Evaluating prognostic value of biliary stone in intrahepatic cholangiocarcinoma by propensity score matching analysis

Yupeng Wang; Ao Huang; Dezhen Guo; Jian Wang; Feiyu Chen; Huichuan Sun; Shuangjian Qiu; Sunyue Zhang; Ya Cao; Xinrong Yang; Jian Zhou

doi:10.7150/jca.74275

Evaluating prognostic value of biliary stone in intrahepatic cholangiocarcinoma by propensity score matching analysis

J Cancer. 2023 May 8;14(7):1257-1271. doi: 10.7150/jca.74275. eCollection 2023.

Authors

Yupeng Wang^{1

2}, Ao Huang^{1

2}, Dezhen Guo^{1

2}, Jian Wang^{1

2}, Feiyu Chen^{1

2}, Huichuan Sun^{1

2}, Shuangjian Qiu^{1

2}, Sunyue Zhang^{1

2}, Ya Cao³, Xinrong Yang^{1

2}, Jian Zhou^{1

2}

Affiliations

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.

Abstract

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: Hepatolithiasis; Intrahepatic Cholangiocarcinoma; Preoperative peripheral inflammation index; Prognosis; Tumor infiltrating immunocytes.