Pancreatolithiasis and Pancreatic Pseudobladder Associated With Pancreatitis in a Cat
Pancreatolithiasis has been documented to occur naturally in humans and cattle. It has been associated with chronic pancreatitis in humans, and, when found, it may signify the presence of chronic pancreatic disease. This is the first report of a case involving a cat that had both an apparent obstruction with pancreatolithiasis as well as concurrent evidence of chronic pancreatic changes on histopathological evaluation. Additionally, this case documents the presence of a suspected congenital abnormality of a feline exocrine pancreas.
Case Report
A 14-year-old, male neutered Maine coon cat was referred to the University of California Veterinary Medical Teaching Hospital (VMTH) for suspected pancreatitis secondary to obstruction of the pancreatic duct by a stone. The cat originally presented to a local veterinarian for a 1- to 2-day history of lethargy, vomiting and diarrhea, and hematuria and a 2-week history of weight loss. Because of progression of his clinical signs despite antibiotic therapy, the cat was subsequently referred to a local specialty hospital. Abnormalities identified on a complete blood count (CBC), serum biochemical analysis, urinalysis, and total thyroxine (TT4) evaluation included a nonregenerative anemia with a hematocrit (Hct) of 26.3% (reference range, 29% to 45%), mature neutrophilia of 17.2 × 103 cells/μL (reference range, 2.5 to 12.5 × 103 cells/μL), aspartate transferase (AST) of 226 IU/L (reference range, 5 to 55 IU/L), albumin of 2.1 g/dL (reference range, 2.4 to 4.1 g/dL), globulin of 3.2 g/dL (reference range, 3.4 to 5.2 g/dL), and TT4 of <0.4 μg/dL (reference range, 0.7 to 5.2 μg/dL). Abdominal radiographs revealed mineral densities in the cranial abdomen and the urinary bladder. An abdominal ultrasound examination was performed and revealed a small amount of free abdominal fluid, a suspected dual gallbladder with calculi, cystic urinary calculi, a stone-obstructed dilated pancreatoduodenal duct, and an enlarged pancreas.
On physical examination at the VMTH, the cat was lethargic, had reduced muscle mass, and an unkempt hair coat. Body weight was 5.0 kg, despite a large body frame. Rectal temperature was 38.9°C. Heart rate was 220 beats per minute, and a 2/6 left-sided systolic murmur with normal breath sounds was ausculted. The abdomen was pendulous and non-painful; calculi were palpable within the urinary bladder. A CBC and liver biochemical analysis revealed a mild normocytic, normochromic, nonregenerative anemia with a Hct of 24.4% (reference range, 30% to 50%) and an AST of 137 IU/L (reference range, 12 to 46 IU/L).
An abdominal ultrasound revealed two distinct gallbladders and multiple shadowing calculi present within the duplicate gallbladder [Figure 1A]. The pancreatic body and left limb were easily visualized, and the surrounding mesentery was moderately echogenic. A calculus was identified within the parenchyma of the pancreas and appeared to be obstructing the pancreatic duct [Figure 1B]. The common bile duct appeared thickened. Other abnormalities included a small amount of ascitic fluid, multiple cystic lymph nodes within the midabdomen, diffuse hypoechoic nodules in the spleen, and calculi within the urinary bladder.
Surgery was recommended to relieve the pancreatic duct obstruction, remove the calculi, place a jejunostomy tube (J-tube) for enteral feeding, and perform biopsies. An echocardiogram was performed preoperatively and revealed mild to moderate tricuspid regurgitation with mild to moderate enlargement of the right atrium and ventricle. The changes were not thought to represent significant limitations for anesthesia or other planned treatment.
On abdominal exploration, the duplicate gallbladder seen on ultrasonography was determined to be a pancreatic pseudobladder, filled with opaque material and calculi, that had an exiting duct entering the pancreatic parenchyma and connecting it with the pancreatic ductal system [Figure 2]. Fluid was aspirated from both the gallbladder and pseudobladder and submitted for cytopathology and culture. The pancreas was enlarged, hyperemic, and granular; within the body of the pancreas, a hard and round structure could be palpated within the body. The pseudobladder was dissected away from the gallbladder and surrounding liver parenchyma. The duct exiting the pseudobladder was incised longitudinally to the level of the stone within the pancreatic parenchyma. The stone was removed, and the duct was flushed with sterile saline toward the pancreas. Sterile saline was seen coming from the major papilla, which could be observed from a previously performed duodenotomy, demonstrating the communication between the pseudobladder duct and the pancreatic ductal system. The duct of the pseudobladder was ligated at the level where the stone had been removed, allowing extirpation of the pseudobladder and its duct. The urinary calculi were removed by standard ventral-approach cystotomy. A splenectomy was performed, and biopsies of the liver, pancreas, stomach, duodenum, jejunum, and mesenteric lymph node were submitted for histopathology. All calculi were submitted for analysis. A J-tube was placed using a size 5-French red rubber tube.
