Korean Journal of
Veterinary Service

Gallbladder mucocele (GBM) is characterized by cystic mucinous hypertrophy of the gallbladder mucosa, in conjunction with excessive mucin production and subsequent distention of the gallbladder (Hill et al., 2022). The abnormal accumulation of mucus and precipitated bile may lead to biliary stasis or even gallbladder rupture, possibly leading to critical conditions in dogs (Smalle et al., 2015). One contributing factor to GBM development appears to be the excessive secretion of mucin by the bile duct epithelium, which forms a gel with anomalous properties (Kesimer et al., 2015). Initial reductions in bile flow and gallbladder motility have been implicated as precursors to GBM formation.

Furthermore, metabolomic analyses of dogs with GBM indicate substantial metabolic alterations associated with conditions of the patients. Metabolic diseases, including hyperadrenocorticism and hypothyroidism, have also been correlated with GBM (Melián et al., 2006; Aicher et al., 2019). Additional studies have linked factors such as prednisolone administration, leptin concentrations, and hyperlipidemia with the development of GBM (Kutsunai et al., 2014; Lee et al., 2019).

For the diagnosis, the observation of echogenic contents within the canine gallbladder by ultrasonography is frequently found. Biliary sludge has been categorized as an incidental occurrence that lacks strong association with biliary disease (Hill et al., 2022). Notably, echogenic bile, or biliary sludge, is characterized by its inability to shadow and its tendency to collect in the dependent region of the gallbladder (Besso et al., 2000). However, echogenic bile that remains static despite changes in the patient’s position signifies a distinguishing characteristic from sludge, exhibiting abnormal distention of a cavity due to an inappropriate accumulation of mucus (Besso et al., 2000). It could be accompanied with inspissated bile, mucinous hyperplasia, cystic hyperplasia, biliary cysts, mucosal cysts, cystic mucinous hypertrophy, mucinous cholecystitis, and cystic glandular cholecystitis (Wennogle et al., 2019). For the treatment, GBM represents one of the most common indications for biliary tract surgery in dogs (Piegols et al., 2021). Surgical intervention via cholecystectomy is considered the treatment of choice for dogs with symptomatic GBM (Parkanzky et al., 2019).

Pheochromocytomas represent a category of functional neoplasms characterized by the secretion of catecholamines, originating from the chromaffin cells of the adrenal medulla. The clinical manifestations associated with these tumors are often nonspecific and intermittent (Enright et al., 2022). Commonly observed signs include episodic hypertension and cardiac arrhythmias, which are secondary to excess catecholamine secretion by the tumors (Zini et al., 2019). Due to their relatively infrequent occurrence and the subtle nature of their clinical presentation, the diagnosis of pheochromocytomas can be particularly challenging. In dogs, a presumptive diagnosis of pheochromocytoma typically relies on a comprehensive evaluation that includes physical examination findings—such as tachyarrhythmia and hypertension—alongside clinical history indicative of weakness or collapse, and radiographic evidence of an adrenal mass (Enright et al., 2022). Notably, urine metanephrine testing is increasingly being adopted in veterinary practice as a supportive diagnostic tool for pheochromocytomas, similar to its utility in human medicine (Salesov et al., 2015).

These tumors are typically unilateral and may present as large masses that partially or completely occupy the adrenal gland, although they can also appear as smaller nodules intimately surrounded by compressed normal adrenal parenchyma (Zini et al., 2019). A salient feature of pheochromocytomas is their potential to invade the adrenal capsule and surrounding tissues, which can extend to the caudal vena cava, contributing to the development of significant thrombi that may partially obstruct or completely occlude the vessel. Local invasiveness is observed in approximately 39% to 50% of cases, with distant metastases occurring in 13% to 24% of cases, affecting local regions such as lymph nodes, liver, lungs, kidneys, spleen, and bone (Barthez et al., 1997). These conditions can lead to complications such as abdominal effusion, resulting in sudden weakness or death in dogs due to acute hemorrhage from either the tumor itself or from adjacent vascular structures (Whittemore et al., 2001).

In human medicine, adrenalectomy is widely regarded as the standard treatment procedure for pheochromocytoma (Salesov et al., 2015). The prognosis for dogs diagnosed with pheochromocytoma is predominantly influenced by surgical factors post-adrenalectomy, though the relevance of local invasion and metastasis in terms of prognostic outcomes remains uncertain (Galac and Korpershoek, 2017). Importantly, the median survival duration extends beyond three years for dogs that survive the surgical procedure and are subsequently discharged. However, many of these animals are lost to follow-up or succumb to unrelated medical conditions (Galac and Korpershoek, 2017). Favorable prognostic factors identified in the literature include a younger diagnosis age and a shorter surgical intervention duration (Mayhew et al., 2019).

