Ch 97 Pancreas Flashcards
anatomy
- right and left lobes, which join to form a small, central body
- right > associated with the proximal duodenum, within mesoduedenum, easily accessible
- left > begins at the pylorus, extends along the greater curvature of the stomach
- 98% total pancreatic mass formed by the exocrine portion
- exocrine = acinar cells, responsible for synthesizing digestive enzymes
blood supply
- originates from the celiac artery
- splenic artery is the primary blood supply to the left limb
- hepatic artery > cranial pancreaticoduodenal artery, suppys body and right limb + duodenum
- caudal pancreaticoduodenal artery (cranial mesenteric) supplys distal right limb
innervated
- by the enteric nervous system and branches of the vagus nerve
- acinar and islet cells are innervated by cholinergic neurons
- Pancreatic juice secretion is stimulated by parasympathetic
What cells form the endocrine pancreas? List all 4 types of this cell and what they produce
Endocrine pancreas is composed of Islets of Langerhans
Alpha cells - glucagon
Beta cells - Insulin
Delta cells - somatostatin
F or PP cells - Produce pancreatic polypeptide
Descrive the typical anatomy of the pancreatic ducts in dogs and cats.
List the main forms of anatomical variation.
DOGS
- 68% typical anatomy.
- The left and right ducts conjoin to form the accessory pancreatic duct (Duct of Santorini), entering via minor duodenal papilla.
- second duct (pancreatic duct or Duct of Wirsung), enters the duodenum adjacent to the CBD at the major papilla.
- The accessory is the larger and secretes the majority of the pancreatic secretions.
CATS
- 80% do NOT have an accessory pancreatic duct
- pancreatic duct fuses with the CBD prior to entering at the papilla.
Variations
- Accessory duct alone in dogs,
- presence of 3 duodenal openings in dogs,
- presence of accessory duct in cats (20%)
What are the main physiologic functions of the pancreas?
Glucose metabolism (Islet cells - endocrine ) and digestion (acinar cells - exocrine )
How do the islet cells regulate glucose metabolism
Insulin secretion - Decreases blood glucose concentration as well as FAs and amino acids, stimulating intracellular conversion of these compounds into glycogen, triglycerides and protein respectively for storage.
Glucagon secretion - Secreted in response to hypoglycaemia. Mobilises energy stores by increasing glycogenolysis, gluconeogenesis and lipolysis,
What is a zymogen?
List the 4 types of pancreatic zymogen
How are the pancreatic zymogens activated?
Zymogens are an inactive precursor of digestive enzymes secreted by the pancreas
Types: Trypsinogen, chymotrypsinogen, proelastases, procarboxypeptidases
Actived via the activation of trypsinogen into trypsin by enterokinase, produced by the duodenal enterocytes. Trypsin then in turn activates the other zymogens via proteolytic cleavage
Prevention of Autodigestion
- proteolytic enzymes are synthesized, stored, and secreted as inactive zymogens
- segregated storage of these zymogens, packaged as membrane-bound granules, within the rough endoplasmic reticulum of the pancreas
- acinar cells synthesize pancreatic secretory trypsin inhibitor to prevent premature activation of the pancreatic zymogens.
How does movement of food into the proximal duodenum stimulate pacreatic secretion?
Duodenal mucosal cells secrete secretin and cholecystokinin
Secretin –> stimulates large vlumes of bicarb rich fluid secretion from the pancreas
Cholecystokinin –> Stimulates secretion of digestive enzymes from the pancreas, Also stimulates contraction of th GB and relaxation of the sphincter of Oddi
pancreatic secretion through vagal stimulation
Healing of the Pancreas
- Injury of acinar cells results in inappropriate protease activation that overcomes endogenous antiprotease defenses.
- The consequence is an initial cellular response of polymorphonuclear leukocyte infiltration
- inflammatory cascade is reversible; however, in some cases, it progresses to necrotizing pancreatitis = acinar necrosis, interstitial microabscess formation, peripancreatic fat necrosis, microvascular thrombosis, and local hemorrhage.
- chronic conditions, irreversible parenchymal destruction and fibrosis
- degree of inflammation incited by surgery of the pancreas
What pre-medication should be avoided in animals undergoing pancreatic surgery
alpha-2 agonists
- In normal animals these medications cause hypoinsulinaemia and hyperglycaemia but their effect in the face of a diseased pancrease in unpredictable
What part of the pancreas is recommended for pancreatic biopsy?
