JHEP reports : innovation in hepatology · 2026
Perineural invasion in intrahepatic cholangiocarcinoma: Meta-analysis of prevalence, association with tumor features, and impact on survival.
СтатьяМетаанализСистематический обзорНазвание и аннотация: Перевод в очереди
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Kolck Johannes, Auer Timo Alexander, Pedersen Camilla Winther, Hosse Clarissa, Ihlow Jana, Krenzien Felix, Schöning Wenzel, Fehrenbach Uli, Geisel Dominik
Аннотация
BACKGROUND & AIMS: Perineural 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.
METHODS: Following 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.
RESULTS: We analyzed 61 studies including 15,502 patients. The pooled prevalence of PNI was 36.0% (95% CI 31.0-41.0%), with substantial heterogeneity (I2 = 98.5%). Meta-regression identified publication year and study size as independent moderators, with more recent and larger studies reporting lower PNI prevalence. PNI positively correlated with lymph node metastasis, lymphovascular invasion, and vascular invasion (all p <0.001), and inversely correlated with the proportion of mass-forming ICC (p = 0.025). Of 44 studies assessing OS, 23 were included in meta-analysis, demonstrating that PNI was associated with worse survival (hazard ratio 1.79, 95% CI 1.38-2.19, p <0.001).
CONCLUSIONS: PNI 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.
METHODS: Following 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.
RESULTS: We analyzed 61 studies including 15,502 patients. The pooled prevalence of PNI was 36.0% (95% CI 31.0-41.0%), with substantial heterogeneity (I2 = 98.5%). Meta-regression identified publication year and study size as independent moderators, with more recent and larger studies reporting lower PNI prevalence. PNI positively correlated with lymph node metastasis, lymphovascular invasion, and vascular invasion (all p <0.001), and inversely correlated with the proportion of mass-forming ICC (p = 0.025). Of 44 studies assessing OS, 23 were included in meta-analysis, demonstrating that PNI was associated with worse survival (hazard ratio 1.79, 95% CI 1.38-2.19, p <0.001).
CONCLUSIONS: PNI 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.