The goal of this clinical trial is to evaluate the safety of two durations of the Pringle maneuver in adults undergoing elective liver resection for malignant tumors. The main questions it aims to answer are:

Is the incidence of post-hepatectomy liver failure different between 15-minute and 45-minute Pringle maneuver durations?

• Do the durations differ in operative time or intraoperative blood loss?
• Researchers will compare patients randomized 1:1 to 15 minutes vs 45 minutes of Pringle clamping to see if outcomes are non-inferior between groups.

Participants will:

• Undergo standard oncologic hepatectomy with the assigned Pringle duration.
• Receive routine perioperative assessments, including laboratory tests and clinical evaluations.
• Attend follow-up visits at approximately 6 months, 1 year, and 3 years after surgery.

Participants who meet the inclusion criteria and provide written informed consent will be randomly assigned, using block randomization with a block size of 10, to one of two study groups. In Group 1, Pringle maneuvers lasting 15 minutes with a 10-minute reperfusion interval will be applied during liver resection. In Group 2, Pringle maneuvers lasting 45 minutes with a 15-minute reperfusion interval will be used. In both groups, the Pringle maneuver will be repeated as needed until completion of liver parenchymal transection. If transection is completed earlier, the maneuver will be discontinued before the randomized time. The operating surgeon and anesthesiologist may also decide to start or interrupt the Pringle maneuver outside the predefined time frames if intraoperative conditions require it.

During each Pringle maneuver, the patient's status will be monitored according to standard practice for liver resection, including blood pressure measurement, urine output, and arterial blood gas analysis. The number and duration of Pringle maneuvers, arterial blood pressure values, the type and doses of vasopressors used, serum lactate levels, the duration of parenchymal transection, total operative time, intraoperative blood loss, and hourly urine output will be recorded in perioperative case report forms.

In the postoperative period, laboratory tests will be performed on postoperative days 0, 1, 3, and 5. The occurrence of postoperative complications up to the time of hospital discharge will be documented in the patient's electronic medical record. Outcomes will be assessed by in-person outpatient visits or telemedicine consultations at approximately 6 months, 1 year, and 3 years after surgery.

The sample size was calculated using the Wald method. Based on an analysis of archival data from the Department of Transplantation and Liver Surgery, the incidence of post-hepatectomy liver failure according to the ISGLS definition is approximately 4%. Assuming 80% power, a one-sided significance level of 0.05, and a noninferiority margin of 5%, 300 participants will be enrolled in each arm.

Collected study data will be analyzed with particular attention to the duration of the Pringle maneuver, the extent and technical complexity of the resection, the primary diagnosis, and the presence of coexisting liver disease, in order to determine their influence on the study endpoints.

An interim analysis is planned after recruitment of 50% of the target sample size. If the interim analysis demonstrates a negative effect of the intervention on postoperative complications, further enrollment will be discontinued.

Inclusion Criteria:

• Diagnosis of a primary or secondary malignant liver tumor.
• Age > 18 years.
• Patient deemed eligible for liver resection.
• WHO performance status ≤ 2.
• Ability to provide written informed consent.

Exclusion Criteria:

• Liver cirrhosis.
• Liver dysfunction classified as Child-Pugh class B or C.
• Repeat hepatectomy.
• Prior ablation or chemoembolization of hepatic lesions.
• Prior portal vein branch embolization.
• Planned or performed ALPPS procedure.
• Concomitant resection of any organ other than the gallbladder during the same operation.

We do not plan to share individual participant data (IPD). The design of this study does not require public IPD sharing for the reliability of the published results. De-identified IPD may be provided to journal peer reviewers under confidentiality during manuscript review.