Download DVM Program 2017 SVS CE Symposium Notes

Seattle Veterinary Specialists
Continuing Education Symposium
DVM Program
April 30, 2017
8am-2:30pm
McCaw Hall
DVM Program 1
Allen Foundation for the Arts Room
DVM Program 2
The Norcliffe Room
Time
Registration | Continental Breakfast
8am-8:40am
8:40 am
Introduction with Dr. Kent Vince
Introduction with Dr. Jim Perry
8:50am-9:30am
Urinary Laser Applications:
Lithotripsy and Ectopic Ureter Ablation
Matt Vaughan, DVM, Diplomate ACVIM
Topsy, Turvy, Twisty, Turny:
Untangling Imaging of Torsions and Volvuluses
Alaina Carr, DVM, Diplomate ACVR
Head Trauma Management in Veterinary Patients
Dani Powers, DVM, Diplomate ACVIM (Neurology)
Feline Lymphoma:
Review and Update on Treatment
Kevin Choy BVSc(Hons) MS DACVIM (Oncology)
Minimally Invasive Abdominal Surgery Options
Stephen Stockdale, DVM, Surgery Resident
Indolent and Less Common Canine Lymphomas
Nicolas Szigetvari, DVM
9:40am-10:20am
10:30am11:10am
11:10am12:10pm
12:10pm12:50pm
Lunch | Grand Lobby
Cell-based Model of Coagulation:
A Thromboelastographic Analysis
Seung Yoo, MS, MBA, DVM, Diplomate ACVP
(Clinical)
Canine Intrahepatic Shunts
Jim Perry, DVM, PhD, Diplomate ACVIM (Oncology), Diplomate
ACVS
Antifibrinolytics: A new therapy for bleeding
Kelly Blackstock, MS, DVM, Diplomate ACVECC
Keeping Up With The Flow of Surgical Extrahepatic Biliary
Diseases
Jessica J. Leeman, DVM
Diagnosis and Treatment of Ureteral Obstruction:
A Case Series
Danielle Pollio, DVM
Updates for Mitral Valve Disease
Mikaela Mueller, DVM, DACVIM (Cardiology)
1pm-1:40pm
1:50pm-2:30pm
www.svsvet.com
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Thank you to our Sponsors for 2017!
Seahawks Level:
Space Needle Level:
2
DVM Speakers 2017:
Kelly Blackstock, DVM, MS, Diplomate ACVECC
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DVM- Colorado State University
Internship- Fifth Avenue Veterinary Specialists, NY
Residency- Cornell University
Diplomate- ACVECC
Dr. Blackstock graduated with her DVM in 2006 from Colorado State University, College of Veterinary
Medicine. She moved to New York, New York where she completed her small animal rotating
internship at Fifth Avenue Veterinary Specialists. Following this, she remained at Fifth Avenue as an
emergency doctor. After this, she completed a small animal Emergency and Critical Care residency at
Cornell University. She obtained her board-certification in Emergency and Critical Care and returned
to Fifth Avenue Veterinary Specialists as a criticalist. During her time there, Dr. Blackstock managed
critically ill patients, emergency patients and supervised the emergency service as well as the
internship program. Dr. Blackstock has a specialist interests in coagulation and respiratory
physiology. In her free time, she enjoys triatholons, cooking, scuba diving and traveling.
Alaina Carr DVM, Diplomate ACVR
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DVM – Washington State University
Internship – VCA Animal Referral and Emergency Center of Arizona
Residency – University of California, Davis
Diplomate- ACVR
Dr. Alaina Carr received her veterinary medical degree from Washington State University in 2008. After
graduation, she joined a small animal referral and emergency hospital for a year-long internship and
then went on to complete a residency in Diagnostic Imaging at the University of California-Davis
Veterinary Medical Teaching Hospital. In addition to her clinical duties as a resident, which included
clinical and didactic teaching of veterinary students, Alaina taught basic and advanced abdominal
ultrasound to veterinarians through continuing education courses. She became board certified by the
American College of Veterinary Radiology in 2012 and served as an acting faculty member at the
University of California, Davis for 1 year. Throughout her post-graduate training, she has maintained
active research projects that have culminated in published peer-reviewed manuscripts. Her particular
research interests involve imaging of the feline urinary tract with ultrasound and computed tomography
(CT). Dr. Carr is originally from Washington State and is very excited to be back in the Pacific Northwest.
She lives with her husband and dog (a Pit Bull mix, Adelaide). In her spare time she can usually be
found at the barn with her Thoroughbred, named Eagle.
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Kevin Choy BVSc (Hons), MS, Diplomate ACVIM
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BVSc(Hons) – University of Melbourne
MS - Washington State Univesrity
Internship – Oregon State University
Residency – Washington State University
Diplomate ACVIM (Medical Oncology)
Dr. Kevin Choy received a Bachelor of Veterinary Science from the University of Melbourne, Australia
in 2006 with first class honors, after earning a Bachelor of Science degree in Animal Science from the
University of British Columbia, Canada in 2003 with honors. He worked in small animal private
practice in the heart of Melbourne, Australia before pursuing specialist training back in the United
States. He completed an internship in small animal medicine and surgery at Oregon State University
in 2009 and a Masters degree and residency in small animal medical oncology at Washington State
University in 2013. As a resident at Washington State University, Dr. Choy received multiple honors
including the Thibodaux Oncology Award, Strickler Award in Oncology, and Pera Scholarship in
Oncology in addition to resident of the year distinction. He is a board certified specialist in medical
oncology as a diplomate of the American College of Veterinary Internal Medicine (ACVIM).
While in Melbourne, Dr. Choy has also served as an emergency relief veterinarian on behalf of
Wildlife Victoria to assess and treat injured Australian fauna including Koalas, Wombats and
Kangaroos as well as provide veterinary access to aboriginal communities in Australia. Dr. Choy's
professional interests include lymphoma, transitional cell carcinoma, localized tumor treatment with
electrochemotherapy and translational cancer research through cooperative clinical trials and
research projects with both local and national institutions including the Fred Hutchinson Cancer
Research Center to improve patient care in both animals and their owners. He has presented both at
national cancer conferences and continuing education seminars with research at Washington State
University investigating transitional cell carcinoma therapy in dogs and has co-authored studies and
book chapters in feline lymphoma and mammary tumors. In his spare time, he enjoys spending time
with his wife, two children and two cats. Personal interests include wildlife photography, Kendo,
following his hometown hockey team (Vancouver Canucks) and traveling the Pacific Northwest.
Jessica Leeman, DVM, Diplomate ACVS-SA
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DVM - University of Florida
Internship - Louisiana State University
Surgery Internship - Seattle Veterinary Specialists
Residency - Seattle Veterinary Specialists
Dr. Jessica Leeman received her bachelors degree from Florida Atlantic University followed by
veterinary school at the University of Florida and a rotating internship at Louisiana State
University. She completed her surgery residency at Seattle Veterinary Specialists and is now a
Diplomate of the American College of Veterinary Surgeons. Her affinity for small animal surgery
began in freshman anatomy and has since developed into a passion for correcting, and sometimes
curing surgical diseases. Her current interests include surgical oncology and reconstructive
procedures. Jessica enjoys yoga, weightlifting, and camping during her spare time. She resides in
Kirkland with her fiancé, son, and Yorkie, Scoop of Ice Cream.
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Mikaela Mueller, DVM, Diplomate ACVIM
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DVM - Tufts University, North Grafton MA
Bachelor of Science, Zoology - Miami University, Oxford OH
Internship - Small Animal Medicine & Surgery, Advanced Veterinary Care Center,
Lawndale CA
Residency - University of California, Davis
Dr. Mikaela Mueller has always related well to animals. Her interest in biological sciences and
medicine grew throughout her schooling. She also likes the idea that she can apply those interests to
helping animals and the people who love them. Her interest in cardiology stems from the fact that
she likes the mechanics of the heart and she is fascinated by the many imaging modalities available
for diagnostics. Dr. Mueller’s clinical interests include complex heart disease and the management of
acquired cardiac disease and congestive heart failure. She enjoys being active and outdoors,
including hiking and athletic pursuits such as riding her horse, Ollivander. She also enjoys quiet time
at home and spending time with her family, her husband, three dogs and a cat.
Jim Perry, DVM, PhD, Diplomate ACVIM, Diplomate ACVS-SA
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DVM - Colorado State University
PhD - Colorado State University
Oncology Residency - Colorado State Univeristy
Diplomate ACVIM (Oncology)
Surgery Residency - Aspen Meadow Veterinary Specialists
Diplomate ACVS-SA
Dr. Perry, originally from Portland, Oregon, received his Bachelor's degree in biochemistry and
cellular biology at the University of Washington in Seattle. He then went on to complete his veterinary
medical degree and PhD in cellular immunology at Colorado State University. After working in private
practice for a year, he returned to the clinics at CSU for his residency in medical oncology followed by
a surgical residency at Aspen Meadow Veterinary Specialists. Dr. Perry's clinical and research
interests include comparative cancer biology, immunology, targeted chemotherapeutics, and surgical
oncology.
Dr. Perry is a diplomate of the American College of Internal Medicine (ACVIM) and the American
college of Veterinary Surgeons (ACVS). He is a member of the American Veterinary Medical
Association, Veterinary Orthopedic Society, Veterinary Cancer Society, Veterinary Society of Surgical
Oncology and the American Association of Immunologists. In his free time, Dr. Perry enjoys biking,
kayaking, and back country skiing with his Tolling Retriever and Border Collie.
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Danielle Pollio, DVM
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DVM- University of Georgia
Small Animal Rotating Internship- Red Bank Veterinary Hospital
Residency- BluePearl Veterinary Partners, Tampa, Florida
Dr. Danielle Pollio grew up in a suburb near Atlanta, Georgia. She attended the University of Georgia
College of Veterinary Medicine, from which she graduated magna cum laude and was awarded the
Dean Emeritus Thomas J. Jones Cup for outstanding professional proficiency and scholastic
achievement. During her time at UGA, Dr. Pollio gained strong experience caring for animals in the
intensive care unit and volunteered with the HSVMA to provide veterinary services to underserved
rural communities. After veterinary school, Dr. Pollio completed a small animal rotating internship at
Red Bank Veterinary Hospital and went on to pursue a three-year residency in emergency and critical
care medicine at BluePearl Veterinary Partners in Tampa, Florida. Dr. Pollio enjoys all aspects of
emergency and critical care and is particularly interested the treatment of polytrauma and sepsis.
In her free time, you may find Dr. Pollio biking along the Burke-Gilman trail with her family, dining at
one of Seattle’s great restaurants, or simply relaxing at home with a good book.
Dani Powers, DVM, Diplomate ACVIM (Neurology)
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DVM - Washington State University
Internship - Seattle Veterinary Specialists
Residency- Seattle Veterinary Specialists
Dr. Powers received her bachelor's degree at Washington State University and then continued to
complete her Doctorate of Veterinary Medicine at Washington State University in 2011. She
completed a small animal rotating internship at Seattle Veterinary Specialists in 2012. Dr. Powers
completed a Neurology and Neurosurgery Residency at Seattle Veterinary Specialists. Her areas of
interest include seizure management, neurosurgery and physical rehabilitation techniques following
neurosurgical interventions. Dr. Powers enjoys spending time with her family including her husband
Jon and children as well as their two cats Tux and Moto. They like to explore the Pacific Northwest
including the great hiking, local sports, food, and wine.
Stephen Stockdale, DVM
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DVM- Washington State University College of Veterinary Medicine
Small Animal Rotating Internship- Seattle Veterinary Specialists, Kirkland
Residency- Seattle Veterinary Specialists, Kirkland
Dr. Stephen Stockdale grew up in the eastside of Seattle. He attended Washington State University
from 2005-2008 where he graduated magna cum laude with a Bachelor of Sciences degree in Animal
Sciences with a minor in Biology. After graduating, he spent a year working in a general veterinary
practice before attending Washington State University College of Veterinary Medicine and obtained
his DVM in 2013. His interests are minimally invasive surgery with laparoscopy and thoracoscopy as
well as soft tissue surgery. Dr. Stockdale completed his rotating internship at SVS and stayed with
SVS for a surgical residency beginning in July, 2014. In his free time, Dr. Stockdale enjoys traveling,
road cycling, bike touring, mountain biking, rock climbing, fly fishing, and running with his dogs.
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Nicolas 'Nick' Szigetvari, DVM, Practice-Limited to Oncology
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DVM - University of Illinois
Internship - University of Wisconsin
Residency - Purdue University
Dr. Szigetvari received his DVM from the University of Illinois. Following his DVM, Dr. Szigetvari was
in general practice for several years then decided to continue his training and specialize. He
completed a small animal rotating internship at the University of Wisconsin. Following his internship,
Dr. Szigetvari went on to complete an oncology residency at Purdue University.
Matt Vaughan, DVM, Diplomate ACVIM (SAIM)
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DVM - University of California Davis
Internship - Texas A&M University
Residency - University of California Davis
Diplomate ACVIM (SA Internal Medicine)
Dr. Matt Vaughan is originally from Philadelphia, Pennsylvania. He attended the University of
California, Santa Cruz for his undergraduate schooling where he graduated with highest honors in
1997. After some well spent time traveling and exploring the world, he attended veterinary school at
the University of California, Davis (UCD) and graduated in 2004. He then completed a one year small
animal internship at Texas A&M University before returning to UCD for a small animal internal
medicine residency between 2005 and 2008. At UCD, Dr. Vaughan served as chief resident during
the third year of his residency. After receiving his board certification in Internal Medicine, Dr. Vaughan
joined Seattle Veterinary Specialists in 2008. Dr. Vaughan holds a special interest in endocrinology
and spent much of his residency involved in research projects focused on canine Cushing's disease
and diabetes mellitus. He also has an interest in interventional radiology and performs procedures
such as tracheal, urethral and ureteral stents.
Seung Yoo, MS, MBA, DVM, Diplomate ACVP (Clinical)
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Bachelor of Science, Master of Science - University of California at Davis
DVM- Colorado State University
MBA- Colorado State University
Small Animal Rotating Internship- Michigan State University
Residency- Colorado State University
Dr. Seung Yoo grew up in South Pasadena, a quiet suburb in balmy Southern California. He received
both a Bachelor of Science and a Master of Science at the University of California at Davis. After
graduating from Colorado State University in 2010 with a combined MBA/DVM degree, he arrived at
Michigan State University for a one year small animal rotating internship. He then completed a
Clinical Pathology residency at Colorado State University in 2014 with additional training in Anatomic
Pathology and accepted a position as a Clinical Pathologist at Seattle Veterinary Specialists. His
professional interests include hemostasis, mineral metabolism, and autoimmune diseases. When not
at work, he enjoys spending time with his wife, dog, and two cats. His hobbies include wood working,
skiing, snowboarding, rock climbing, hiking, bread baking,brewing beer, fishing, and ice hockey.
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Urinary Laser Applications: Lithotripsy and Ectopic Ureter Ablation
Matt Vaughan, DVM, Dip ACVIM Internal Medicine
Seattle Veterinary Specialists
Seattle, WA
LASER LITHOTRIPSY
Uroliths are a common cause of urinary tract obstruction, irritation and a complicating factor of urinary
tract infections in cats and dogs. Although some types of calculi can be dissolved, many need to be
physically removed. Traditionally, cystotomy has been the treatment of choice for urocystoliths and if
urethral calculi are present they are retropulsed into the bladder to allow removal via cystotomy. For
cases where calculi cannot be retropulsed to the bladder, urethrostomy is an option to relieve
obstruction.
Lithotripsy is a procedure where calculi are broken into small fragments and literally means “breaking
of the stone”. Lithotripsy can be performed by applying external shock waves (extracorporeal shock
wave lithotripsy) or can be performed by using a laser directly on the calculi via endoscopic guidance.
Shock wave lithotripsy is utilized in some facilities for fragmentation of small nephroliths (NOT available
at SVS).
Laser lithotripsy utilizes a Holmium:YAG laser. The laser energy is transmitted using flexible quartz
fibers passed through the working channel of a cystoscope or nephroscope. The laser energy is
absorbed in <0.5mm of fluid, which allows for stone fragmentation with minimal risk of damage to
surrounding tissue. The Ho;YAG laser can fragment all types of uroliths. This laser can also be used
if desired to cut tissue that it is directly in contact with.
Stone fragmentation is via a photothermal effect (thermal drilling) as opposed to shock waves. This
photothermal effect may change stone composition of small fragments however stone analysis is
typically reliable on retrieved fragments.
Lithotripsy is used to fragment the uroliths to a size that can be removed through the urethra. These
fragments are then removed via a combination of basket retrieval and urohydropropulsion with the goal
being removal of all fragments. Fragments are then submitted for stone analysis.
Benefits of laser lithotripsy include a success rate equaling cystotomy as well as a reduced recovery
time and no incision care. Complication rates are low with lithotripsy and are comparable to or lower
than with cystotomy. Possible complications include anesthetic complications, urethral swelling,
hematuria, inability to remove all fragments, urethral tear or bladder rupture.
Lithotripsy does require general anesthesia and depending on the size and amount of stones present
may take as long as or longer than surgery. For this reason, the best candidates for lithotripsy are
those with smaller or fewer stones. Lithotripsy can be performed on an outpatient basis however it is
typically recommended that they spend the night after the procedure to monitor for any difficulty
urinating as well as treat any pain or irritation.
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Laser lithotripsy can be performed in male and female dogs as well as female cats. It is not possible in
male cats due to the small urethral size. Small male dogs (<5kg) may not be possible due to small
urethral size (the urethroscope is 7.5fr). Prior to attempting the procedure in small male dogs, an 8fr
red rubber catheter is placed to ensure adequate urethral diameter to accommodate the scope. Given
the small urethral size and cystoscope limitations, male dogs are more difficult and male candidates
are best limited to those with a very small stone burden. Stones that are within the male urethra are
good candidates and can be treated easily with lithotripsy (as long as there are not a large amount of
urocystoliths present as well). Laser lithotripsy cannot be performed on stones in the ureter or kidney
using a cystocopic approach (see below).
The Holmium:YAG laser can also be utilized for other non-invasive urologic procedures including polyp
removal, debulking of urethral tumors and ectopic ureter ablation.
Indications
Candidates
Complications
Urocystoliths
Female dogs
Inability to remove all
fragments
Urethroliths
Male dogs (8fr red rubber
catheter able to pass)
Urethral/bladder tear
Female cats
Transient
stranguria/hematuria
Low stone burden
Incontinence
Nephroliths can be removed via surgery, extracorporeal shock wave lithotripsy (if small) or
percutaneous nephrolithotomy (PCNL). PCNL involves placement of a wire into the renal pelvis via
ether a percutaneous or surgically assisted approach. A tract is dilated over the wire with a balloon
and a sheath is then put in place through which a nephroscope is advanced. Lithrotripsy is then
performed using a laser or ultrasonic lithotripter and fragments are extracted through the sheath. This
procedure results in less nephron damage than traditional surgical approaches. This procedure is not
currently being offered at SVS however may be in the future. Nephroliths are typically only removed if
causing obstruction or causing recurring urinary tract infections and attempts at dietary dissolution is
recommended prior to consideration of removal.
ECTOPIC URETERAL LASER ABLATION
Ectopic ureteral ablation is a non-invasive procedure performed through the cystoscope to correct
ectopic ureters with a success rate equals traditional surgery but has the benefit of being performed as
an outpatient procedure with faster recovery. This procedure can be performed to correct intramural
ectopic ureters however cannot be performed if the ectopic ureters are extramural.
Cystoscopy is typically utilized to confirm and identify types of ectopic ureters prior to surgery. Laser
ablation can be performed at the same time the diagnosis is made. A retrograde ureterogram is
performed during cystoscopy using fluoroscopic guidance to confirm that the ureter is intramural and
identify location where the ureter leaves the bladder wall. The laser fiber is then advanced through the
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working channel of the cystoscope and the luminal wall of the ectopic ureter is ablated under direct
visualization to move the ureterovesicular junction to within the bladder.
Success rate has been reported at 53% with ablation alone, which is similar to surgical success rates.
Failure of this procedure, as with surgical procedures, is due to concurrent causes of incontinence
(urethral sphincter mechanism incontinence, urethral hypoplasia, etc). For dogs that are not
successfully treated with ablation alone, the addition of medical therapy (phenylpropanolamine,
estrogen) and /or urethral occluding device improves success rate to 77%.
Indications
Candidates
Complications
Ectopic ureters
Female dogs
Continued incontinence
Can be performed at time
of initial diagnosis
Male dogs >10kg
Urethral/bladder
perforation
REFERENCES
Bevan JM, Lulich JP, Albasan H, Osborne CA. Comparison of laser lithotripsy and cystotomy for the management of dogs
with urolithiasis. J Am Vet Med Assoc. 2009 May 15;234(10):1286-94.
Lulich JP, Osborne CA, Albasan H, Monga M, Bevan JM. Efficacy and safety of laser lithotripsy in fragmentation of
urocystoliths and urethroliths for removal in dogs. J Am Vet Med Assoc. 2009 May 15;234(10):1279-85.
Grant DC, Werre SR, Gevedon ML. Holmium: YAG laser lithotripsy for urolithiasis in dogs. J Vet Intern Med. 2008 MayJun;22(3):534-9.
Berent AC, Weisse C, Mayhew PD, Todd K, Wright M, Bagley D. Evaluation of cystoscopic-guided laser ablation of
intramural ectopic ureters in female dogs. J Am Vet Med Assoc. 2012 Mar 15;240(6):716-25.
Berent AC, Mayhew PD, Porat-Mosenco Y. Use of cystoscopic-guided laser ablation for treatment of intramural ureteral
ectopia in male dogs: four cases (2006-2007). J Am Vet Med Assoc. 2008 Apr 1;232(7):1026-34.
Reichler IM, Eckrich Specker C, Hubler M, Boos A, Haessig M, Arnold S. Ectopic ureters in dogs: clinical features, surgical
techniques and outcome. Vet Surg. 2012 May;41(4):515-22.
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Head Trauma Management in Veterinary Patients
Dani Powers DVM, DACVIM Neurology
Seattle Veterinary Specialists
Kirkland, WA
Clinical Presentation:
The veterinary patient that presents with head trauma most commonly is secondary to an incident with
a car, however there are several causes that can lead to head trauma.
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Animal bite wound
Impact
Falling
Gunshot wound
Unknown Trauma
If head trauma is suspected then patients should be handled very carefully. A thorough triage history
and basic database can be used to help evaluate these patients.
Triage:
A good history includes questions about consciousness after the incident (or at the present time),
mentation status (see below), presence of seizures, when the incident occurred, any other illness or
comorbidities (fractures, abdominal or thoracic wounds, etc.).
Diagnostics:
The following diagnostics should be performed on patients with suspected head trauma. During
handling, it is important to minimize stress and avoid causing a patient to struggle. Sedation and
general anesthesia are generally contraindicated unless absolutely necessary. Managing pain (if
needed) with opioid drugs may be helpful in handling these patients, and not cause too much sedation
or hypotension.
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CBC and Serum Biochemical Profile; avoid jugular venipuncture as compression of the jugular
vein can increase intracranial pressure.
Blood Pressure(s) (preferably with a Doppler Unit)
Blood Gases or SpO2 (pulse oximetry)
Urinalysis
Assess for other wounds and treat as needed (chest radiographs, abdominal ultrasound to
look for free fluid)
Neurologic evaluation in the triage setting (preferably done prior to any medications); evaluate
pupil size, pupil symmetry and responsiveness to light, assess the mentation status (is the
patient alert, quiet, depressed, obtunded, stuporous, or comatose), assess the ambulatory
status of the patient.
o Alert: The patient is mentally appropriate. They are responsive to external stimuli.
o Quiet: The patient is mentally appropriate. They are responsive to external stimuli,
although not as robustly in the alert patient.