This case study reports a rare instance of mucocele and pheochromocytoma in an 11-year-old spayed female Bichon Frise. The treatment involved performing both cholecystectomy and adrenalectomy in a single procedure, which required advanced surgical techniques and intensive care. The surgery was successfully achieved, and the patient was discharged without any postoperative complications.

An 11-year-old spayed female Bichon Frise dog was referred to a regional surgical center with a history of severe anorexia, lethargy, and acute multiple episodes of vomiting over the past three days. The patient weighed 5.5 kg and exhibited moderate abdominal pain responses, such as showing tension and whimpering during abdominal palpation, but no other specific physical reactions were observed. The patient was immediately hospitalized, and laboratory tests, including CBC, biochemistry, and electrolyte analysis, were performed along with radiography and ultrasonography.

Laboratory tests revealed a severe inflammatory response, indicated by a marked increase in cCRP (141.6 mg/L; reference range: 10∼20 mg/L) and severe leukocytosis (WBC 25.9×10³/μL; reference range: 5∼17×10³/μL). Additionally, there was severe hyperbilirubinemia (1.1 mg/dL; reference range: 0.1∼0.5 mg/dL) along with significantly elevated levels of ALP (1,222 U/L; reference range: 40∼254 U/L), ALT (640 U/L; reference range: 17∼78 U/L), and GGT (31 U/L; reference range: 5∼14 U/L), suggestive of biliary tract disease.

Mean arterial pressure was measured at 120 mmHg, suggesting hypertension without arrhythmia. Ultrasonography revealed severe cholecystitis with bile duct obstruction (Fig. 1A). Additionally, a tumorous enlargement of the left adrenal gland (1.6×4 cm) was identified (Fig. 1B), prompting further adrenal-related testing. The urine cortisol-to-creatinine ratio result was normal (24; abnormal ≥34), but urinary metanephrine (12.47 nmol/L; reference range: 0.3∼4.1 nmol/L) and normetanephrine (31.81 nmol/L; reference range: 0.9∼6.6 nmol/L) were significantly elevated, suggesting pheochromocytoma rather than an adrenal cortical tumor. The primary life-threatening condition for the patient was severe cholecystitis and the associated complication of bile duct obstruction. However, the owner also requested adrenal tumor removal.

Figure 1. Ultrasound scan of the abdomen for abnormalities. (A) Gall bladder, (B) The tumor from the left adrenal gland.

The owner was thoroughly informed about the patient being an advanced-age dog, the risks associated with anesthesia, the risks of each surgery, and the potentially life-threatening complications that could occur post-surgery. Despite emphasizing the increased risk of performing both procedures simultaneously, the owner strongly insisted on conducting both surgeries under a single general anesthesia to avoid multiple sessions. Although the risk was high, the procedures were performed simultaneously as the surgeon’s experience indicated a sufficient likelihood of success.

The cholecystectomy was performed first (Fig. 2), followed by the adrenalectomy (Fig. 3). The surgery was successfully completed, and the dog was admitted to the ICU for intensive care. The patient was continuously monitored for postoperative complications, and comprehensive blood tests were conducted once daily to assess the condition. Antibiotic therapy, including Cefepime, Marbofloxacin, and Metronidazole, was administered intravenously. Medications such as Ursodeoxycholic acid, Biphenyl-dimethyl-dicarboxylate, and L-ornithine-L-aspartate were provided to support bile dissolution and liver detoxification. For inpatient care, an esophageal feeding tube and a urinary catheter were placed. Enteral nutrition was administered via the esophageal feeding tube, and urine output was continuously monitored.

Figure 2. (A∼C) Cholecystectomy performed in the chronological order.

Figure 3. (A∼D) Adrenalectomy performed in the chronological order.

Fortunately, severe postoperative complications, such as liver failure, cholestasis, and Addisonian crisis, did not occur. After a total of 7 days of intensive care, the dog was discharged in good health. The patient was rechecked once a month during the first 6 months and every 3 months. Three years after the surgery, the patient is living well without any recurrence or notable issues.

After the surgical procedures, the collected adrenal mass was submitted for histopathological examination. The histopathological examination found tumor cells originating from the medulla of the adrenal gland, which were presented from small cuboidal or polyhedral cells to moderate pleomorphism (Fig. 4). The cytoplasm of neoplastic cells appeared lightly eosinophilic, demonstrating finely granular texture with indistinct plasma membranes. The tumor cells were typically organized into small lobules, delineated by delicate connective tissue septa and interspersed capillaries, indicating pheochromocytoma secreting epinephrine or norepinephrine.

