Background: The influence of morphological status on the long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) is poorly defined. We sought to study the impact of morphological status on overall survival (OS) of patients undergoing curative-intent resection for ICC. Methods: A total of 1083 patients who underwent liver resection for ICC between 1990 and 2015 were identified. Data on clinicopathological characteristics, operative details, and morphological status were recorded and analyzed. A propensity score-matched analysis was performed to reduce confounding biases. Results: Among 1083 patients, 941(86.9%) had a mass-forming (MF) or intraductal-growth (IG) type, while 142 (13.1%) had a periductal-infiltrating (PI) or MF with PI components (MF + PI) ICC. Patients with an MF/IG ICC had a 5-year OS of 41.8% (95% confidence interval [CI] 37.7–45.9) compared with 25.5% (95% CI 17.3–34.4) for patients with a PI/MF + PI (p < 0.001). Morphological type was found to be an independent predictor of OS as patients with a PI/MF + PI ICC had a higher hazard of death (hazard ratio [HR] 1.42, 95% CI 1.11–1.82; p = 0.006) compared with patients who had an MF/IG ICC. Compared with T1a–T1b–T2 MF/IG tumors, T1a–T1b–T2 PI/MF + PI and T3–T4 PI/MF + PI tumors were associated with an increased risk of death (HR 1.47 vs. 3.59). Conversely, patients with T3–T4 MF/IG tumors had a similar risk of death compared with T1a–T1b–T2 MF/IG patients (p = 0.95). Conclusion: Among patients undergoing curative-intent resection of ICC, morphological status was a predictor of long-term outcome. Patients with PI or MF + PI ICC had an approximately 45% increased risk of death long-term compared with patients who had an MF or IG ICC.
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