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o Depressed: The patient is not mentally appropriate for the situation. They are still
responsive to stimuli, but more likely require direct stimulation.
o Obtunded: The patient is not mentally appropriate. They require more vigorous
stimulation to have a response. They may seem disoriented or confused.
o Stuporous: The patient is not mentally appropriate and appears unconscious. They are
minimally responsive to external stimuli. With aggressive noxious stimuli, they should
respond.
o Comatose: The patient is non-responsive to any stimuli. They are unconscious.
Advanced imaging of the brain.
o Usually an MR brain scan is the imaging modality of choice; however, CT scans may
also be utilized to view the boney structures for fractures.
 This should be performed only if needed and after cardiovascular stabilization.
 Both require general anesthesia and should be avoided in the immediate period
unless the patient is declining.
o Radiographs can sometimes be useful to identify a skull fractures, but are often hard to
interpret and may require sedation to achieve diagnostic films, and as previously
mentioned sedation should be avoided unless absolutely necessary.
Treatment:
Treatment for the acute head trauma patient will depend on the patients’ status and comorbidities.
Many patients are in cardiovascular shock and with general treatment for this they can improve
dramatically. Remember that severe shock and hypotension can lead to a patient that is mentally dull
and weak. Simple treatments with IV fluids and oxygen support can go far to ameliorate the abnormal
mentation changes.
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IV Catheter(s). Place a large gauge catheter to facilitate quick and effective fluid delivery.
o Cats: 22-20 gauge
o Dogs Less than 10kg: 22-20 gauge
o Dogs 10-20kg: 20-18 gauge
o Dogs greater than 20kg: 18 gauge or larger.
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IV Fluids; dose and rate will be determined by patient status, blood pressure and exam
findings.
o Typically, a ¼ shock dose is utilized initially and then the patient is reassessed for the
above-mentioned parameters.
o Additional boluses are utilized as deemed necessary.
o Normal shock dose is 90ml/kg for dogs and 60ml/kg for cats of isotonic fluids
(plasmalyte, LRS, Normosol R)
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Oxygen; supplemental flow-by, nasal cannulas and endotracheal intubation are the best at
providing oxygen as opposed to closed cage oxygen chambers.
o Patients with head injury are more likely to require constant monitoring and oxygen
chambers would not be ideal in these situations.
o A pulse oximeter reading of greater than 90, and even more so greater than 95 should
be the goal in these patients.
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o If flow-by is not adequate in maintaining pulse oximetry reading at the above values
then sedation and endotracheal intubation should be considered.
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Controlling Increased Intracranial Pressure
o Hypertonic saline 5ml/kg IV over 5-20 minutes depending on mental status
o Mannitol 1gram/kg or 5ml/kg of 20% Mannitol over 10-20 minutes +/- furosemide at
1mg/kg 15 minutes later
o Raise head to 30 degrees to help decrease intracranial pressure.
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Control seizures; valium 0.5mg/kg IV to effect (see below in seizure section).
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Maintain carbon dioxide status
o If intubated ventilate to keep CO2 between 25-30 mm Hg (PaCO2) or as measured by
End Tidal CO2 monitors, which prevents excessive brain vasodilation thereby
decreasing ICP. Excessive hyperventilation can cause brain vasoconstriction which can
also be deleterious and lead to decreased cerebral perfusion pressure and brain
ischemia.
o Blood gases if available, can also be utilized to evaluate CO2 status in the patient.
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Maintain Cerebral Perfusion Pressure (CPP); which is characterized by CPP=Mean Arterial
blood pressure –Intracranial blood pressure.
o Maintaining cerebral perfusion pressure will help to maximize cerebral metabolic
functions and minimize secondary brain injury.
o This is difficult to measure and not often done in veterinary clinical practice.
o CPP is best managed between certain systolic blood pressure values, which are easier
to monitor. Ideally trying to maintain blood pressure between 80-150mm Hg systolic will
aid in normal cerebral perfusion pressure.
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Recumbency care.
o Recumbency care should be performed every 4 hours. Flipping the hips can be done if
the patient is remaining sternal, or a complete flip if they do not stay sternal.
o Avoid flipping in the short-term assessment of the patient if there is a suspicion for
spinal fracture.
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Bladder care
o A urinary catheter can be placed easily in male dogs to quantify urine, and with some
practice female dogs can also be catheterized.
o Use of a Foley catheter connected to a closed system collection bag is the most helpful
for maintaining sterility and allowing quantification.
o If a urinary catheter is not possible then use gentle bladder expression every 6-8 hours.
o Patients that are conscious can probably urinate on their own and may resist bladder
expression.
o Corn starch can be used safely used to prevent or help treat urine scald.
o Placement of absorbent pee pads is important to prevent urine scald.
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Controlled Hypothermia
o Rectal temperatures between 91-95 degrees Fahrenheit may be beneficial in some
cases of head trauma.
o Cooling may help to decrease seizures and intracranial pressure, as well as decrease
cerebral metabolic rate.
o In addition, cooling can help decrease inflammatory cascades that add to secondary
bran injury and help to maintain the blood brain barrier.
o The literature in animals has utilized controlled hypothermia in the face of intractable
seizures that did not respond adequately to pharmacologic intervention.
o In human medicine controlled cooling has been utilized in the emergency setting if there
is history of head trauma and/or if the intracranial pressure is elevated.
o The most recent information in humans (brain trauma foundation) does not suggest
cooling of patients with head trauma as there are studies supporting and refuting this
medical procedure without a clear consensus.
o Controlled cooling should only be performed under direct supervision of a veterinarian
and is not substantiated at this time as a first line of defense in acute head trauma
patients.
o Ideally cooling is done to normal temperatures and not below. Patients that are
normothermic should avoid being overheated.
-
Anti-inflammatories (Steroids)
o Multiple different steroids have been utilized to help decrease intracranial pressure in
patients with head trauma.
o This is not a first line defense for treating head trauma patients in human medicine as
studies have not shown significantly different outcomes with patients receiving and not
receiving steroids.
o Some studies have shown increased mortality rates in patients receiving steroids in
human literature.
o Most human studies have focused on high dose therapy as opposed to low dose
therapy. There may be some desirable effect at lower dosages.
o Simultaneous use of gastroprotectants such as famotidine or pantoprazole should be
considered. (Later oral formulations such as omeprazole, sucralfate, and misoprostol
may be used if GI side effects are recognized).
-
Pain management
o Most opioids are adequate, with the exception of buprenorphine, which is not easily
reversed in cases of declining cardiovascular or mental status.
-
Preventing Pressure Sores
o Avoid shaving over boney prominences
o Fur provides protection to these areas and helps to avoid pressure sores from
developing.
o Recumbency care becomes very important to help prevent pressure sores.
14
-
Nutrition
o Oral feeding, including water, is often postponed until the patient can adequately
prehend food and swallow effectively.
o Check a gag reflex or monitor for normal tongue movement if not allowing gag reflex
prior to oral medications, food or water.
o Feeding by the 7th day following brain injury in people has been associated with lower
mortality rates.
o Optional feeding routes may include nasogastric tubes or parenteral nutrition.
-
Preventing Aspiration Pneumonia
o Suction mouth as needed for excessive saliva, gastric reflux, blood, etc.
o Gentle suctioning and oral care is important to prevent laryngeal/pharyngeal damage.
o Avoid oral administration of food, water or PO medications until the patient can swallow
on their own. Level of alertness also plays a role in the timing of oral feedings.
o Clean and rinse mouth every 2-4 hours, or as needed.
o If aspiration is suspected or known to have occurred then consider broad spectrum
antibiotics to treat secondary infection. In addition, nebulization may be added, with
controlled coupage if the patient is deemed OK to have that procedure performed
-
Prevent Corneal Ulcers
o Lubricate eyes every 2-4 hours or as needed to maintain hydration in patients that are
not blinking spontaneously.
o Monitor closely for presence or appearance of corneal ulcers; treat accordingly.
-
Multiple other medications and treatments have been utilized with equivocal success. These
may or may not be helpful and are clinician’s preference when using as a treatment for head
injury.
o Calcium Channel blocking drugs, NMDA antagonists, CSF drainage
Types of Injury Occurring in the Brain:
-
-
-
Primary brain injury occurs at the time of impact and is due to direct impact to the brain
parenchyma including contusions, lacerations, and diffuse axonal injury. Damaged blood
vessels can lead to intracranial hemorrhage and vasogenic edema.
Secondary brain injury occurs following the impact and is a result of a domino effect of
biochemical pathways that lead to depleted energy supply, increase in free radical production
and increases in intracranial pressure.
Edema
o Cytotoxic edema occurs with hypoxia and ischemia and leads to decreased energy
supply to the cells (ATP) leading to failure of Na – K pumps and eventually causes fluid
to rush into the cell causing swelling, release of excitatory neurotransmitters
(glutamate), increase intracellular calcium results leading to initiation of the proinflammatory and oxidative pathways and eventually cell death
o Vasogenic edema occurs when there is breakdown of the blood brain barrier leading to
extravasation of protein rich fluid
15
-
Hemorrhage can cause immediate and delayed effects.
Ischemia/hypoxia
Secondary infection from penetrating wounds is also possible which can further exacerbate
brain damage.
Seizures:
-
-
-
Seizures following traumatic brain injury are common in people and also in dogs.
Immediate post-injury seizures are common as well as in hospital (prior to discharge) seizure
activity.
Post discharge seizure activity can occur up to 4 years following the brain injury.
The longer the patients go without seizures, the less likely they are to develop seizures.
Main treatment consists of anti-convulsant medications (valium, lorazepam, phenobarbital,
Keppra,)
o Valium 0.5mg/kg IV to effect (5mg/ml concentration valium; approximate doses: 1ml
small, 2ml medium, 3ml large) +/- Valium CRI
Other treatments may include propofol and general anesthesia for intractable seizures.
o Propofol has been shown to have neuroprotective effects and so may be useful on
many levels for patients with head trauma.
o General anesthesia with isoflurane gas can double intracranial pressure and should be
avoid unless absolutely necessary for patients with head trauma.
Long term seizure management is usually continued in cases of known seizure activity
following head trauma. In some cases, this can be tapered if the patient is seizure free for
greater than 6-12 months while on medications.
Prognosis:
-
-
Modified Glasgow Coma Score
o This is an objective measurement of the alertness of the patient and the level of
consciousness.
o It has been modified from the commonly used human Glasgow Coma Score, which is
an algorithm to guide treatment and prognosis in patients with head injury.
o Not as commonly used in veterinary patients, but can be used in prospective or
retrospective studies as an objective evaluation of patients.
The prognosis depends on the injury sustained, how long the injury occurred before medical
intervention and the treatment options available to the patient.
In people the prognosis is significantly correlated with the level of oxygenation and systolic
blood pressure prior to and during medical intervention.
Head trauma in veterinary patients carries and excellent to guarded prognosis depending on
the degree of injury.
16
Degree of Recovery
-
-
-
The degree of recovery in humans is measured by the outcome of the patient functionally.
From normal, to mild neurologic deficit, severe neurologic deficit, and death.
In veterinary patients, the degree of recovery may be less important if they can perform the
tasks required as a companion animal, as opposed to a working animal or person for that
matter.
Some veterinary patients may have recognizable deficits and some may have subclinical
deficits.
Our patients do not need to re-learn to speak, balance a checkbook, or drive a car and so the
level of functionality tends to be less important. Good quality of life is most commonly based on
degree of comfort, willingness to eat and drink, ability to get around (walk), and general
behavior and attitude.
Furthermore, time is often a very important tool for any patient with neurologic dysfunction and
the ability to improve.
17
Modified Glasgow Coma Score:
-
There are three levels of evaluation for the MGCA including motor function, brainstem reflexes
and level of consciousness. A prognosis can be applied to the MGCS.
-
Platt 2001
-
18
Important Take Home Points:
-
Immediate action with IV fluid support to maintain normal blood pressure, as well as
supplemental oxygenation is critical for patients that have sustained head injury.
Prevent hypoxia, hypotension, hypercarbia and hypovolemia.
By preventing the hypovolemia and hypoxemia secondary to shock often the brain function will
improve without necessarily treating the brain trauma directly.
Supportive care and time are of utmost importance in patients with head trauma and brain
injury.
The post injury supportive care and attention to detail will make the difference between
patients that leave the hospital and those that do not.
References
1. Badjatia N, Carney N, Crocco TJ, Fallat ME, et al. Prehospital Emergency Care. Official Journal of the
National Association of EMS Physicians. January / March 2007. Supplement to Volume 12 / Number 1.
2. Carney N, et. al. Guidelines for the management of severe traumatic brain injury. 4 th Edition. Brain Trauma
Foundation September 2016. Braintrauma.org
3. Chen JWY, Ruff RL, Eavey R, Wasterlain CG. Posttraumatic Epilepsy and Treatment. Journal of
Rehabilitation Research and Development. Vol. 46 No. 2009, pp 685-696.
4. Freidenberg SG, Butler AL, Wei L, Moore SA, Cooper ES. Seizures following head trauma in dogs: 259 cases
(1999-2009). JAVMA, Vol 241, No. 11, December 1, 2012.
5. Hayes GM. Severe seizures associated with traumatic brain injury manages by controlled hypothermia,
pharmacologic coma, and mechanical ventilation in a dog. J Vet Emerg and Crit Care. 19(6) 2009, pp 629634.
6. Fox JL, Vu EN, Doyle-Waters M, Brubacher JR, et al. Prophylactic hypothermia for traumatic brain injury: a
quantitative systematic review. CJEM 2010; 12(4):355-364.
7. Garosi L, Adamantos S. Head trauma in the cat. Assessment and management of traumatic brain injury. J of
Feline Medicine and Surgery. (2011) 13, 815-823.
8. Sande A, West C. Traumatic brain injury: a review of pathophysiology and management. J of Emerg and Crit
Care. 20 (2) 2010, pp 177-190.
9. Platt SR, Radaelli ST, McDonnell JJ. The Prognostic Value of the Modified Glasgow Coma Scale in Head
Trauma in Dogs. J Vet Intern Med 2001; 15:581-584.
19
Laparoscopic Surgery
Stephen Stockdale DVM
Seattle Veterinary Specialists
Kirkland, WA
Introduction
While we think of laparoscopy as being high-tech and relatively novel, multiple renditions have been present
through multiple era. Hippocrates used a simple speculum for rectal exams in 460-377BC.1 German physician
Phillip Bozzini developed the Lichtleiter (light conductor) for inspection of cervix, urethra, rectum, nasal cavity,
ears, etc. in the late 1700s.2 This instrument utilized a wax candle as a light source and was an advancement
of the simple speculum. In the late 1800s, French urologist Antoine Jean Desormeaux modified Bozzini’s
Lichtleiter by adding a mirror to reflect light from a kerosene lamp through a metal channel tube and named it
“endoscope.” In the 1930s Janos Varess developed the spring loaded varess needle to create pneumothorax
for patients with tuberculosis. Laparoscopists realized the potential of the instrument to create a safe
pneumoperitoneum.
In the mid 20th century (1940-1960), there was a lag in progression due to controversy associated with
complications of insufflation and electrocautery equipment. None the less, progress continued on. Kurt
Semm was highly progressive and developed intracorporeal knot tying techniques, loop applicators, as well as
a pressure regulated insufflator. He was highly criticized for his first appendectomy; as it was considered
unethical. His colleagues questioned if he had truly even performed the procedure or if it were a hoax. His
medical license was challenged by his colleagues.
The first laparoscopic cholecystectomy was performed by Erich Boblingen in 1985 and ignited the interest in
laparoscopy application in humans. It is now the preferred technique in humans. Veterinarians followed soon
thereafter.
Veterinary endoscopy did not follow such a controversial path. Veterinary laparoscopy really started growing
in the 1970’s with purely diagnostic techniques. Dr. Rawlings and Freeman were some of the pioneers to
laparoscopic and laparoscopic-assisted techniques in veterinary medicine in the later 90’s and early 2000’s.
Dr. Eric Monnet founded the Veterinary Endoscopy Society in 2003 which gathers annually around the world
to share experiences and advancements in the field. Annual attendance continues to steadily rise.
Laparoscopy is now being taught in multiple academic and private practice residency programs.
Benefits
There are a multitude of reasons why laparoscopy can be favored over a traditional open approach. The most
notable difference is the size of the incisions. With smaller incisions, postoperative incision site dehiscence
carries a less severe consequence compared to a traditional open surgical approach. This is especially
important for patients with anticipated delayed wound healing (chronic renal failure, hyperadrenocorticism,
hypoproteinemia). With smaller incisions, it has been shown time and time again that postoperative pain is
decreased.3-5,20 This has been shown in human surgery as well as veterinary surgery based on visual analog
scores, serum cortisol levels, blood glucose levels, accelerometers and direct pressure tolerance. Smaller
incisions also take a shorter amount of time to close.
Laparoscopy offers the advantage of significant magnification to the surgeon. This offers both enhanced detail
of the organs being observed but also improved visualization of tissue planes when dissecting between vital
structures. Certain dyes (indocyanin green) can be utilized to highlight certain structures introperatively with
the appropriate video systems.
20
Laparoscopy can be both diagnostic and therapeutic. True abdominal and thoracic explores are possible with
very little patient morbidity compared to open laparotomy/thoracotomy. This can be performed initially to
determine if surgery is warranted prior to conversion to a traditional open procedure or performing a
laparoscopic/thoracoscopic procedure. Operation times can be shortened for some procedures with
laparoscopy compared to open procedures. Once proficient in laparoscopy, surgical times end up being
similar.
Clients are asking for this modality more and more with the increased use in human medicine. People want
the same options for their pets that they are offered. Clients tend to appreciate the smaller scar line. Because
of smaller incision sites, there has been shown to be a decreased risk of surgical site infections for clean
contaminated minimally invasive surgeries. Because of this, antibiotics are rarely used outside of the
perioperative period.
Detriments
There is a steeper learning curve for laparoscopic surgery due to the use of long instruments through small
channels. This causes hand movements to be awkward initially. For single incision laparoscopy (SILS, Covidien
Medtronic, MN), instruments are positioned very close and can cross over within the body cavity. This has led
to the development of articulating and roticulating instruments which add additional hurdles to overcome.
There is a loss of tactile sensation (haptic feedback) with long metallic instruments that you don’t have with
open surgery. Typically, an assistant is needed to manipulate the camera which can make laparoscopy
application in a general practice more difficult. This leads to no personal bubble by any means. Additional
difficulty comes from inherent monocular vision associated with a camera screen (That being said, a threedimensional camera system has recently become available). Remember, laparoscopy strives to transfer
discomfort away from the patient and inherently transfers it to the surgeon.
Equipment cost can be significant (See below). Unfortunately, this does translate into higher costs for our
customers. Interestingly, as our clients become more informed, they are willing to pay the extra cost in most
cases for the more rapid recovery. This was documented in one study where 90% of clients polled preferred
laparoscopic approaches to surgery if available and 78.3% of clients polled would pay between $800-$2000
more over a traditional surgical approach.21 While operating time can be reduced in many cases, it is typically
prolonged initially when first learning. The decreased postoperative morbidity of the patient still outweighs
the increased surgery time in my eyes.
Surgeon skills
The basic skills necessary for any new laparoscopist are ambidexterity, hand-eye coordination, instrument
accuracy, and determining a sense of depth.2 This all stems from the fact that you are utilizing monocular
vision in a tight space with long instruments working against a fulcrum. It is important to be precise in
movement because any small movement out of the body can be translated into a large one within the
abdomen. Additionally, any instrument out of your visual field within the abdomen can become a liability if it
contacts an unintended organ. Communication between the laparoscopist and the camera operator is
paramount.
Training prior to surgery is key to efficient operating time and patient outcome in the operating room. A study
from 2014 showed that on average it took a surgeon ~80 laparoscopic ovariectomies to become “proficient”
at the procedure.6 Proficiency was defined as a reduction in complications. Minimally invasive training in the
veterinary field has historically been absent in veterinary schools with the exception of surgery residencies.
This stems from the shift away from working with research animals, the limited availability and “shelf life” of
21
cadavers, and funding. In human medical surgery residencies, there is now a requirement for simulator based
laparoscopic surgery training which has been shown to translate into proficiency in the operating room.
Research is being performed in veterinary training with simulators which mirrors these results. Like any task,
practice helps fine tune the fundamental skills associated with completing it.
Training simulators are a great way to obtain practice. This varies from box simulators (mass produced and
homemade), virtual reality, and augmented reality (hybrid VR). An example of an inexpensive homemade box
trainer uses a plastic tote container with a laptop placed on top. A webcam connected via USB adapter is
mounted within the box trainer and instrument ports are placed through the top of the box to execute
exercises inside the box. Common core exercises include peg transfer, pattern cutting, ligature loop
placement, extra- and intracorporeal knot tying.2 Variable simulators exist in academic settings that can
range in cost up to $90,000. Multiple studies have shown that human and veterinary surgeons who play
and/or train with recreational video games are the fastest to adopt laparoscopic surgical skills.7-13
Formal training programs for veterinarians are offered through Colorado State University as well as University
of Georgia and range from $1700-2000. These are set up as basic and advanced courses. Additional courses
for surgery residents and veterinary surgeons are available at the annual ACVS meetings.
Equipment
The most basic laparoscopy set up includes a light source, light-transmitting cable, endoscope, camera, and
monitor. A carbon dioxide insufflator is also essential for most laparoscopy. With thoracoscopy, insufflation is
not necessary and can actually be harmful from a cardiovascular standpoint. Because of the added
equipment, a larger operating room is often necessary for minimally invasive surgery (MIS). Keep in mind that
there is the need for a laparoscopy tower, anesthesia tower, operating table with room for long instruments,
and room for the surgeon and assistant to move about the room.
An HD laparoscopy tower with insufflator and basic instruments can approach $100,000 in cost however there
are refurbished and used towers that can be acquired through multiple resources for a considerable discount.
More compact systems (Telepak Vet X LED, Storz) exist that incorporate the light source, monitor, computer,
and insufflator into one compact package which ends up costing approximately $50,000 but has different
quality compared to the HD systems (Information provided through correspondence with Storz
representative). A recent prospective study14 showed that introduction of rigid laparoscopy into a general
practice can be feasible and lucrative.
An entry level laparoscopy pack should include a 5mm 0-degree telescope, a light cable, insufflator tubing,
endoscopic video camera, a Veress needle (if desired for pneumoperitoneum creation), three 5-mm cannulas
with two sharp trochars and one blunt-tipped trochar, one to two 10-mm cannulas with one sharp and one
blunt trochar, two reducer caps (from 10mm to 5mm), 10-mm double action Babcock forceps, 5-mm double
action babcock forceps, two 5-mm Kelly or Maryland grasping forceps, 5-mm Metzenbaum scissors, 5-mm cup
biopsy forceps, 5-mm punch biopsy forceps, a 5-mm palpation/measurement probe, and an ovariectomy
hook.2 For more advanced surgeons, right angled dissecting forceps, needle drivers (two pairs), a fan retractor,
a 5-mm 30-degree telescope, bipolar vessel sealing equipment (ligasure, Covidien Medtronic, MN), miniature
equipment and telescope (3mm), and single-port access equipment and instruments can be added. Additional
equipment that can be helpful are specimen retrieval bags, suction/irrigation equipment and wound
retractors for lap-assisted surgery. Laparoscopic clip applicators and stapling devices are extremely helpful for
advanced procedures like cholecystectomies, nephrectomies, and lung lobectomies.
