Ultra Rare Pancreatic Disease in Cats
Patient Information:
Age: 15 years, 9 months
Gender: Male Neutered
Breed: DLH
Species: Feline
History:
This patient has experienced vomiting, on and off, for the past 2 years. Patient was recently treated at an emergency facility for inappetence and frequent vomiting. Symptomatic therapy was initiated. Recommendation for abdominal ultrasound was made at the time of the emergency visit
Significant Ultrasonographic Findings:
Liver: Subjectively normal size, normal shape and mildly hypoechoic echogenicity with coarse echotexture. No focal lesions are appreciated.
The gall bladder is moderately distended with anechoic and dense hyperechoic organizing bilious sludge adhering to the gallbladder wall. Gallbladder wall appears thickened with areas of severely hyperechoic comet-tails concerning for emphysematous cholecystitis. Significant common bile duct dilation is seen, max diameter measured approximately 0.5 cm. The gallbladder is diffusely severely dilated to the level of the major duodenal papilla. There is a homogenous hyperechoic mass in the region of the major duodenal papilla measuring approximately 0.4 cm diameter.
Kidneys: Normal size (Lt/Rt = 3.2/3.3 cm) and shape with hyperechoic renal cortices which are disproportionately enlarged and decreased corticomedullary dimensions. No pyelectasia visualized.
Spleen: Enlarged size (1.2 cm at the hilus), shape, and echogenicity. No focal lesions appreciated.
Intestines: The stomach is empty and collapsed with normal rugal folds and layering. The pylorus is free of obstruction. Some small intestinal loops have prominent muscularis bowel layering, increased thickness, and subjectively normal motility. No loss of layering, obstruction, or masses seen. The colon has normal wall thickness and layering throughout.
Duodenum: 3.5 mm
Jejunum: 2.1-2.8 mm
Colon: 1.6 mm
Pancreas: Enlarged size, deranged shape, and heterogenous hypoechoic echogenicity. The pancreatic tissue is diminished due to diffuse severe pancreatic duct dilation, max dilation is approximately 1.0 cm.
There appears to be an irregular crystalline severely hyperechoic calculus within the lumen of the distal left pancreatic duct measuring 1.1 x 0.7 cm, there are smaller mineral opacities throughout the pancreas.
Peripancreatic fat is severely hyperechoic.
Serosal surfaces: Mesentery throughout the abdomen is diffusely hyperechoic.
Abdominal ultrasound interpretation:
Liver : the findings are mild - DDx:
a) Chronic vs. Acute hepatitis or cholangiohepatitis (bacterial vs. sterile vs. toxin)
b) Steroid hepatopathy / Vacuolar hepatopathy / Glycogen storage disease
c) Infiltrative neoplasia (lymphosarcoma)
d) Hepatic lipidosis
Pancreas DDx: pancreatitis vs. pancreatic neoplasia (adenocarcinoma) vs. remotely abscess formation (pancreatic vs. free abdominal). Pancreatitis is likely in this case but cannot rule-out pancreatic neoplasia. Base prognosis on response to therapy.
Intestines: the findings are mild-moderate - DDX: inflammatory bowel disease vs. infiltrative neoplasia (small-cell lymphosarcoma). Inflammatory bowel disease in cats can be chronic and long-standing but in many cases will transition into small-cell lymphosarcoma and it is not possible with ultrasound alone to determine in this case whether the disease is benign or infiltrative.
[The combination of findings is suggestive feline triaditis (inflammatory bowel disease, pancreatitis and cholangiohepatitis).]
Common bile duct dilation: the findings are severe- DDX: pancreatitis, cholangitis, hepatitis, duodenitis, neoplasia, cholelithiasis, fibrosis, less likely mucus plugs, foreign bodies, liver flukes
Pancreaticolithiasis: the findings are severe - DDx: chronic pancreatitis, pancreatic nodular hyperplasia, pancreatic pseudobladder, duplicate gallbladder, inflammatory bowel disease and exocrine pancreatic insufficiency; the last may result from pancreatic duct obstruction
Splenomegaly: the findings are mild - DDx: neoplasia (mast cell, lymphoma, carcinoma, metastatic disease) vs. fungal (Histoplasmosis) vs. reactive lymphoid hyperplasia vs. splenitis vs. congestion vs. extramedullary hematopoiesis (EMH).
