Routine Intraoperative White Test for Bile Leak Detection in Liver Resection (DELiveR)

Routine White Test for Early Detection of Bile Leak in Elective Liver Resection - A Study Protocol for Randomized Controlled Trial (DELiveR Trial).

Bile leakage (BL) remains one of the most frequent complications following liver resection and is associated with increased postoperative morbidity and mortality, higher reintervention rates, prolonged hospital stay, and increased healthcare costs. Effective intraoperative identification and closure of open bile ducts may reduce the risk of postoperative BL. The White Test, which involves retrograde injection of a lipid emulsion into the biliary tree, enables active detection of bile leaks during surgery; however, its routine use has not been established in randomized clinical trials across all types of liver resection.

This is a single-center, prospective, randomized, parallel-group, single-blinded superiority trial designed to evaluate the effectiveness of routine intraoperative use of the White Test compared with standard intraoperative bile leak detection using a white gauze test. Adult patients undergoing elective liver resection (major or minor, including both anatomic and non-anatomic resections) who meet eligibility criteria will be enrolled after providing written informed consent.

Participants will be randomized in a 1:1 ratio to either the intervention group (White Test) or the control group (standard gauze test), 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, while the operating surgeon cannot be blinded due to the nature of the intervention.

In the intervention group, following completion of liver parenchymal transection and achievement of hemostasis, the cystic duct stump will be identified and cannulated. The distal bile duct will be temporarily occluded, and 10-20 mL of lipid emulsion will be injected retrogradely into the biliary tree. The transection surface will be inspected for leakage of the white emulsion. Identified leaks will be managed by 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 by applying sterile white gauze to the transection surface with visual inspection, followed by suturing of identified leaks as needed.

All patients will have intra-abdominal drainage placed at the resection site. Drain fluid bilirubin concentration will be measured on postoperative day three. Patients will be followed for 30 days after surgery.

The primary outcome is the incidence of postoperative bile leakage within 30 days, defined according to the International Study Group of Liver Surgery (ISGLS) criteria. Secondary outcomes include severity of bile leakage (ISGLS grades A-C), postoperative morbidity (Clavien-Dindo classification), need for postoperative interventions (endoscopic, radiological, or surgical), intensive care unit (ICU) admission and length of ICU stay, and total hospital length of stay.

The primary analysis will follow the intention-to-treat principle and will be performed separately within strata defined by resection type (major vs minor). Secondary and subgroup analyses will be considered exploratory. No formal interim analysis is planned; however, patient safety will be continuously monitored throughout the study.

The results of this trial are expected to clarify the role of routine intraoperative White Test in liver surgery and its potential to reduce postoperative bile leakage and improve clinical outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatectomy; Bile Leak; Liver Resection; Bile Leakage; Bile Duct Disorder
• Intervention / Treatment: Procedure: White Test; Procedure: Standard Gauze Test

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paweł Topolewski, MD; Phone Number: +48 22 599 25 45; Email: pawel.topolewski@wum.edu.pl
• Study Contact Backup: Name: Piotr Remiszewski, MD, PhD; Phone Number: +48 22 599 25 45; Email: piotr.remiszewski@wum.edu.pl

Study Locations

• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-097
      • Department of General, Transplant and Liver Surgery, Medical Univeristy of Warsaw
      • Contact: Piotr Remiszewski, MD, PhD; Phone Number: +48 22 599 25 45; Email: piotr.remiszewski@wum.edu.pl
      • Contact: Paweł Topolewski, MD; Phone Number: +48 22 599 2545; Email: pawel.topolewski@wum.edu.pl
      • Principal Investigator: Paweł Topolewski, MD
      • Principal Investigator: Piotr Remiszewski, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Undergoing elective liver surgery (regardless its modality): a) major hepatectomy OR b) minor hepatectomy (anatomic liver resection or non-anatomic liver resection).
• Possibility of performing the WT: intraoperative, simultaneous cholecystectomy or prior cholecystectomy with identifiable cystic stump allowing bile duct access.
• Written informed consent.

Exclusion Criteria:

• Undergoing intraoperative hepaticojejunostomy.
• Previous cholecystectomy without accessible cystic stump.
• Unresectable disease found intraoperatively.
• Allergy to SMOFlipid 5% components.
• Pregnancy or lactation.
• Emergency liver resection.
• Refusal for participation in trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm - White Test; Participants assigned to this arm will undergo intraoperative bile leak detection using the White Test. After completion of liver parenchymal transection and achievement of hemostasis, the cystic duct stump will be cannulated, and the distal bile duct will be temporarily occluded. A lipid emulsion (10-20 mL) will be injected retrogradely into the biliary tree. The transection surface will be inspected for leakage of the white emulsion. Identified leaks will be managed by ligation or suturing, and the test may be repeated until no further leakage is observed.	Procedure: White Test; The White Test is an intraoperative technique for bile leak detection performed after completion of liver parenchymal transection and achievement of hemostasis. The cystic duct stump is cannulated, and the distal bile duct is temporarily occluded. A lipid emulsion (10-20 mL) is injected retrogradely into the biliary tree to increase intrabiliary pressure and enable visualization of bile leaks at the transection surface. Detected leaks are managed by ligation or suturing, and the test may be repeated until no further leakage is observed.
Active Comparator: Control Arm - Standard Gauze Test; Participants assigned to this arm will undergo standard intraoperative bile leak detection using a sterile white surgical gauze applied to the liver transection surface. The gauze and transection site will be inspected for evidence of bile leakage. Identified leaks will be managed by ligation or suturing, and the assessment may be repeated as needed according to standard surgical practice.	Procedure: Standard Gauze Test; The standard gauze test is a conventional intraoperative method for bile leak detection. A sterile white surgical gauze is applied to the liver transection surface, and both the gauze and the surgical field are visually inspected for evidence of bile leakage. Detected leaks are managed by ligation or suturing, and the assessment may be repeated as needed according to standard surgical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative bile leakage	Occurrence of bile leakage within 30 days after liver resection, defined according to the International Study Group of Liver Surgery (ISGLS) criteria as bilirubin concentration in drain fluid at least three times higher than serum bilirubin on or after postoperative day 3, or the need for intervention due to bile leakage.	Within 30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of bile leakage	Severity of postoperative bile leakage classified according to ISGLS criteria (grades A-C).	Within 30 days after surgery
Postoperative morbidity	Overall postoperative complications classified according to the Clavien-Dindo classification.	Within 30 days after surgery
Postoperative interventions	Number and type of postoperative interventions required due to complications, including endoscopic, radiological, or surgical procedures.	Within 30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU admission and length of stay	Rate of intensive care unit (ICU) admission and duration of ICU stay measured in days.	Within 30 days after surgery
Hospital length of stay	Total duration of hospitalization measured in days from surgery to discharge.	Within 30 days after surgery

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Investigators: Study Director: Piotr Remiszewski, MD, PhD, Medical University of Warsaw; Principal Investigator: Paweł Topolewski, MD, Medical University of Warsaw; Study Chair: Michał Grąt, Professor (Full), MD, PhD,, Medical University of Warsaw

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: liver resection; hepatectomy; bile ducts; white test
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases
• Other Study ID Numbers: KB/47/2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to institutional data protection policies and ethical considerations. The dataset contains clinical information collected in a single-center study, and despite anonymization, there is a potential risk of re-identification. Access to the full dataset is restricted to authorized study investigators. Aggregated results will be published in peer-reviewed journals.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No