22
Complications
During laparoscopy, it is important for the anesthetists to remain aware of the patient status as
pneumoperitoneum is established and maintained. By insufflating the abdomen to 10-15mmHg, hepatic,
renal, and mesenteric blood flow is decreased. Between 16-20mmHg, portal venous, mesenteric, and celiac
venous blood flow is decreased. Above 20mmHg, renal blood flow and GFR decrease by greater than 75% and
anuria occurs.2 It is important to maintain as low of pneumoperitoneum pressure as possible during
sustained surgeries. I typically aim for 7-10mmHg. Cats are especially susceptible to the hemodynamic effects
of pneumoperitoneum. Case et al. showed that with even low pressure pneumoperitoneum (6mmHg) there
was significant rise in venous partial pressure of CO2 (PvCO2) and heart rate with a concurrent decrease in
stroke volume while maintaining cardiac output.15 These signs were worsened with the duration of the
procedure but resolved with completion of the surgery. Based on this information, cats should be operated
on when a laparoscopist is proficient with canine patients who are more accommodating to the effects of
pneumoperitoneum.
In humans, low pressure pneumoperitoneum reduces the incidence of postoperative “shoulder-tip” pain
which we have not yet recognized in veterinary patients.16 Shoulder-tip pain (Kehr's sign) is a classic example
of referred pain wherein irritation of the diaphragm during pneumoperitoneum is signaled by the phrenic
nerve as pain in the area above the collarbone. This is because the supraclavicular nerves have the same
cervical nerves origin as the phrenic nerve, C3 and C4.
Patient positioning with head down (Trendelenberg positioning) or head up (reverse Trendelenberg or Fowler
positioning) can also lead to respiratory and hemodynamic compromise.
The pertinent risks of laparoscopic surgery include vascular and visceral injury. The rate of vascular injury is
low but something that should always be discussed with owners prior to surgery. Vascular injury risk is the
highest upon initial entry into the abdomen. The risk of vascular injury is slightly higher for a closed technique
(Veress and direct trochar insertion) at 0.04% versus an open (Hasson) technique at 0.01%. 17 Indications to
convert include hemorrhage that cannot be corrected laparoscopically, hemodynamic compromise in the face
of hemorrhage, or progressive retroperitoneal hemorrhage. Visceral injuries can occur with either technique
however with the open technique, the problem is often immediately identified and can be corrected. History
of previous abdominal surgery makes the likelihood of adhesions higher and thus a greater risk for inadvertent
visceral injury. Injuries to the small bowel or large bowel need to be corrected while injuries to the stomach
can often be treated conservatively.
Thermal burns can occur with any electrosurgical equipment but is highest with monopolar equipment.
Examples of burns include direct coupling (contact with unwanted tissue leading to burn), indirect coupling
(leaking in an insulation barrier allows energy to escape and contact tissue), and capacitive coupling (build-up
of energy between two conducting substances separated by an insulating substance. This is most common
with hybrid plastic/metal cannulas and can be reduced with full plastic or full metal cannulas). Thermal
injuries are often not identified at the time of initial surgery and show up later postoperatively as flank
bruising or burns.
23
Relative anatomic contraindications for MIS surgery (Adopted from Frannson et al.)
Obesity
Reoperative abdomen or thorax (Adhesions)
Aberrant anatomy
Cirrhosis, portal hypertension (vascular varicosities)
Small bowel obstruction (decreased working space with dilated bowel)
Septic peritonitis (inability to find source as well as increased risk of bacterial translocation
into circulation with insufflation
Disseminated abdominal cancer (port site metastasis extremely rare)
Relative physiologic contraindications for MIS surgery (Adopted from Frannson et al.)
Pulmonary disease (hypercarbia and hypoventilation)
Cardiovascular disease (decreased pre-load and cardiac output with insufflation)
Intracranial disease
Coagulopathy
Pregnancy
Shock
Procedures
Diagnostic laparoscopy of the GI tract (beginner to intermediate)
● Typically performed in a combination of laparoscopy and lap-assisted techniques
● The gastric antrum, caudal duodenal flexure, and ileocecocolic junction are difficult to evaluate
externally due to their deep attachments therefore they are typically visualized and palpated
laparoscopically
● The small intestines can be exteriorized through a wound retractor (Alexis, Allied Medical) and
explored manually by palpation in a hand-over-hand technique
Laparoscopic-assisted gastrotomy, enterotomy, enterectomy, and anasatamosis (beginner to advanced)
● Very helpful to have an array of different sized radial wound retractors (Alexis, Applied Medical)
● Section of bowel is extFeriorized or brought to the body wall surface with stay sutures
● Surgery is performed outside of the body wall
Laparoscopic-assisted gastrostomy or enterostomy tube placement (beginner)
● The respective segment of the GI tract is grasped under laparoscopic guidance and pulled to the body
wall (2 port technique)
● The port with the instrument grasping the bowel is extended into a mini-laparotomy is performed and
the feeding tube is placed through a stab incision in the affected segment of bowel
● A purse string and four-quadrant pexy is performed to secure the segment of the GI tract to the body
wall
Laparoscopic or laparoscopic-assisted gastropexy (intermediate)
● For total laparoscopic gastropexy, two laparoscopic needle drivers are necessary
● Barbed suture (V-Loc or Quill) makes the total laparoscopic procedure much easier because
extracorporeal knots are not required and the suture maintains tissue apposition when tightened
● Total laparoscopic is more technically demanding but has a more cosmetic outcome
● Lap-assisted gastropexy often leads to a transient seroma in the paramedian incision site
24
Laparoscopic and laparoscopic-assisted splenectomy (intermediate)
● Important case selection (no peritoneal effusion, masses less than 6cm in diameter, no massive
splenomegaly)
● Reported risk includes hemorrhage with manipulation of the spleen
● Complication rate reported at 15.5% for laparoscopic splenectomy compared to 26.6% in traditional
open splenectomy based on large meta-analysis
Liver biopsy and cholecystocentesis (beginner)
● Can be performed through a single-port technique (SILS or 10mm operating scope) or multiport
● Very low complication rate even in patients with coagulopathy or ascites
● Biopsy quality is excellent
Laparoscopic cholecystectomy (intermediate to advanced)
● Low complication rate with appropriate case selection
● Cases with no elevation in total bilirubin
● In humans, intraoperative cholangiograms are performed under fluoroscopic guidance which allows
flushing of the common bile duct and proving patency in bilirubinemic patients (stay tuned for
veterinary medicine)
● Check coagulation status
● A clip applicator makes the procedure easier and negates the need for extracorporeal knot tying
● Vessel sealing device has not been verified for use on the cystic duct
Laparoscopic adrenalectomy (intermediate to advanced)
● A vessel sealing device is highly recommended
● Low complication rate with appropriate case selection
● Invasion into phrenicoabdominal vein is okay; caval invasion is contraindicated.
● No difference in risk for postoperative thromboembolism
● Reduces risks associated with hyperadrenocorticism and delayed wound healing
Laparoscopic renal biopsy (intermediate)
● Indications include progressive proteinuria or acute kidney injury of an unknown cause
● Chronic severe kidney disease will likely not benefit from a renal biopsy as the progression is
predictable
● Other contraindications include uncontrolled systemic hypertension, hydronephrosis, uncontrolled
pyelonephritis, cystic renal disease, coagulopathy
● Biopsies obtained from renal cortex only to avoid bleeding
● Biopsies should be analyzed by light, immunofluorescence, and electron microscopy by an experienced
nephropathologist
● In general, this is a safe procedure when performed laparoscopically however patients should be
monitored for postoperative hemorrhage
Laparoscopic ureteronephrectomy (advanced)
● Indications include primary renal neoplasia, hydronephrosis, chronic renal infection, renal dysplasia,
nephrolithiasis, and idiopathic renal hematuria
● Ideally assessment of the GFR of the contralateral kidney is warranted before removal (scintigraphy or
contrast-enhanced CT)
● This is an advanced procedure for doctors with extensive open nephrectomy experience as well as
extensive laparoscopy experience
● A vessel sealing device or clip applicator is highly desired for this procedure
25
Laparoscopic-assisted cystoscopy and “percutaneous cystolithotomy” (intermediate)
● Indicated for urolith removal as well as polyp removal
● Preferred technique for pediatric humans since transurethral removal is not possible with small
urethral diameter
● Contraindications to this technique are large stones that would require a larger incision to be made in
general
● Complete stone removal in 96% of cases due to direct visualization and dilation of mucosal folds
whereas traditional cystotomy leads to 10-20% retained stones18,19
Laparoscopic ovariectomy, ovariohysterectomy, hysterectomy (beginner to intermediate)
● Ovariectomy is just as effective at sterilization as OHE
● Vessel sealing device is highly desirable for this procedure
● Single- versus multi-port techniques exist
● Tilt tables are useful
● OHE can be performed safely for mild uterine horn pathology (mucometra and pyometra)
● Hysterectomy can be performed in a lap-assisted technique to retain ovary if desired
Cryptorchidectomy and vasectomy (beginner)
● Highly effective as a laparoscopic technique
● Single- or multi-port technique exist
● Vessel sealing device is highly desired for this procedure
● Palpation of the inguinal region prior to surgery is recommended
● The inguinal ring is visualized at the time of surgery (visualization of a single structure (gubernaculum)
confirms abdominal cryptorchid; visualization of two structures (ductus deferens and testicular
artery/vein) confirms that the testicle has completed migration into the inguinal canal and conversion
to inguinal approach is typically necessary
● Vasectomy involves sealing and dividing the ductus deferens as it exits the inguinal canal
● Can be performed at the time of and in combination with other procedures (gastropexy)
Diaphragmatic and inguinal herniorrhaphy (advanced)
● Useful for acute diaphragmatic hernias
● Low pressure (3mmHg) insufflation utilized due to open thoracic cavity
● Barbed suture is highly desired as well as laparoscopic needle drivers
● Liver and spleen can be the most difficult organs to reduce
● May need to combine thoracoscopic and abdominal laparoscopy to both push and pull simultaneously
26
References
1. Mishra, RK. Chronological advances in minimal access surgery. Textbook of Practical Laparoscopic Surgery. 2 nd ed. Jaypee
Brothers Medical Publishers pp 3-8.
2. Frannson BA, Mayhew PD. Small Animal Laparoscopy and Thoracoscopy. Wiley Blackwell.
3. Hancock RB, Lanz OI, Waldron DR, et al. Comparison of Postoperative Pain After Ovariohysterectomy by Harmonic ScalpelAssisted Laparoscopy Compared with Median Celiotomy and Ligation in Dogs. Veterinary Surgery 2005;34(3):273-282.
4. Devitt CM, Cox RE, Hailey JJ. Duration, complications, stress, and pain of open ovariohysterectomy versus a simple method
of laparoscopic assisted ovariohysterectomy in dogs. JAVMA 2005; 227(6):921-927.
5. Gauthier O, Holopherne-Doran D, Gendarme T, et al. Assessment of postoperative pain in cats after ovariectomy by
laparoscopy, median celiotomy, or flank laparotomy. Vet Surgery 2015;44:O23-O30.
6. Pope JFA, Knowles TG. Retrospective Analysis of the Learning Curve Associated with Laparoscopic Ovariectomy in Dogs and
Associated Perioperative Complication Rates. Vet Surgery 2014; 43:668-677.
7. Badurdeen S, Abdul-Samad O, Story G, et al. Nintendo Wii video-gaming ability predicts laparoscopic skill. Surgical
Endoscopy 2010; 24(8):1824-1828.
8. Boyle E, Kennedy AM, Traynor O, et al. Training surgical skills using nonsurgical tasks- can Nintendo Wii improve surgical
performance? Journal Surgery Education 2011;68(2)148-154.
9. Adams BJ, Margaron F, Kaplan BJ. Comparing video games and laparoscopic simulators in the development of laparoscopic
skills in surgical residents. Journal Surgery Education 2012;69(6):717-717.
10. Grantcharov TP, Funch-Jensen P. Can everyone achieve proficiency with the laparoscopic technique? Learning curve
patterns in technical skills acquisition. American Journal of Surgery 2009;197(4):447-449.
11. Shane MD, Pettitt BJ, Morgenthal CB, et al. Should surgical novices trade their retractors for joy-sticks? Videogame
experiences decrease the time needed to acquire surgical skills. Surg Endosc 2008;22(5):1294-1297.
12. Towle Millard HAMR, Freeman LJ. Association between Wii video gaming ability, 3-D spatial analysis skills, and laparoscopic
performance and the level of surgical interest and gender in third year veterinary students. Presented at the 11 th Annual
Scientific Meeting of the Veterinary Endoscopy Society. Florence, Italy, May 15-17 2014.
13. Rosser JC, Lynch PJ, Cuddihy L, et al. The impact of video games on training surgeons in the 21 st century. Arch Surg
2007;142(2):181-186.
14. Jones K, Case JB, Evans B, et al. Evaluation of the economic and clinical feasibility of introducing rigid endoscopy and
laparoscopy to a small animal general practice. JAVMA 2017;250(7):795-800.
15. Shih AC, Case JB, Coisman JG, et al. Cardipulmonary Effects of Laparoscopic Ovariectomy of Variable Duration in Cats. Vet
Surgery 2015;44:O2-O6.
16. Sarli L, Costi R, Sansebastiano G, et al. Prospective randomized trial of low-pressure pneumoperitoneum for reduction of
shoulder-tip pain following laparoscopy. British Journal of Surgery 2000; 87(9): 1161-1165.
17. Malloy D, Kaloo PD, Cooper M, et al. Laparoscopic entry: a literature review and analysis of techniques and complications of
primary port entry. Aus N Z J Obstetrics Gynaecology 2002; 42(3):246-254.
18. Lulich JP, Osborn CA, Thumchai R, et al. Management of canine calcium oxalate urolith recurrence. Compendium Continuing
Education Practice 1998; 20(2):178.
19. Grant DC, Harper TAM, Werre SR. Frequency of incomplete urolith removal, complications, and diagnostics imaging
following cystotomy for removal of uroliths from the lower urinary tract in dogs: 128 cases (1994-2006). JAVMA 236(7):736766.
20. Walsh PJ, Remedios AM, Ferguson JF, et al. Thoracoscopic Versus Open Partial Pericardiectomy in Dogs: Comparison of
Postoperative Pain and Morbidity. Veterinary Surgery 1999;28(6):472-479.
21. Buoute NJ. Client and referring veterinarian perceptions about laparoscopy in an urban setting. Presented at the 13 th
Annual Scientific Meeting of the Veterinary Endoscopy Society. Jackson Hole, Wyoming, June 2016.
27
Cell-based model of coagulation: a thromboelastographic analysis
Seung Yoo MS MBA DVM DACVP (Clinical Pathology)
Seattle Veterinary Specialists – BluePearl
Kirkland, WA
Overview of hemostasis
Hemostasis is an essential protective process that acts to prevent blood loss by providing a mechanical seal on
the vascular system. This process involves a complex and dynamic response that results in a thrombus. Under
normal physiologic conditions, there are many known (and likely unknown) well-regulated mechanisms that
regulate this thrombus formation and its eventual dissolution. Both cellular and protein components participate
in an interlinked meshwork of relationships that can ultimately result in a phenotype between uncontrolled
bleeding and pathologic thrombosis. A thorough understanding of these relationships is vital to anticipating the
clinical consequences that can occur due to dysfunction of these pathways. A list of key molecules for
hemostasis is provided in Table 1.
Blood needs to flow
Vascular endothelium plays many roles besides merely acting as a physical barrier between blood and
extravascular tissues. Endothelium plays a critical role in coagulation and fibrinolysis, regulating blood pressure
with vasodilation and vasoconstriction, leukocyte translocation and thus inflammation, and lipoprotein
trafficking. Undisrupted vascular endothelium is naturally anti-coagulant. There are numerous anticoagulants
that prevent or delay uncontrolled thrombus formation. Heparan sulfate glycosaminoglycans (HSPGs) are
expressed by endothelial cells. These large molecules contain a neutral membrane charge which is unable to
support coagulation reactions. Antithrombin (AT) is bound to endothelial cells via interactions with these
surface heparans. This complex inhibits several circulating coagulation factors in both the intrinsic and extrinsic
pathways. Free AT has very weak inhibitory effects on the coagulation factors. This molecular interaction is the
pharmacologic basis for anti-coagulant heparin therapy.
Tissue factor pathway inhibitor (TFPI) is the key regulator of the extrinsic pathway. Endothelium expresses
tissue factor pathway inhibitor (TFPI) which prevents thrombin generation by inhibiting factor Xa and TF-FVIIa
complex. Endothelial cells also express nitric oxide, adenosine diphosphatase (ADPase), and PGI2 (prostacyclin)
in response to several stimuli. All three molecules inhibit platelet activation with nitric oxide and PGI2 resulting
in vascular relaxation.
Thrombomodulin is also expressed by intact vascular endothelium. Thrombomodulin binds to thrombin and
limits coagulation by both deactivating this molecule and by activating other anticoagulant molecules such as
protein C and TFPI. Thus, any circulating thrombin is rapidly deactivated by endothelial bound thrombomodulin,
localizing thrombin activity to vascular damage.
Blood flow needs to cease
Primary hemostasis - Upon disruption of the endothelial barrier, vWF is released which plays a key role in
mediating platelet adherence via interaction with the platelet receptor Gp1b. vWF binds to subendothelial
collagen and activates bound platelets. During subsequent platelet activation, platelet aggregation mediators
28
such as thromboxane (TXA2) and adenosine diphosphate (ADP) further activate nearby platelets leading to the
beginning of a platelet plug. Once activated, platelets also express functional fibrinogen receptors that are
derived from the platelet integrin glycoprotein IIbIIIa receptor. This results in further interplatelet binding and
aggregation resulting in a relatively weak physical barrier to blood loss.
Secondary hemostasis (Figure 1) - After endothelial injury, tissue factor (TF) is exposed on subendothelial
collagen, activating the extrinsic coagulation pathway. TF binds to FVII, activating this pathway. FVIIa activates
FX to FXa which subsequently leads to formation of thrombin FIIa. FIIa then catalyzes the reaction from
fibrinogen to fibrin. In the traditional cascade model of coagulation, the intrinsic pathway can also lead to
formation of fibrin. The formation of FXIIa on activated platelet surfaces initiates the intrinsic pathway. FXIIa
promotes the formation of FXIa which subsequently promotes the formation of FIXa. FIXa binds with FVIIIa to
form the FIXa-FVIIIa enzyme complex, also referred to as ‘tenase’ due to its substrate, FX. FXa binds with FVa
to form the prothrombinase complex, which catalyzes the formation of thrombin (FIIa) from prothrombin (FII).
Thrombin then cleaves fibrinogen to form fibrin, forming the intercellular ‘glue’ that meshes the platelets
together within the platelet aggregate. This results in a stronger physical barrier to blood loss.
Thrombin also catalyzes the formation of FXIIIa from FXIII. After fibrin is polymerized into an insoluble dimer,
crosslinking forms lateral bonds, strengthening the fibrin meshwork. FXIIIa promotes this crosslinking, forming
a stable clot.
Figure 1: Traditional cascade model of hemostasis
Blood needs to flow again
After clot formation, blood flow must be restored by fibrinolysis. Fibrinolysis is mediated by several activators,
inhibitors, and receptors, all of which have controlled roles. Plasminogen is a pro-enzyme that circulates in
plasma which is a precursor to plasmin. Plasminogen is enzymatically cleaved into plasmin by tissue
plasminogen activator (tPA) and urokinase plasminogen activator (uPA). It is thought that tPA is the primary
plasminogen activator within the vasculature and uPA is the primary plasminogen activator within extravascular
tissue. Plasmin then cleaves fibrin to form fibrin degradation products, including D-dimers. Just as clot
29
formation is carefully controlled, fibrinolysis is primarily controlled by plasminogen activator inhibitor 1 (PAI-1).
PAI-1 binds to tPA and uPA, preventing their actions. α2-antiplasmin binds to plasminogen, preventing its
interaction with fibrin, thus preventing fibrinolysis. Thrombin activatable fibrinolysis inhibitor (TAFI) inhibits
fibrinolysis by removing binding sites for plasminogen and its activators, tPA and uPA.
The cell based model of hemostasis
The development of the cell based model of coagulation was prompted by recognized deficiencies in the
traditional cascade model of coagulation. For example, some mammalian species (whales, dolphins) do not
express FXII which raises some doubt about the absolute necessity of this factor. Also, deficiencies in FXII are
not associated with bleeding in mice or humans, despite a significant prolongation in APTT time. Another
example highlighting the insufficiencies of the cascade model is hemophilia. Deficiencies of either FVIII
(hemophilia A) or FIX (hemophilia B) will result in moderate to severe bleeding despite the presence of an intact
extrinsic pathway. Hemophilia C (FXI deficiency) will result in variable bleeding in humans. Lack of FVII is
associated with mild to moderate bleeding despite the presence of an intact intrinsic pathway. While the
cascade model of coagulation may be useful for understanding the kinetics and enzyme interactions during
hemostasis in vitro, it is evident that this model is incomplete in describing the process of coagulation as it
occurs in vivo. Instead of considering the intrinsic and extrinsic pathways as separate redundant pathways that
interact independently with the common pathway, all three pathways are necessary for functional coagulation
to occur. The cell based model of hemostasis proposes two primary changes in evaluating coagulation: 1) tissue
factor is the primary physiologic activator of coagulation in vivo, and 2) coagulation requires cell surfaces for
regulation and localization. The following figures (2-4) diagrams the cell surface interactions of key players
leading up to fibrin formation. The cell based model of hemostasis is based upon three interacting phases,
initiation, amplification, and propogation.
Inititation
After vascular injury, TF is exposed on cells that generally reside in the extravascular space (Figure 2). Circulating
FVIIa binds to TF and this complex promotes the formation of more TF-FVIIa complex which, in turn, promotes
the formation of prothrombinase complex (Xa-Va). The subsequent small scale production of thrombin
activates localized platelets. Any FXa that is released from the cell surface is deactivated by circulating TFPI or
AT, limiting this process to TF at the cell surface. FIXa is also produced by TF-FVIIa complex.
Figure 2: Initiation
30
Amplification
Vascular wall damage also exposes sites for platelet adhesion (not pictured). Thrombin binding to these platelets
results in activated platelets, leading to conformational changes and release of granule contents, further
promoting the process of coagulation (Figure 3). Thrombin also activates surface bound FXI and FV to their
active forms. Circulating vWF-FVIII complexes are cleaved by thrombin, releasing vWF that promotes platelet
to platelet adhesion and further aggregation. The released FVIII is also activated by thrombin. After platelet
activation and production of FVa, FXIa, FVIIIa, and assembly of procoagulant complexes, thrombin can be
produced en masse.
Figure 3: Amplification
Propagation
FIXa, FXa, and FXIa have high affinity binding sites on platelets where it is thought that the following reactions
take place (Figure 4). FVIIIa-FIXa complex (tenase) and FXa-FVa complex (prothrombinase) assemble on the
platelet surface leading to large scale thrombin production. FVIIIa-FIXa complexes activate surface bound FX
where the resulting FXa can move into a complex with its cofactor FVa to produce the ‘thrombin burst’ that is
needed to form an effective fibrin clot. Circulating and platelet released fibrinogen is cleaved by thrombin to
form fibrin monomers that spontaneously polymerize to form fibrin polymers.
31
Figure 4: Propogation
This model explains the bleeding tendencies from deficiencies in FVIII, FIX, and FXI as these factors are required
for the generation of FXa, and subsequent production of thrombin, on TF bearing cell surfaces and platelet
surfaces. A better understanding of hemostasis using this model instead of the traditional cascade model has
spurred the development and use of viscoelastic point of care devices.
