Effect of 25- or 15-minute intermittent Pringle maneuver on early recurrence of hepatocellular carcinoma after hepatectomy: a protocol for a randomized controlled trial

Abstract Background: Among various blood flow control techniques, the intermittent Pringle’s maneuver (IPM) remains the most convenient and widely used method to reduce bleeding during hepatic resection (HR). Now, the impact of IPM on human hepatocellular carcinoma (HCC) recurrence is still unclear. Currently, there has no randomized controlled trial (RCT) to directly confirm the impact of IPM on the tumor recurrence for HCC patients undergoing HR. Since 2019, our team has been investigating the effect of 25-min IPM on liver function and post-hepatectomy safety in HCC patients. To date, we have published two RCTs to directly confirm the safety and feasibility of 25-min IPM for those HCC patients with Child-Pugh grade A liver function. However, our previous RCTs only focused on the short-term outcomes of HCC patients after HR. They did not answer the hot topic of whether the 25-min IPM would increase postoperative HCC recurrence after HR. Therefore, we design this RCT to compare the effects of 25-min IPM and 15-min IPM on early tumor recurrence for HCC patients undergoing HR. Methods: This will be a single-center, parallel, double-blinded, randomized controlled trial. A total of 334 consecutive patients who are eligible for the inclusion and exclusion criteria will be enrolled and randomized into either the 25-min IPM group or the 15-min IPM group in a ratio of 1:1 using a randomization protocol. After the completion of surgical intervention, patients will be included in a 2-year follow-up program. Discussion: We design this protocol to compare the effects of the above two different IPM methods on tumor recurrence for HCC patients undergoing HR, which will have an important guiding significance for surgeons. Firstly, this RCT will be easy to implement and carry out. Secondly, this RCT will include various types of HR procedures (laparoscopic or open HR, minor or major hepatectomy, etc.), which will have well representativeness of clinical application. Thirdly, this RCT has well originality, which is the first RCT to compare the effects of 25-min and 15-min IPM on early tumor recurrence after HR. Trial registration This trial was registered on 29 April 2024, in the Chinese Clinical Trial Registry (http:// www.chictr.org.cn), ChiCTR2400083647. The protocol version is V1.0 (20240429).