J Cancer 2023; 14(7):1257-1271. doi:10.7150/jca.74275 This issue Cite
1. Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200437, China.
2. Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai, 200437, China.
3. Cancer Research Institute, Central South University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, China.
† Contributed equally to this work
Background: To explore biliary tract stone (BTS) as prognostic factors of intrahepatic cholangiocarcinoma (ICC).
Methods: Clinical data of 985 ICC patients were classified into no BTS group and BTS group-subgrouped into hepatolithiasis (HL) and non-hepatolithiasis (NHL) group. Propensity score matching was utilized to mitigate baseline characteristics. Preoperative peripheral inflammation parameters (PPIP) were further investigated. Immunostaining of CD3, CD4, CD8, CD68, PD1 and PD-L1 were conducted.
Results: Overall survival (OS) of patients without BTS surpassed BTS group (P = 0.040) while no difference of time to recurrence (TTR) was observed (P = 0.146). HL group had shorter OS and TTR than HL-matched group (P < 0.001 and P = 0.017, respectively) and survival time of NHL group differed not with NHL-matched group (P > 0.05). PPIP like neutrophils to lymphocytes ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune inflammation (SII) of HL group exceeded no BTS group or NHL group (all P < 0.05). Associations of PPIP and tumorous immunocytes differed vastly among HL group, NHL group and no BTS group. Tumorous CD4+/CD3+ ratio and PD1+/CD3+ ratio of HL group surpassed those in no BTS group (P = 0.036 and P < 0.001, respectively) and NHL group (P = 0.015 and 0.002, respectively). Para-tumorous CD68+ macrophages exceeded that in tumor samples of HL group (P < 0.001). No difference of CD8+/CD3+ lymphocyte ratio and PD-L1 rank were detected.
Conclusions: Hepatolithiasis, rather than extra-hepatic biliary stone, is a poor prognostic indicator of ICC. Immunotherapy is promising in treating HL-related ICC.
Keywords: Intrahepatic Cholangiocarcinoma, Hepatolithiasis, Prognosis, Preoperative peripheral inflammation index, Tumor infiltrating immunocytes