Viscoelastic devices provide in vitro evaluation of global coagulation in a whole blood sample, including the
beginning of clot formation to fibrinolysis. These devices are considered a better method of evaluating
hemostasis with the interaction of all cellular and clotting factor interactions in whole blood compared to
conventional coagulation assays. The time to clot formation, rate of formation, clot strength, and clot stability
can be evaluated, providing information on the ability of the clot to provide hemostasis. In human medicine,
TEG is used to provide valuable guidance during organ transplantation surgeries, cardiopulmonary bypass, and
trauma assessment. These instruments allow for monitoring of the different phases of hemostasis so that
specific administration of drugs or blood products can be used to address the primary hemostatic dysfunction,
potentially decreasing costs and morbidity/mortality. There are three primary viscoelastic techniques:
thromboelastograph (TEG), rotational thromboelastometry (ROTEM), and Sonoclot. These techniques use
different methods of measuring hemostasis and should not be used interchangeably. However, all three
methods can measure speed and strength of clot formation and fibrinolysis. For the purposes of this article,
only TEG will be discussed.
TEG evaluates the physical properties of a clot under low shear conditions using a cup that holds a blood sample
while rotating through a small angle (Figure 5). A pin is suspended from a torsion wire within the blood-filled
sample cup. When clotting occurs, the formation of fibrin and platelet aggregates between the pin and walls of
the cup causes movement of this pin. This movement is converted by a transducer into an electrical signal that
is translated into a graphical output over time. Typically, whole blood is used but modified plasma based TEG
32
has also been evaluated. The procedure can be performed with fresh whole blood with or without anticoagulant
sodium citrated blood. If performed with anticoagulant, a standard amount of CaCl 2 is added to the sample to
initiate the coagulation process. Samples can be run with or without activation. Kaolin or celite can be used to
activate the intrinsic pathway and tissue factor is typically used to activate the extrinsic pathway for a more
rapid analysis.
Figure 5
In veterinary medicine, TEG is utilized mostly in research settings although there are anecdotal reports of
promise in clinical applications. TEG has been used to monitor hemostasis in dogs with IMHA, parvovirus
infections, hyperadrenocorticism, and cancer. One of the main advantages of TEG is the ability to monitor
hypercoagulability, whereas most other traditional tests for coagulation only test for hypocoagulability.
However, there are no reports of using TEG to predict thrombosis. It is important to understand that
hypercoagulability as shown by TEG does not necessarily indicate pathologic dysfunction of the hemostatic
system. The degree of hypercoagulability has not been shown to correlate with risk of thrombosis. In fact, there
is some evidence that suggests that lack of hypercoagulability may be associated with thrombosis. There has
been an increase in recent research for utilizing TEG to monitor hemostasis with acute trauma, critical illness
associated coagulopathy, and anticoagulant drug therapy. There is much potential for future clinical research
as an improved understanding of hemostasis with the incorporation of cellular components will give us better
tools for diagnosis and treatment of hemostatic dysfunction. As the tests become more standardized and
equipment costs decrease, clinical application may become more common.
33
TEG parameters
A TEG tracing (Figure 6) provides an abundant of both qualitative and quantitative data. The commonly
used parameters are:
R (min) – value over time from the beginning of the tracing until the amplitude of deflection is 2 mm. This
value provides the time elapsed from the initiation of the run until clot formation begins. This value is influenced
by the coagulation factors in the extrinsic, intrinsic, and common pathways.
K (min) – the time from the end of R until the amplitude is 20 mm apart. This somewhat arbitrary value
signifies a standard level of clot firmness. K is influenced by the coagulation factors in the extrinsic, intrinsic, and
common pathways. This value is also influenced by platelet count and function, fibrinogen/fibrin, and
hematocrit.
α (degrees) – the angle formed with a tangential line starting from the end of R to the TEG tracing. This angle
is influenced by the same components as K; the coagulation factors in the extrinsic, intrinsic, and common
pathways. This value is also influenced by platelet count and function, fibrinogen/fibrin, and hematocrit.
MA (mm) – this is maximum distance between the two arms of the tracing. MA represents the maximum
strength of the clot. It is influenced by fibrinogen/fibrin, platelet count and function, thrombin, FXIII, and
hematocrit.
Figure 6: TEG tracing
CI (coagulation index) – given by the formula derived from a combination of all the above parameters.
CI = 0.1227(R) + 0.0092(K) + 0.1655(MA) – 0.0241(α) – 5.0220
A normal CI value ranges from -4.0 to 4.0. With values less than -4.0 representing a hypocoagulable state and
values greater than 4.0 representing a hypercoagulable state. This equation simplifies interpretation of
coagulation status but we lose the ability to evaluate the individual components of the tracing.
LY30, LY60 – this value denotes the percent decrease of the TEG tracing from MA from 30 or 60 minutes
respectively. This value represents rate of fibrinolysis.
34
G (dynes/sec) – this value is calculated from MA using the formula G=5000 x MA/(100-MA). This value is
thought to better represent the physical strength of the clot as this value increases exponentially with increased
MA.
Other parameters that are used less frequently include the following (Figure 7):
MRTG (dynes/cm2/s) – maximum rate of thrombin generation is determined from the first derivative of the
TEG curve. This corresponds to the steepest portion of the TEG tracing.
TMRTG (min) – time to maximum rate of thrombin generation is defined as the time interval observed prior
to maximum speed of clot growth.
TTG (dynes/cm2) – total thrombin generation is defined as the total area under the velocity curve during clot
formation.
Figure 7: Elastic modulus tracing in green
Extrinsic pathway
TF
FVII
Tissue Factor
Factor VII
Intrinsic pathway
FXII
Factor XII
FXII
FIX
FVII
I
Common
pathway
FX
FV
Pro
Fg
Fb
FXIII
Factor XI
Factor IX
Fibrinolysi
s
promoters
Fibrinolysi
s
inhibitors
Factor VIII
Factor X
Factor V
Prothrombin
Fibrinogen
Fibrin
Factor XIII
Anticoagulant
PLG
PLM
uPA
tPA
Plasminogen
Plasmin
Urokinase plasminogen activator
Tissue-type plasminogen activator
α2AP
PAI-1
TAFI
α2-antiplasmin
Plasminogen activator inhibitor-1
Thrombin
activatable
fibrinolysis
inhibitor
AT
TFPI
PC
PS
TM
PZ
Antithrombin
Tissue factor pathway inhibitor
Protein C
Protein S
Thrombomodulin
Protein Z
Table 1: Key molecules for hemostasis
35
Suggested readings
Abelson, A.L., O’Toole, T.E., Johnston, A., Respess, M., and de Laforcade, A.M. (2013). Hypoperfusion and acute traumatic
coagulopathy in severely traumatized canine patients: Coagulopathy and severe trauma. Journal of Veterinary Emergency and Critical
Care 23, 395–401.
Brainard, B.M., Goggs, R., Mendez-Angulo, J.L., Mudge, M.C., Ralph, A.G., and Wiinberg, B. (2014). Systematic evaluation of evidence
on veterinary viscoelastic testing Part 5: Nonstandard assays: PROVETS-Nonstandard assays. Journal of Veterinary Emergency and
Critical Care 24, 57–62.
Flatland, B., Koenigshof, A.M., Rozanski, E.A., Goggs, R., and Wiinberg, B. (2014). Systematic evaluation of evidence on veterinary
viscoelastic testing Part 2: Sample acquisition and handling: PROVETS - Sample handling. Journal of Veterinary Emergency and Critical
Care 24, 30–36.
Hanel, R.M., Chan, D.L., Conner, B., Gauthier, V., Holowaychuk, M., Istvan, S., Walker, J.M., Wood, D., Goggs, R., and Wiinberg, B.
(2014). Systematic evaluation of evidence on veterinary viscoelastic testing Part 4: Definitions and data reporting: PROVETS-Definitions
and data reporting. Journal of Veterinary Emergency and Critical Care 24, 47–56.
de Laforcade, A., Goggs, R., and Wiinberg, B. (2014). Systematic evaluation of evidence on veterinary viscoelastic testing Part 3: Assay
activation and test protocol: PROVETS-Activation and test protocol. Journal of Veterinary Emergency and Critical Care 24, 37–46.
McMichael, M. (2012). New Models of Hemostasis. Topics in Companion Animal Medicine 27, 40–45.
McMichael, M.A., and Smith, S.A. (2011). Viscoelastic coagulation testing: technology, applications, and limitations: Viscoelastic
coagulation testing. Veterinary Clinical Pathology 40, 140–153.
McMichael, M., Goggs, R., Smith, S., Wagg, C., Warman, S., and Wiinberg, B. (2014). Systematic evaluation of evidence on veterinary
viscoelastic testing Part 1: System comparability: PROVETS - System comparability. Journal of Veterinary Emergency and Critical Care
24, 23–29.
Palmer, L., and Martin, L. (2014). Traumatic coagulopathy-Part 1: Pathophysiology and diagnosis: Traumatic coagulopathy: Part 1.
Journal of Veterinary Emergency and Critical Care 24, 63–74.
Smith, S.A. (2009). The cell-based model of coagulation. Journal of Veterinary Emergency and Critical Care 19, 3–10.
36
Ureteral Obstructions: Diagnosis and Treatment Options
Danielle Pollio, DVM (Practice Limited to Emergency and Critical Care)
Seattle Veterinary Specialists
Kirkland, WA
Common presentations
Cats with ureteral obstruction typically present with non-specific signs (vomiting, lethargy, hiding, decreased
appetite, and weight loss).1 More severe signs such as oral ulcerations, weakness and anorexia are not typically
observed unless the patient is markedly azotemic. Signs of dysuria are not typically seen unless the patient has
concurrent bladder/urethral stones or urinary tract infection. Pain on palpation of the affected kidney(s) may
also be appreciated in patients with acute obstructions.1
Dogs with ureteral obstructions will often show signs of dysuria (incontinence, stranguria, hematuria, polyuria,
pollakiuria) and systemic signs (vomiting, decreased appetite, lethargy).1
Causes of ureteral obstruction
Ureteroliths
Stricture
Inflammation
Neoplasia
Iatrogenic (e.g. ligation of ureters)
Trauma
Diagnosis
On physical examination, cats will commonly have one enlarged, sometimes painful kidney and one small
kidney. In dogs, renal pain is more common, likely due to concurrent renal infection and inflammation.1 Pale
mucus membranes and a heart murmur are also commonly identified in cats with ureteral obstruction. 1
Abnormal biochemical findings in cats include azotemia (83%), anemia (48%), hyperphosphatemia (54%),
hyperkalemia (35%), hypocalcemia (22%) and hypercalcemia (14%).1 The degree of azotemia on presentation
does not appear to be associated with outcome if successful decompression is achieved. 2 On urine analysis,
crystals were documented in 29% of cats (amorphous and calcium oxalate crystals were most common).
Approximately 33% of cats have concurrent urinary or kidney infections based on positive urine or stone
culture.1 Over 98% of feline ureteroliths are composed of calcium oxalate; however, other stone types including
dried solidified blood calculi and struvite stones have been reported.3,4
In dogs, common biochemical abnormalities include azotemia (50%), thrombocytopenia (44%), and moderate
to severe neutrophilia.1 Approximately 77% of dogs also have concurrent pyelonephritis and cystitis based on
positive urine or stone culture.1
The combination of abdominal radiographs and abdominal ultrasound is the preferred method of diagnosis for
ureteral obstruction. Stone size, number, location and the presence of concurrent nephrolithiasis may be
documented with radiographs, whereas this information can be underestimated with ultrasound. 1 Nonradiopaque calculi or the presence of fecal material in the colon can obscure visualization of the ureter and
associated renal pelvis with abdominal radiographs.1
37
Ultrasound can be used to document hydroureter, hydronephrosis and help pinpoint the exact location of the
obstructive lesion. Bilateral ureteral obstructions are seen in 19% of cats and 12.5% of dogs. 1 Approximately
62% of cats and 50% of dogs had concurrent nephroliths.1 Identification of concurrent uroliths and obtaining
measurements of the renal pelvis help the clinician choose which treatment option is ideal for the patient.
Percutaneous antegrade pyelography, retrograde ureteropyelopgraphy and computed tomography can also be
used to help differentiate between partial or complete obstructions and may be used in cases with traditional
surgical intervention.1 The measurement of glomerular filtration rate may assist in the decision to treat
unilateral or bilateral obstructions or to perform a nephrectomy if absolutely indicated. 1
Medical management of ureteral obstructions
Medical management should be started immediately after diagnosis of ureteral obstruction, as most patients
are azotemic and also have concurrent chronic renal disease. Medical management alone has reported to be
effective in 17% of cats in one study and there are no reports in dogs.1 Although there is a small rate of success,
medical management should always be considered prior to more invasive interventions. Medical management
consists of IV fluid therapy, mannitol CRI for patients without cardiac compromise (assessed via thoracic
radiography, auscultation, and echocardiography), supportive medications (anti-emetics, antacid, and pain
medication) and broad-spectrum antimicrobial therapy if indicated. Amitriptyline, prazosin, tamsulosin,
verapamil and glucagon have been tried to promote ureteral smooth muscle relaxation and passage of calculi;
however, these are all anecdotal reports and no studies have shown a benefit of one treatment over another
for ureteral obstruction.1 The author’s preference is amitriptyline or prazosin (if no hypotension is present).
If the patient is unstable, or medical management is not successful in 48-72 hours, additional interventions
should be considered to avoid ongoing loss of renal function. Temporary interventions for ureteral obstruction
may include nephrostomy tube placement (for external renal drainage, elimination of excessive hydrostatic
pressure, and patient stabilization before a more permanent fixation), or dialysis (for patients with severe
hyperkalemia or life-threatening fluid overload).1
Surgical management of ureteral obstructions
Traditional surgical interventions for treatment of ureteral obstruction include ureterotomy, ureteral
reimplantation, ureteronephrectomy and renal transplantation.
Ureterotomy and ureteral reimplantation are the most commonly performed surgical techniques for treatment
of ureteral obstructions in dogs and cats.1 Complications include edema at the surgical site, recurrence of
ureteral obstruction from stones passing from the renal pelvis (occurred in 40% of cats in 1 study), stricture
formation, and urine leakage from the surgery site.1 More than 10% of cats that survived surgical complications
required a second surgical procedure during the same visit, and 30% of these patients were euthanized or died
due to serial complications.1 Despite these complications, survival rates were higher with surgical management
than with medical management alone.
Ureteronephrectomy is a less complicated surgical procedure than ureteral reimplantation, but as more than
50% of cats and 40% of dogs remain azotemic after treatment for ureteral obstruction, this procedure is not
recommended in order to preserve as much renal function as possible.1
38
Interventional management of ureteral obstructions
Interventional methods for treatment of ureteral obstruction include nephrostomy tube placement, ureteral
stenting, subcutaneous ureteral bypass placement, extracorporeal shock-wave lithotripsy (ESWL) and
percutaneous nephroureterolithotomy (PCNUL).
Nephrostomy tube placement requires fluoroscopy and ultrasound guidance and is typically a temporary
procedure to allow external renal drainage, elimination of excessive hydrostatic pressure and patient
stabilization before a more permanent procedure can be performed.1
Ureteral stenting has multiple benefits, including (1) bypass of ureteral obstruction, (2) passive ureteral dilation,
(3) decreased surgical tension on the ureter after/during surgery, (4) aiding in extracorporeal shockwave
lithotripsy and (5) prevention of migration of nephroliths that could result in future ureteral obstruction. 1 The
main type of ureteral stent used in veterinary medicine is an indwelling double pigtail ureteral stent.1 This type
of stent can remain in places for months to years if necessary and may be considered a longer-term treatment
option (i.e. >4 years) for various causes of ureteral obstruction in dogs and cats.1
Intraoperative complications of ureteral stent placement include ureteral tear, ureterotomy leakage, renal
pelvic rupture, advancement of the stent from the renal pelvis into the renal parenchyma and bladder stay
suture site leakage.2,5 Anesthesia-related complications in cats included bradycardia (22%), hypotension (41%),
and hypothermia (87%).6
Immediate post-operative complications associated with ureteral stent placement in cats include uroabdomen
(8/117 cats in 1 study, 6/69 cats in another study) and subcutaneous leakage of urine around the nephrostomy
tube.2,5 Short-term complications (<1 week) include dysuria (pollakiuria or stranguria), which was typically selflimiting in 7-10 days or resolved with a weaning dose of glucocorticoids.5,2 Nonurinary complications included
congestive heart failure, pancreatitis, hepatic lipidosis and sepsis.5,2
Long-term complications (>1 month) included pollakiuria, stent migration, ureteritis, ureteral reobstruction,
stricture, pyelonephritis, tissue in-growth on the stent, chronic mild hematuria, ureterovesicular reflux and
urinary tract infections.1,7 Despite these complications, less than 10% of feline patients had serious adverse
events from ureteral stent placement.1,5,2 Approximately 95% of cats had an improvement in serum creatinine
after ureteral stent placement.1 Dogs have similar, but fewer reported complications than cats.1,5
Subcutaneous ureteral bypass (SUB) is used for treatment of feline ureteral obstruction when stent placement
is not feasible or has failed.1 This is an indwelling device that uses a combination of locking-loop nephrostomy
and cystotomy catheters, which are connected to a subcutaneous port. The device is placed with fluoroscopic
and surgical assistance. Once implanted, the device can be accessed for sampling or flushing as needed. The
port site is first clipped and prepared aseptically, then a Huber needle is used to penetrate the port. It is
important that only a Huber needle be used as other needle types will damage the port and potentially cause
device leakage. Ultrasound or fluoroscopy may be used to assess port patency. Cystocentesis should never be
performed without ultrasound guidance and if indicated, should be done on the side opposite the SUB device. 1
Complications reported in the literature for SUB placement include leakage from nephrostomy site and port site
and SUB occlusion.1,8 Additional complications include infection of the SUB device and hemorrhage. 1
Predictors significantly associated with a decreased overall survival for cats undergoing ureteral stent or SUB
placement included presenting BUN, overhydration during hospitalization and creatinine value prior to hospital
discharge.8
39
Extracorporeal shock-wave lithiotripsy (ESWL) delivers external shockwaves through a water medium directed
under fluoroscopic guidance in 2 planes. The ureteral stone will implode and the powder debris is left to pass
down the ureter into the bladder over 1-2 weeks.1 The procedure can be performed in ureteroliths <5 mm in
dogs and <3-5 mm in cats.1 ESWL is not typically performed in cats because the fragments are rarely <1 mm and
as the feline ureter is 0.3 to 0.4 mm in diameter this creates a high risk of ureteral obstruction.3 A ureteral stent
may be placed prior to ESWL to aid in stone debris passage, imaging and immediate relief of ureteral
obstruction.1
Percutaneous nephroureterolithotomy (PCNUL) is a procedure in which antegrade nephroureteroscopy is
performed via renal access. If a stone is identified in the ureter, a stone basket can be used to remove the stone
via the access sheath, or it can be broken with a laser lithotrite. 1 In feline patients this procedure is often
performed with surgical assistance so kidney can be manually stabilized and the access point be closed primarily,
avoiding the need for a temporary nephrostomy tube.3
Ureteroscopy is possible in large dogs (>20 kg). Ureteral access is gained via cystoscopy. A guidewire and flexible
endoscope are used to assess the ureter. Once the cause of obstruction is identified, the proper management
strategy (i.e. laser lithotripsy, balloon dilation for stricture) can be used to treat the problem. 1
Summary
Many new options are now available for treatment of ureteral obstructions in dogs and cats. There are inherent
risks with any surgical or interventional procedure, but with the proper patient selection, preparation, and postoperative care, these new modalities may provide significantly improved outcomes.
References
1. Berent AC. Ureteral obstructions in dogs and cats: A review of traditional and new interventional diagnostic and therapeutic
options. J Vet Emerg Crit Care. 2011;21(2):86-103. doi:10.1111/j.1476-4431.2011.00628.x.
2. Wormser C, Clarke DL, Aronson LR. Outcomes of ureteral surgery and ureteral stenting in cats: 117 cases (2006–2014). J Am
Vet Med Assoc. 2016;248(5):518-525. doi:10.2460/javma.248.5.518.
3. Berent A. New techniques on the horizon: interventional radiology and interventional endoscopy of the urinary tract
(’endourology’). J Feline Med Surg. 2014;16(1):51-65. doi:10.1177/1098612X13516572.
4. Palm CA, Culp WTN. Nephroureteral Obstructions: The Use of Stents and Ureteral Bypass Systems for Renal Decompression.
Vet Clin North Am - Small Anim Pract. 2016;46(6):1183-1192. doi:10.1016/j.cvsm.2016.06.008.
5. Berent AC, Weisse CW, Todd K, Bagley DH. Technical and clinical outcomes of ureteral. J Am Vet Med Assoc.
2010;244(5):559-576. doi:10.2460/javma.244.5.559.
6. Garcia de Carellan Mateo A, Brodbelt D, Kulendra N, Alibhai H. Retrospective study of the perioperative management and
complications of ureteral obstruction in 37 cats. Vet Anaesth Analg. 2015;42(6):570-579. doi:10.1111/vaa.12250.
7. Manassero M, Decambron A, Viateau V, et al. Indwelling double pigtail ureteral stent combined or not with surgery for
feline ureterolithiasis: complications and outcome in 15 cases. J Feline Med Surg. 2014;16(8):623-630.
doi:10.1177/1098612X13514423.
8. Horowitz C, Berent A, Weisse C, Langston C, Bagley D. Predictors of outcome for cats with ureteral obstructions after
interventional management using ureteral stents or a subcutaneous ureteral bypass device. J Feline Med Surg.
2013;15(12):1052-1062. doi:10.1177/1098612X13489055.
40
Antifibrinolytics: A new therapy for bleeding
Kelly Blackstock, MS, DVM, DACVECC
Seattle Veterinary Specialists
Kirkland, WA
Before jumping into drugs that influence bleeding, it is important to have an understanding of the basics of
coagulation and fibrinolysis. Traditionally, coagulation was taught in veterinary school as a “y” shaped model
of numbers that cascaded down with the end result of the conversion of fibrinogen to fibrin. We know now
that the endothelium is also a key player of this system, and that there is much more of a cell-based interaction
among the factors, platelets and endothelium. The primary role of healthy endothelial cells is to prevent
thrombus formation. They do so by inhibiting platelet activation via the secretion of nitric oxide (NO),
prostacycline (PG-I2), and ADP-dephosphatases. They also contain binding surfaces for heparin sulfate and
thrombomodulin, both of which inhibit activated clotting factors. Lastly, endothelial cells also secrete tissue
plasminogen activator (t-PA), whose activation of plasminogen cleaves any formed fibrin.
Should damage to the endothelial layer occur, the damaged cells secrete vonWillebrand factor, which leads to
platelet adherence and activation. Once platelets are activated, secondary factors enter into the cell-based
model of coagulation. The steps of this include initiation, amplification and propagation. The hallmark of the
initiation phase is the generation of a small amount of thrombin. Thrombin formation further activates
platelets, and factors, amplifying the substrates responsible for clot formation. The process is propagated by
the amplified platelets and coagulation factors, leading to a burst of thrombin. The end result is an insoluble
fibrin matrix known as a clot.
The final phase of coagulation is the removal of the clot a process known as fibrinolysis. The basic mechanism
of action for fibrinolysis involves the conversion of plasminogen to plasmin. Plasmin degrades fibrin into fibrin
degradation products (FDPs) and D-dimers. Plasminogen can be activated by t-PA and urokinase plasminogen
activator (u-PA). It can be inhibited by plasminogen activator inhibitor (PAI 1 and 2), thrombin activatable
fibrinolysis inhibitor (TAFI), and α2-antiplasmin. Aminocaproic acid (EACA) and tranexamic acid (TEA) are
synthetic lysine analogs. They are capable of inhibition of fibrinolysis by competitively binding to lysine-binding
sites to reduce the conversion of plasminogen to plasmin. At higher doses they are also capable of direct
inhibition of plasmin’s degradation of glycoprotein 1b receptors on platelets. This receptor is a key player for
the initiation and amplification phase of coagulation.
