Bile leakage remains one of the most clinically relevant complications following liver resection, contributing to increased postoperative morbidity, higher reintervention rates, prolonged hospitalization, and increased healthcare costs. Despite improvements in surgical techniques and perioperative care, the incidence of bile leakage remains significant. Effective intraoperative identification and closure of open bile ducts is therefore a key component of risk reduction strategies.
Conventional intraoperative methods for bile leak detection, such as visual inspection of the transection surface or application of surgical gauze, are based on passive identification of bile outflow and may fail to detect small or occult leaks. Several alternative techniques have been proposed, including saline injection tests, indocyanine green fluorescence imaging, and intraoperative cholangiography; however, none have been universally adopted as standard practice due to limitations in sensitivity, availability, or practicality.
The White Test is an intraoperative technique designed to actively identify bile leaks by transiently increasing intrabiliary pressure through retrograde injection of a lipid emulsion into the biliary tree. This approach enables visualization of bile leakage at the transection surface and allows immediate surgical correction. The method is technically simple, inexpensive, and does not require specialized equipment. Previous studies have suggested that the White Test may improve detection of bile leaks and reduce postoperative bile leakage rates; however, the available evidence is primarily derived from observational studies and heterogeneous interventional designs. Its routine use across all types of liver resection has not been adequately evaluated in a randomized controlled trial.
This study is a prospective, single-center, randomized, parallel-group, single-blinded superiority trial designed to evaluate whether routine intraoperative use of the White Test reduces the incidence of postoperative bile leakage compared with standard intraoperative bile leak detection. Adult patients undergoing elective liver resection will be enrolled after providing written informed consent. The study population includes both major and minor liver resections, encompassing anatomic and non-anatomic procedures, to reflect real-world clinical practice while allowing stratified analysis according to resection type.
Participants will be randomized in a 1:1 ratio to either the intervention group or the control group using stratified block randomization according to the type of resection (major vs minor). Allocation will be concealed using sequentially numbered, opaque, sealed envelopes. Patients will remain blinded to group assignment, whereas blinding of the operating surgeon is not feasible due to the nature of the intervention.
In the intervention group, the White Test will be performed after completion of liver parenchymal transection and achievement of hemostasis. The cystic duct stump will be identified and cannulated, and the distal bile duct will be temporarily occluded. A lipid emulsion will be injected retrogradely into the biliary tree to increase intrabiliary pressure and facilitate visualization of bile leaks at the transection surface. Detected leaks will be managed intraoperatively using standard surgical techniques, including ligation or suturing, and the test may be repeated until no further leakage is observed.
In the control group, bile leak detection will be performed using a standard approach based on application of sterile white surgical gauze to the transection surface and visual inspection for bile staining. Detected leaks will be managed according to standard surgical practice.
All patients will undergo standardized perioperative management according to institutional protocols. Intra-abdominal drainage will be placed at the resection site. Drain fluid bilirubin concentration will be measured postoperatively, and clinical management decisions will be made independently of study allocation. Patients will be followed for 30 days after surgery.
The primary analysis will follow the intention-to-treat principle. Analyses will be performed separately within strata defined by resection type (major vs minor) to account for differences in baseline risk of bile leakage. Secondary and exploratory analyses will further evaluate clinical outcomes and potential effect modifiers.
Safety will be continuously monitored throughout the study. Although no formal interim analysis is planned, the trial may be terminated prematurely if a significantly increased rate of serious adverse events is observed in the intervention group.
The results of this study are expected to provide high-quality evidence regarding the clinical utility of routine intraoperative bile leak testing using the White Test. If effective, this technique may represent a simple and widely implementable strategy to reduce postoperative bile leakage and improve outcomes following liver resection. Conversely, if no benefit is demonstrated, the findings may help to refine indications for its selective use and optimize intraoperative decision-making in hepatobiliary surgery.