Figure 4. Histopathological features of tumor of the adrenal gland. (A) Tumor cells are cuboidal or polyhedral with finely granular cytoplasm, forming packets separated by fine connective tissue stroma, characterized by chromaffin cells of the medulla of the adrenal gland. (B) The cytoplasm is lightly eosinophilic with an indistinct plasma membrane, and the nucleus exhibits moderate pleomorphism.

GBM is a pathological condition characterized by cystic mucinous hypertrophy of the gallbladder mucosa, accompanied by excessive production of mucin, which ultimately results in distension of the gallbladder. This abnormal accumulation of mucus, in conjunction with precipitated bile, can precipitate biliary stasis and may potentially lead to severe complications, including gallbladder rupture, posing significant health risks for dogs (Smalle et al., 2015). GBM presents various histopathological changes, including inspissated bile, mucinous hyperplasia, cystic hyperplasia, biliary cysts, mucosal cysts, cystic mucinous hypertrophy, mucinous cholecystitis, and cystic glandular cholecystitis (Wennogle et al., 2019). GBM constitutes one of the most prevalent indications for biliary tract surgery in canine patients (Piegols et al., 2021). Given the potential for serious outcomes, current treatment paradigms favor surgical intervention through cholecystectomy as the preferred therapeutic approach for dogs exhibiting symptomatic GBM (Parkanzky et al., 2019).

However, canine biliary surgery presents several significant perioperative complications, including hypotension, systemic inflammatory response, pancreatitis, disseminated intravascular coagulation, pulmonary thromboembolism, and multiple organ dysfunction manifesting as respiratory and renal failure (Parkanzky et al., 2019). Additional risks encompass anemia and even mortality, with recent studies indicating that the mortality rates associated with cholecystectomy in dogs remain concerningly high (Hill et al., 2022). Notably, a recent report documented a 20% rate of failure to survive to hospital discharge in dogs undergoing preventive cholecystectomy (Malek et al., 2013).

The practice of intraoperative catheterization and flushing of the common bile duct (CBD) has been proposed as an alternative to cholecystectomy to ensure the patency of the CBD, including techniques such as normograde catheterization via cholecystostomy and retrograde catheterization via duodenotomy (Mehler, 2011). The advantages of intraoperative flushing include a reduced risk of obstructed bile flow postoperatively due to residual bile plugs or choleliths (Smalle et al., 2015).

However, the necessity of routine catheterization and flushing of the biliary system remains a topic of debate within the veterinary surgical community (Piegols et al., 2021). A significant association between the use of catheterization and postoperative outcomes has not been established. Moreover, studies found that outcomes for dogs undergoing catheterization were comparable to those in a control group of dogs that did not receive catheterization (Mehler, 2011). Consequently, the benefits of catheterization and flushing may not be universally applicable and could potentially be limited to particular subsets of canine patients with specific clinical indications (Piegols et al., 2021).

As of now, cholecystectomy is a choice of treatment despite the high risk of complications above and the requirement of high experience and technique. Here, we performed the surgery successfully without any complications. As a limitation of this study, we could not proceed with a histopathological examination of the gall bladder to explore the pathogenic mechanism due to the failure of sample collection.

Pheochromocytomas, classified as malignant tumors, are characterized by their potential to invade the adrenal capsule and surrounding tissues, which may extend to critical vascular structures such as the caudal vena cava. This invasiveness can lead to the formation of significant thrombi, posing risks of partial or complete obstruction of the vessel system (Zini et al., 2019). Epidemiological data suggest that local invasiveness occurs in approximately 39% to 50% of cases, while distant metastases are reported in 13% to 24% of instances, impacting various local regions, including lymph nodes, liver, lungs, kidneys, spleen, and bone (Barthez et al., 1997). Remarkably, in the presented case study, there was no evidence of tumor invasion into adjacent tissues or vessels, nor any metastasis observed in other organs, thereby validating adrenalectomy as a viable treatment option.

In this particular case, cholecystectomy and adrenalectomy were performed concurrently at the request of the pet owner, demonstrating our commitment to comprehensive surgical management despite the inherent complexities of simultaneous procedures. Histopathological evaluation revealed tumor cells originating from the medulla of the left adrenal gland, arranged in small lobules and separated by delicate fibrovascular septa, resembling tumors of neuroendocrine origin. The presence of catecholamine-producing neoplastic cells confirmed a diagnosis of pheochromocytoma in the left adrenal gland.

In summary, this case highlights a rare presentation of mucocele and pheochromocytoma in an 11-year-old spayed female, Bichon Frise. The dual surgical intervention of cholecystectomy and adrenalectomy was executed with advanced surgical techniques and necessitated intensive postoperative care. The procedure was successful, and the patient was discharged without any complications. As of three years post-surgery, the patient continues to thrive without recurrence or significant health issues, underscoring the effectiveness of the surgical approach in managing such complex cases.

No potential conflict of interest relevant to this article was reported.