Historically, when presented with a patient with the complication of bleeding, the only treatment option
available has been the transfusion of blood products. These therapies, while lifesaving are not without cost.
Acquisition and storage of these products are expensive, and screening tests such as blood typing and crossmatch can increase the financial burden placed on an owner. Transfusion related complications are also well
documented, ranging from mild acute hypersensitivity reactions, severe hemolytic or anaphylactic reactions1,
immunosuppression, and transfusion-related lung injury (TRALI). In addition, recent studies have associated
increased blood product administration and risk of mortality in critically ill people, a finding that was
independent of severity of illness.2 For these reasons, having alternative options of therapy either in the
prevention or improvement in bleeding might prove beneficial.
Diagnosing problems with fibrinolysis is challenging, making identification of the patient populations at risk
difficult. Hyperfibrinolysis is one of the hallmarks of acute traumatic coagulopathy (ATC). This syndrome is
thought to be triggered by severe tissue injury, hypoperfusion and endothelial damage, leading to excessive
activation of Protein C and disseminated intravascular coagulation (DIC).3 Although research is lacking with ATC
41
in animals, a recent case report documented hyperfibrinolysis in a dog following presumptive vehicular trauma.
Likely for similar reasons, hyperfibrinolysis was found to be a component of coagulation abnormalities isolated
in dogs with spontaneous hemoperitoneum.5 Hepatobiliary disease has also been associated with increased clot
break down.6 Lastly, a subset of Greyhound dogs has been noted to bleed following surgical interventions.
Investigation failed to show any differences in primary or secondary hemostasis 7, and treatment with EACA
prevents this bleeding, suggesting that they, too, experience hyperfibrinolysis.8,9
The use of lysine analogs, EACA and TEA, has had documented benefit in people undergoing cardiovascular,
pediatric, and orthopedic surgeries, dental procedures and trauma. 10 In a Cochrane review evaluating 3,836
people in 53 trials undergoing elective surgery, TEA administration lead to a reduction in the requirement for
blood transfusions by a third as compared to controls.11 The CRASH-2 trial, a randomized placebo controlled
prospective study, evaluated the use of TEA in 20,211 adult trauma patients at risk of significant bleeding. As
compared to controls, patients who received TEA had a significantly lower all-cause mortality rate and bleedingassociated deaths.
There is evidence that dogs are hyperfibrinolytic compared to humans. This was first observed in studies of
pulmonary embolism in the 1960’s, in which experimentally induced emboli in dogs were found to resolve within
hours to days, rather than the months to years typically seen in human patients. Ultimately, creation of a canine
model of chronic pulmonary embolism was only possible after instituting treatment with TEA. 13,14 In addition,
when therapeutic doses of EACA and TEA were specifically compared between humans and dogs in a TEG model
of hyperfibrinolysis, dogs required much higher concentrations of both drugs to achieve the same level of
effect.15 Increase in fibrinolysis in dogs is thought to be attributable to increased secretion of plasminogen
activator by the pulmonary endothelium, increased plasminogen activator activity, and greater platelet
thrombolytic activity.16
As dogs are believed to be hyperfibrinolytic, as compared to humans, it may stand to reason that they, too, may
benefit from these drugs, perhaps even more so. As always the research on the veterinary side is limited, but
interest is growing and the data is mounting. The first known publication for the use of EACA in dogs was a case
series out of the Keio Journal of Medicine in 1959. In that report, oozing, created by activation of plasmin, from
surgical incisions made in research dogs, was subjectively stopped quicker with the use of EACA.17 More recently
EACA was evaluated in Greyhounds following surgical procedures. Lara-Garcia, et al., documented that roughly
30% of Greyhounds have been shown to have substantial bleeding roughly 36-48 hours following surgery for
gonadectomy.18 In a prospective study evaluating EACA use in this population of dogs, post-operative bleeding
was decreased by 20%.19 In another study looking at Greyhounds undergoing limb amputation, dogs that did
not receive EACA were 5.7 times more likely to bleed, and this was irrespective of plasma administration. 20 In
a more recent evaluation of the use of EACA in all cause bleeding, no correlations were found between EACA
dose and dose of packed red blood cells or the packed cell volume (PCV) prior to transfusion. 21 There is perhaps
even less data in the evaluation of TEA. There is only one study that retrospectively reviewed administration of
TEA to dogs with various bleeding disorders. Statistically, TEA treatment did not reduce the number nor the
dose of transfused blood products when compared to those not treated. 22 When given to healthy dogs, TEA
administration failed to create the anti-fibrinolytic properties as expected on thromboelastographic (TEG)
analysis.23 Anecdotally I would add, that clinically I use higher doses than those used in these studies. In
addition, although we have some limited data suggesting therapeutic concentrations15, we lack pharmacokinetic
data to validate the recommended administrative dose. All doses currently recommended have been
extrapolated from human medicine, or are based on opinion.
42
Side effects of EACA and TEA in people are similar and can include gastrointestinal upset, pain/muscle aches,
dizziness, headache, allergic reactions, fever, seizures, bradycardia, hypotension and thrombotic effects.
Although some of these may be difficult to detect in veterinary patients, the literature thus far has failed to
show dramatic adverse effects. In the retrospective evaluation of TEA on all causes of bleeding, no adverse
events were seen.22 When TEA was administered to healthy dogs, vomiting was noted, but only at higher
dosages.23 In 122 dogs treated with EACA for various bleeding disorders, only 3 experienced possible drug
related adverse effects. These included diarrhea, decreased appetite, and toenail loss. The latter was noted
with administration of the drug for 2 months.21
In summary, given the high cost of blood products, the potential risks associated with their administration, and
the fact that cost of veterinary care can drive some owners to the decision of euthanasia, antifibrinolytic drugs
may offer a novel, low cost solution for patients at risk of bleeding. As is always the case with veterinary
medicine addition research is needed into the areas of safety, efficacy and appropriate dosing.
References:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Prittie JE. Triggers for use, optimal dosing, and problems associated with red cell transfusions. Vet Clin North Am Small Animal Pract 2003; 33:
1261-1275.
Carless PA, Henry DA, et al. Transfusion thresholds and other strategies for guiding allogenic red blood cell transfusion. Cochrane Database
Syst Rev 2010; 10:CD002042.
Palmer, L, Martin LM. Traumatic coagulopathy-Part 1: Pathophysiology and diagnosis 2014; 24 (1): 63-74.
Yoo SH, Venn E, et al. Thromboelastographic evidence of inhibition of fibrinolysis after aminocaproic acid administration in a dog with acute
traumatic coagulopathy. J of Vet Emer Crit Care 2016: 26 (5): 737-742.
Fletcher DJ, Rozanski EA, et al. Assessment of the relationships among coagulopathy, hyperfibrinolysis, plasma lactate, and protein C in dogs
with spontaneous hemoperitoneum. J of Vet Emer Crit Care 2016; 26(1): 41-51.
Kananagh C, Shaw S, et al. Coagulation in hepatobiliary disease. J of Vet Emer Crit Care 2011; 21(6); 589-604.
Lara-Garci A, Couto CG, et al. Postoperative Bleeding in Retired Racing Greyhounds. J of Vet Inter Med 2008; 22: 525-533.
Marin LM, Iazbik C, et al. Retrospective evaluation of the effectiveness of epsilon aminocaprioic acid for the prevention of postamputation
bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003-2008). J of Vet Emer Crit Care 2012; 22(3); 332-340.
Marin LM, Iazbik C, et al. Epsilon Aminocaproic Acid for the Prevention of Delayed Postoperative Bleeding in Retired Racing Greyhounds
Undergoing Gonadectomy. Vet Surg 2012; 41: 594-603.
Kelmer E, Segev G, et al. Effects of intravenous administration of tranexamic acid on hematological, hemostatic, and thromboelastographic
analytes in healthy adult dogs. J of Vet Emer Crit Care 2015: 25(4): 495-501.
Henry DA, Moxey AJ, et al. Anti-fibrinolytic use for minimizing perioperative allogenic blood transfusion. Cochrane Database Syst Rev 2001;
(1): CD001886.
CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with
significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 377(9771): 1096-1101.
Moser KM, Guisan M, Bartimmo EE, et al. In vivo and post mortem dissolution rates of pulmonary emboli and venous thrombi in the dog.
Circulation 1973; 48: 170–178.
Moser KM, Cantor J, Olman M, et al. Chronic pulmonary thromboembolism in dogs treated with tranexamic acid. Circulation 1991; 83: 1371–
1379.
Fletcher D, Blackstock KB, et al. Evaluation of tranexamic acid and ε-aminocaproic acid concentrations required to inhibit fibrinolysis in plasma
of dogs and humans. Am J Vet Res 2014; 75: 731–738.
Lang IM, Marsh JJ, Konopka RG, et al. Factors contributing to increased vascular fibrinolytic activity in mongrel dogs. Circulation 1993;
87:1990–2000.
Okamoto S, Nakajima T, et al. A suppressing effect of aminocaproic acid on bleeding of dogs, produced with stimulation of plasmin in
circulating blood. Keio J Med 1959; 8(4): 247-266.
Lara-Garcia A, Couto CG, et al. Postoperative Bleeding in Retired Racing Greyhounds. J of Vet Med 2008; 22(3): 525-533.
Marin LM, Iazbik CM, et al. Epsilon Aminocaproic Acid for the Prevention of Delayed Postoperative Bleeding in Retired Racing Greyhounds
Undergoing Gonadectomy. Vet Sx 2012; 41: 594-603.
Marin LM, Iazbik CM, et al. Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation
bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003-2008). J of Vet Emer Crit Care 2012; 222(3): 332-340.
Davis M, Bracker K. Retrospective Study of 122 Dogs that Were Treated with the Antifibrinolytic Drug Aminocaproic Acid: 2010-2012. J Am
Anim Hosp Assoc 2016; 52: 144-148.
Kelmer E, Marer K, et al. Retrospective evaluation of the safety and the efficacy of tranexamic acid for the treatment of bleeding disorders in
dogs. Isr Vet Med J 2013; 68(2): 94-100.
Kelmer E, Segev G, et al. Effects of intravenous administration of tranexamic acid on hematological, hemostatic and thromboelastographic
analytes in healthy adult dogs. J Vet Emer Crit Care 2015; 25(4): 494-501.
43
Topsy, Turvy, Twisty, Turny: Untangling Imaging of Torsions and Volvuluses
Alaina H. Carr, DVM, DACVR
Seattle Veterinary Specialists
Kirkland, WA
Introduction
Torsions and volvuluses are uncommon events in veterinary patients, but when present, usually signify a surgical
emergency, with variable prognosis depending on the organ affected, chronicity of pathology, and degree of
vascular compromise. A torsion can be defined as twisting of a body part or organ around its own axis, and a
volvulus is defined as rotation of an organ around itself and the mesentery that supports it. However, in
veterinary medicine these terms can be used interchangeably. All of the diagnoses discussed below will often
present with non-specific clinical signs and have particular imaging findings that aid diagnosis.
Lung Lobe Torsion
Lung lobe torsion occurs when a lobe rotates longitudinally, usually at the hilus. This results in occlusion of the
pulmonary veins, lymphatics and bronchi but arterial blood vessels often remain initially patent, causing
congestion. It can occur in both dogs and cats but is more commonly recognized in the canine. Affected patients
have a wide age range and may present with respiratory signs (coughing, dyspnea, hemoptysis) or less specific
signs (lethargy, anorexia, pyrexia). There may be reduced heart/lung sounds on thoracic auscultation. Based on
the literature, underlying pulmonary pathology is less commonly present but underlying or concurrent pleural
pathology- especially chylous effusion- is more frequently identified. Potential predisposing factors include
trauma, chronic pleural disease, diaphragmatic hernia and pulmonary parenchymal disease but multiple case
reports are also characterized by spontaneous torsion with no known underlying cause. However, effusions may
develop after lung torsion, if not previously present, due to lung congestion and necrosis, as well as decreased
pleural lymphatic drainage. There appears to be a breed (or at least a body conformation) predisposition. Deep
chested dogs such as Afghans and Whippets have a tendency to torse their right middle lung lobe, thought to
be due to the long, narrow lung shape and loose attachments. However, barrel chested/small
chondrodystrophic dogs such as Pugs (overrepresented breed) can also present with lung lobe torsion, but tend
to torse their left cranial lung lobe, which can lack the mediastinal attachments of other lobes. Lung lobe torsions
are uncommon in cats but have been reported in the right cranial/middle lung lobes.
Radiographic hallmarks of lung lobe torsion include a vesiculated gas pattern (78%) which can progress in
severity on serial radiographic exams, atypical positioning and enlargement of the affected lung which can cause
a contralateral mediastinal shift or an ipsilateral shift due to atelectasis (likely earlier in disease progression),
pleural effusion (100%) which may be distributed more to the ispilateral side as the lung lobe torsion, and
bronchial narrowing, attenuation or abnormal positioning. The vesiculated gas pattern may occur secondary to
a variety of underlying causes, including bronchial tearing resulting in air trapping from a one-way valve effect,
necrosis or anaerobic infection. Air bronchograms may be present initially in affected lung, but often disappear
over time with progressive congestion and filling of the bronchus with fluid. Pneumomediastinum or
pneumothorax may occur secondary to bronchial tearing. Differentials for lung lobe torsion can include
pneumonia, contusion or coagulopathy, neoplasia, atelectasis, pulmonary thromboembolism, herniation,
pyothorax, inflammation secondary to a migrating foreign body, or pulmonary abscess. Computed tomography
(CT) findings are overall similar to those reported radiographically, but CT allows for more definitive evaluation
of bronchial position or attenuation. Lack of contrast enhancement in the affected lung has also been reported,
and in some cases CT allows for detection of underlying or concurrent intra-thoracic pathology that may not be
44
visible radiographically, but may change prognosis and long-term therapeutic recommendations. Most
importantly, pleural effusion does not represent a significant limitation on CT, compared to radiographic
examination.
Initial therapy is aimed at improving respiratory function with oxygen supplementation, removing pleural
effusion and cardiovascular stabilization as needed. Antibiotic therapy may be appropriate if there is suspicion
for secondary infection. Exploratory thoracotomy and lung lobectomy are the definitive treatment, and lung
lobe torsion is considered a surgical emergency with improved prognoses associated with prompt recognition
and treatment. Prognosis is moderate to fair for recovery but is partially dependent on any underlying
pathology.
Gastric Dilation-Volvulus (GDV)
Gastric dilation-volvulus is a well-recognized disorder resulting from rotation of the stomach, most commonly
approximately 180 degrees. Large breed dogs are over-represented; possible underlying causes and
predisposing have been discussed at length. Patients frequently present for signs of abdominal discomfort,
abdominal distension, retching behavior, anorexia or hypovolemic shock. However, many less-well recognized
variations of GDV have been reported as well, and identification of these variants, as well as differentiation of
GDV from other gastric pathology, is important both for diagnosis and prognosis.
A single right lateral radiograph of the abdomen has been reported to be the only view needed for diagnosis of
GDV in 90% of patients. Additional views may be needed in less straightforward cases, to more accurately
characterize other organs such as the spleen and small intestine, and to aid recognition of additional lesions
which may have prognostic value. Classic radiographic signs of a 180 degree gastric dilation with volvulus
include severe gas dilation of the stomach, with displacement of a gas-filled pylorus to the dorsal aspect of the
abdomen (as seen on a right lateral projection). Diffuse variable dilation of the small bowel is usually present
due to a combination of aerophagia and functional ileus (attributed to altered blood flow through mesenteric
vessels). Gas dilation of the esophagus is also frequently identified. The spleen is usually abnormally positioned
as well, and varies in size but is most frequently enlarged. Differentials for GDV include severe distension of the
stomach secondary to aerophagia, obstruction (pyloric or proximal small intestinal), or ‘food bloat.’ However in
these cases, the pylorus should still be normally positioned, and abnormal splenic position/small intestinal ileus
are usually not present. A left lateral projection of the abdomen is usually most helpful for assessment of the
pylorus when it is in a normal position.
Variations in the classic appearance of a GDV can include pneumatosis, other degrees of rotation such as 360
degrees, or gastric torsion. Gastric pneumatosis is visualized as a thin, irregular linear, curvilinear or cystic region
of gas within/parallel to the gastric wall, identified within the fundus or body. Pneumatosis may present in
conjunction with pneumoperitoneum, which can be iatrogenic if trocharization has occurred prior to
radiographic exam. Pneumatosis has not been shown to accurately predict gastric wall necrosis at surgery; if
present there is a 40% chance that the patient will require gastric resection but lack of pneumatosis does not
decrease the possibility of the presence of necrosis. Radiographic signs of 360 degree torsion include severe gas
distension of the stomach which may be relatively more severe than identified with 180 degree torsions, and
more variable visualization/definition of the pylorus. Dorsal or medial displacement of the descending
duodenum can be appreciated, and a “J” or “hook” shaped segment of gas filled bowel may be seen cranial to
the stomach, represented a gas filled duodenum wrapped around the cardia. Severe splenic displacement is
also appreciated. Gastric torsion occurs when the stomach twists on its long axis, causing compartmentalization
of the stomach into orad/fundic and aborad/pyloric segments. Variable displacement of the small bowel into
the cranial/dorsal abdomen may occur, and the spleen is displaced as well. Small intestinal ileus is usually
present.
45
Use of additional imaging modalities are usually unnecessary for diagnosis and may delay treatment
(exploratory laparotomy for de-rotation, possibly partial gastrectomy and/or splenectomy if indicated).
Colonic Torsion/Volvulus
Intestinal or colonic torsion occurs when the bowel twists on its long axis, potentially resulting in a mechanical
obstruction, as opposed to a volvulus which occurs when there is rotation about the mesentery (mesenteric
torsion is discussed below).
Colonic torsion/volvulus usually affects young to middle aged, medium and large breed dogs. Patients present
with non-specific GI signs, most commonly diarrhea although vomiting, mild abdominal distension, abdominal
pain, lack of feces and tenesmus have often been described. Clinical signs may be partially dependent on
whether the colon has undergone a torsion or a volvulus. Patients may also present in hypovolemic shock. There
may be a predisposition in patients with previous gastric dilation/volvulus or other disorders of gastrointestinal
motility. Inclusion of the cecum in the volvulus (ceco-colic volvulus) has been reported to involve the cranial
mesenteric artery; when this occurs there is impairment of blood flow to the small bowel as well, similar to the
etiology of a full mesenteric volvulus.
Radiographic signs of colonic torsion include severe fluid or gas dilation of the colon, altered colonic location,
and altered location/inability to visualize the ileocolic junction and cecum. Concurrent small intestinal ileus may
be identified. Splenic position is normal. Ultrasonographically, a fluid or gas-distended colon in an abnormal
position is again identified. Sites of luminal narrowing may or may not be visualized; the cecum and ileocolic
junction may be difficult to identify, or in an abnormal position. Additionally, mesenteric vessels can sometimes
be visualized in an abnormal position, with altered or diminished blood flow on Doppler interrogation.
Treatment involves exploratory laparotomy, with de-rotation of the colon. Partial colonic resection may be
needed if necrosis is identified. Prognosis varies depending on severity of colonic wall viability.
Mesenteric Volvulus
Mesenteric volvulus occurs when the intestine twists around the root of the mesentery, causing ischemia and
eventual necrosis due to occlusion of the cranial mesenteric artery. Mesenteric volvulus is differentiated from
intestinal torsion, which occurs when the bowel twists longitudinally or around a loop of itself. Patients present
with acute, rapid onset of severe cardiovascular compromise and abdominal distension; other signs such as
vomiting, retching and hematochezia have also been reported. This is most commonly reported in male, adult,
medium and large-breed dogs (German Shepherd dogs and English Pointers are more frequently reported).
Volvulus may involve part of the small bowel, the entire small bowel, and/or the cecum/proximal colon.
Concurrent gastric-dilation volvulus has been also reported. Mortality rates are high, reported to range from
42% to 100%. Risk factors have not been definitively identified, but conditions that have been hypothesized to
increase risk of torsion include exocrine pancreatic insufficiency, prior surgery (with or without adhesion
formation), intestinal parasitism or viral infections, foreign body obstruction, IBD, trauma,
pregnancy/parturition, and GDV.
Radiographic signs of mesenteric volvulus include severe, diffuse gas and fluid dilation of the small intestine,
usually with no indications of peristalsis. Serosal detail may be decreased due to peritonitis or fluid
accumulation. Similarly, ultrasound will also identify severe diffuse intestinal dilation with lack of motility.
Intestinal wall layering may be decreased with transmural thickening and loss of wall layer distinction. Doppler
interrogation will identify severe decreased or absent blood flow within the intestinal wall and mesenteric
46
vessels, and the position of the mesenteric vessels may be abnormal. Computed tomography has been shown
to be helpful in diagnosis of mesenteric volvulus as well; contrast-enhanced CT can detect a spiral shape and
narrowing of the arteries (“whirl sign”), venous congestion, as well as diffuse intestinal pathology.
Surgical intervention for de-rotation is required for treatment; prompt recognition and surgery may improve
outcome. Survival rates may be higher when rotation is less than 180 degrees and with rapid diagnosis/surgery.
Even if an adequate portion of the bowel remains viable (a significant portion of patients are euthanized at
surgery due to widespread intestinal necrosis), patients may succumb to reperfusion injury, and short bowel
syndrome can occur if massive intestinal resection is required.
Splenic Torsion
Torsion of the spleen occurs when the spleen rotates around, or there is disruption of the gastrosplenic and/or
splenocolic ligaments. It is an uncommon diagnosis when not associated with GDV, but constitutes a surgical
emergency. Splenic torsion most commonly occurs in large to giant breed dogs, usually with deep-chested
conformation such as German Shepherds and Great Danes. Males seem to be more commonly affected than
females. Definitive underlying etiology is unclear but GDV has been identified as a predisposing factor or comorbidity. Patient presentation is non-specific with signs of acute abdomen such as anorexia, lethargy, vomiting,
depression, retching and abdominal distension/discomfort, but patients have also been reported to present
with more chronic signs in cases of chronic, intermittent or partial torsion. Patients may also present with signs
of hypovolemic shock. A mass may be palpable, representing distension and abnormal positioning of the spleen.
Patients may have anemia or leukocytosis but overall bloodwork is usually non-specific. Abdominal fluid may be
a pure transudate, exudate or hemorrhagic.
Radiographic findings of splenic torsion include decreased serosal detail, enlargement and abnormal position of
the spleen (“reverse C”), lack of visualization of the splenic head in the left cranial abdominal quadrant and
cranial/dorsal/caudal displacement of intestine, but are often considered non-specific for splenic torsion when
trying to differentiate from other splenic pathology. Appearance of the spleen may be partially dependent on
chronicity of disease as well, and evaluation of the spleen can be challenging if concurrent peritoneal effusion
is present. Medial displacement of the descending duodenum and ascending colon is inconsistently identified.
