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Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma
BACKGROUND: 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 immunotherap...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347737/ https://www.ncbi.nlm.nih.gov/pubmed/37442960 http://dx.doi.org/10.1186/s12885-023-11128-2 |
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author | Huang, Qingyu Wang, Fuhao Zhang, Xiang Liu, Jing Dou, Xue Feng, Rui Zhu, Kunli Jiang, Shumei Zhang, Yun Yue, Jinbo |
author_facet | Huang, Qingyu Wang, Fuhao Zhang, Xiang Liu, Jing Dou, Xue Feng, Rui Zhu, Kunli Jiang, Shumei Zhang, Yun Yue, Jinbo |
author_sort | Huang, Qingyu |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11128-2. |
format | Online Article Text |
id | pubmed-10347737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103477372023-07-15 Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma Huang, Qingyu Wang, Fuhao Zhang, Xiang Liu, Jing Dou, Xue Feng, Rui Zhu, Kunli Jiang, Shumei Zhang, Yun Yue, Jinbo BMC Cancer Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11128-2. BioMed Central 2023-07-13 /pmc/articles/PMC10347737/ /pubmed/37442960 http://dx.doi.org/10.1186/s12885-023-11128-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Huang, Qingyu Wang, Fuhao Zhang, Xiang Liu, Jing Dou, Xue Feng, Rui Zhu, Kunli Jiang, Shumei Zhang, Yun Yue, Jinbo Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma |
title | Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma |
title_full | Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma |
title_fullStr | Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma |
title_full_unstemmed | Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma |
title_short | Percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma |
title_sort | percutaneous transhepatic cholangial drainage or antibiotic therapy worsens response to immunotherapy in advanced cholangiocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347737/ https://www.ncbi.nlm.nih.gov/pubmed/37442960 http://dx.doi.org/10.1186/s12885-023-11128-2 |
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