Associations of Type 2 Diabetes with Tumor Budding and Microvascular Invasion in Resected Hepatocellular Carcinoma.

PURPOSE: Type 2 diabetes mellitus (DM) may influence invasive tumor phenotypes in hepatocellular carcinoma (HCC). We evaluated associations of pre-existing DM with tumor budding (TB), microvascular invasion (MVI), and postoperative outcomes. PATIENTS AND METHODS: This single-center retrospective cohort included 924 patients with pathologically confirmed HCC who underwent curative-intent hepatectomy from 2015 to 2020. Two blinded pathologists assessed TB and MVI. Logistic regression evaluated pathological associations, and Kaplan-Meier and Cox models evaluated recurrence-free survival (RFS) and overall survival (OS). Glycemic and treatment analyses in patients with DM were exploratory and used variable-specific available cases. RESULTS: Among 924 patients, 124 (13.4%) had DM, 314 (34.0%) were TB-positive, and 493 (53.4%) were MVI-positive. DM was associated with TB-positive status (adjusted odds ratio [OR], 3.508; 95% confidence interval [CI], 2.287-5.381; P < 0.001) and MVI-positive status (adjusted OR, 3.364; 95% CI, 2.083-5.434; P < 0.001). In the primary overlap-weighted PS analysis, DM was not associated with RFS (hazard ratio [HR], 1.453; 95% CI, 0.778-2.714; P = 0.240) or OS (HR, 1.127; 95% CI, 0.556-2.284; P = 0.740). TB remained associated with RFS but not OS in expanded Cox models, whereas MVI was associated with both outcomes. CONCLUSION: Pre-existing DM was associated with TB-positive and MVI-positive status after hepatectomy for HCC. The primary PS analysis did not provide evidence of an independent DM survival association. Glycemic-control and treatment findings were exploratory and require prospective external validation.