On ultrasound, the spleen appears severely, diffusely enlarged with significant decrease in parenchymal
echogenicity. The parenchyma may be heterogenous as well, with linear regions of increased echogenicity
separating more hypoechoic areas. Positioning of the spleen and hilar vessels is abnormal and splenic veins may
be distended, with increased echogencity of the fat at the hilus as well (a hyperechoic “triangle” may be
identified between splenic veins). Vascular thrombosis can be identified and the spleen will have minimal to no
Doppler signal on vascular interrogation. Differentials include a splenic mass, splenic thrombosis which can
occur due to many underlying disease processes that results in a hypercoagulable state, and diffuse enlargement
of the spleen can occur without torsion due to neoplastic infiltration (particularly round cell neoplasia), severe
extramedullary hematopoiesis, systemic inflammation, vascular congestion as a sequelae of portal
hypertension, or as an anatomic variant in certain breeds such as German Shepherds or Greyhounds. Diffuse
splenic enlargement can also occur secondary to many sedatives or anesthestics, including opioids.
Splenic torsion is also considered a surgical emergency. Splenectomy is the definitive treatment; on
histopathology there is evidence of severe vascular congestion, potentially with necrosis depending on duration
of torsion prior to intervention. Secondary bacterial infection is rare but can occur with abscess formation due
to agents such as E. coli and Clostridium. The prognosis is generally good with prompt intervention.
47
References
● Thrall DE: Textbook of Veterinary Diagnostic Radiology, Saunders 6 th ed. 2013.
● Penninck D and D’Anjou MA: Atlas of Small Animal Ultrasonography, Blackwell Pub. 1st ed. 2008.
● Fossum TW: Small Animal Surgery, Mosby Co. 4th ed. 2013
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● Patsikas MN et al. Computed Tomography diagnosis of isolated splenic torsion in a dog. Vet Rad US 2001; 42(3): 235-237.
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48
Feline Lymphoma: Review & Treatment Update
Kevin Choy BVSc (Hons), MS, DACVIM (Oncology)
Seattle Veterinary Specialists
Kirkland, WA
Excerpt from: The Cat: Clinical Medicine & Management – 2nd Ed Chapter 31 (Lymphoma)
Incidence, Etiology, and Risk Factors
Lymphoma (also termed malignant lymphoma and lymphosarcoma) is the most common feline neoplasm,
comprising more than half of all hemolymphatic tumors in the cat. Lymphoma can be found in cats of any age,
breed, or sex, although purebred cats such as the Manx, Burmese, and Siamese appear to be overrepresented.
The precise etiology of feline lymphoma in many cases is unknown; however, viral causes of feline lymphoma
are well described, with both feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infections
implicated. Before the widespread use of FeLV testing and control regimens that began in the 1970s, up to 70%
of diagnosed feline lymphoma was caused by FeLV infection, with a progressive decline in FeLV associated
tumors over the past decades. More recent studies indicate that only 14% to 25% of cats with lymphoma have
documented FeLV infection despite an overall increase in lymphoma diagnoses. Although FeLV has a direct role
in tumorigenesis, FIV is thought to indirectly contribute to an increased risk of feline lymphoma by immune
dysregulation resulting in amplification of oncogenic mutations and decreased immune surveillance. This
association with immune dysregulation is further supported by studies evaluating over two-hundred feline renal
transplant patients receiving long-term immunosuppressive therapy with cyclosporine of which 9.5-13% of cats
developed lymphoma within 2 years of transplantation. FeLV infection in one study increased the risk of
lymphoma 62-fold, FIV infection 6-fold, and concurrent FeLV and FIV infection 77-fold.
Exposure to second-hand tobacco smoke is also reported to increase relative risk of developing lymphoma
depending on duration of exposure from 2.4-fold (any exposure) to 3.2-fold (>5 years exposure). Chronic
inflammation may play a role in the development of feline lymphoma. An association has been suggested
between inflammatory bowel disease (IBD) and intestinal lymphoma in which one progresses to the other (IBD
to small cell lymphoma to large cell lymphoma), although definitive supporting evidence is currently not well
characterized.
Clinical Features
Cats with lymphoma exhibit a bimodal temporal pattern of clinical presentation. The first group is comprised of
young cats less than 4 years old with FeLV-associated disease, typically with mediastinal lymph node
involvement and pleural effusion resulting in dyspnea. The second group is comprised of mature cats 6 to 12
years of age that are serologically FeLV negative and present with alimentary (particularly intestinal) lymphoma
or lymphoma in a peripheral nodal or extranodal pattern. Clinical signs of alimentary lymphoma commonly
include vomiting, diarrhea, anorexia, and weight loss. An abdominal mass or diffuse thickening of the intestinal
tract is often palpable in the abdomen. Non-alimentary locations for lymphoma are quite varied and can include
virtually every tissue in the body; renal, mediastinal, respiratory (nasal, tracheal), CNS (brain and spinal),
peripheral nodal/multicentric (lymph node), cutaneous, skeletal muscle, ocular/conjunctival, hepatobiliary,
cardiac, pericardial and uterine lymphoma have been reported in the cat, with clinical signs referable to the
respective organ system dysfunction. Paraneoplastic syndromes such as hypercalcemia can also be seen, but
are less common than in canine lymphoma. Prevalence, presenting clinical signs, and biological behavior of
feline lymphoma vary significantly with geographical location and may reflect regional differences in feline
populations as well as differences in retroviral strains and prevalence.
49
Diagnosis and Staging
Because feline lymphoma is a neoplasm of the lymphoid system that has the ability to affect multiple locations,
a thorough diagnostic evaluation is recommended to confirm diagnosis and anatomic localization(s) and to
establish baseline data to guide prognostication and therapy. Clinically, it is most useful to classify feline
lymphoma by anatomic location rather than the traditional World Health Organization (WHO) staging scheme
commonly used in dogs, with each site of origin each having different presentation, clinical behavior, therapy
considerations, and prognosis (Table 1).
Diagnosis of most anatomic forms of lymphoma in the cat can be made from cytologic examination of fineneedle aspirates of an enlarged lymph node, affected tissues, or cavitary fluids (e.g., pleural effusions in
mediastinal lymphoma). When cytologic findings are equivocal, histopathology with immunohistochemistry (for
B- and T-cell phenotyping) are recommended. Histopathology is particularly important in diagnosis of alimentary
lymphoma in which endoscopic (partial thickness) or surgical (full thickness) biopsies of the gastrointestinal tract
are generally required for a diagnosis to differentiate between severe lymphoplasmacytic
enteritis/inflammatory bowel disease (IBD) and malignant lymphoma as they both can have similar
ultrasonographic appearance with diffuse thickening of the muscularis propria (with no loss of intestinal wall
layering). As such, inclusion of the intestinal muscularis is necessary for a definitive diagnosis of lymphoma. Full
thickness surgical biopsy is considered a superior diagnostic method though is more invasive. If histopathology
is inconclusive, molecular analysis techniques such as flow cytometry and polymerase chain reaction for antigen
receptor rearrangement (PARR) test for T and B cell receptor gene clonality assessment can provide further
support for malignancy, but sensitivity and specificity of this test is highly dependent on methodology and
primers specific to each testing laboratory. Other described biomarkers for differentiating between IBD and
alimentary lymphoma include Bcl-2 gene expression, serum LDH and serum thymidine kinase activity though
few are routinely used and commercially available to diagnostic laboratories for clinical use.
Nasal lymphoma also commonly requires a biopsy using a blind or rhinoscopic approach, with
immunohistochemistry useful in definitively confirming a nasal lymphoma diagnosis. Advanced imaging such as
computed tomography (CT) is helpful in further differentiating inflammatory vs neoplastic disease and extent
of tumor burden.
After the diagnosis of lymphoma, complete staging should include a detailed physical examination, with
particular attention to lymph node size (including tonsils), abdominal palpation (masses, thickened intestinal
loops, organomegaly), cranial thoracic compression (to screen for mediastinal mass), and ophthalmic
examination. Peripheral lymphadenopathy (seen in nodal lymphoma) is less frequently observed in cats than in
dogs. Laboratory evaluation should include a CBC, serum biochemistry profile, urinalysis with culture and
sensitivity (to assess for preexisting urinary tract infections that may represent a nidus for sepsis during
myelosuppressive chemotherapy), and FIV and FeLV serology. Three-view thoracic radiographs (right lateral,
left lateral, and ventrodorsal views) should be made to assess lymph node, pulmonary, mediastinal, and pleural
structures. Abdominal ultrasound examination is useful to assess gastrointestinal wall thickness, mesenteric
lymph node size, and organ size and echotexture (liver, spleen, and kidney). Ultrasound-guided fine-needle
aspirates should be performed where appropriate. Bone marrow aspirates should also be considered as part of
complete staging, particularly in patients with unexplained cytopenias or if cytologic diagnosis of lymphoma has
not been confirmed despite prior staging diagnostics and high clinical suspicion. If abnormal or elevated
circulating lymphocytes are noted, flow cytometry of peripheral blood may also helpful in characterizing this
cell population. Complete staging with anatomic classification will guide appropriate therapy selection,
minimize toxicity, and reduce therapy-associated complications.
50
TABLE 1: Summary of Selected Anatomic Forms of Lymphoma in Cats
Anatomic Form
Prevalence
Median
Age (y)
Common
Phenotype
General
Prognosis
Treatment
Modality
Comments
Gastrointestinal
-small cell
(low grade)
Common
13
T-cell
Fair to good
Chemotherapy
Typically
responds well
to
less
aggressive
oral
maintenance
protocols
Moderate
10
B-cell
Poor
Chemotherapy
+/- Surgery
Uncommon
<4
T-cell
Poor to fair
Chemotherapy
Nodal
Nodal
Uncommon
7
-
Poor
Chemotherapy
Extranodal
- Nasal
Uncommon
9.5
B-cell
Good
- Laryngeal/tracheal
Rare
9
-
Fair to good
- Renal
Rare
9
B-cell
Poor
Radiation
Chemotherapy
Chemotherapy
+/- Radiation
Chemotherapy
- Hepatic (primary)
- Cutaneous
Rare
Rare
12
10-13
T-cell
T-cell
Poor
Fair
- Occular
Rare
10
B-cell
Fair
- CNS
Rare
4-10
-
Poor
-large
cell
(intermediate/high
grade)
Mediastinal
Mediastinal
Chemotherapy
Chemotherapy
+/- Surgery
Surgery
+/Chemotherapy
Chemotherapy
+/- Radiation
FeLV-negative
patients may
have
longterm
remissions
Elevated risk
of
CNS
metastasis
Elevated risk
of
CNS
metastasis
Biological Behavior
Most anatomical classifications of feline lymphoma start as localized (non-Hodgkin–like) disease that tends to
progress to systemic involvement over time as opposed to multicentric disease seen commonly in dogs and
humans. Because of the anatomic syndromic nature of lymphoma in cats, the clinical signs associated with the
site of origin are most important for prognostication. Lymphoma immunophenotype varies by location, etiology
and anatomic form ((can help in the diagnosis of anatomic forms of lymphoma (Table 1). Age, weight, sex, FIV
status and stage (based on WHO criteria)) also do not appear to be prognostic in cats. FeLV infection has been
shown by some studies to be a negative prognostic factor because of a more rapid emergence of drug resistance,
but other studies have not found a similar association. The most important prognostic factor for feline
lymphoma are anatomic localization of disease and response to therapy, particularly within the first few weeks
of treatment.
Treatment and Prognosis
Systemic chemotherapy is the primary treatment modality for most anatomic forms of feline lymphoma, with
surgery or radiotherapy being options in specific forms that are solitary or localized. Without medical therapy
mortality rates in cats with lymphoma are approximately 40% and 75% at 4 and 8 weeks after diagnosis,
respectively. A substantial amount of literature exists on the many anatomic forms of feline lymphoma, each
51
with a highly variable treatment regimens and prognoses that is outside the scope of this chapter to describe
each form in detail. A selection of the most commonly encountered clinical presentations are described in the
following sections.
Alimentary (gastrointestinal) lymphoma is the most commonly diagnosed anatomic form in cats. The two most
common forms of alimentary lymphoma are (1) low-grade small T-cell lymphomas principally confined to the
mucosa but diffusely distributed in the small intestine, and (2) intermediate to high-grade large B-cell or T-cell
lymphomas that are transmural, causing destruction of normal intestinal wall layering and can affect focal or
multi-focal regions of the gastrointestinal tract.
Low-grade gastrointestinal lymphoma (also termed lymphocytic intestinal lymphoma) is considered a slowgrowing, indolent neoplasm that can be managed successfully with maintenance oral chemotherapy.
Combination of daily prednisone or prednisolone (2 mg/kg orally daily tapering to 1 mg/kg orally every 48 hours
over several weeks) and chlorambucil therapy (20 mg/m orally every 2 weeks, favored by the author) or
15 mg/m orally every 24 hours for 4 consecutive days every 3 weeks has been reported. Prognosis is typically
good, with overall response rates of up to 96%, up to 76% of cats achieving complete remission, and median
clinical remission durations of approximately 19 to 30 months or longer reported. In the event of clinical relapse,
many cats with small cell lymphoma can be successfully with alternate oral alkylator chemotherapy regimens
including cyclophosphamide and lomustine. Please refer to Chapter 23 for further information on the
management of gastrointestinal small cell lymphoma.
Intermediate to high-grade gastrointestinal lymphomas are aggressive with rapid disease progression and
shorter duration of remission and survival. As such multi-agent chemotherapy is considered the standard of
care, with a variety of protocols and response rates reported. However, there is a general lack of consensus
regarding the gold-standard protocol. Consequently, many treatment regimens are specific to a particular
institution or practice.
Multiple variations of the multi-agent protocol COP (cyclophosphamide, vincristine, and prednisone) have been
reported to result in complete remission in 50% to 75% of cats, with a median survival time (MST) ranging from
2 to 10 months. Single-agent doxorubicin chemotherapy has been less successful than in dogs, with a response
rate of 42% and median duration of response of 64 days in cats. However, when doxorubicin is included into
multi-agent protocols either as part of a CHOP (H = doxorubicin) protocol or as maintenance therapy (COP
followed by doxorubicin), significantly longer durations of remission have been reported in cats that responded
compared with cats that received only COP therapy. These reports suggest that a subset of cats may benefit
from the addition of doxorubicin. Doxorubicin has been reported to be nephrotoxic and cardiotoxic in cats; thus
a COP-based protocol may be preferable for cats with preexisting renal or cardiac disease, but consultation with
a veterinary oncologist is recommended before starting induction therapy. The most reliable prognostic
indicator is response to therapy; individuals achieving complete remission typically enjoy the best outcomes,
with MST approaching 1 year and longer-term survival reported.
Conversely, failure to achieve complete remission is generally associated with MST of several weeks. Singleagent therapy with prednisolone at 2 mg/kg orally once daily for 2 weeks and then tapered to 1 mg/kg
thereafter may provide varying degrees of palliation, with reported MST of approximately 30-60 days. Alternate
and rescue protocols are not well defined in cats. Single-agent lomustine (CCNU) has been used in cats as
primary therapy or in a rescue setting at reported dosages of 30 to 60 mg/m orally every 3 to 6 weeks depending
on degree and duration of myelosuppression. The advantages are simplicity, and relative lower cost, but
response rates, long term survival and toxicity are less well defined. A recent retrospective study evaluating 32
cats receiving maintenance oral lomustine chemotherapy as first line therapy revealed a response rate of 50%
with median duration of response of 302 days (64-1450) and overall MST of 108 days (4-1488). Chronic
52
administration of lomustine has been associated with severe thrombocytopenia and pulmonary fibrosis in cats
and regular thoracic radiographs should be considered in patients receiving long term lomustine chemotherapy.
Regular biochemical monitoring for hepatotoxicity should also be performed in cats receiving lomustine, though
apparent risk may be low, with only 2 of 29 cats (6.8%) developing elevations ALT in in one report following at
least one dose of lomustine.
Whole-abdomen irradiation has been used as adjuvant or rescue therapy for gastrointestinal lymphoma. In one
pilot study eight cats with gastrointestinal or abdominal lymphoma that achieved remission during an
abbreviated 6-week CHOP chemotherapy protocol received abdominal radiation therapy 2 weeks later. Five
cats remained in remission for at least 266 days after starting therapy, with a range from 266 to 1332 days. In
another study a rapid abdominal radiation protocol delivered over 2 days for cats with relapsed or
chemotherapy-resistant gastrointestinal lymphoma resulted in a response in 10 of 11 cats, with a postirradiation MST of 214 days.
Mediastinal lymphoma can involve the thymus, mediastinal and sternal lymph nodes. Pleural effusion with
resulting dyspnea is a common presentation. Hypercalcemia is not a common feature. Affected cats tend to be
young (2-4 years) and FeLV positive with a T-cell phenotype. FeLV infection has been shown by some studies to
be a negative prognostic factor because of a more rapid emergence of drug resistance, but other studies have
not found a similar association. Mediastinal lymphoma FeLV-positive cats typically have a poor prognosis with
MST of less than 2-3 months due to poor response to COP or CHOP-based protocols. A recent study of
mediastinal lymphoma in FeLV-negative cats however revealed significantly higher remission rates approaching
95% with no significance difference between COP or CHOP based protocols. Overall median survival of these
cats on COP based chemotherapy was 484 days (20-980d) with cats that achieved complete remission surviving
much longer (980 days vs 42 days respectively).
Nodal lymphoma is the form of lymphoma describing disease limited to peripheral lymph nodes. While
common in dogs and humans, this presentation is uncommon in cats. Peripheral nodal lymphoma has been
reported to be the most common anatomic form of the disease in cats under 1 year. A distinct form of nodal
lymphoma is “Hodgkin’s-like” lymphoma that typically present with enlarged mandibular or cervical lymph
nodes only. Pathology of affected lymph nodes typically have classic Reed-Sternberg-like cells and is frequently
described as a “T-cell rich, B-cell lymphoma”. Prognosis and treatment is highly variable and dependent on
clinical presentation and extent of lymph node involvement. Localized lymph node involvement with no
systemic disease may respond to radiation therapy or surgical removal of the affect nodes with reported survival
of a year. However, recurrence is common. Generalized nodal lymphoma may respond to systemic
chemotherapy but will depend on type of lymphoma with the author using chlorambucil- and prednisolonebased therapies for low-grade forms and COP or CHOP-based protocols for high-grade forms.
Nasal lymphoma is the most common extranodal lymphoma in cats. It is typically localized with fewer than
20% of cats presenting with distant metastasis. Primarily seen in older cats (9-10 years old), the majority are
intermediate to large B-cell epitheliotropic lymphomas. Because lymphocytes are highly radiosensitive, so
definitive multi-fraction radiation therapy protocols (consisting of 15-20 doses of radiation) are effective for
treating localized lymphoma with complete remission rates of 75-95% reported and MST ranging from 1.5-3
years. Hypo fractionated radiation protocols consisting of 2-6 doses of radiation reported in a recent study also
showed benefit, with improvement in clinical signs in 86% of cats, but more modest improvement in overall
survival of 432 days. Nasal lymphoma is also moderately responsive to systemic chemotherapy (COP or CHOP
based) with reported response rates of 75% and survival times ranging from 1-2 years in cats that achieve
complete remission.
53
Renal Lymphoma is the second most common extranodal lymphoma in cats, arising in one or both kidneys.
Most are intermediate to high-grade B-cell phenotype. Cats with renal lymphoma have a 40-50% risk of CNS
metastasis. As such, it is recommended to include a form of chemotherapy that crosses the blood brain barrier,
such as cytosine arabinoside, to a standard COP protocol (COAP) to reduce risk of CNS metastasis.
Large granular lymphoma is an uncommon, morphologically distinct variant of lymphoma in cats that carries a
poor prognosis. This population of cells represent cytotoxic T-cells and NK cells with characteristic cytoplasmic
azurophilic granules on pathology. Response to chemotherapy is generally poor with a reported MST from 4557 days in cats that responded to COP based chemotherapy.
Regardless of the anatomic form, most cats with lymphoma benefit from supportive care, particularly cats that
are anorexic, vomiting, or severely debilitated because of chronic disease progression. Nutritional and fluid
support is critical for cats that are inappetent because of either the malignancy or the chemotherapy. This is
particularly important in alimentary lymphoma where body weight changes during chemotherapy has been seen
to be a significant prognostic indicator with cats. Cats with stable to increased body weight during the first 4
weeks of treatment surviving much longer than patients that lost >5% of their starting weight with MST 7m (463) versus 3.1m (2.3-5.1) respectively.
The placement of an esophageal, gastric, or jejunal feeding tube (bypassing the affected tissues) can allow
adequate nutrition, hydration, and administration of oral medication, particularly during early stages of
treatment. Appetite stimulants, anti-emetics, and thorough nursing care may also be necessary to improve
body condition and tolerance to therapy.
Selected References
1. Little S. The Cat: Clinical Medicine & Management. 1st edition. St Louis, Saunders; 2011. Chapter 31, Feline Lymphoma p.
782-786 (Choy K, Bryan J)
2. Little S. The Cat: Clinical Medicine & Management. 2nd edition. St Louis, Saunders; 2017. Chapter 31, Feline Lymphoma
(Choy K, Bryan J)
3. Meuten DJ: Tumors in domestic animals, ed 4, Ames, Iowa, 2002, Blackwell, pp 144-151.
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5. Argyle DJ, Brearly MJ, Turek MM: Decision making in small animal oncology—feline lymphoma and leukemia, Ames, Iowa,
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6. Bryan JN: Feline lymphoma. In Henry CJ, Higginbotham ML, editors: Cancer management in small animal practice, ed 1, St
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9. Durham AC, Mariano AD, Holmes ES, et al: Characterization of post transplantation lymphoma in feline renal transplant
recipients, J Comp Pathol, Feb-Apr;150(2-3):162-8, 2014
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11. Moore A: Extranodal lymphoma in the cat: Prognostic factors and treatment options, J Feline Med and Surgery 15, 379-390;
2013.
12. Fabrizo F, Calam AE, Dobson JM, et al: Feline mediastinal lymphoma: a retrospective study of signalment, retroviral status,
reponse to chemotherapy and prognostic indicators, J Feline Med Surg Aug;16(8):637-44, 2014.
13. Kleinschmidt S, Harder J, Nolte I, et al: Chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract in
cats: diagnostic advantages of full-thickness intestinal and extra intestinal biopsies, J Feline Med Surg Feb;12(2):97-103, 2010.
14. Scott KD, Zoran DL, Mansell J, et at: Utility of endoscopic biopsies of the duodenum and ileum for diagnosis of inflammatory
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54
Dec;14(12):910-2, 2012.
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2015.
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Animal Pract, Feb;56(2):125-9, 2015.
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Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003), J Am Vet Med Assoc 227:1118, 2005.
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in domestic animals, Vet Rec 79:693, 1966.
29. Zwahlen CH, Lucroy MD, Kraegel SA et al: Results of chemotherapy for cats with alimentary malignant lymphoma: 21 cases
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30. Krick EL, Moore RH, Cohen RB, Sorenmo KU: Prognostic significance of weight changes during treatment of feline
lymphoma, J Feline Med Surg, Dec;13(12):976-83, 2011.
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Mar;14(3):191-201, 2012.
32. Gustafson TL, Villamil A, Taylor BE, et al: A retrospective study of feline gastric lymphoma in 16-chemotherapy treated cats.
J Am Anim Hosp Assoc, Jan-Feb;50(1):46-52, 2014.
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for lymphoma in cats, J Vet Intern Med, Jan-Feb;27(1):134-40, 2013.
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of 19 cases (1994-1997), J Vet Intern Med 15:125, 2001.
35. Rau SE, Burgess KE. A retrospective evaluation of lomustine (CeeNU) in 32 treatment naïve cats with intermediate to large
cell gastrointestinal lymphoma (2006-2013), Vet Comp Oncol Jun 9, 2016.
36. Dutelle AL, Bulman-Feliming JC, Lewis CA, et al: Evaluation of lomustine as a rescue agent for cats with resistant lymphoma,
J Feline Med Surg, Oct;14(10):694-700, 2012.
