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

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 ).