Postoperatively, the cat was managed with crystalloid and colloid fluid support. With cultures pending, ampicillin (25 mg/kg body weight, intravenously [IV] q 6 hours) and enrofloxacin (4.5 mg/kg body weight, IV q 12 hours) were started. The day after surgery, water was administered through the J-tube, followed by a commercial, human, low-fat liquid dieta modified by the addition of 19.8 g per day of protein supplement,b 250 mg per day of taurine, and 1,000 mg per day of arginine at 5 mL per hour. Over 2 days, this was increased to a maintenance rate of 15 mL per hour.
Cytopathology of the material removed from the pseudobladder revealed markedly purulent inflammation with gram-negative rods seen on examination of a Gram stain smear. Culture of this material revealed growth of Escherichia coli susceptible to all antibiotics tested, including ampicillin and enrofloxacin. Culture of the bile was negative for bacteria.
On histopathological examination, there was evidence of severe, diffuse, chronic, suppurative and necrotizing pancreatitis with duct ectasia, interstitial fibrosis, and peripancreatic fat necrosis [Figures 3A, 3B]. Additionally, the islets of the pancreas had severe multifocal amyloidosis; however, immunohistochemical stains revealed numerous islet cells that were positive for insulin, stomatostatin, and glucagon. The pseudobladder was consistent with moderate, diffuse, chronic, suppurative dochitis. Hepatic histopathological findings included moderate, diffuse, acute, neutrophilic hepatitis with multifocal necrosis and Kupffer cell hyperplasia as well as mild, multifocal, chronic, lymphocytic portal hepatitis. Sections of duodenum revealed moderate, diffuse, chronic, lymphoplasmacytic and neutrophilic enteritis with villus atrophy, crypt abscess formation, and acute hemorrhage. The spleen was found to have severe, multifocal, chronic lymphoid hyperplasia within the marginal zone. No other significant histopathological lesions were identified.
The calculi from the pancreas, pseudobladder, and urinary bladder were submitted for analysis by quantitative optical crystallographic analysis.c The exteriors of the pancreatic and pseudobladder calculi were rough-textured, coral-like in appearance, and light tan in color; all were composed of 100% calcium carbonate [Figure 4]. The urinary calculi were composed of 100% whewellite (i.e., calcium oxalate monohydrate).
The cat’s attitude improved markedly over the next several days. He was alert, interactive, and had no pain on abdominal palpation. An abdominal ultrasound was repeated 8 days after the surgery and revealed a less visible pancreas with mildly echogenic mesentery—changes that were consistent with resolving pancreatitis. At that time and while still receiving J-tube feedings, the cat was offered water orally and drank small amounts. On day 9 postoperatively, the patient was offered and ate a small amount of boiled chicken. In the evening, several hours following the oral meal, the cat began vomiting and was found to be obtunded and hypothermic with a temperature of 33.5°C. Blood work performed included a packed cell volume, total solids, electrolytes, and lactate. The only significant abnormality was a lactate of 6.06 mmol/L (reference range, <1 mmol/L), which was consistent with poor perfusion or oxygenation delivery. Despite fluid resuscitation, oxygen supplementation, and warming, the cat remained unresponsive. Due to the patient’s deterioration and guarded prognosis, the owners requested euthanasia; a necropsy was declined.
Discussion
Most cases of feline pancreatitis, acute or chronic, are thought to be idiopathic in etiology.1– 3 Previously specified reported causes include trauma, ascending bacterial infections, herpes or feline infectious peritonitis viral infections, toxoplasmosis, infestation by flukes (e.g., Amphimerus pseudofelinus), or organophosphate exposure.1 3– 9 Additionally, some causes which are well documented in dogs and humans, including ischemia or drug exposure, may also be possible etiologies in cats.10 11 In humans, gallstones have been considered one of the most common causes of acute pancreatic disease,10 while pancreatic calculi are considered rarer causes of obstruction and tend to be associated with chronic pancreatic disease.12– 14 To the authors’ knowledge, this is the first clinical report of pancreatitis associated with a pancreatic calculus in the cat.