Images:
Image 1: Sagittal view of the distal left pancreas with mineralized structure(pancreaticolith) within the pancreatic duct.
Image 2: Sagittal image of the major duodenal papilla which appears abnormally enlarged due to suspected mass effect.
Image 3:Transverse view of the common bile duct which appears abnormally dilated. Dilation likely is secondary to blockage of flow at the level of the major duodenal papilla.
Image 4: Transverse image of the pancreatic body with severe duct dilation.
Image 5: Sagittal view of the right pancreas showing a severely dilated right pancreatic duct.
Image 6: Sagittal view of the gallbladder showing suspected gas infiltration of the gallbladder wall. Emphysematous cholecystitis is likely a sign of severity of infection in the gallbladder.
Recommendations:
Referral of this patient to a veterinary surgeon for advanced imaging (i.e. CT scan) and to discuss possible therapeutic options is highly recommended
Cholecystocentesis with culture and sensitivity is recommended. Initiation of fluoroquinolone +/- metronidazole for suspected hepatitis/cholangitis is recommended. It is NOT recommended to treat patients with evidence of common bile duct obstruction with Ursodiol.
Appropriate pain medication, anti-emetics and other supportive care therapy is recommended.
Thoracic radiographs (3-view, metastasis check) is recommended.
If further diagnostics are not pursued, consider palliative/symptomatic therapy to maintain quality of life.
Discussion:
Pancreaticolithiasis is a well-documented human medical condition, however as of 2021 there have been only 5 reported cases in felines based on searches in veterinary literature. Pancreatolithiasis can occur in up to 50–90% of humans as a sequela to chronic pancreatitis, regardless of the etiology. In most cats, as in humans, the pancreatic duct joins the common bile duct before entering the duodenum at the Ampulla of Vater, behind the duodenal papilla. Pancreatolithic obstruction of the pancreatic duct can result in the development of ductal, and subsequent parenchymal hypertension, leading to pain as the predominant clinical sign. The most frequently identified causes of chronic pancreatitis in humans are idiopathic chronic pancreatitis and chronic pancreatitis secondary to chronic alcoholism. Pancreatolithiasis has been reproduced experimentally in dogs by surgically induced partial obstruction of the pancreatic duct; however, the etiology of pancreatolith formation in cats is poorly understood.
In human pancreatolithiasis, a reduction in pancreatic stone protein is thought to result in a supersaturation of calcium carbonate, which is then deposited over an inner nidus to form a pancreatolith. Given that most reported feline pancreatoliths to date are composed of 100% cal-
cium carbonate, it is postulated that a similar pathomechanism may be involved in feline pancreatolith formation. Furthermore, [a recent reported] case adds weight to the association between pancreatolithiasis as a sequela to chronic pancreatitis, as reported in the human literature.
Disease associations reported in cases of feline pancreatolithiasis include chronic pancreatitis, pancreatic nodular hyperplasia, pancreatic pseudobladder, duplicate gallbladder, inflammatory bowel disease and exocrine pancreatic insufficiency; the last may result from pancreatic duct obstruction.
Previously documented hematological abnormalities in cats with pancreatolithiasis include non-regenerative anemia and neutrophilia, although one case presented with mild neutropenia; serum biochemistry abnormalities included increases in AST and ALT activity, hypoalbuminemia and hypocholesterolemia. Interestingly, in 3/4 cases in which serum biochemistry values are reported, ALP, gamma-glutamyl transferase and bilirubin were within normal limits indicating that biochemical evidence of cholestasis is not always a significant feature in these cases. This hypothesis was supported in [a recent] case by the lack of extrahepatic biliary tract obstruction, wherein normal common bile duct dimensions were present ultrasonographically. Hypercalcemia has not previously been reported in feline pancreatolithiasis. In fact, one previous case had hypocalcemia, which was suspected to result from underlying pancreatitis due to sequestration of calcium in peripancreatic fat as a result of saponification, increased circulating free fatty acid concentrations, increased calcitonin concentrations secondary to hyperglucagonemia and deficiency secondary to hypomagnesaemia.
