Impact of Intermittent Pringle Maneuver on Long-Term Survival After Hepatectomy for Hepatocellular Carcinoma: Result from Two Combined Randomized Controlled Trials

Abstract

Background: Hepatectomy remains an important curative treatment for hepatocellular carcinoma (HCC). Intermittent Pringle maneuver (IPM) is commonly applied during hepatectomy for control of bleeding. Whether the ischemia/reperfusion injury brought by IPM adversely affects the operative outcomes is controversial. This study aims to examine whether the application of IPM during hepatectomy affects the long-term outcomes. Methods: Two randomized controlled trials (RCT) have been carried out previously to evaluate the short-term outcomes of IPM. The present study represented a post hoc analysis on the HCC patients from the first RCT and all patients from the second RCT, and the long-term outcomes were evaluated. Results: There were 88 patients each in the IPM group and the no-Pringle-maneuver (NPM) group. The patient demographics, type and extent of liver resection and histopathological findings were comparable between the two groups. The 1-, 3-, 5-year overall survival in the IPM and NPM groups was 92.0%, 82.0%, 72.1% and 93.2%, 68.8%, 58.1%, respectively (P = 0.030). The 1-, 3-, 5-year disease-free survival in the IPM and NPM groups was 73.6%, 56.2%, 49.7% and 71.6%, 49.4%, 40.3%, respectively (P = 0.366). On multivariable analysis, IPM was a favorable factor for overall survival (P = 0.035). Subgroup analysis showed that a clamp time of 16–30 min (P = 0.024) and cirrhotic patients with IPM (P = 0.009) had better overall survival. Conclusion: IPM provided a better overall survival after hepatectomy for patients with HCC. Such survival benefit was noted in cirrhotic patients, and the beneficial duration of clamp was 16–30 min. Trial registration: NCT00730743 and NCT01759901 (http://www.clinicaltrials.gov).