Gangrenous and Hemorrhagic Cholecystitis are both severe life-threatening conditions that are considered the final stages of disease in the spectrum of cholecystitis [6]. They usually appear as separate entities and have varying underlying etiologies; however, in this case of metastatic pancreatic cancer, both features were present, which was a perplexing finding. To our knowledge, this is the first case of gangrenous and hemorrhagic acalculous cholecystitis co-occurring and as a manifestation of pancreatic cancer. Metastatic pancreatic cancer is characterized by a pancreatic tumor with widespread lymphatic and organ involvement in areas such as the lungs, liver, bone, and biliary system, including the gallbladder [1]. Tobacco use and excessive alcohol intake are two of the most common risk factors [1]. Typically, patients develop cholelithiasis, acute calculous cholecystitis, and cholangitis in the setting of pancreatic cancer due to tumor compression of the bile ducts and subsequent stasis and infection of the biliary system [4]. However, there is a scarcity of literature on the incidence of hemorrhagic and gangrenous cholecystitis as a complication of pancreatic cancer.

Gangrenous cholecystitis is characterized by widespread necrosis of the gallbladder tissue and is caused by prolonged compression of the cystic duct and artery [7]. The most common contributing factors are the male sex, advanced age, and delayed surgery. The cystic artery is a branch of the right hepatic artery originating from the Superior Mesenteric Artery (SMA). It lies in the Calot triangle, bordered inferiorly by the cystic duct, and supplies blood to the gallbladder [8]. In pancreatic cancer, there is a high incidence of vascular invasion, with increased involvement of the SMA and its branches [9]. Persistent obstruction of the cystic duct and artery by metastasis can increase gallbladder wall tension and precipitate epithelial cell injury, which subsequently stimulates the release of phospholipases that mount a severe inflammatory response [7]. This inflammation and vascular insufficiency rapidly lead to tissue necrosis, accelerating gangrene formation.

Hemorrhagic Cholecystitis (HC) is characterized by bleeding into the gallbladder or biliary system (hemobilia) and is often due to trauma or anticoagulation use [5]. While there is a known association of HC in patients with chronic illnesses, a cohort study found that patients with cancer have a greater risk of developing complicated cholecystitis than the general population, with an even greater risk in patients over the age of 70 [7]. Gallbladder bleeding or HC can be secondarily caused by pancreatic cancer due to protease upregulation and activation and downregulation of protease inhibitors [10]. These active proteases invade and break down the blood vessel stroma and endothelium to allow malignant cell migration, resulting in bleeding and HC [10].

Common manifestations of gangrenous and hemorrhagic cholecystitis include tachycardia, chills, and fever in addition to the typical features of cholecystitis such as right upper abdominal pain that worsens on palpation, nausea, and vomiting [3]. These conditions are difficult to diagnose preoperatively. Laboratory results that increase the diagnostic suspicion for cholecystitis are elevated Liver Function Tests (LFT) and leukocytosis. Right Upper Quadrant Ultrasound (RUQ U/S) continues to be the first step in diagnostic imaging, which shows gallbladder wall thickening, indicative of cholecystitis [11]. There is some difficulty visualizing cholecystitis complications on U/S, so Computed Tomography (CT) is often used to make an early diagnosis [12].  Studies show that early cholecystectomy is effective and can lower the mortality of cholecystitis [13]. As previously stated, in this patient’s case, the U/S showed gallbladder distension with wall thickening and dilation of the common bile duct indicating blockage by the pancreatic mass. However, the presence of this mass ultimately led to extensive damage to the gallbladder by blocking its cystic and common bile outflow as well as eroding its arterial supply, which caused simultaneous gangrene and hemobilia.

This case discovers how late-stage pancreatic cancer can lead to acalculous cholecystitis, progressing to gangrenous and hemorrhagic cholecystitis over time, especially in the event of delayed treatment. A high degree of clinical suspicion is required in the setting of RUQ pain with the positive finding of pancreatic malignancy to prevent the development of gangrene and hemorrhagic bile formation. Management with emergent cholecystectomy is paramount to prevent a fatal outcome.