Definitive diagnosis of acute or chronic pancreatitis in the cat may be challenging. Historical and physical examination findings can be vague, and routine hematological and biochemical tests may be either nonspecific or of debated sensitivity, including serum amylase, serum lipase, or feline trypsin-like immunoreactivity.15 16 With the added possibility of concurrent hepatic or intestinal disease, the diagnosis of pancreatitis is difficult without a biopsy. Radiographic and ultrasonographic imaging have improved efforts to arrive at a diagnosis in some cases of feline pancreatitis, and computed tomographic imaging has been recently investigated as an alternative imaging modality.3 15 17 18 Although radiography is considered in human medicine to be the simplest and least expensive method for detection of pancreatic calculi, ultrasonography has been used to evaluate for pancreatic stones and may help to localize them within specific pancreatic ducts.19 This cat had ultrasonographic changes previously reported in cases of feline pancreatitis, including a dilated pancreatic duct and hyperechoic mesentery surrounding an easily visible pancreas.17 In addition, ultrasonography permitted a diagnosis of a pancreatic duct obstruction with a pancreatolith and identified an anomalous cystic structure with calculi, determined following surgery to be a pancreatic pseudobladder.
Pancreatic stones in humans have been documented as early as the 17th century and have been associated with chronic pancreatitis.13 14 Although it has been debated whether pancreatic calculi are equivalent to parenchymal calcification, the current opinion is that stones are formed within pancreatic ducts and not the parenchyma.20 The etiology of pancreatic calculus formation is not completely understood. One hypothesis is that partial obstruction of pancreatic ducts and stasis of pancreatic secretions during chronic pancreatitis are prerequisites for pancreatic stone formation.13 Experimental evidence in dogs supports the partial obstruction hypothesis.21 Additionally, the clinical significance of pancreatic stones is not always clear, as they have been implicated as a cause of pain in some patients with chronic pancreatitis22 and have also been found in asymptomatic patients having no history or histopathological proof of pancreatic disease.23
Naturally occurring pancreatic stones have been reported in humans and cattle13 14 23 24 and have been experimentally induced in dogs.21 Pancreatic stones have been composed predominantly of calcium carbonate in humans, cattle, and dogs.21 24 25 Stone analysis of the pancreatic calculus in the cat of this report revealed a similar mineral composition to those reported in other species. Additionally, the cat in this report was found to have pancreatic fibrosis suggestive of previous acute bouts of pancreatitis or chronic pancreatitis, another finding common to pancreatolithiasis in humans.14 In humans, further investigation of pancreatic calculi beyond the mineral component has identified a protein, originally called pancreatic stone protein (PSP), that seems to form the matrix of most pancreatic stones. The protein has been identified in pancreatic secretions from individuals with and without stones.26 Recently this same protein was shown to be an inhibitor of calcium carbonate crystal formation and has provided an explanation for the ability of normal pancreatic juice to be supersaturated with the crystal components without stone formation.27 Pancreatic stone protein was renamed Lithostathine, meaning “stone has been stopped.”28 Lithostathine appears to play a role in inhibiting calcium stone formation, analogous to other proteins like statherin, gallstone protein, and nephrocalcine, which have been identified in other calcium-containing fluids such as saliva, bile, and urine, respectively.29 Lithostathine has also been detected in other mammalian species (although the cat was not among the species investigated) and was found to have similar inhibitory characteristics as in humans.30 The cat in this report had calculi in the pancreas and pancreatic pseudobladder as well as in the urinary bladder. Although all the calculi contained calcium, the other components (i.e., carbonate or oxalate) varied between the two organ systems. An underlying cause such as hypercalcemia was not identified in the cat’s presurgical evaluation. While it is the authors’ belief that the calculi arose from unrelated processes, a possible generalized deficiency in stone-inhibiting proteins could not be ruled out. Evaluating the presence and role of lithostathine and other stone-inhibiting proteins in feline calculi formation requires further investigation.
