In this case, gallbladder amyloidosis was suspected preoperatively based on the symptoms of gallbladder dyskinesia in a patient with a background of amyloidosis. We performed surgery electively and safely before cholecystitis onset in a patient with preexisting amyloidosis.

Preoperative diagnosis of gallbladder amyloidosis is extremely difficult [6]. In case reports to date, the diagnosis has been confirmed using postoperative histopathological specimens. The reason is that gallbladder amyloidosis is difficult to differentiate from commonly experienced cholecystitis because there are no characteristic imaging findings. In addition, the disease is rare [6, 7]. A search in PubMed using the MeSH keyterms “amyloidosis” and “gallbladder” revealed six case reports in English literature within the period 2000–2022. These cases are summarized in Table 1, including our case [5,6,7,8,9,10]. The median age of the patients was 63 (range 49–76); 86% were male patients. Amyloid A amyloidosis was reported in three patients, and amyloid light chain amyloidosis in the other three. The most frequent preoperative diagnosis was cholecystitis. However, additional patients were diagnosed with gallbladder tumors. Of the seven patients including our case, five did not exhibit gallbladder stones formation. Preoperative imaging findings showed variability and lacked specificity, as in our case. Some patients had underlying chronic renal failure, multiple myeloma, or a monoclonal gammopathy of undetermined significance. One patient who had a fatal outcome expired of renal failure and cirrhosis due to progressive systemic amyloidosis after surgery.

The patient underwent surgery for colic attacks due to gallbladder dyskinesia before developing cholecystitis. The patient had a history of multiple myeloma and cardiac amyloidosis. Abdominal ultrasonography revealed bile sludge without gallstones formation. After PTGBA, the patient continued to have a gallbladder effusion and recurrent right upper quadrant pain, leading to the suspicion of gallbladder contraction failure. Flopropione was markedly effective in relieving this symptom, leading to the diagnosis of gallbladder dyskinesia. Flopropione had anticholinergic properties and was thought to be significantly effective in the tension type of dyskinesia of the gallbladder [11]. Systemic amyloidosis is characterized by amyloid deposits in the heart, kidneys, and gastrointestinal tract [12]. As Table 1 presents, all patients with gallbladder amyloidosis have systemic amyloidosis. Therefore, the possibility of gallbladder amyloidosis was suspected preoperatively in this case.

Emergency cholecystectomy is recommended for acute cholecystitis when surgery is possible. According to the guidelines for acute cholecystitis, the mortality rate is generally less than 1% [13]. However, acute cholecystitis due to gallbladder amyloidosis carries the risk of coexisting organ damage other than that of the gallbladder and requires caution. Patients with cardiac amyloidosis are at risk of having difficult airways to secure due to macroglossia, hemodynamic instability due to diastolic dysfunction, decreased cardiac outputs, and serious arrhythmias due to conduction system dysfunctions with amyloid deposition in the myocardial fibers [14]. In addition, a significantly higher mortality rate has been reported in patients with heart failure who develop acute cholecystitis compared with others [15, 16]. Surgical complications that should be noted in patients with amyloidosis include hemorrhage. This is because amyloidosis is associated with many defects in platelet function and coagulation, including abnormal platelet aggregation, increased vascular fragility, factor IX and factor X deficiency, decreased alpha-2-plasmin inhibitor levels, and increased plasminogen levels [17, 18]. A high rate of liver biopsy-related bleeding requiring blood transfusion has been reported in patients with hepatic amyloidosis [19].

If gallbladder amyloidosis was not suspected, cholecystectomy may have been performed at the time of inflammatory exacerbation, which might lead to worsening of heart failure and increased bleeding. A preoperative diagnosis was also advantageous in that the patient could receive adequate support from other departments and the operation was safely performed while the patient's general condition was relatively stable.

In this case, the patient underwent a laparoscopic cholecystectomy on a standby basis. The patient's heart failure was stabilized by the intervention by a cardiologist, and the multiple myeloma was stabilized using chemotherapy. The patient underwent surgery after consultation with the Department of Cardiology and the Department of Clinical Oncology. Surgery could be performed before cholecystitis onset and was relatively safe with minimal blood loss without postoperative worsening of heart failure. The patient was discharged on postoperative day 5.

Two mechanisms are thought to be involved in the pathogenesis of gallbladder amyloidosis causing cholecystitis: (1) rapid edematous changes due to deposition of amyloid protein in the walls of microvessels and (2) vascular obstruction caused by deposited amyloid proteins, which results in contractile dysfunction of the gallbladder and bile retention [6, 20]. In this case, there was mild chronic inflammation and fibrosis in the gallbladder wall. Amyloid deposition was observed from the mucosal intrinsic layer to the submucosal layer but did not lead to ischemia. A new finding in this case was the presence of amyloid deposits in the peripheral nerves. To the best of our knowledge, this is the first case report of gallbladder amyloidosis in which amyloids were deposited in the peripheral nerves of the gallbladder. It is possible that amyloid deposition in the peripheral nerves and contractile dysfunction of the gallbladder have caused the dyskinesia symptoms in this case.