SynthesisJHEP reports : innovation in hepatology2026
Perineural invasion in intrahepatic cholangiocarcinoma: Meta-analysis of prevalence, association with tumor features, and impact on survival.
Synthesis in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsPerineural invasion (PNI) is a recognized marker of tumor aggressiveness in several malignancies, but its prevalence and prognostic significance in intrahepatic cholangiocarcinoma (ICC) remain uncertain. This systematic review and meta-analysis aimed to estimate the pooled prevalence of PNI and evaluate its association with overall survival (OS) in ICC.
methodsFollowing PRISMA guidelines, PubMed, Web of Science, and the Cochrane Library were searched through August 2025. The PNI prevalence was pooled using a random-effects model. Where available, multivariable hazard ratios for OS were pooled using a random-effects meta-analysis. Heterogeneity was assessed and potential moderators were explored using meta-regression. Pairwise ecological correlations between PNI and other tumor features were analyzed using Pearson's correlation coefficient.
resultsWe analyzed 61 studies including 15,502 patients. The pooled prevalence of PNI was 36.0% (95% CI 31.0-41.0%), with substantial heterogeneity (I
conclusionsPNI occurs in approximately one-third of patients with ICC, is associated with poorer outcomes, and clusters with lymph node metastasis and vascular invasion, reflecting aggressive tumor biology. Despite the heterogeneity of the available data, its adverse prognostic impact is consistent. IMPACT AND IMPLICATIONS: Perineural invasion (PNI) is a proposed marker of tumor aggressiveness in intrahepatic cholangiocarcinoma (ICC); however, its prevalence and prognostic significance have remained uncertain, warranting systematic evaluation. This study provides the most comprehensive synthesis to date of PNI in ICC demonstrating that PNI occurs in approximately one-third of ICC cases and clusters with adverse pathological features, although its independent impact on survival remains debatable. These findings are relevant for clinicians and researchers involved in ICC management, as they suggest that PNI may contribute to more refined risk stratification, particularly in early-stage disease. In practice, PNI assessment could support clinical decision-making and patient counseling. However, future standardized and prospective studies are needed to clarify its prognostic value and potential role in guiding treatment strategies.
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