Indocyanine Green-Guided Versus Standard Laparoscopic Distal Pancreatectomy for Pancreatic Body and Tail Lesions

Indocyanine Green Fluorescence-Guided Versus Standard Laparoscopic Distal Pancreatectomy: A Prospective Randomized Controlled Trial

Postoperative pancreatic fistula is the most important complication after laparoscopic distal pancreatectomy for tumors of the body and tail of the pancreas. It can cause infection, bleeding, longer hospital stay, and even death. New imaging technology using indocyanine green (ICG) dye and near-infrared fluorescence may help surgeons see blood flow to the pancreatic stump, spleen, and nearby vessels during surgery and make safer decisions about where to cut and which structures to preserve.

This study will compare two standard laparoscopic operations for pancreatic body and tail lesions: one with ICG fluorescence imaging at key steps of the procedure and one without ICG imaging. Adult patients who need elective laparoscopic distal pancreatectomy will be randomly assigned to one of the two groups. All other aspects of care before, during, and after surgery will be the same.

The main goal is to find out whether using ICG fluorescence can reduce the rate of clinically relevant postoperative pancreatic fistula (Grade B or C) within 90 days after surgery. Secondary goals include comparing blood loss, operating time, need to convert to open surgery, spleen preservation, complications, hospital stay, and oncologic outcomes such as margin status and lymph node yield.

Laparoscopic distal pancreatectomy is now widely used for lesions of the pancreatic body and tail, but postoperative pancreatic fistula (POPF) remains a frequent and serious problem. POPF is associated with prolonged hospital stay, sepsis, post-pancreatectomy hemorrhage, and higher perioperative mortality. Current methods for choosing the pancreatic transection line and judging stump and splenic perfusion rely mainly on the surgeon's visual assessment and experience. There is increasing interest in using indocyanine green (ICG) fluorescence imaging to provide real-time information about tissue perfusion, vessel anatomy, and lymphatic drainage during pancreatic surgery. However, existing evidence is mostly from small retrospective series and case reports, and the overall benefit of ICG guidance in laparoscopic distal pancreatectomy has not been tested in a randomized clinical trial.

This prospective, single-center, parallel-group randomized controlled trial will compare ICG fluorescence-guided laparoscopic distal pancreatectomy (ICG-LDP) with standard laparoscopic distal pancreatectomy (S-LDP) in adult patients with pancreatic body and/or tail lesions scheduled for elective minimally invasive surgery. Eligible patients (age ≥ 18 years, BMI ≤ 40 kg/m², ECOG performance status 0-2, resectable lesion suitable for laparoscopy) will be randomized in a 1:1 ratio. Randomization will be stratified by intended spleen preservation (yes/no), malignant versus benign or premalignant diagnosis, and neoadjuvant therapy status. Allocation concealment will be ensured using sequentially numbered, opaque, sealed envelopes.

In the ICG-LDP arm, patients will undergo standard laparoscopic distal pancreatectomy with integration of four predefined ICG fluorescence steps using a near-infrared-enabled laparoscopic camera. A low-dose ICG injection will first be used for real-time mapping of the splenic artery and vein to support safer dissection and potentially reduce bleeding and conversion. A second injection after splenic vessel division (in spleen-preserving cases) will assess splenic perfusion and guide the decision to preserve or remove the spleen. A third injection before pancreatic transection will evaluate perfusion at the proposed stump margin; if perfusion is poor, the transection line may be adjusted to a better-perfused segment to reduce ischemia-related POPF. In oncologic cases, a higher-dose ICG injection during lymphadenectomy will highlight fluorescent lymph nodes along key vascular territories, which will be removed in addition to the standard nodal dissection.

In the standard S-LDP arm, the same laparoscopic approach, anesthesia, and surgical team will be used, but no ICG will be administered and no fluorescence imaging will be available. Decisions about dissection planes, pancreatic transection level, spleen preservation, and lymphadenectomy will be based on conventional white-light visualization and surgeon judgment. Perioperative management will be standardized in both groups, including prophylactic antibiotics, venous thromboembolism prophylaxis, stapled closure of the pancreatic remnant, routine drain placement with a predefined amylase-based removal protocol, multimodal analgesia, and an enhanced recovery after surgery pathway.

The primary outcome is the rate of clinically relevant postoperative pancreatic fistula (Grade B or C) within 90 days after surgery, according to the 2016 International Study Group on Pancreatic Surgery definition. Drain fluid amylase will be measured on postoperative days 1 and 3, and clinically relevant fistulas will be recorded. Secondary outcomes include intraoperative blood loss, operative time, conversion to open surgery, unplanned splenectomy when spleen preservation was intended, R0 resection rate, lymph node yield in malignant cases, length of hospital stay, time to first oral intake, time to drain removal, overall postoperative morbidity (Clavien-Dindo), post-pancreatectomy hemorrhage, delayed gastric emptying, 30-day and 90-day readmission, and 30-day and 90-day mortality.

Based on published data, the expected rate of clinically relevant POPF after standard laparoscopic distal pancreatectomy is around 40%. Preliminary studies suggest that ICG-guided assessment of stump perfusion may reduce this rate to about 10%. Using these estimates, a two-sided alpha of 0.05, and 80% power, the trial plans to enroll 72 patients (36 per arm), allowing for an anticipated dropout rate of approximately 10%. The primary analysis will follow the intention-to-treat principle. Categorical variables, including POPF rates, will be compared using chi-square or Fisher's exact tests as appropriate. Continuous variables will be analyzed with t-tests or non-parametric methods depending on distribution, and time-to-event outcomes such as time to drain removal or hospital discharge may be evaluated using Kaplan-Meier methods with log-rank testing.

All participants will provide written informed consent before enrollment. The study has been designed in accordance with CONSORT and SPIRIT recommendations, and will be conducted under the oversight of the institutional ethics committee. The findings are expected to clarify whether routine integration of ICG fluorescence imaging into laparoscopic distal pancreatectomy improves safety and perioperative outcomes sufficiently to justify its broader adoption as a standard adjunct in pancreatic surgery.

Inclusion Criteria:

• Age ≥ 18 years.
• Body mass index (BMI) ≤ 40 kg/m².
• Radiologically confirmed lesion(s) of the pancreatic body and/or tail requiring elective distal pancreatectomy, with or without splenectomy.
• Lesion amenable to a laparoscopic approach as determined by the operating surgeon on preoperative CT or MRI imaging.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate hepatic function: serum bilirubin ≤ 2 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
• Patients who have received neoadjuvant chemotherapy, chemoradiotherapy, or radiotherapy are eligible if resectability is confirmed on restaging imaging and at least 3 weeks have elapsed since the last treatment dose.
• Ability to provide written informed consent and willingness to comply with study follow-up.

Exclusion Criteria:

• Known allergy or hypersensitivity to indocyanine green (ICG), iodine, or iodinated contrast agents.
• Uncorrected coagulopathy (international normalized ratio > 1.5 or platelet count < 80 × 10⁹/L).
• Pregnancy or breastfeeding.
• Prior major upper abdominal surgery precluding safe laparoscopic access (for example previous pancreatectomy or gastrectomy) as judged by the surgeon.
• Presence of distant metastases or locally advanced disease requiring vascular resection at the time of surgery.
• American Society of Anesthesiologists (ASA) physical status classification IV or V.
• Severe hepatic impairment (Child-Pugh class C).
• Inability or unwillingness to comply with scheduled follow-up visits and assessments.
• Concurrent participation in another interventional clinical trial.