Prognostic Value of Inflammatory and Tumour Markers in Small-Duct Subtype Intrahepatic Cholangiocarcinoma after Curative-Intent Resection

Abstract

Intrahepatic cholangiocarcinoma (ICC) is characterised by heterogeneity, and it can be subdivided into small-duct and large-duct types. Inflammatory and tumour markers could effectively predict prognosis in many cancers, but no similar studies have been conducted in the histological subtypes of ICC. A total of 102 and 72 patients with ICC undergoing curative-intent resection were retrospectively subclassified into large-duct and small-duct types by chemical staining, respectively. The prognostic value of inflammatory and tumour markers was studied for the first time in histological subtypes of ICC by using a Cox regression model. A novel predictor named prognostic inflammatory index (PII) was proposed and defined as neutrophil × monocyte / lymphocyte count (109/L). Survival analysis showed that PII, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and ferritin were all predictors of DFS and OS in patients with ICC ( P < 0.040 ). Subgroup analysis showed that PII, CA19-9, and ferritin were risk predictors of disease-free survival (DFS) and overall survival (OS) in small-duct type ICC ( P < 0.015 ). In addition, in small-duct type ICC, NLR and LMR were correlated with OS ( P < 0.025 ), whilst CEA and CA242 were correlated with DFS ( P ≤ 0.010 ). In conclusion, PII is a convenient and efficient inflammatory predictor of DFS and OS in ICCs and their small-duct type. NLR and LMR, rather than platelet-to-lymphocyte ratio, were correlated with OS in small-duct type ICC. In addition, ferritin may be a supplement to CA19-9 in stratifying the survival outcome of patients with small-duct type ICC.

The Value of Platelet-to-Lymphocyte Ratio as a Prognostic Marker in Cholangiocarcinoma: A Systematic Review and Meta-Analysis

“…The remaining 111 studies were further vetted for eligibility after the titles and abstracts were reviewed. Ultimately, 20 studies were included in the analysis [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”

“…Eight studies identified the PLR as an independent predictor for impaired OS in patients with CCA [ 22 , 28 , 29 , 33 , 34 , 36 , 38 , 41 ], while the PLR was not prognostic for OS in twelve studies [ 23 , 24 , 25 , 26 , 27 , 30 , 31 , 32 , 35 , 37 , 39 , 40 ]. The combined analysis of all twenty publications showed that the PLR values higher than the defined cut-off values predicted a worse OS (HR = 1.14, 95% CI = 1.06–1.24, p < 0.01) with high heterogeneity (I 2 = 55%, p < 0.01, Figure 2 ).…”

“…Five cohort studies showed that the PLR was an independent indicator of poor DFS in patients with CCA [ 28 , 29 , 31 , 32 , 36 ], whereas three publications detected no significant relationship between the PLR and DFS [ 22 , 23 , 36 ]. The pooled analysis of all eight studies revealed that a higher PLR was associated with worse DFS (HR = 1.57, 95% CI = 1.19–2.07, p < 0.01) with high heterogeneity (I 2 = 76%, p < 0.01, Figure 3 ).…”

The prognostic value of neutrophil-to-lymphocyte ratio in cholangiocarcinoma: a systematic review and meta-analysis

“…Among the 32 publications related to OS, 19 original papers reported that NLR was an independent predictor for impaired OS 18 , 20 , 23 – 27 , 32 – 34 , 38 – 40 .…”

“…Among the 15 publications which reported DFS, 7 cohort studies showed that NLR was an independent predictor of reduced DFS in patients with CCA 18 , 23 , 39 , 40 , 42 , 43 , 48 , whereas 7 publications observed no significant relationship between NLR 19 , 25 , 30 , 33 , 35 , 36 , 44 and DFS and one study showed NLR was a prognostic for a longer DFS 47 . The pooled analysis of all studies showed that a higher NLR level was associated with impaired DFS (HR 1.39, 95% CI 1.17–1.66, p < 0.01) with high heterogeneity (I 2 = 73%, p = 0.02, Fig.…”