List the options for performing a pancreatic biopsy
Distal right limb of the pancrease is the idea location - Good distance from the duct system, easily accessible and its vascular supply is not the primary blood sorce to other organs
Tru-Cut
Punch biopsy
Wedge biopsy
Blunt dissection
Suture fraction
Open vs Laparoscopic Pancreatic Biopsy
- 5-mm cup, clamshell, or punch biopsy forceps; a pretied loop ligature (Figure 97.10); vessel-sealing device; hemostatic clips
Is there a reported clinical or histological difference between biopsy techniques?
- Studies have shown no clinical difference or difference in amylase and lipase measurements between biopsy techniques.
- Histo exam showed a more severe inflammatory reaction in those undergoin suture fraction however there was no clinical significance to this finding.
How much pancreas can be removed without impairing the endocrine or exocrine function?
75 - 95% can be removed as long as the duct to the remaining pancreas is left intact
substantial regenerative capacity
What is the main limiting factor of total pancreatectomy?
Maintaining duodenal blood supply.
Total Pancreatectomy
- indications are few: acute trauma, intractable pancreatitis, and severe chronic fibrosis
- Obstruction of the splenic artery requires splenectomy, if occurs
- At the angle of the pancreas, care is taken to identify and preserve the gastroduodenal artery and its terminal branch, the cranial pancreaticoduodenal artery, to maintain blood flow to the proximal duodenum.
- adhesions, fibrosis, and edema are frequently too extensive in clinical cases to allow removal of the right limb of the pancreas without disruption of duodenal blood supply.
- Resultant exocrine pancreatic insufficiency and diabetes mellitus
techniques
- avulsion: blunt dissection from the pancreaticoduodenal vessels while maintaining blood supply to the duodenum
- preserve blood supply to the duodenum through preservation of the recurrent duodenal branch of the right gastroepiploic artery with ligation of pancreaticpduodenal
Pancreaticoduodenectomy
- when pancreatectomy is required and preservation of duodenal blood supply is not possible
- rarely performed because of the associated high rate of morbidity and mortality.
- Cholecystoenterostomy is required to establish biliary drainage.
List the main considerations for post-op care in patients undergoing pancreatic surgery
- Nutrition - need for a feeding tube placement during surgery?
- Fluid support - Need for colloids?
- Analgesia - Opioids mainstau but can cause ileus, constipation, vomiting. Consider ketamine and lidocain CRIs also
- Antiemetics
- Gastric Acid Reduction - if evidence of gastroduodenal ulceration or oesophagitis
How does maropitant work?
Blocks centrally and peripherally mediate emesis through blockage of neurokinin-1 receptors and substance P production
Blockage of neurokinin-1 receptors could also reduce visceral pain and lung injury
How often may Spec CPLI and SNAP CPLI give a false positive result for pancreatits?
Approximately 40%
Pancreatitis
Pathophysiology
risk factors
- dietary indiscretion,
- obesity,
- hyperlipidemia,
- corticosteroid administration,
- ischemia (i.e surgical or anaesthetic)
- genetic predisposition
- pancreatic duct obstruction
Acute pancreatitis
- inflammation of the pancreas that is sudden in onset and reversible
Chronic pancreatitis
- continuous, often subclinical inflammation accompanied by irreversible histologic changes > fibrosis and atrophy.
- If severe, permanent impairment of pancreatic function may result.
diagnosis
- most common CS: vomiting and anorexia dogs, anorexia and lethargy cats
- No single laboratory test available in veterinary medicine is definitively diagnostic
- Hyperbilirubinemia may result from bile duct obstruction or severe hepatocellular damage
- Systemic manifestations: respiratory distress, neurologic signs, cardiac abnormalities, and bleeding disorders, diabetes mellitus
- SNAP cPLI is sensitive but semiquantitative and is therefore primarily used as a rapid screening test
imaging
- Ultrasound examination may identify decreased pancreatic echodensity, increased pancreatic echodensity with pancreatic fibrosis, a mass or cystic mass
- In acute pancreatitis the surrounding mesentery is often hyperechoic
Management
surgery rarely indicated for pancreatitis
- reestablishment and maintenance of the patient’s fluid and electrolyte balances and treatment with analgesics and antiemetics.