37. Skorupski KA, Durman AC, Duda L et al: Pulmonary fibrosis after high cumulative dose nitrosourea chemotherapy in a cat,
Vet Comp Oncol 6(2):120, 2008.
38. Williams LE, Pruitt AF, Thrall DE: Chemotherapy followed by abdominal cavity irradiation for feline lymphoblastic
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39. Parshley DL, LaRue SM, Kitchell B et al: Abdominal irradiation as rescue therapy for feline gastrointestinal lymphoma: a
retrospective study of 11 cats (2001-2008), J Fel Med Surg 13:63, 2011.
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41. Fujiwara-Igarashi A, Fujimori T, Oka M, et al: Evaluation of outcomes and radiation complications in 65 cats with nasal
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55
Indolent and Less Common Canine Lymphoma
Nicholas Szigetvari, MS, DVM (Board eligible)
Seattle Veterinary Specialists
Downtown Seattle
Classifying lymphoma
Lymphoma is a cancer comprised of over fifteen different subtypes that are classified based on
immunophenotype (T-cell vs B-cell), anatomic location, and histologic characteristics (see table 1). The
treatment and prognosis may overlap for many types of lymphoma. However, there are several types
of lymphoma/leukemia and that have significant disparity in prognosis and treatment recommendations.
The most common type of lymphoma in dogs is high-grade multicentric lymphoma. Exact prevalence
statistics varies from study-to-study but high-grade lymphoma comprises between 70 to 85% of cases
diagnosed. This would include diffuse, large B-cell lymphoma and peripheral T-cell lymphoma. These
cases typically present with acute enlargement of multiple peripheral lymph nodes +/-spleen or liver
involvement. Treatment requires maximum tolerated pulse dosing of chemotherapy. For example,
CHOP or single agent IV/or chemotherapy such doxorubicin or lomustine plus steroids.
Indolent lymphoma and chronic leukemia comprises remaining 15-30% cases of lymphoma.i,ii Some
of the more commonly diagnosed indolent lymphoma/leukemia are small cell lymphoma, T-zone
lymphoma, chronic lymphocytic leukemia (CLL), and marginal zone lymphoma. These cases generally
present with a more slow, insidious history with sometimes incidental finding of splenomegaly or
lymphocytosis +/- anemia or thrombocytopenia. Particular breeds also seem to be overrepresented.
For example, golden retrievers comprised majority T-zone lymphoma cases in one report. Another
study found small and toy breed dogs and bulldogs to be the most common breeds affected with CLL.
Diagnosis
Diagnosis of low-grade lymphoma or chronic leukemia is possible with cytology of lymph nodes, blood
smear, or splenic aspirate. However, these subtypes are comprised of mostly mature, small
lymphocytes. Therefore, it may be difficult for pathologists to rule out reactive lymph node or
lymphocytosis from low-grade lymphoma/leukemia. Biopsy of a lymph node or bone marrow can
typically confirm diagnosis in these cases. Histology is also the only test that can classify all of the
distinct types of lymphoma. Unlike cytology, histology is able to assess the architecture of the lymph
node relative to the population neoplastic lymphocytes disrupting normal lymph node anatomy.
Histology can also provide the grade based on assessment of architecture, mitotic index, cell
morphology, and cell size.
Although unable to classify all forms of lymphoma/leukemia, molecular testing can aid in diagnosis of
lymphoma/leukemia. PARR and flow cytometry help corroborate diagnosis if it is equivocal based on
cytology. Flow cytometry can also distinguish between several of the more clinical distinct forms of
lymphoma/leukemia.
PARR is a PCR test that looks for similarity (ie clonality) of the DNA sequence that codes for the antigen
receptor on B-cell and T-cells. A population of lymphocytes from non-neoplastic lymph node,
circulation, effusion, or other lymph tissues should have variety in this DNA sequence. Finding the
large majority of the cells with the same DNA sequence indicates lymphoma/leukemia. The primers
are specific for B-cell receptor or T-cell receptor so PARR is able to form diagnosis of lymphoma or
leukemia and specify B-cell or T-cell. PARR cannot distinguish between different forms of lymphoma
or leukemia. Since PARR merely needs DNA if can be performed on blood smears or lymph node
smear that are days or weeks old. It can even be performed on previously stained samples. The
56
sensitivity of PARR varies between each laboratory. One study reported PARR sensitivity of 67% and
75% for B-cell and T-cell lymphoma, respectively.iii Concordance between PARR and IHC was 67%.3
Flow cytometry uses soluble, live cell sample, such as aspirated cells put in a buffered solution or whole
blood. Sample must be collected and then immediately sent for analysis. Fluorescent antibodies are
then used to label cells based type of lymphocytes. Sensors can also measure cell size and complexity.
Therefore, flow cytometry can aid in initial diagnosis, determine immunophenotype, and distinguish
between several of the different subtypes of lymphoma/leukemia. Specifically, flow cytometry can
classify lymphoma as either large cell, B-cell lymphoma (typically high-grade lymphoma), intermediate
T-cell (typically high-grade), acute leukemia, or chronic leukemia/low-grade lymphoma. Sensitivity is
91% and 100% for flow cytometry diagnosing B-cell and T-cell lymphoma, respectively.3 Agreement
between flow cytometry and IHC is 94%.3
Treatment
Establishing diagnosis of low-grade lymphoma or leukemia generally leads to more conservative
therapy recommendation. Small cell lymphoma, T-zone lymphoma, and chronic lymphocytic leukemia
is treated with metronomic chemotherapy and steroids. First line therapy is chlorambucil 0.2 mg/kg/day
for 7-14 days and then 0.1 mg/kg/day indefinitely plus prednisone 1 mg/kg/day for 14 days and then
0.5 mg/kg/day thereafter. Monitoring alone is also acceptable for cases that are clinical well without
significant cytopenia. Marginal zone lymphoma is generally found in the spleen lymphoma and possible
node enlargement. Regardless of other organ involvement it is treated with splenectomy alone.
Prognosis
Prognosis is generally better for these forms of lymphoma and leukemia despite more conservative
therapy. Outcome for chronic leukemia is perhaps influenced by immunophenotype according to one
study. T-cell CLL, the most common cell type, was found to have a 930 day median survival time (MST)
in 1 study.4 Meanwhile B-cell CLL has a MST of 480 days, and atypical CLL MST of 22 days.iv
T-zone lymphoma has a similarly good long term outcome. MST was 647 days in one report.5 If the
same report 40% of dogs were golden retrievers and majority of cases had lymphocytosis with
lymphadenopathy.v The latter point perhaps shows stage is of less impactful on prognosis for lowgrade lymphoma.
Lastly, marginal zone lymphoma treated with splenectomy had an overall MST of 383 days in 1 report.
Dogs diagnosed incidentally had MST of over 1,000 days while dogs with clinical signs attributable to
splenic disease had MST of 301 days. Outcome was not affected by use of chemotherapy after
surgery, lymph node involvement, anemia, nor hemoabdomen.vi
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Table 1. Summary of Canine Malignant Lymphoma Revised From the
Revised European-American Classification of Lymphoid Neoplasms/
World Health Organization Classification of Lymphoid Neoplasms
B Cell Neoplasms
Precursor B cell neoplasms
Precursor B lymphoblastic leukemia/lymphoma
Mature (peripheral) B cell neoplasms
B cell chronic lymphocytic leukemia/prolymphocytic
Leukemia/small lymphocytic lymphoma
B cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma
Splenic marginal zone B cell lymphoma
Plasma cell myeloma/plasmacytoma
Extranodal marginal zone B cell lymphoma of mucosa-associated
lymphoid tissue type
Nodal marginal zone lymphoma
Follicular lymphoma
Mantle cell lymphoma
Diffuse large B cell lymphomaa
Mediastinal large B cell lymphoma
Burkitt’s lymphoma/Burkitt’s cell leukemia
Provisional entity: high-grade B cell lymphoma
Burkitt’s-likea
Primary effusion lymphoma
T Cell and Putative Natural Killer Cell Neoplasms
Precursor T cell neoplasm
Precursor T lymphoblastic
Lymphoma/leukemia
Mature (peripheral) T cell and natural killer cell neoplasms
T cell prolymphocytic leukemia
Large granular lymphocyte leukemia (LGL)
Aggressive natural killer (NK) cell leukemia
Peripheral T cell lymphomas, unspecifieda
Adult T cell lymphoma/leukemia
Intestinal T cell lymphoma (+enteropathy associated)
Hepatosplenic gdT cell lymphoma
Subcutaneous panniculitis-like T cell lymphoma
Mycosis fungoides/Sezary syndrome
Anaplastic large cell lymphoma, T and null cell primary cutaneous
type
Peripheral T cell lymphoma not otherwise specified
Angioimmunoblastic T cell lymphoma
Angiocentric T cell lymphoma
a Peripheral T cell lymphomas are those that are not otherwise specified
(NOS) to a specific subtype by further definition. See PTCL (Fig.3 a-d)
58
________________________________________________
1
Valli, V. E., San Myint, M., Barthel, A., Bienzle, D., Caswell, J., Colbatzky, F., et al. (2011). Classification of canine
malignant lymphomas according to the World Health Organization criteria. Veterinary Pathology, 48(1), 198–211.
1 Carter RF, Valli VE and Lumsden JH. The cytology, histology and prevalence of cell types in canine lymphoma
classified according to the National Cancer Institute Working Formulation. Canadian Journal of Veterinary Research 1986;
50: 154–164.
1 Thalheim, L., Williams, L. E., Borst, L. B., Fogle, J. E., & Suter, S. E. (2013). Lymphoma immunophenotype of dogs
determined by immunohistochemistry, flow cytometry, and polymerase chain reaction for antigen receptor
rearrangements. Journal of Veterinary Internal Medicine, 27(6), 1509–1516.
1 Comazzi, S., Gelain, M. E., Martini, V., Riondato, F., Miniscalco, B., Marconato, L., et al. (2011). Immunophenotype
predicts survival time in dogs with chronic lymphocytic leukemia. Journal of Veterinary Internal Medicine, 25(1), 100–106.
1 Seelig, D. M., Avery, P., Webb, T., Yoshimoto, J., Bromberek, J., Ehrhart, E. J., & Avery, A. C. (2014). Canine T-zone
lymphoma: unique immunophenotypic features, outcome, and population characteristics. Journal of Veterinary Internal
Medicine, 28(3), 878–886.
1
O'Brien, D., Moore, P. F., Vernau, W., Peauroi, J. R., Rebhun, R. B., Rodriguez, C. O., & Skorupski, K. A. (2013). Clinical characteristics
and outcome in dogs with splenic marginal zone lymphoma. Journal of Veterinary Internal Medicine, 27(4), 949–954.
59
Intrahepatic Portosystemic Shunts: Diagnosis and Treatment Advances.
Jim Perry, DVM, PhD, Diplomate ACVIM (Oncology), Diplomate ACVS
Seattle Veterinary Specialists
Seattle, WA
Congenital portosystemic shunts are defined as aberrant connections between the portal and central venous
systems that result in the delivery of portal blood to the systemic venous system without first being filtered
through the liver. The result precludes normal detoxification of portal blood by the liver prior. This shunting also
reduces the amount of oxygen and nutrients being received by the liver, which normally supports liver
development, growth, and function of the liver itself.1
Congenital portosystemic shunts can occur in two primary forms—extrahepatic and intrahepatic. Extrahepatic
shunts, as the name implies, occur between the portal and central venous systems prior to the porta hepitus
(entrance of the portal vein into the liver). Examples of extrahepatic portosystemic shunts include direct
portocaval shunts, portoazygous shunts, splenocaval shunts, gastrocaval shunts, etc. In contrast, intrahepatic
shunts occur when branches of the intrahepatic portal vein (either right, left or central) anastomose to a hepatic
vein or directly with the intrahepatic caudal vena cava. Extrahepatic portosystemic shunts are often amenable
to open surgical attenuation with good to excellent outcomes, while historically; open surgical treatment of
intrahepatic portosystemic shunts has been associated with much higher morbidity and mortality.
The purpose of the discussion here will be to focus on the less common, but often more challenging, intrahepatic
form and current minimally invasive treatment options.
In contrast to their extrahepatic counterparts, which typically occur in small breed dogs (Yorkies, Maltese, Pugs,
etc.), intrahepatic shunts most commonly occur in large breed dogs. Dog breeds that have been shown to be
overrepresented include the Labrador Retriever, Husky, Irish Wolfhound, and certain herding breeds such as
Australian Shepherds. Intrahepatic shunts can also occur in smaller dogs, however, these are much less common
than extrahepatic shunts in these breeds.
The clinical signs associated with portosystemic shunts often become apparent early in life (<3 months) and are
similar regardless of whether the shunt is classified as intrahepatic or extrahepatic. Because intrahepatic shunts
often result in a higher degree of shunting, the clinical signs can become apparent earlier in the dogs life
compared to dogs with extrahepatic shunts. Clinical signs associated with portosystemic shunts include stunted
growth, slow recovery from anesthesia, and signs of hepatic encephalopathy. Signs of hepatic encephalopathy
are often subtle initially and non-specific, including anorexia, depression and lethargy, but can become more
significant with advancement of the disease to include ataxia, head pressing, circline/pacing, cortical blindness,
and even seizures/coma. Urinary tract signs (polakiuria, stranguria and hematuria) secondary to ammonium
biurate crystalluria/urolithiasis can also be observed but are more common in slightly older untreated animals.
Biochemical and hematological changes seen in dogs with portosystemic shunts are also similar between intra
and extrahepatic forms. Such abnormalities seen on routine blood work include non-regenerative microcytic
anemia, hypoglycemia, hypocholesterolemia, low BUN, hypoalbuminemia, hypoglycemia, and elevation in liver
enzymes. Elevations in pre and post-prandial bile acids are also a hallmark of portosystemic shunting and
1
The normal liver receives 80% of its blood supply and 50% of its oxygen from the portal system. In cases where
portosystemic shunting is occurring, the liver relies much more on atrial blood and as a consequence fails to
develop appropriately and can lead to fibrosis and ultimate liver failure in addition to the signs associated with
portosystemic shunts in general.
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secondary liver dysfunction. High levels of blood ammonia can be used to support the diagnosis of
portosystemic shunting, however the absolute level of blood ammonia does not correlate with the type of
shunting, the degree of shunting, or to the severity of hepatic encephalopathy.
The suspicion of a portosystemic shunt is suggested by the clinical signs and biochemical changes discussed
above, while the diagnosis is confirmed via imaging. Abdominal ultrasonography is an excellent means of
diagnosing portosystemic shunting and for classifying whether the shunting is occurring in an extrahepatic or
intrahepatic fashion. In cases where ultrasound fails to identify or characterize the shunt, advanced imaging
such as nuclear scintigraphy or, now more commonly, CT angiography, can be used. Ideally, CT is also performed
prior to any transvenous approach to allow for accurate delineation of the anatomy and for measurement
purposes (figure 1).
FIGURE 1: CT ANGIOGRAM:
FIGURE 1: CT ANGIOGRAM:
Prior to advances in percutaneous approaches, intrahepatic shunts where typically either managed medically or
through open surgical approaches. Reports evaluating dogs treated with medical management alone typically
show survival times ranging from 6-12 months from the time of diagnosis/initiation of medical management to
euthanasia/death. Open surgical treatment, when performed successfully can significantly extend these survival
times, however, the intra and perioperative mortality using this approach can reach as high as 50 percent. This
relatively high mortality rate associated with open surgical approaches, and the advances in interventional
radiology, has led to the development of safer, less invasive, percutaneous options as discussed below.
Fluoroscopically guided percutaneous transjugular coil embolization (PTCE) has markedly reduced the
intraoperative and perioperative complication rates, and early data suggest similar if not better long-term
outcomes compared to successful open surgical attenuation/ligation. The percutaneous transjugular approach
involves fluoroscopic catheterization of the caudal vena cava and shunt vessel through a 10-12F venous access
sheath placed in the jugular vein. Once isolated, a properly sized mesh Nitinol stent (Infiniti Medical) is placed
within the lumen of the vena cava such that the stent spans the shunt’s osteum. Placement of the caval stent
prevents migration of the soon to be deployed coils from the shunt vessel into the vena cava/systemic
circulation. Once the stent is placed, the shunting vessel is re-catheterized and deployment of often multiple
thrombogenic coils is performed until ideal portal pressures/pressure changes are achieved as measured intraoperatively. Figures 2A and B show the post-operative placement of both the caval stent and thrombogenic coils
within the shunting vessel.
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FIGURE 2: POST OP STENT AND COIL PLACEMENT
Ultimately, the goal of PTCE is similar to that performed for extrahepatic shunt treatment—gradually attenuate
the flow of blood through the shunting vessel such that the normal portal system can adapt without the
development of portal hypertension. The ideal endpoints for absolute portal pressure following the procedure
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as well as change in pressure remain unknown, but theoretical intra-operative goals are portal pressure to
central venous pressure gradients of 5-10mmHg or maximum changes in portal pressure of 5-6mmHg. A drop
in central venous pressure of >1mmHg is also considered a stopping point for further attenuation. Following the
procedure, patients are typically monitored in hospital for 1-2 days for clinical signs associated with acute portal
hypertension (pain, abdominal distension/ascites, diarrhea, systemic hypotension) and the development of
neurological sequelae (seizures, coma). Once home, monitoring is continued as the onset of both portal
hypertension and neurological side effects can occur several days to weeks after shunt vessel attenuation. The
prognosis when acute portal hypertension or neurological sequaelae develop is very poor. When chronic portal
hypertension develops, many dogs can improve with time or can be medically managed as acquired shunts
develop.
The risk for developing neurological sequelae, specifically seizures, is thought to be reduced by pre-treating dogs
with Keppra. Patients are typically started on Keppra at the time of shunt diagnosis along with medications
aimed at reducing signs of hepatic encephalopathy (lactulose, metronidazole, amoxicillin, low protein diet) and
those that decrease gastric acid secretion (H2 blockers or proton pump inhibitors).
Following the procedure, these medications are continued for a minimum of 2 weeks. At that time, the Keppra
is tapered and antibiotics/lactulose are discontinued. The low protein diet is transitioned after 8 weeks as long
as the patient is doing well. Continuation of a proton pump inhibitor is recommended life long as GI ulceration
is a known long-term sequelae of portosystemic shunt attenuation. Bile acids are typically rechecked at the 8
week time point for monitoring purposes.
As mentioned above, occasionally a chronic low-grade portal hypertension can occur, especially in cases that
have portal vein hypoplasia within other regions of the liver. This chronic portal hypertension can lead to the
development of multiple acquired portosystemic shunts as well as ascites and recurrence of signs associated
with portosystemic shunting (encephalopathy, urate stones, etc.). When this occurs, there is unfortunately little
that can be done other than re-instatement of medical management (lactulose, antibiotics, low protein diet,
etc.) and supportive care. Even when this occurs, however, dogs can often live with these signs for months to
years while enjoying an overall good quality of life with medical management.
As with any “new” technique, many questions remain unanswered with regards to long-term prognosis and
factors affecting outcomes. Such questions include:
1) What is the ideal pressure gradient or change between the portal and caval systems after attenuation?
5-6mmHg? Absolute portal pressure <12-18mmHg?
2) How should we monitor “success” or “failure” in these cases? Serial bile acids testing? Recheck
ultrasound or CT imaging? Clinical signs only?
3) Should the goal be to eliminate all shunting through the vessel or is some residual shunting OK long
term? Should a second procedure be performed to add more coils when shunting persists? Is there a
balance between residual shunting and safe portal pressures?
4) What is the optimal age for treatment? 4-6 months?
5) If acquired shunts develop secondary to chronic portal hypertension, how does this effect prognosis? Do
these patients have improved quality of life compared to those not treated at all?
While we are still building our caseload at SVS, a recent report from Dr. Weisse et al. out of the Animal Medical
Center in NY, which reviewed 100 cases, showed good to excellent outcomes in 81% of dogs treated with PTCE.
Major intra and post-operative complications occurred in <20% of dogs and the median survival times exceeded
6 years. Similar unpublished findings have been observed at UC Davis with Dr. Culp’s group. Thus far here, all
dogs treated have been discharged from the hospital within 24 hours of treatment and none have experienced
63
portal hypertension or recurrence of clinical signs after weaning of medical management. Longer term follow
up is currently limited as we just started offering the procedure in 2016.
Perhaps the largest hurdle in performing PTCE is cost. The average client cost for the work-up (CT angiogram,
initial medical management, blood work, etc.) and procedure (fluoroscopic PTCE and hospitalization) is $8,000$10,000. The hospital costs for the catheters and implants alone often exceeds $4000, making this procedure a
difficult “sell” for many clients, especially if they do not have insurance. However, as this procedure hopefully
becomes more mainstream, and pet insurance becomes more prevalent, we hope that this procedure will
become more available to pets diagnosed with intrahepatic shunts.
References and Suggested Reading
Bussadori R, Bussadori C, Milan L et al: Transvenous coil embolization for the treatment of single congenital portosystemic shunts in
six dogs. Vet J 176:221-226, 2008.
Gonzalo-Orden JM, Altonaga JR, Costilla S: Transvenous coil embolization of an intrahepatic portosystemic shunt in a dog. Vet Radiol
Ultrasound 41:516-518, 2000.
Leveille R, Johnson SE, Birchard SJ: Transvenous coil embolization of portosystemic shunt in dogs. Vet Radiol Ultrasound 44:32-36,
2003.
Partington BP, Partington CR, Biller DS, et al: Transvenous coil embolization for treatment of patent ductus venosus in a dog. J Am Vet
Med Assoc 202:281-284, 1993.
Weisse C, Berent AC, Todd K, Solomon JA, Cope C. Endovascular evaluation and treatment of intrahepatic portosystemic shunts in
dogs: 100 cases (2001-2011). J Am Vet Med Assoc. 1;244(1): 78-94, 2014.
64
“Keeping Up with the Flow of Extrahepatic Biliary Surgery”
Jessica J. Leeman DVM, DACVS-SA
Seattle Veterinary Specialists
Kirkland, WA
Anatomy & Physiology
The extrahepatic biliary system is composed of the
hepatic ducts, gallbladder, cystic duct, and the
common bile duct (CBD). The CBD enters the major
duodenal papilla in dogs and cats, however it is
conjoined with the pancreatic duct before entering the
papilla in cats. The CBD usually measures
approximately 5cm in length and 2-4mm in diameter
in an average sized dog. It enters the major duodenal
papilla about 1.5-6cm distal to the pylorus; the
intramural portion is about 2cm. There are typically 26 hepatic ducts.
One of the many functions of the liver is to secrete
bile, normally between 600-1000mL/day in people.
Bile acids, a component of bile, play an important role
in fat digestion by emulsifying the larger fat particles
of food into smaller particles so that lipase can act on
those particles appropriately. Bile acids aid in the
absorption of these digested fat end products through
the intestinal mucosal surface by the formation of
micelles. Vitamin K is a fat soluble vitamin that
requires dietary fat emulsification for absorption by
the ileum. Bile also serves as a means for excretion of several waste products, including bilirubin and
excess cholesterol, and can bind to endotoxin and bacteria of the small intestine to prevent absorption
into the portal circulation.
In addition to bilirubin and cholesterol, bile is composed (Table 64-2) of many other molecules and
electrolytes. Bile is secreted by the liver in two stages. The initial portion contains large amounts of bile
acids, cholesterol, and other organic constituents. It is secreted by hepatocytes. A watery solution of
sodium and bicarbonate is added to the bile as it flows through the hepatic ducts, which can increase
the volume of bile up to 100%.
