Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Genome Analysis Center, Yamanashi Central Hospital, Kofu, Japan.
J Hepatobiliary Pancreat Sci. 2024 May;31(5):329-338. doi: 10.1002/jhbp.1432. Epub 2024 Mar 24.
Diagnosing biliary tract cancer is difficult because endoscopic retrograde cholangiopancreatography (ERCP) is performed fluoroscopically, and the sensitivity of bile cytology is low. Liquid biopsy of bile using targeted sequencing is expected to improve diagnosis and treatment, but few studies have been conducted. In this study, we examined whether liquid biopsy of bile improves the diagnostic sensitivity of biliary strictures.
A total of 72 patients with biliary strictures who underwent ERCP at Chiba University Hospital between April 2018 and March 2021 were examined. Of these, 43 and 29 were clinically and pathologically diagnosed as having malignant and benign biliary strictures, respectively. We performed targeted sequencing of bile obtained from these patients, and the sensitivity of this method was compared with that of bile cytology. Detection of at least one oncogenic mutation was defined as having malignancy.
The sensitivity of bile cytology was 27.9%, whereas that of genomic analysis was 46.5%. Comparing bile cytology alone with the combination of cytology and genomic analysis, the latter was more sensitive (53.5%, p < .001). Among the 43 patients with malignant biliary strictures, mutations with FDA-approved drugs were detected in 11 (26%).
Liquid biopsy of bile can potentially diagnose malignancy and detect therapeutic targets.
由于内镜逆行胰胆管造影术（ERCP）是在荧光透视下进行的，且胆汁细胞学的敏感性较低，因此诊断胆道癌较为困难。使用靶向测序对胆汁进行液体活检有望改善诊断和治疗，但此类研究较少。本研究旨在探讨胆汁液体活检是否能提高胆道狭窄的诊断敏感性。
本研究共纳入 2018 年 4 月至 2021 年 3 月期间在千叶大学医院接受 ERCP 的 72 例胆道狭窄患者。其中，43 例经临床和病理诊断为恶性胆道狭窄，29 例为良性胆道狭窄。对这些患者的胆汁进行靶向测序，并将该方法的敏感性与胆汁细胞学进行比较。至少检测到一个致癌突变被定义为恶性。
胆汁细胞学的敏感性为 27.9%，而基因组分析的敏感性为 46.5%。与单独使用细胞学相比，细胞学联合基因组分析的敏感性更高（53.5%，p<0.001）。在 43 例恶性胆道狭窄患者中，检测到 11 例（26%）存在 FDA 批准药物的靶点突变。
胆汁液体活检可能有助于诊断恶性肿瘤并检测治疗靶点。