- enteral feeding decreases villus atrophy, bacterial translocation, and pancreatic inflammation
surgery
- Indicationsinfection; biliary obstruction or pancreatic abscess; biopsy; and lack of response to aggressive medical management
- survival after surgery : 80% extrahepatic biliary obstruction, 64% necrosectomy, and 40% abscess
Pancreatic Abscess
Pathophysiology
- most commonly as a sequela to pancreatitis,
- collection of pus and necrotic tissue within the pancreatic parenchyma or extending from it into adjacent tissues (+/- bacteria)
- most pancreatic abscesses reported in the veterinary literature are sterile
- ddx neoplasia, cyst
What is the reported prognosis for sugical treatment of a pancreatic abscess?
Overall 40% survival however this may be skewed by intraop euthanasia.
One study reported a 62% survival for abscess omentalisation
Abscess Sx
- debridement of necrotic pancreas,
- partial pancreatectomy,
- cholecystoenterostomy,
- provision of drainage,
- omentalization,
surgical placement of some form of feeding tube is appropriate
bacterial culture
- reliability of bacteriologic culture depends on the tissue obtained for culture.
- Specimens from multiple sites in the abdominal cavity should be submitted
How do you diagnose a pancreatic pseudocyst?
Aspiration of the fluid filled contect and assessment of concentration of amylase and lipase. Higher concentrations in the pseudocyst fluid than of serum confirms the diagnosis
majority of pseudocysts are reported in the left limb
When does a pancreatic pseudocyst require surgical intervention?
What are the surgical treatment options?
- Clinical signs perist after aspiration
- Pseudocyst enlarges or fails to resolve
- Percutaneous aspiration is not possible
- Recurrence
- Causing a pancreatic duct obstruction
Treatment options:
- u/s guided aspiration (may need repeat)
* Omentalisation
* Cystoduodenotomy
* Cystojejunostomy
* Cystogastrostomy
* Complete excision
>75% have been treated successfully and survived
Pancreatic Torsion
of the free left limb
What id the prognosis for pancreatic carcinoma in dogs and cats?
What biochemiscal parameter may be suggestive of pancreatic carcinoma in dogs?
Pancreatic Exocrine Tumors
extremely poor
- Aggressive behaviour,
- majority have metastasised to liver and local lymoh nodes at time of diagnosis,
- resistant to chemotherapy.
- Surgical options should not be highly considered but if obstructive, a gastrojejunostomy can be considered for palliation.
Serum lipase concentration over 25x the normal upper limit
- In many cases, pancreatic carcinoma cannot be differentiated from pancreatitis on the basis of clinical signs, diagnostic imaging, or serum biochemistry results.
Insulinoma
Pathophysiology
from beta cells
- 60% of insulinomas are carcinomas; the remainder are adenomas
- On histology, many of these tumors appear benign; however, their biologic behavior is aggressive
- 50% of affected dogs having metastatic disease at the time of diagnosis
- lymph nodes and liver are the most common sites of metastasis
- When glucose concentrations are less than 80 mg/dL in a normal animal, insulin secretion is inhibited.
- beta cell tumors secrete insulin in excessive amounts, resulting in profound, and in some cases life-threatening, hypoglycemia.
- hyperinsulinism with concurrent hypoglycemia results
CS
-9 to 10 years
- clinical signs related to hypoglycemia, including seizures, weakness, collapse, ataxia, and mental dullness.
- precipitated by excitement, exercise, or fasting
How can an insulinos lead to irreversible para/tetraparesis and ataxia?
Chronic hypoglycaemia can lead to neuronal demyelination and axonal degeneration. Can also cause facial nerve paralysis, oesophageal dysfunction, decreased anal tone and peripheral polyneuropathies
How do you diagnose an insulinoma?
Normal to increased insulin concentrations at a time of documented hypoglycaemia is diagnostic. Decreased fructosamine concentration is also supportive.
normal [5 to 26 µU/mL]
- On cytology, beta cell tumors lack the pink zymogen granules commonly seen in exocrine cells
imaging
- Ultrasonography for the diagnosis of insulinoma and evaluation for metastatic disease.
- pancreatic mass and abdominal metastasis identified in 56% and 19% of cases
- contrast u/s: uniformly hypervascular and may therefore be differentiated from the more hypovascular exocrine carcinoma
- CT reportedly had increased sensitivity
What treatment options are available fore pre-op stabilisation of blood glucose concentrations prior to surgery?
