Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250117, China.
School of Clinical Medicine, Weifang Medical University, Weifang, 261053, China.
BMC Cancer. 2023 Jul 13;23(1):657. doi: 10.1186/s12885-023-11128-2.
Bile duct obstruction is a common issue for patients with advanced cholangiocarcinoma (CCA). Percutaneous transhepatic cholangial drainage (PTCD) is often required to relieve the obstruction. However, PTCD may alter the intestinal microbiota, which can affect the efficacy of immunotherapy. Antibiotics (ATB) can also have significant immunomodulatory effects by perturbing the gut microbiota. Therefore, this study aimed to investigate whether PTCD or ATB therapy is associated with overall survival (OS) or progression-free survival (PFS) in patients with advanced CCA receiving first-line chemotherapy plus immune checkpoint blockade (ICB) in clinical practice. We also explored whether the gut microbiota changes after receiving PTCD.
We conducted a single-center retrospective analysis of PTCD and ATB therapy in patients with advanced CCA. PTCD was performed before ICB initiation, and ATB was administered within 1 month before and 6 weeks after ICB initiation. Our primary outcomes were PFS and OS. Moreover, we used 16s rRNA sequencing to analyze fecal and bile samples obtained from patients who underwent PTCD.
In total, 107 patients with CCA were included. Among patients who did not undergo PTCD, ICB plus chemotherapy significantly improved OS vs. chemotherapy alone (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.09-0.45, p < 0.0001). PFS was also significantly improved in patients who received ICB plus chemotherapy compared with chemotherapy alone (HR 0.36, 95% CI 0.16-0.80, p = 0.0024). However, ICB plus chemotherapy did not improve survival compared with chemotherapy alone among patients who received PTCD. Overall changes in the fecal microbiota of patients after PTCD involved significant reductions in which Escherichia - Shigella.
The use of ATB or PTCD in patients with CCA receiving ICB was associated with worse OS compared with chemotherapy alone, and PTCD affects the gut microbiota. Escherichia - Shigella was significantly reduced in feces of patients after PTCD.
胆管阻塞是晚期胆管癌（CCA）患者常见的问题。常需要经皮经肝胆管引流（PTCD）来缓解阻塞。然而，PTCD 可能会改变肠道微生物群，从而影响免疫治疗的疗效。抗生素（ATB）通过扰乱肠道微生物群也具有显著的免疫调节作用。因此，本研究旨在探讨在临床实践中，接受一线化疗联合免疫检查点阻断（ICB）的晚期 CCA 患者中，PTCD 或 ATB 治疗与总生存期（OS）或无进展生存期（PFS）的关系。我们还探讨了接受 PTCD 后肠道微生物群是否发生变化。
我们对接受 ICB 治疗前接受 PTCD 治疗和 ATB 治疗的晚期 CCA 患者进行了单中心回顾性分析。PTCD 在 ICB 开始前进行，ATB 在 ICB 开始前 1 个月内和 ICB 开始后 6 周内给予。我们的主要结局是 PFS 和 OS。此外，我们使用 16s rRNA 测序分析了接受 PTCD 的患者的粪便和胆汁样本。
共纳入 107 例 CCA 患者。在未接受 PTCD 的患者中，与单独化疗相比，ICB 联合化疗显著改善了 OS（风险比 [HR] 0.21，95%置信区间 [CI] 0.09-0.45，p<0.0001）。与单独化疗相比，接受 ICB 联合化疗的患者 PFS 也显著改善（HR 0.36，95%CI 0.16-0.80，p=0.0024）。然而，在接受 PTCD 的患者中，与单独化疗相比，ICB 联合化疗并未改善生存。PTCD 后患者粪便微生物群的总体变化涉及大肠埃希氏菌-志贺氏菌的显著减少。
在接受 ICB 的 CCA 患者中使用 ATB 或 PTCD 与单独化疗相比，OS 更差，PTCD 会影响肠道微生物群。PTCD 后患者粪便中的大肠埃希氏菌-志贺氏菌显著减少。