Bile is secreted continuously, but is mostly stored in the
gallbladder until needed in the duodenum to aid in
digestion. The maximum volume that the gallbladder
can hold is only 30-60mLs, however it is continually
absorbing water and electrolytes to concentrate the
remaining bile constituents. The secretion of the watery
solution from the hepatic ducts is stimulated by secretin
of the duodenum to help with neutralization of the acidic
chyme.
65
Cholecystokinin from the “I” cells of the duodenum and jejunum stimulates gallbladder contraction and
the relaxation of the sphincter of Oddi, mainly in response to fatty foods. Gallbladder contraction is also
stimulated by the vagus nerve and enteric nervous system, however to a lesser degree.
Pathophysiology
Extrahepatic biliary obstruction can be caused by pancreatitis, neoplasia, gallbladder mucocele,
cholangitis, and/or cholelithiasis. Less commonly, it has been reported in cases of parasitic infection
and diaphragmatic hernias. Biliary mucoceles form due to hypersecretion of mucous within the
gallbladder lumen and cause secondary obstruction of the biliary tree. Sheltland sheepdogs and dogs
diagnosed with hyperadrenocorticism or hypothyroidism are more likely to develop gallbladder
mucoceles. The underlying mechanism is incompletely understood. Gall stones in people form
secondary to an increased concentration of bile cholesterol. High fat diets and low grade
inflammation/infection have been shown to cause precipitation of gall stones. Gall stones are primarily
composed of calcium bilirubinate in dogs and calcium carbonate in cats. The cause of gall stones in
small animals is unknown.
Consequences to biliary obstruction, primarily reported in surgical patients, include hypotension,
decreased myocardial contractility, acute renal failure, gastrointestinal hemorrhage, and delayed
wound healing. The exact mechanism by which these complications occur remains unclear, however it
is thought to be related to the absence of bile acids in the intestines leading to bacterial overgrowth and
systemic endotoxin absorption. Concurrently, the liver’s reticuloendothelial (immune) system (RES) is
downregulated during this time. Coagulopathies tend to occur secondary to decreased absorption of
dietary vitamin K from the small intestines, which is responsible in helping the liver convert
procoagulation factors II, VII, IX, X into their active forms. Since factor VII has the shortest half-life of
the routinely measured coagulation factors in dogs and cats, it would be expected that prothrombin
time (PT) would be prolonged prior to partial thromboplastin time (PTT). Prolongation of both values
have been associated with a poorer prognosis.
Bile peritonitis occurs when there is release of bile into the peritoneum from the biliary tree. It may be
diagnosed when the bilirubin of the peritoneal fluid is twice that of the serum concentration. This may
occur as a sequelae to biliary obstruction because of dehiscence, failure of ligatures, or pressure
necrosis of the biliary tree’s wall. Free abdominal bile salts cause inflammation, hemolysis, and tissue
necrosis. Their hyperosmolality lead to significant fluid shifts from the vascular space into the abdominal
cavity, which causes dehydration and hypovolemic shock. Bile is normally sterile, however it can
become infected by ascending microbes, bacterial translocation within the intestines, or colonization by
66
resident hepatic anaerobes. Cultured bacteria in cases of cholecystitis and bactibilia have included
Klebsiella spp, Clostridia spp, Corynebacterium spp, Bacteroides spp, Streptococcus faecalis spp,
Peptostreptococcus anaerobius, and Escherichia coli. If an infection is present, septic bile peritonitis
often carries a poorer prognosis. There is a 27-45% survival rate for dogs with septic bile peritonitis
and an 87-100% survival rate for dogs with a sterile process.
Case Evaluation & Stabilization
Patients presenting with biliary obstruction with or without bile peritonitis often have non-specific clinical
signs, such as vomiting, diarrhea, lethargy, anorexia. However, icterus will likely prompt a closer
evaluation of pre-hepatic, hepatic, and post-hepatic etiologies.
Biochemical abnormalities often include hyperbilirubinemia, hypoalbuminemia, increased cholesterol,
and increased liver enzymes. Hematologic abnormalities often include an inflammatory leukocytosis
and possible hemoconcentration. Prolongation of coagulation times are also often appreciated as well.
Less commonly, a fluke infestation may be identified by fecal evaluation.
Abdominal ultrasonography is the best imaging modality for evaluating the extrahepatic biliary tree.
Abnormal ultrasound findings may include evidence of biliary dilation, gallbladder mucocele,
pancreatitis, neoplasia, and cholelithiasis. Ductule distention may be detected as early as 4 hours after
experimental biliary occlusion. Abdominal radiographs typically do not reveal any specific findings
consistent with biliary obstruction. However, radiopaque choleliths in 50% of dogs and 80% of cats and
mineralization of the hepatic ducts may be appreciated with survey radiographs. The presence of these
findings may represent a cause of the obstruction, however they may also be an incidental finding.
Other imaging modalities performed less commonly for biliary obstruction include scintigraphy, CT/MRI
cholangiopancreatography, and endoscopic retrograde cholangiopancreatography. The latter two
modalities are more common in human medicine, however endoscopic retrograde cholangiography
with biliary stenting has been recently described in two dogs.
Patients with obstructive biliary disease are often hypovolemic and hypotensive due to significant fluid
shifts. They should be resuscitated using crystalloids and/or colloids, and electrolyte abnormalities
should be supplemented accordingly. Vitamin K may be administered for the proper function of its
dependent clotting factors II, VII, IX, and X. In the event there is prolongation of the coagulation times
due to the relative vitamin K deficiency, fresh frozen plasma may be administered for supplementation.
Surgery & Outcome
Cholecystectomy is the most common biliary procedure performed. Indications for this procedure
include mucocele formation, necrotizing cholecystitis, cholelithiasis, gallbladder neoplasia, and severe
gallbladder trauma. The procedure may be performed by laparoscopy or laparotomy. After dissection
from the adjacent hepatic parenchyma, the gallbladder is excised at the level of the cystic duct. Care
must be taken to preserve the nearby hepatic artery. The patency of the common bile duct is checked
prior to ligation by passing a small red rubber catheter normograde through the lumen of the cystic duct
and major duodenal papilla. A red rubber catheter may also be passed retrograde through the major
duodenal papilla via duodenotomy. The cystic duct is then closed using suture material or vascular
clips/staples. The excised gallbladder is then submitted for culture and histopathology. Conversion rate
from laparoscopic to open cholecystectomy is 30%, and has occurred in cases where there has been
the inability to ligate the cystic duct, evidence of gallbladder rupture, leakage from the cystic duct during
dissection, and cardiac arrest. Potential complications for both procedures include bile leakage from
failure of cystic duct ligatures, hemorrhage secondary to failure of cystic artery ligations, or from
damage to the liver parenchyma during gallbladder dissection, and failure to document CBD patency
prior to cholecystectomy. Mortality rate is 22-40% following cholecystectomy for biliary mucoceles.
Post-operative hypotension and hyperlactatemia have been associated with poorer outcomes.
67
Cholecystoenterostomy is a rerouting procedure where a stoma is created between the gallbladder and
small intestines, either the duodenum or jejunum, to redirect flow of the bile from the CBD to the newly
created stoma. The procedure may be performed by laparoscopy or laparotomy, however the
laparoscopic approach is currently not recommended in small animals due to a high complication rate.
About 75% of cases were found to leak when a laparoscopic cholecystoduodenostomy was performed
in a group of canine cadavers. Cholecystoenterostomy is typically performed when the primary cause
of the obstruction cannot be alleviated or the alleviation risks outweigh the benefits, thus increasing the
patient’s morbidity. Such cases include cholelithiasis or neoplasia of the CBD. Another indication for
the procedure is when a gastrojejununostomy (Billroth II) is performed. In these cases, the duodenum
is excised along with the pancreas and major duodenal papilla. A cholecystoduodenostomy is always
preferred over cholecystojejunostomy because it is more physiologic. Gastric acid secretion is inhibited
by the presence of bile within the duodenum. If this inhibitory feedback is lost, gastric acid oversecretion may occur, resulting in an elevated incidence of ulcer formation. Bile also contains
bicarbonate that is responsible for neutralizing gastric contents entering the duodenum and is important
in fat digestion as previously noted.
During cholecystoenterostomies, the gallbladder may be mobilized from the hepatic fossa to reduce
tension at stoma site. The liver parenchyma may bleed, but hemostasis is generally achieved easily
using direct pressure or topic hemostatic agents. Four simple continuous suture lines are created in
total during the procedure: two on each side of the stoma. The procedure may also be performed using
an EndoGIA stapling device. The stomas should be created as long as possible, which is typically
around 4cm, because there will be significant contracture of the stoma during the healing period.
Generally, the stoma will decease about 50% during the healing period. If a healed stoma is <2.5cm,
there is risk for obstruction and ascending cholangiohepatitis. Additional complications associated with
this procedure include hemorrhage, dehiscence, and enteric reflux into the biliary tree.
Choledochal stenting is most commonly performed for treatment of temporary conditions, such as when
pancreatitis or cholangiohepatitis cause obstruction of the CBD. It may also be performed in cases
where the CBD is damaged and primary repair is indicated. Stenting following primary repair of the
CBD or choledochotomy allows the stent to support the repair during the healing phase. Red rubber
catheters are commonly used for stenting of the CBD and the catheter size will vary depending on the
size of the animal. The largest stent that does not fill the CBD lumen should be chosen. Approximately
2-4cm of the catheter should remain within the duodenal lumen for anchoring using an absorbable
monofilament suture for temporary use or non-absorbable monofilament suture for permanent use.
Spontaneous passage of the catheter is common, however retrieval of the stent may be performed via
endoscopy up to several months following resolution of the underlying disease. Choledochal stenting
is generally performed via laparotomy, however there are few reports of endoscopically placed biliary
stents. Re-obstruction and ascending cholangiohepatitis are two complications that may follow
choledochal stenting.
Sphincter-altering procedures are performed when a cholelith is lodged in the terminal CBD adjacent
to the major duodenal papilla. This procedure is performed by incising a portion of the intramural portion
of the CBD and removing the stone within the duodenum.
Choledochotomy is generally not performed due to the small size of the CBD and the significant risk of
dehiscence and stricture formation. The wall of the CBD is generally thin and extremely friable in
diseased states.
Cholecystotomy is a rarely indicated procedure. It may be performed if choleliths need to be removed,
however a cholecystectomy is typically performed to prevent recurrence of stones. Cholecystotomy
may also be performed to gain access to the gallbladder lumen to check patency of the CBD prior to
performing a cholecystoenterotomy, obtain full-thickness biopsy samples, or obtain mucosal samples
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for culture. Closure is performed using an absorbable monofilament in a single- or double-layer closure
with full-thickness bites to ensure submucosa incorporation. Potential complications include recurrence
of cholelith formation and incisional dehiscence.
Post-operative Care
Anecdotally, most patients remain hospitalized for about 3-5 days following surgery. Their vitals (HR,
RR, temp, BP) are monitored closely throughout this time. Serial labwork is performed throughout their
stay for monitoring of hematologic and biochemical abnormalities. Serial coagulation profiles are also
monitored as indicated. Patients receive intravenous fluids (crystalloids, colloids), analgesia (fentanyl,
lidocaine), antibiotics (ampicillin, enrofloxacin, metronidazole), Denamarin, and urosodial. Vitamin K
and fresh frozen plasma are administered as indicated. Feeding tubes and abdominal drains are also
placed on a case by case basis.
Prognosis
Prognosis associated with extrahepatic biliary tract disease is considered guarded in most cases.
Reported mortality rates for dogs and cats are 20-40% and 40-60%, respectively. Those with early
recognition and diagnosis of extrabiliary tract obstruction, along with surgical intervention in a timely
manner, may have a much better outcome.
References
Berent A, Weisse C, Schatter M, et al. Initial experience with endoscopic retrograde cholangiography and endoscopic
retrograde biliary stenting for treatment of extrahepatic bile duct obstruction in dogs. J Am Vet Med Assoc 2015;246:436446.
Besso JG, Wrigley RH, Gliatto JM, et al. Ultrasonographic appearance and clinical findings in 14 dogs with gallbladder
mucocele. Vet Radiol Ultrasound 2000;41:261-271.
Guyton AC and Hall JE. Texbook of Medical Physiology. Philadelphia:Elsevier-Saunders, 2006.
Lawrence YA, Ruaux CG, Nemanic S, et al. Characterization, treatment, and outcome of bacterial cholecystitis and
bactibilia in dogs. J Am Vet Med Assoc 2015;246:982-989.
Malek S, Sinclair E, Hosgood G, et al. Clinical findings and prognostic factors for dogs undergoing cholecystectomy for
gallbladder mucocele. Vet Sure 2013;42:418-426.
Martin-Portugues ID, Matos-Azevedo AM, Sans SE, et al. Laparoscopic cholecsytoduodenostomy in dogs: canine
cadaver feasibility study. Vet Surg 2016;45:34-40.
Mehler SJ. Complications of extrahepatic biliary surgery. Vet Clin Small Anim 2011;41:949-967.
Pike FS, Berg J, King NW, et al. Gallbladder mucocele in dogs: 30 cases (2000-2002). J Am Vet Med Assoc
2004;224:1615-1622.
Scott J, Singh A, Mayhew PD, et al. Perioperative complications and outcome of laparoscopic cholecystectomy in 20
dogs. Vet Surg 2016;45:49-59.
Tobias KM and Johnston SA. Veterinary Surgery Small Animal. St. Louis:Elsevier-Saunders, 2012.
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Updates for Mitral Valve Disease
Mikaela Mueller, DVM, DACVIM (Cardiology)
Seattle Veterinary Specialists
Kirkland, WA
Introduction - Degenerative Valve Disease
Degenerative valve disease is the most common cardiac condition seen in canine medicine. A genetic
predisposition has been identified in multiple breeds, including Cavalier King Charles Spaniels (CKCS),
Chihuahuas, Miniature Poodles, Dachshunds, Miniature Schnauzers, Whippets, Shih Tzus, Maltese, Cocker
Spaniels, and Pomeranians. While characteristically seen in small-breed dogs, it is also seen in some large breed
dogs. The spongiosa layer of the mitral valve becomes progressively and irregularly thickened, leading to poor
coaptation of the leaflet tips. At the same time, the chordae tendinae become elongated and sometimes break,
leading to progressive prolapse of the leaflets. These changes are most notable in the mitral valve, but
frequently affect multiple valves of the heart.
As the condition advances, there is progressive leaking of the mitral valve. Decreased forward flow leads to fluid
retention by the kidneys, causing increased circulatory volume and compensatory enlargement of the left side
of the heart. As the pressure in the left side of the heart rises, fluid and pressure back up into the pulmonary
circulation (post-capillary pulmonary hypertension), eventually leading to pulmonary edema (congestive heart
failure, CHF).
The ACVIM Consensus classification system identifies the following stages of degenerative valve disease:
A - Patients at high risk for developing heart disease (genetic predisposition), but with no current identifiable
lesions.
B - Patients with structural heart disease who have never had clinical signs of heart failure
- B1 - Patients with structural heart disease who have no radiographic or
echocardiographic evidence of cardiac remodeling in response to chronic
valvular disease (cardiac enlargement).
- B2 - Patients with structural heart disease with radiographic and/or
echocardiographic evidence of left-sided heart enlargement, indicating
hemodynamically significant valve regurgitation.
C - Patients with past or current clinical signs of congestive heart failure.
D - Patients with end-stage disease and clinical signs of CHF that are refractory to standard therapy.
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Traditional treatment of CHF revolves around 5 main approaches:
1. Preload reduction (furosemide, torsemide, hydrochlorothiazide) - Diuretics reduce circulatory
volume to reduce left-sided filling pressure.
2. Afterload reduction (amlodipine, hydralazine, nitroglycerin/nitroprusside) - Decreased systemic
blood pressure (vasodilation) encourages forward blood flow, resulting in decreased left atrial
pressure.
3. RAAS inhibition (ACE-inhibitors, spironolactone) - RAAS inhibition decreases fluid retention, helps
to prevent cardiac fibrosis and arrhythmogenesis, and has minimal decrease in systemic blood
pressure.
4. Inotropic support (pimobendan, dobutamine) - Improve contractility (and dilate systemic
circulation, in the case of pimobendan) to improve forward flow, increasing circulation to organs
and reducing left atrial pressure.
5. Normalize heart rate and rhythm by treating arrhythmias to maximize cardiac output.
What about before the onset of CHF? The EPIC Trial
In the past, pre-CHF treatment of degenerative valve disease has involved the “watch and wait” approach, or,
often, the use of ACE-inhibitors. Several studies have been conducted to assess the efficacy of ACE-inhibitors in
delaying the onset of CHF. So far, we’ve shown a trend towards increased time to onset of clinical signs, however
a statistically significant increase in time has not been proven.
The results of the EPIC trial were announced at ACVIM in 2016, and later published in November in JVIM. In the
trial, pimobendan (Vetmedin) was started prior to the onset of CHF in dogs with cardiomegaly due to
degenerative valve disease. Results were spectacular, showing a 15-month increase in the time to the primary
endpoint (onset of CHF, cardiac-related death, or euthanasia), which was a 60% increase in the amount of time
that patients spent in the asymptomatic stage (B2). Additionally, dogs who were started on pimobendan when
diagnosed with cardiomegaly lived 10% longer than dogs who did not start pimobendan until the onset of CHF
of later.
The results of the EPIC trial are remarkable enough that it rapidly launches pimobendan as the standard of care
for patients with cardiomegaly due to degenerative valve disease. However, chronic administration of
pimobendan has its disadvantages. All medications can have side effects, and some patients show
gastrointestinal side effects to pimobendan. Additionally, pimobendan is currently a fairly expensive
medication, particularly for large-breed dogs. Vetmedin’s patent expired in September 2015, however we have
yet to develop a more price-effective generic formulation in the USA. Many dogs remain in stage B2 for years,
which can add up to a large amount of money. Many patients with degenerative valve disease would never
reach stage C, succumbing instead to different disease processes that often accompany advanced age. It is our
job as veterinarians to help owners to make the best decision for their pet and family of whether or not to start
pimobendan.
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Cardiac Biomarkers in Degenerative Valve Disease
Cardiac biomarkers, specifically natriuretic peptides (NT-proBNP, NT-proANP) and cardiac troponins (cTnI) have
gained usefulness in the clinical setting. NT-proBNP has become more useful since it is now available in external
laboratory panels as well as cage-side tests. Increased NT-proBNP is an indicator of cardiomyocyte stretch
(increased chamber pressure). A study performed in 2012 (the PREDICT cohort study) showed that NT-proBNP
increases most significantly in the time period leading up to the onset of CHF, and a level of 1500 pmol/L was
found to be an independent risk factor for the development of CHF. Another study by Eriksson et al. found that
patients with NT-proANP >1000 pmol/L have a median of 11 months until the onset of CHF, while patients with
NT-proANP < 1000 pmol/L have a median of 54 months until the onset of CHF. NT-proBNP is not a substitute for
conventional diagnostics, but it has clinical uses as a supportive measurement, including screening for clinically
significant heart disease in patients with heart murmurs, prior to anesthesia and in the evaluation of the
coughing dog with a concurrent heart murmur. Cardiac troponin (such as cTnI) are sensitive and specific markers
of myocardial injury, and have been shown to be increased in canine patients who are at risk for cardiac-related
death. Future work is needed to determine if cardiac troponins can be effectively used to guide treatment.
Fixing Broken Hearts - Surgical Options
There are currently multiple procedures and devices in clinical trials for surgical correction of advanced
degenerative valve disease. One of these experimental devices is the MitralSeal, which is being developed
through a collaborative effort between Colorado State University and Avalon Medical. The MitralSeal is a
transcatheter mitral valve replacement device that is placed using a hybrid procedure. A thoracotomy is
performed and the device is deployed via a catheter through the left ventricular apex using radiographic or
echocardiographic guidance. The device is placed on the left atrial surface of the mitral valve and tethered
externally against the left ventricle.
The Mitrex device is another experimental device that is being developed by Infiniti Medical. It is an external
annuloplasty device, placed by a team of a surgeon and a cardiologist. The device is sized with echocardiographic
guidance during the procedure with the goal of reducing the mitral valve annulus by external pressure,
increasing coaptation of the thickened mitral valve leaflets to reduce mitral valve regurgitation. The device is
placed around the mitral valve on the epicardial surface of the heart and anchored to the left ventricle. Results
of the 6-month pre-clinical trial have so far been promising.
Both of these devices are examples of devices that are being developed with the goals of producing a simple
and cost-effective solution, with potential availability to patients all over the world. Pending clinical trials, it is
promising that these devices, or other similar devices, may provide options that are accessible to our patients
since they do not require the specialization of cardiopulmonary bypass and cardioplegia.
While procedures such as placement of the MitralSeal or the Mitrex devices are in the experimental stages,
mitral valve repair surgery is already an option for patients with degenerative valve disease. It is a highly
specialized procedure involving a team of veterinarians to perform the surgery, run anesthesia, and manage
cardiopulmonary bypass (CPB). The patient is cooled under general anesthesia to reduce cellular metabolism.
The patient is then placed on CPB via the carotid artery and jugular vein. Cardioplegia is maintained throughout
the procedure to aid the surgeon and to reduce cardiac metabolism while the patient is on CPB. The mitral valve
is repaired via a left atrial approach. Depending on the changes present in each case, mitral valve repair is
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primarily accomplished by artificial chordal replacement and circumferential mitral annuloplasty. This
procedure has been perfected by Dr. Masami Uechi and his surgical team at the JASMINE (Japan Animal Specialty
Medical Institute) Veterinary Cardiovascular Medical Center, with a published 94% success rate. Dr. Uechi and
his team perform mitral valve repair from their medical center in Japan, and travel bimonthly to France and
Singapore for additional cases. Mitral valve repair is an extravagant treatment, but it is curative and has a high
success rate. It is a great option to consider for patients with stage B2 and early stage C degenerative valve
disease who have owners with no financial constraints.
References
•
Atkins CE, et al. Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. J Vet Intern Med
2009;23(6):1142-50.
•
Atkins CE, et al. Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated
with enalapril alone for compensated, naturally occurring mitral valve insufficiency (VETPROOF). J Am Vet Med Assoc
2007;231(7):1061-9.
•
BENCH (Benazepril in Canine Heart Disease) Study Group. The effect of benazepril on survival times and clinical signs of dogs
with congestive heart failure: Results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, longterm clinical trial. J Vet Cardiol 1999;1(1):7-18.
•
Boswood A, et al. Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: The
EPIC study - A randomized clinical trial. J Vet Intern Med 2016;30(6):1765-79.
•
Eriksson AS, et al. Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles Spaniels with mitral
regurgitation caused by myxomatous valve disease. J Vet Cardiol 2014;16(2):141-54.
•
Kvart C, et al. Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and
asymptomatic mitral regurgitation. J Vet Intern Med 2002;16(1):80-88.
•
Langhorn R and Willesen JL. Cardiac troponins in dogs and cats. J Vet Intern Med 2016;30(1):36-50.
•
Reynolds,CA, et al. Prediction of first onset of congestive heart failure in dogs with degenerative mitral valve disease: The
PREDICT cohort study. J Vet Cardiol 2012;14(1):193-202.
•
Sargent J, et al. Echocardiographic predictors of survival in dogs with myxomatous mitral valve disease. J Vet Cardiol
2015;17(1):1-12.
•
Uechi M. Mitral valve repair in dogs. J Vet Cardiol 2012;14(1):185-92.
•
Uechi M, et al. Mitral valve repair under cardiopulmonary bypass in small-breed dogs: 48 cases (2006-2009). J Am Vet Med
Assoc 2012;240(10):1194-201.
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