BACKGROUND Intrahepatic cholangiocarcinoma is a public health threat because of its aggressiveness. Its genetic background differs from other biliary cancers. The aim of this study was to investigate the impact of genetic alterations on long-term outcomes. METHODS PubMed, MEDLINE, Scopus, and Cochrane Library databases were systematically searched for studies assessing long-term outcomes after resection of intrahepatic cholangiocarcinoma according to genetic mutational profiling until 31 May 2022. The main outcome was the impact of genetic alterations on long-term outcomes in these patients. HR (95% c.i.) was used for effect size. Publication bias was investigated. RESULTS A total of 24 retrospective studies were included. KRAS, IDH1/2, and TP53 were identified as the only three genes whose mutation correlated with survival (HR: 2.476, 95% c.i. 1.67-3.671, P < 0.01 for KRAS; HR: 0.624, 95% c.i. 0.450-0.867, P < 0.01 for IDH1/2; and HR: 2.771, 95% c.i. 2.034-3.775, P < 0.01 for TP53). The prevalence of KRAS and IDH1/2 mutations differed between western and eastern studies (P < 0.001 for both genes). CONCLUSION Determining the overall prevalence of the most common actionable and undruggable mutations may help to expand target therapy indications in the adjuvant setting. Inconsistent results have been found for some infrequent gene alterations; their rare involvement could potentially bias their prognostic meaning.

中文翻译：

---

基因改变对可切除肝内胆管癌长期预后的影响：荟萃分析。


背景 肝内胆管癌因其侵袭性而对公共卫生构成威胁。它的遗传背景与其他胆道癌不同。本研究的目的是调查遗传改变对长期结果的影响。方法 系统检索 PubMed、MEDLINE、Scopus 和 Cochrane Library 数据库，以查找根据基因突变分析评估肝内胆管癌切除术后长期结局的研究，直至 2022 年 5 月 31 日。主要结局是基因改变对这些患者长期结局的影响。HR （95% ci.i.） 用于效应大小。调查了发表偏倚。结果 共纳入 24 篇回顾性研究。KRAS 、 IDH1/2 和 TP53 被确定为仅有的三个突变与生存相关的基因 （HR： 2.476,95% CI 1.67-3.671，KRAS 的 P < 0.01;HR： 0.624,95% CI 0.450-0.867，ID 1/2 的 P < 0.01;和 HR：2.771,95% CI 2.034-3.775，TP53 的 P < 0.01）。KRAS 和 IDH1/2 突变的患病率在西方和东方研究中存在差异 （P < 0.001）。结论 确定最常见的可操作和不可成药突变的总体患病率可能有助于扩大辅助治疗的靶向治疗适应症。对于一些不常见的基因改变，已发现结果不一致;他们罕见的参与可能会使他们的预后意义产生偏差。