- Small, frequent feeds of a high protein, high complex carbohydrate diet
- Glucocorticoid therapy - Increases hepatic glucose production and decreases cellular glucose uptake
- 5% dextrose CRI - Can stimulate insulin secretion causing hypoglycaemia so close monitoring is necessary
- Glucagon CRI - Use for intractable hypoglycaemia
- Avoid pre-op fasting, instead offer a small amount of canned food 2-3hr prior to surgery
surgery
- surgery is not usually curative because of the frequency of metastatic disease
- reducing the amount of neoplastic tissue will improve response to medical management and survival time
- Frequent monitoring of [glucose] throughout the procedure critical to prevent life-threatening hypoglycemia
- 80% of dogs, a solitary 0.5 to 4 cm nodule is evident
- A partial pancreatectomy is performed (vessel sealing device quicker, no pancreatitis)
- occasionally tumor thrombi that extend into the pancreaticoduodenal vein
- Liver metastases are frequently identified as pale nodule
- Pancreatitis may develop after manipulation of the pancreas
What can be done during surgery of the insulinom cannot be identified? What is a reported complication of this technique?
If cannot identify insulinoma can inject 3mg/kg of 1% methylene blue in 250ml of 9% saline over 30 minutes. Maximal staining is achieved within approx 30 min.
- Heinz body anaemia has been reported as a complication
What are the options of treatment of persistent or recurrent hypoglycaemia after surgical removal of an insulinoma?
Medical management
* Streptozocin - a chemotherapeutic, nitrosurea antibiotic which selectively destroys beta cells in the pancreas or at metastatic sites. Requires saline diuresis during administration to minimise nephrotoxicity (Adverse events includ GI toxicity 63% and diabetes mellitus 42%)
* Diazoxide - Inhibits insuline secretion and stimulates hepatic gluconeogenesis
* Octreotide - Long-acting systemic somatostatin analogue. Inhibits insulin secretion and synthesis. Insulin suppression only lasts 3-4hr
* Glucocorticoids
What is the prognosis for insulinomas in dogs?
Depends on stage of disease at time of diagnosis and what paper you read..
- Dogs undergoing surgery +/- medical management more likely to become euglycaemic, remain euglycaemic and have longer survival than those which do not undergo surgery (Tobin et.al)
- No detectable mets at time of surgery remained euglycaemic for 14 months vs 2.5m with mets. MST with no detectable mets at time of surgery 18m vs 7-9m with mets (Caywood et.al)
- MST for partial pancreatectomy 785d, if treated with pred at time of relapse increased to 1316d (Polton et al)
- Poorer prognosis if tumour >2cm, has metastasised to the liver and lymph nodes, Ki67 index >2.5% (Buishand et al)
What is a gastrinoma?
Malignant transformation of the somatostatin-secreting delta islet cells into cells which secrete excessive gastin.
- This results in gastric acid hypersecretion and subsequent oesophageal and gastroduodenal erosions and ulcerations
- Metastasis at the time of diagnosis in approximately 70%
non–beta cell neuroendocrine tumor
What term is given to the syndrome in which there is a non-beta cell neuroendocrine pancreatic tumour, hypergastrinaemia and gastrointestinal ulceration?
- Zollinger-Ellison syndrome
How do you diagnose a gastrinoma?
increased fasting gastrin serum concentration is highly suggestive of gastrinoma, especially in the prescense of gastric hyperacidity (pH<3)
tumors are extremely small, imaging often fails to identify the tumor
What are the treatment options for gastrinoma?
Medical management:
* proton pump inhibitors (omeprazole)
* Gastroprotectants (sucralfate, misoprostal)
* Octreotide - Suppresion of gastrin secretion with a somatostatin analogue
Surgical Management
* Partial pancreatectomy with staging biopsies of LNs and liver (approx 70% mets at time of diagnosis)
* Resection of GI ulceration if necessary
What is the main presenting complaint for dogs with a glucagonona (rare)
pancreatic alpha cells
Superficial necrolytic dermatitis (hepatocutaneous syndrome).
CS
- primary effect is to increase blood glucose concentrations, affected dogs may have hyperglycemia, or even overt diabetes mellitus resistant to insulin treatment
Prognosis for glucagonoma is poort due to high rate of surgical complications and high rate of early metastasis
Laparoscopic resection of pancreatic masses in 12 dogs
Poggi 2024
Retrospective study.
