Work

Perineural invasion is a prognostic factor in cholangiocarcinoma, regardless of anatomical location: A systematic review and meta-analysis

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: BACKGROUND & AIMS: Cholangiocarcinoma (CCA), a heterogeneous malignancy that includes intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) subtypes, often exhibits perineural invasion (PNI). Despite PNI being associated with postoperative recurrence, evidence on its prognostic impact remains inconsistent. To clarify this, we conducted a systematic review and meta-analysis. METHODS: A comprehensive literature search was conducted across the Medline-PubMed, Embase, and Web of Science databases from their inception through February 27, 2025. We included studies involving patients diagnosed with CCA who underwent surgery and for whom PNI data were available. The primary outcomes were overall survival (OS) and disease-free survival (DFS), extracted from both univariable and multivariable analyses. The study is registered in PROSPERO (CRD42024575458). RESULTS: = 70.5%)). Prognostic consistency was observed across anatomical subgroups. Univariable OS HRs were 2.14 for iCCA, 1.69 for pCCA, and 1.66 for dCCA. Corresponding multivariable HRs were 1.74, 1.60, and 1.66, respectively. CONCLUSIONS: PNI is a prognostic factor for both DFS and OS in CCA, regardless of anatomical location. Further research is needed to elucidate its biological mechanisms and potential therapeutic implications. IMPACT AND IMPLICATIONS: This comprehensive review and meta-analysis confirms that perineural invasion (PNI) predicts poorer overall and disease-free survival in cholangiocarcinoma, independent of tumor location. These results highlight the potential of PNI as a reliable histopathological marker to stratify postoperative risk and inform patient management. While most evidence is retrospective and smaller studies may overstate the effect, the consistent findings emphasize the need for large, multicenter prospective studies with standardized pathological assessment. Such efforts could facilitate the integration of PNI into prognostic models and support more individualized treatment strategies for patients with cholangiocarcinoma.

Source: JHEP Reports

DOI: 10.1016/j.jhepr.2026.101770