Acute Acalculous Cholecystitis in a Patient with Metastatic Renal Cell Carcinoma Treated with Sunitinib

Abstract

A 55-year old man was treated with sunitinib 50 mg/day for 4 weeks on and 2 weeks off, as a first-line therapy for metastatic renal cell carcinoma. During the fourth week of the first cycle, he was admitted to the Emergency Department with abdominal pain and vomiting. Acute acalculous cholecystitis was diagnosed. Sunitnib-associated cholecystitis is a rare adverse event previously reported in few cases. The mechanism behind this complication is not fully understood, although vascular endothelial dysfunction may play a role. The use of this drug is expanding in clinical oncology, and physicians should be aware of this life-threating adverse event.

Acalculous Perforated Hemorrhagic Emphysematous Cholecystitis Caused byClostridium perfringensin a Patient with Myeloma Taking Daratumumab

“…Kassar et al [4] and Pielacinski et al [5] describe acalculous cholecystitis arising during chemotherapy for acute myeloblastic and lymphoblastic leukemia, respectively; both patients were neutropenic at the time of diagnosis. Interestingly, there are also reports of acalculous cholecystitis without associated neutropenia in patients receiving small molecule inhibitors for solid organ tumors, such as sunitinib and sorafenib [6,7]. We found only a single case report of acalculous cholecystitis in a patient on monoclonal antibody therapy, that of a 15-year-old female on infliximab for juvenile polyarticular rheumatoid arthritis.…”

Repeated Perforation of the Gallbladder in a Patient with Hepatocellular Carcinoma Receiving Lenvatinib

“…Of note, the patient had received treatment with multiple TKIs for a long time, so long-term treatment with TKIs might have induced the gallbladder perforation. However, previous reports (8)(9)(10)(11)(12) showed that cholecystitis developed about four weeks after initiating TKIs. These findings suggest that TKI-related cholecystitis developed after a relatively short treatment duration.…”

“…In patients with thyroid cancer treated with lenvatinib, five cases of acalculous cholecystitis were reported in post-marketing surveillance from 2015 to 2017 in Japan. In contrast, five cases of acute acalculous cholecystitis in patients treated with other tyrosine kinase inhibitors (TKIs) were reported, including two patients with sorafenib and three with sunitinib (8)(9)(10)(11)(12).…”

“…The homeostasis between the vascular endothelium and platelets may be disturbed by lenvatinib-mediated damage to vascular endothelial cells, allowing platelets to aggregate more readily on the surface of the vascular endothelium and inducing ischemic damage (21). Although the relationship between TKIs and cholecystitis is unclear, previous reports suggest that this TKI-related ischemic damage is likely the pathologic mechanism of sorafenib and sunitinib-related cholecystitis (8)(9)(10)(11). In fact, in the present case, AMI developed during sorafenib treatment; thus, the vascular endothelial cells may be susceptible to damage by TKIs.…”

“…Finally, VEGF plays a role in modulating cholangiocyte proliferation in response to cholestasis and cholangiocytes express VEGFRs (22). Inhibiting VEGFRs in the biliary tract cells can induce an imbalance in stress adaption, causing biliary disease, including cholecystitis (11).…”