High preoperative values of inflammatory markers, specifically neutrophil to lymphocyte ratio (NLR), are associated with worse postoperative prognosis in patients with intrahepatic cholangiocarcinoma (CCA), a new study published in Cancer Medicine found.

Although radical hepatectomy remains the most effective treatment for CCA, the short median survival after surgery produces the need to discover prognostic markers to help select the best therapeutic option for each patient.

Inflammatory biomarkers such as NLR, platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) have prognostic value in many malignancies, including breast cancer and colorectal cancer. However, its prognostic value in CCA remains uncertain.

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“The associations between NLR, LMR, PLR, and clinical outcomes in patients with [CCA] have been explored in various studies, but there is no consensus in results,” the authors wrote. Unlike previous meta-analyses regarding the role of preoperative values of inflammatory markers in CCA, this study focused exclusively on intrahepatic CCA and excluded patients that received preoperative therapy.

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The authors extensively searched databases such as PubMed, Cochrane Library, and EMBASE, retrieving over 5000 studies and selecting 15 after applying exclusion criteria. The 15 studies combined a total of over 4000 patients. All selected studies were published between 2015 and 2021 in China, Japan, America, and Singapore.

The correlation between preoperative inflammatory markers and overall survival, recurrence-free survival, and disease-free survival, was assessed by combining hazard ratios (HRs) and 95% CI using a fixed or random-effects model depending on the heterogeneity between studies. In all cases, subgroup stratified analyses were done to identify factors that could affect the heterogeneity.

The meta-analysis showed a strong association (HR 1.04) between elevated preoperatory NLR and shorter overall survival and recurrence-free survival; nevertheless, NLR was not associated with poorer disease-free survival. Neither PLR nor LMR showed a significant association (HRs 1) with overall survival, disease-free survival, or recurrence-free survival. Further sensitivity and publication bias analyses supported the results of the meta-analysis.

“As NLR can be easily determined via routine blood tests, this parameter may have great clinical application potential to guide decision-making in clinical settings,” the authors concluded.


Cui H, Li Y, Li S, Liu G. Prognostic utility of preoperative inflammatory markers in patients with intrahepatic cholangiocarcinoma after hepatic resection: a systematic review and meta‐analysis. Cancer Med. Published online June 12, 2022. doi:10.1002/cam4.4935