Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1466, Houston, TX, 77030, USA.
Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA.
J Immunother Cancer. 2019 May 3;7(1):118. doi: 10.1186/s40425-019-0604-2.
Immune checkpoint inhibitors (ICIs) represent a promising novel class of cancer therapy, but immune-mediated adverse events can complicate ICI treatment. Acute cholecystitis in patients receiving ICI therapy has not been characterized. We aimed to describe the clinical features of patients who developed ICI-related cholecystitis.
We evaluated a case series of patients at a tertiary cancer center who received ICI therapy and developed cholecystitis, diagnosed by clinical presentation and diagnostic imaging, during 2010-2018. Patients with a history of chronic cholecystitis or other etiologies of acute cholecystitis, such as cholelithiasis, were excluded. A chi-square test was used to compare the frequency of cholecystitis between ICI regimens. Kaplan-Meier and log rank analyses were used to compare survival between subgroups.
Of the 4253 patients who received ICIs in the study period, 25 (0.6%) patients developed suspected ICI-related cholecystitis. Alternatively, of the 31,426 cancer-matched patients who received non-ICI therapy, 72 (0.2%) developed acalculous cholecystitis (P < 0.001). Among the 25 included patients, the median time from ICI initiation to cholecystitis was 6 months (range, 0.1-31 months). Fifteen (60%) patients received an inhibitor of programmed death protein 1 (anti-PD-1) or of its ligand (anti-PD-L1) as a single agent, and 10 (40%) patients received an inhibitor of cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) therapy alone or combined with anti-PD-1/L1. Anti-CTLA-4 monotherapy was associated with a higher risk of cholecystitis (P = 0.006). ICI therapy was discontinued in 20 patients, in three (12%) as a result of acute cholecystitis. Two (8%) patients developed sepsis, and four (16%) had perforation of the gallbladder wall. Five (20%) patients underwent surgical cholecystectomy, and eight (32%) underwent percutaneous drainage. Five (20%) patients were treated with steroids; two of them required surgery. Ten (40%) patients were able to restart ICI therapy. Patients who received a combination of anti-CTLA-4 and anti-PD-1/L1 had more complications of cholecystitis than did patients who received either agent alone (P = 0.03).
ICI treatment can result in a clinical condition similar to typical acute cholecystitis in a minority of patients. ICI-related cholecystitis should be managed in a similar fashion to typical cholecystitis. The efficacy of steroids for the treatment of ICI-related cholecystitis is unclear.
免疫检查点抑制剂（ICI）代表了一种有前途的新型癌症治疗方法，但免疫介导的不良反应可能会使 ICI 治疗复杂化。接受 ICI 治疗的患者发生急性胆囊炎尚未得到明确描述。我们旨在描述接受 ICI 治疗的患者发生 ICI 相关胆囊炎的临床特征。
我们评估了 2010 年至 2018 年间在一家三级癌症中心接受 ICI 治疗并在诊断成像中诊断出胆囊炎的患者的病例系列。排除了有慢性胆囊炎病史或其他急性胆囊炎病因（如胆石症）的患者。使用卡方检验比较不同 ICI 方案中胆囊炎的发生率。使用 Kaplan-Meier 和对数秩检验比较亚组之间的生存率。
在研究期间接受 ICI 治疗的 4253 例患者中，有 25 例（0.6%）患者疑似发生 ICI 相关胆囊炎。相比之下，在接受非 ICI 治疗的 31426 例癌症匹配患者中，有 72 例（0.2%）发生无结石性胆囊炎（P < 0.001）。在 25 例纳入的患者中，从 ICI 开始到胆囊炎的中位时间为 6 个月（范围，0.1-31 个月）。15 例（60%）患者接受了程序性死亡蛋白 1（抗 PD-1）或其配体（抗 PD-L1）抑制剂作为单一药物治疗，10 例（40%）患者接受了细胞毒性 T 淋巴细胞相关蛋白 4（抗 CTLA-4）抑制剂单独或联合抗 PD-1/L1 治疗。抗 CTLA-4 单药治疗与胆囊炎风险增加相关（P = 0.006）。20 例患者停止了 ICI 治疗，其中 3 例（12%）因急性胆囊炎而停药。2 例（8%）患者发生败血症，4 例（16%）患者发生胆囊壁穿孔。5 例（20%）患者接受了胆囊切除术，8 例（32%）患者接受了经皮引流。5 例（20%）患者接受了类固醇治疗；其中 2 例需要手术。10 例（40%）患者能够重新开始 ICI 治疗。接受抗 CTLA-4 和抗 PD-1/L1 联合治疗的患者比接受单一药物治疗的患者胆囊炎并发症更多（P = 0.03）。
ICI 治疗可导致少数患者出现类似于典型急性胆囊炎的临床状况。ICI 相关胆囊炎的治疗应类似于典型胆囊炎。类固醇治疗 ICI 相关胆囊炎的疗效尚不清楚。
