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Preoperative sustained C-reactive protein elevation shortens patient survival after liver resection for perihilar cholangiocarcinoma : A retrospective cohort study with propensity score analyses

  1. 1Department of Gastroenterological Surgery 1, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
  2. 2Department of Surgery, Fukuoka Wajiro Hospital, Fukuoka, Japan
  3. 3Department of Biostatistics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.

Abstract

Preoperative inflammation occurs frequently in perihilar cholangiocarcinoma (P-CCA). However, the prognostic significance of maximum preoperative inflammatory markers and the necessity of monitoring preoperative inflammation in P-CCA remain underexplored. We aimed to clarify the clinical impact of preoperative inflammation on survival in P-CCA patients by assessing changes in C-reactive protein (CRP) levels (maximum and 1–2 days before surgery), thereby informing optimal management strategies for P-CCA. This retrospective study included patients with P-CCA who underwent extrahepatic bile duct resection and hepatectomy at the Department of Gastroenterological Surgery 1, Hokkaido University Hospital, between 2000 and 2019. In addition to inflammatory markers measured 1 to 2 days before surgery (referred to as “values prior to surgery”), maximum preoperative CRP was also recorded. The primary outcome was overall survival (OS), and a multivariate Cox regression model was used to assess clinicopathological factors associated with OS. One-to-one propensity score matching was performed to match tumor characteristics and maximum preoperative CRP levels between the alleviated and sustained CRP groups. We identified 100 patients, of whom 89 (89%) had a clinically meaningful preoperative inflammatory response; 39% had cholangitis, and 65% underwent percutaneous transhepatic portal embolization. The median OS was 34.5 months (interquartile range [IQR]: 16.6–65.2), and the 5-year OS rate was 34.4%. In the univariate and multivariate analyses, elevated CRP prior to surgery was associated with shorter OS (multivariate hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.04–1.42), whereas no association was found between the maximum preoperative CRP and OS. Additionally, preoperative cholangitis (HR, 1.91; 95% CI, 1.17–3.14) and an elevated neutrophil-to-lymphocyte ratio (HR, 1.10; 95% CI, 1.00–1.17) were associated with a worse outcome in the univariate analyses. Furthermore, after propensity score matching, patients whose CRP normalized before surgery (alleviated CRP group) had better OS than those with sustained CRP elevation (sustained CRP group; median OS: 49.8 vs 22.6 months, respectively; P = .017). This study revealed the negative prognostic impact of preoperative inflammation in P-CCA. Notably, persistent elevation of CRP prior to surgery predicted poor prognosis in P-CCA, suggesting that waiting for CRP normalization may improve survival outcomes.

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BibTeX
@article{fujii2026preoperative,
  title = {{Preoperative sustained C-reactive protein elevation shortens patient survival after liver resection for perihilar cholangiocarcinoma : A retrospective cohort study with propensity score analyses}},
  author = {Yuki Fujii and Tatsuhiko Kakisaka and Hirofumi Kamachi and Hiroki Nakamoto and Tatsuya Orimo and Akihisa Nagatsu and Takeshi Aiyama and Kazuki Wakizaka and Shunsuke Shichi and Ken Imaizumi and Akinobu Taketomi},
  journal = {Medicine},
  year = {2026},
  month = oct,
  doi = {10.1097/md.0000000000051245},
  url = {https://europepmc.org/article/PMC/PMC13727158},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Preoperative sustained C-reactive protein elevation shortens patient survival after liver resection for perihilar cholangiocarcinoma : A retrospective cohort study with propensity score analyses
AU  - Yuki Fujii
AU  - Tatsuhiko Kakisaka
AU  - Hirofumi Kamachi
AU  - Hiroki Nakamoto
AU  - Tatsuya Orimo
AU  - Akihisa Nagatsu
AU  - Takeshi Aiyama
AU  - Kazuki Wakizaka
AU  - Shunsuke Shichi
AU  - Ken Imaizumi
AU  - Akinobu Taketomi
PY  - 2026
DA  - 2026/10/30
JO  - Medicine
DO  - 10.1097/md.0000000000051245
UR  - https://europepmc.org/article/PMC/PMC13727158
AB  - Preoperative inflammation occurs frequently in perihilar cholangiocarcinoma (P-CCA). However, the prognostic significance of maximum preoperative inflammatory markers and the necessity of monitoring preoperative inflammation in P-CCA remain underexplored. We aimed to clarify the clinical impact of preoperative inflammation on survival in P-CCA patients by assessing changes in C-reactive protein (CRP) levels (maximum and 1–2 days before surgery), thereby informing optimal management strategies for P-CCA. This retrospective study included patients with P-CCA who underwent extrahepatic bile duct resection and hepatectomy at the Department of Gastroenterological Surgery 1, Hokkaido University Hospital, between 2000 and 2019. In addition to inflammatory markers measured 1 to 2 days before surgery (referred to as “values prior to surgery”), maximum preoperative CRP was also recorded. The primary outcome was overall survival (OS), and a multivariate Cox regression model was used to assess clinicopathological factors associated with OS. One-to-one propensity score matching was performed to match tumor characteristics and maximum preoperative CRP levels between the alleviated and sustained CRP groups. We identified 100 patients, of whom 89 (89%) had a clinically meaningful preoperative inflammatory response; 39% had cholangitis, and 65% underwent percutaneous transhepatic portal embolization. The median OS was 34.5 months (interquartile range [IQR]: 16.6–65.2), and the 5-year OS rate was 34.4%. In the univariate and multivariate analyses, elevated CRP prior to surgery was associated with shorter OS (multivariate hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.04–1.42), whereas no association was found between the maximum preoperative CRP and OS. Additionally, preoperative cholangitis (HR, 1.91; 95% CI, 1.17–3.14) and an elevated neutrophil-to-lymphocyte ratio (HR, 1.10; 95% CI, 1.00–1.17) were associated with a worse outcome in the univariate analyses. Furthermore, after propensity score matching, patients whose CRP normalized before surgery (alleviated CRP group) had better OS than those with sustained CRP elevation (sustained CRP group; median OS: 49.8 vs 22.6 months, respectively; P = .017). This study revealed the negative prognostic impact of preoperative inflammation in P-CCA. Notably, persistent elevation of CRP prior to surgery predicted poor prognosis in P-CCA, suggesting that waiting for CRP normalization may improve survival outcomes.
SN  - 0304-5412
SN  - 1536-5964
SN  - 0025-7974
ER  -