Patterns of Discordance Between Pretransplant Imaging Stage of Hepatocellular Carcinoma and Posttransplant Pathologic Stage: A Contemporary Appraisal of the Milan Criteria

AbstractBackgroundPatients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood.MethodsPatients who underwent orthotopic liver transplantation (OLT) for HCC following preoperative MRI were identified in a prospectively collected institutional database (1/2003-12/2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were utilized to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival.ResultsOf 318 patients with HCC meeting Milan criteria by MRI at the time of OLT, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 vs. 140.0 months, p=0.002) and overall survival (96.0 vs. 143.0 months, p=0.005), and did not vary between patients exceeding criteria due to tumor explant >5 cm, >3 tumor foci, or a tumor >3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum AFP level (OR 2.82, 95% CI 1.37-5.79, p=0.005).ConclusionsUnderestimating HCC burden prior to liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing AFP prior to transplantation may benefit from more frequent testing or novel neoadjuvant therapies. Background Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood. Methods Patients who underwent orthotopic liver transplantation (OLT) for HCC following preoperative MRI were identified in a prospectively collected institutional database (1/2003-12/2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were utilized to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival. Results Of 318 patients with HCC meeting Milan criteria by MRI at the time of OLT, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 vs. 140.0 months, p=0.002) and overall survival (96.0 vs. 143.0 months, p=0.005), and did not vary between patients exceeding criteria due to tumor explant >5 cm, >3 tumor foci, or a tumor >3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum AFP level (OR 2.82, 95% CI 1.37-5.79, p=0.005). Conclusions Underestimating HCC burden prior to liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing AFP prior to transplantation may benefit from more frequent testing or novel neoadjuvant therapies. Corresponding Author: Matthew H. Levine, MD, PhD, 3400 Spruce Street, 1 Founders, University of Pennsylvania, Philadelphia, Pennsylvania 19104, Phone: 215.662.7367. E-mail: matthew.levine@uphs.upenn.edu. Author contributions: 1) conception and design (Ecker, Hoteit, Shaked, Olthoff, Levine), acquisition of data (Ecker), or analysis and interpretation of data (all authors); 2) drafting (Ecker, Levine) or revising (all authors) 3) final approval of the version to be published (all authors) Disclosures: The authors report no conflicts of interest Funding: none Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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