Besides the pancreatic calculus, the other unusual finding associated with the pancreas in this cat was the presence of a pancreatic pseudobladder filled with purulent material. Histopathology confirmed that the structure was lined by epithelial cells, indicating that it was not a pseudocyst. The infection present was suspected to be a retrograde infection of the pancreatic ductal system. Although the aspirate of bile from the gallbladder was negative on culture, and there were no organisms seen on biopsy of other organs, the history of antibiotic usage in this patient at the referring veterinary hospital makes the true distribution of infection impossible to document. Pancreatic anatomical anomalies, such as pancreatic bladders, have been mentioned in the veterinary literature, but they are likely rare.2 The authors’ terminology of pancreatic pseudobladder was chosen over pancreatic bladder, because the normal anatomy of the pancreatic ductal system in common domesticated mammals does not include a true bladder for excretory secretion storage, as seen in the biliary and urinary systems. Structures with a similar ultrasound appearance include pancreatic cysts or pseudocysts, a massively dilated pancreatic duct, pancreatic abscess, or extrapancreatic structures such as a bipartite gallbladder; some of these structures have been previously identified in cats.18 31 Congenital pancreatic anomalies, including cysts, have been described in humans but are poorly documented in animals.32 If clinical signs develop with congenital pancreatic abnormalities, the age for onset of clinical signs is generally in the juvenile years. Despite the advanced age of the cat at the time of discovery of the pseudobladder, the structure’s relation to the liver, pancreas, and pancreatic ductal system is consistent with a congenital anomaly. The authors suspect that in this patient, the pancreatic stones formed over time, following the development and progression of chronic pancreatic inflammation, similar to pancreatic stones in humans. The stones may have been a predisposing factor for the pseudobladder infection.
Based on the histopathological evaluation of pancreatic tissue, the cat reported here was suspected to have a congenital anatomical pancreatic anomaly and chronic pancreatitis not recognized by the owner. Clinical signs were vague and primarily consisted of weight loss with more acute vomiting and diarrhea. It is surmised that the stones formed during the historical occult disease, ultimately leading to acute pancreatic ductal obstruction and pancreatitis. Ultrasonographic findings were useful in identifying pancreatolithiasis and other anatomical anomalies. Surgical exploration of the abdominal cavity was required to remove the stones in the pancreatic duct, pseudobladder, and urinary bladder. Similar to what is reported in humans, the pancreatic ductal stone in this cat with chronic pancreatitis was composed of calcium carbonate. The mechanism of stone formation remains unclear.
Ensure Light; Abbott Laboratories, Abbott Park, IL
ProMod; Ross Products Division, Abbott Laboratories, Columbus, OH
Urinary Stone Analysis Laboratory, University of California, Davis, CA
Acknowledgments
The authors thank Dr. Andrea Struble of Pacific Veterinary Specialists and Emergency Service, Capitola, California, for case referral and Dr. Jill Tessler for the medical illustration used.
Citation: Journal of the American Animal Hospital Association 40, 1; 10.5326/0400069
Citation: Journal of the American Animal Hospital Association 40, 1; 10.5326/0400069
Citation: Journal of the American Animal Hospital Association 40, 1; 10.5326/0400069
Citation: Journal of the American Animal Hospital Association 40, 1; 10.5326/0400069
Citation: Journal of the American Animal Hospital Association 40, 1; 10.5326/0400069
Citation: Journal of the American Animal Hospital Association 40, 1; 10.5326/0400069
Abdominal ultrasound in a 14-year-old Maine coon cat with suspected pancreatic duct obstruction showing gallbladder (A), “duplicate” gallbladder (B), and cystic calculi (white arrow). Each hatch mark on the right scale=0.5 cm.
Low-magnification view of pancreatic biopsy from the cat in Figures 1A, 1B, and 2, showing marked lobular fibrosis with chronic inflammation, dilatation of ducts (black arrow), and neutrophilic inflammatory infiltrates. Islets are partially replaced by amyloid (white arrows) (Hematoxylin and eosin stain, bar=300 μm).
High-magnification view of pancreatic body from the cat in Figures 1A, 1B, and 2, showing two islets (white arrows) with deposition of eosinophilic, homogenous material consistent with amyloid. Neutrophils are also present within the parenchyma and infiltrating the islets (Hematoxylin and eosin stain, bar=50 μm).