Pancreatic tumors were located in the left lobe (7), in the right lobe
(4) and in the body of the pancreas (1). A 3- or 4-port technique
Ligasure in nine dogs, a harmonic scalpel in two dogs
no conversion to open laparotomy
All dogs survived the surgical procedure,
were discharged
Major complications (2/12). The first dog had idiopathic seizures, The second
dog had signs of pancreatitis
particularly for small tumors located in the distal aspect of the pancreatic lobes.
should be considered that large tumors (>60 mm)
located in the left limb or in the body of the pancreas
could be more challenging to excise using laparoscopy,
and an open approach should be considered.
Laparoscopic partial pancreatectomy of the left limb using
a harmonic scalpel in nine cats
Case 2024
(1/9; 11%) resulting
in minor hemorrhage from a caudal splenic vein branch. A grade 2 postoperative
complication occurred within 3 days after surgery in one cat (1/9; 11%),
involving localized, sterile peritonitis
Laparoscopic pancreatectomy of the left limb
results in adequate exocrine and endocrine function in the long-term
Canine insulinomas appear hyperintense on MRI T2-weighted
images and isointense on T1-weighted images
Blood glucose monitoring during surgery in dogs
to assess completeness of surgical resection
of insulinoma: 11 cases
Collgros 2023
blood glucose increased in 11/11 cases intra-op (mean increase 6.35±4.5mmol/L)
- ongoing exploration and resection of abnormal tissue until increased glucose noted
- initial increase then decrease → subsequent increase following further excision
- MST 762d
- 3/11 metastatectomy → longer survival
- tumour stage not associated with outcome
Left pancreaticoduodenostomy after removal of the right
lobe and the head of the pancreas in a cat
Benoît Cruciani 2022
excision of the right lobe and head of pancreas → left pancreaticoduodenostomy in
a cat
- cat presented with fluid-filled cavity in place of the right pancreatic duct
- excision of cavity and right pancreatic lobe and body
- 1.5cm strip of cyst/pancreas wall adjacent to duodenum not dissected
- left pancreatic duct isolated → end-to-side anastomosis to duodenum
- Left pancreatic duct was severely dilated
- no complications; death due to metastatic carcinomatosis at 225d post-op
Perioperative outcomes in dogs and cats
undergoing pancreatic surgery: 81 cases
(2008-2019)
M. L. Wolfe 2022
partial pancreatectomy 63.2%
(36/57) and in cats was pancreatic biopsy 62.5% (15/24).
The most common histologic diagnosis in
dogs was pancreatic islet cell carcinoma 50.9% (29/57) and in cats was pancreatitis 41.7% (10/24).
mortality rate 14d
10.5% (6/57) mortality rate in dogs
20.8% (5/24) mortality rate in cats.
- Three dogs were euthanased and three died on their own.
Three cats were euthanased and two died on their own.
86.5% survival rate in the first 14 days
Clinical findings, neurological manifestations and survival of dogs with insulinoma: 116 cases (2009-2020)
D. Ryan 2021
- clinical signs: weakness (59.5%), seizures (33.6%), altered mentation (27.6%)
- 32/116 altered neurological examination: obtundation, decreased withdrawal, absent menace
- overall survival: surgery 20m; medical 8m – associated with px
- presence of metastasis → shorter survival
The appearance of canine insulinoma
on dual phase computed tomographic
angiography
P. Coss 2021
pancreatic nodule (33/35 detected) with hyperattenuation in arterial phase (27/33 overall; 20/21 confirmed insulinoma detected)
- mean size 15.1mm
- hypoattenuation and isoattenuation uncommon; deformation of pancreatic shape in 18/21 confirmed, 8/12 suspected insulinoma
Prevalence of portal vein thrombosis
detected by computed tomography
angiography in dogs
L. E. von Stade
Twenty-eight dogs (13%) had portal vein thrombosis. The pancreatitis category contained the highest percentage of portal vein thrombosis at 42%
Aupperle-Lellbach 2019 – characterization of pancreatic carcinoma in 22 dogs and review
- simultaneous pancreatitis may mask detection of carcinoma
- histological types: acinar more common than ductal
- acinar carcinoma growth patterns: solid, acinar, clear cell, mucinous, trabecular, rosette-like
- single pattern or combinations
- clinical findings in pancreatic carcinoma non-specific
- metastasis in 14/22 (63.6%) - liver, mesenteric LN, spleen, omentum
- survival time 1-28d – 6 euthanased intra-op