While idiopathic hypercalcemia has been reported to be the most common etiology for feline hypercalcemia, followed by chronic kidney disease (CKD) and neoplasia, this is a diagnosis of exclusion. The lack of parathyroid hormone (PTH), PTH-related peptide (PTHrP) and vitamin D metabolite testing represents a limitation of [a recent] report. Despite the histological evidence of CKD, renal secondary hyperparathyroidism was deemed unlikely as this patient was non-azotemic and normophosphatemic. Previous reports of feline pancreatolithiasis in which histopathology of the pancreas was performed were all consistent with chronic pancreatitis, which correlates with the histopathological findings in [one] case. However, [one recent study was] the first report to describe histopathologically confirmed triaditis as a disease associated with feline pancreatolithiasis. While the underlying etiology in the majority of cases of feline pancreatitis remains unknown, reported causes include pancreatic ductal obstruction, acute hypercalcemia, pancreatic neoplasia, trauma, ischemia and organophosphate intoxication. Associations with T. gondii and certain viral diseases (such as coronavirus, parvovirus, herpesvirus and calicivirus infections) have been recognized but are uncommon. While it is assumed that chronic pancreatitis is the primary disease process leading to pancreatolithiasis, it is possible that acute hypercalcemia and ductal obstruction due to the pancreatolithiasis itself led to acute exacerbation in this case.
Serum biochemistry derangements are often vague and non-specific for pancreatic disease; DGGR lipase has been reported to have excellent sensitivity (100%) and good specificity (63%) for acute pancreatitis but poor sensitivity (48%) in chronic pancreatitis. A finding of low fTLI is suggestive of a >90% reduction of exocrine pancreatic function and is regarded as the gold-standard test when diagnosing exocrine pancreatic insufficiency but it is poorly sensitive for pancreatitis. The lack of decrease in fTLI, despite histopathological evidence of pancreatic acinar atrophy and ductal obstruction, is an interesting finding. It has been described that patients with EPI may have normal TLI if the pancreatic duct is obstructed; however, no cases have been reported in the literature. The mechanism of this is unclear; however, the authors postulate ductal obstruction may result in an inability of trypsinogen to pass into the duodenum and therefore it is subsequently reabsorbed into the circulation. Pancreatic inflammation secondary to obstruction could also play a role by causing increased leakage of trypsin and trypsinogen into the vascular space, resulting in subsequently increased amounts in the circulation. Interestingly, a study evaluating fTLI in cats with pancreatitis found 5/9 cats with pancreatic fibrosis to have fTLI within normal reference intervals, two of which had histological evidence of severe exocrine atrophy. The findings of normal fTLI in both [the most current] case and those in the aforementioned study highlight the possibility that fTLI can be unremarkable, despite histological evidence of pancreatic exocrine atrophy. Trypsinogen is typically cleared by glomerular filtration and another explanation for normal fTLI in [the most recent] case is that the patient may have had reduced excretion due to CKD, leading to falsely elevated fTLI. Additionally, the histopathological report of 95% acinar atrophy is a subjective assessment based upon visualization of the histological sections and may not completely reflect functional capacity of the pancreas.
Treatment options in human medicine for pancreatolithiasis consist of endoscopic management, which includes extracorporeal shockwave lithotripsy and stone extraction; surgical management, which includes pancreatic resection; and medical dissolution with trimethadione; however, the last is rarely used owing to limited evidence and significant side effects. Extracorporeal shockwave lithotripsy has been reported to achieve complete clearance in 80% of humans; however, this is not routinely available in veterinary medicine. Treatment options for pancreatolithiasis are limited in cats, likely as a consequence of both the paucity of available literature and rarity of this condition. Although surgical removal of pancreatoliths has been described in three cats, with survival times ranging from 9 days to 2 years postoperatively, with the third case lost to follow-up having survived 5 days to discharge, no other treatments have been reported.
* Frederik Allan , Anne-Lorraine Peschard,Luca Schiavo, Will Bayton, Davide Corbetta, and Katie E McCallum; “Obstructive Pancreatolithiasis in a Cat with Triaditis and Concurrent Hypercalcaemia” Journal of Feline Medicine and Surgery Open
Reports,18; 2021
Patient outcome:
This patient was advised of recommendations by the primary care veterinarian. After multiple calls to obtain updates on Oliver’s condition, no communication with the owner could be achieved. Patient outcome was unfortunately lost to follow up.
Sonographer:
Mallory Repellin, DVM
A very special ‘thank you’ to Dr. Julie Augustine from Montgomery Animal Hospital for sharing patient details and allowing for an in-depth discussion of their patient.