03

Basophils 0-0.2 (x103/µL) 0.06

Platelets 147-423 (x103/µL) 355

Chemistry parameters

Reference ranges

2 days pre-operative

2 days post-operative

BUN 8-32 mg/dL 7 9

Creatinine 0.4-1.2 mg/dL 0.6 0.7

Total Proteins 5.4-6.8 g/dL 6.3 5.7

Albumin 3.2-4.1 g/dL 3.7 2.6

Globulines 2-3.2 g/dL 2.6 3.1

Glucose 84-120 mg/dL 122 156

Calcium 10-11.9 mg/dL 9.9 9.2

Phosphatase 2.6-5.8 mg/dL 5.4 2.3

ALP 15-164 µ/L 221 381

ALT 21-97 µ/L 192 84

AST 15-51 µ/L 29 46

Sodium 142-149 mEq/L - 157

Potassium 3.1-4.8 mEq/L - 4.5

Chloride 109-117 mEq/L - 124

Bicarbonate 14-22 mmol/L - 18.0

Total bilirubin 0.2-0.5 mg/dL 0.2 0.2

Creatine kinase 49-324 µ/L 122 293

Cholesterol 148-337 mg/dL 245 191

Magnesium 0.7-0.9 mmol/L 0.8 1.0

Table 4 – Katie’s CBC on second day post-operative. A mild neutrophilia is visible

but overall it’s mostly unremarkable.

Table 5 – Evolution of Katie’s biochemistry panel. Beside the

increased ALP and ALT, the changes are very subtle.

35

APPENDIX III – SOFT TISSUE SURGERY

ACTH stimulation test

Reference ranges Prior to Surgery

2 days posterior to Surgery

Baseline 2.1-58.8 ng/L 57.5 31.5

Post-estimulation 65.0-174.6 ng/L 114.2 29.6

Table 6 – Results of ACTH stimulation test prior and posterior to adrenalectomy.

The first cortisol values were obtained approximately 1 month prior to surgery,

while Katie was not receiving exogenous glucocorticoid supplementation.

Posteriorly, with one remaining atrophied adrenal gland, the cortisol levels

decreased considerably even when on prednisone.

Fig. 7 – Right adrenal mass that later confirmed to be an adrenocortical

carcinoma (~ size 1,63 cm). Beside the invasion of the caudal vena cava, no other

metastatic disease was found on CT.

36

APPENDIX IV – OPHTHALMOLOGY

CBC parameters Reference ranges 16/12/2013 20/12/2013 Day of surgery

WBC 5.1-14 (x103/µL) 38.1 21.0

RBC 5.6-8.7 (x106/µL) 5.19 5.49

HGB 14.7-21.6 (g/dL) 12.8 13.6

HCT 41-60 % 37.8 40.8

MCV 62-74 fL 72.8 74.3

MCH 22-26.1 pg 24.6 24.8

MCHC 34.5-36.3 g/dL 33.8 33.4

RDW 11.4-13.6 % 15.7 16.6

Segmented neutrophils 2.65-9.8 (x103/µL) 27.98 16.8

Band neutrophils 0-0.3 (x103/µL) 2.23 1.26

Lymphocytes 1.1-4.6 (x103/µL) 0.64 0.84

Monocytes 0.165-0.85 (x103/µL) 0.95 1.89

Eosinophils 0-0.85 (x103/µL) - 0.21

Platelets 147-423 (x103/µL) 214 319

Chemistry parameters

Reference ranges

12/16/2013 12/20/2013 Day of

surgery

BUN 8-32 mg/dL 14 10

Creatinine 0.4-1.2 mg/dL 0.6 0.6

Total Proteins 5.4-6.8 g/dL 5.7 6.3

Albumin 3.2-4.1 g/dL 3.0 3.3

Globulines 2-3.2 g/dL 2.7 3.0

A:G ratio - 1.1 1.1

Glucose 84-120 mg/dL 113 108

Calcium 10-11.9 mg/dL 9.8 9.5

Phosphatase 2.6-5.8 mg/dL 9.0 5.8

ALP 15-164 µ/L 4200 4720

ALT 21-97 µ/L 1167 1328

AST 15-51 µ/L 152 149

Sodium 142-149 mEq/L 146 146

Potassium 3.1-4.8 mEq/L 4.5 4.4

Chloride 109-117 mEq/L 103 102

Bicarbonate 14-22 mmol/L 21.0 22.0

Anion Gap 13-22 27.0 26.0

Total bilirubin 0.2-0.5 mg/dL 0.6 0.3

Creatine kinase 49-324 µ/L 274 254

Cholesterol 148-337 mg/dL 342 388

Magnesium 0.7-0.9 mmol/L 0.8 0.9

Table 7 – Buster’s CBC.

Table 8 – Buster’s chemistry panel prior and posterior to

prednisone dose adjustment. Note the general disarrange of

values, particularly the mild hyperphosphatemia and severe

increased hepatic enzymes.

Table 7 – CBC of Buster. Note the moderate increase of white blood cells, reduced

hemoconcentration, moderate left shifted neutrophilia and monocytosis.

37

Fig. 9 – Buster’s left eye 4 days post-operative. Note

the vessels that are growing into the cornea and are

cooperating with the healing process. The large

amount of pigment is seen on conjunctiva and

cornea. (Courtesy Dr. Lori Best, Ophthalmology

service of College of Veterinary Medicine, University

of Tennessee).

Fig. 8 – Buster’s left eye 1 day after conjunctival

hood graft. (Courtesy Dr. Lori Best, Ophthalmology

service of College of Veterinary Medicine, University

of Tennessee).

uyy

APPENDIX IV – OPHTHALMOLOGY

Fig. 10 – Buster’s left eye 1 month post-operative.

(Courtesy Dr. Lori Best, Ophthalmology service of

College of Veterinary Medicine, University of

Tennessee).

uyy

38

APPENDIX V – ONCOLOGY

Canine Hemangiosarcoma

Localization Involvement Classification

Primary tumor (T)

No evidence of tumor T0

Tumor less than 5 cm, confined to primary site

T1

Tumor with 5 cm or greater or ruptured. Invading subcutaneous tissues

T2

Tumor invading adjacent structures, including muscle

T3

Regional Lymph Nodes (N)

No regional lymph node involvement N0

Regional lymph node involvement N1

Distant lymph node involvement N2

Distant Metastasis (M)

No evidence of distant metastasis M0

Distant metastasis M1

Stages

I T0 or T1; N0; M0

II T1 or T2; N0 or N1; M0

III T2 or T3; N0, N1 or N2; M1

Table 9 – Clinical Staging System for Canine Hemangiosarcoma (adapted and changed from Withrow & MacEwen’s, 2013)

Fig. 11 – Left lateral view of thorax, approximately 5

weeks post-operative. Mild bronchial mineralization

but pulmonary parenchyma is otherwise normal.

Mineralization of the costal arches is observed.

Normal geriatric thorax with no evidence of nodular

pulmonary metastatic disease.

Fig. 12 – Right lateral view of abdomen,

approximately 5 weeks post-operative. No

radiographic evidence of metastatic disease.