Abstract Introduction Accurate preoperative nodal staging remains challenging in gallbladder cancer (GBC), and a substantial proportion of patients presumed to be clinically node-negative have nodal metastasis at surgery. This study aimed to quantify the burden of occult nodal disease (OND)—defined as pathologic node-positive disease among clinically node-negative patients—and to identify preoperative factors associated with OND. Methods Patients who underwent upfront curative-intent resection with regional lymphadenectomy for GBC were identified from an international multi-institutional database. Among patients staged as clinically node-negative (cN0) on preoperative imaging, multivariable logistic regression was used to identify preoperative predictors of OND. CA19-9 and the systemic immune-inflammation index (SII) were log-transformed for modeling purposes. Results Among 187 patients, 142 (75.9%) were classified as cN0 preoperatively, among whom 47 (33.1%) had OND on final pathology. On multivariable analysis, higher ln(SII) (odds ratio OR 1.69, 95% confidence interval CI 1.05–2.86), higher ln(CA19-9) (OR 1.30, 95% CI 1.12–1.53), and preoperative jaundice (OR 3.68, 95% CI 1.21–11.76) were independently associated with OND. The observed OND rate increased stepwise with the number of elevated preoperative markers (SII > 890.2, CA19-9 > 37 U/mL, and jaundice): 17.1% with 0 markers, 44.8% with 1 marker, and 73.6% with 2–3 markers. Conclusions OND was present in approximately one-third of clinically node-negative GBC patients undergoing lymphadenectomy. Preoperative jaundice, elevated CA19-9, and elevated SII independently predicted OND and provided simple risk stratification. Incorporating these readily available markers into preoperative assessment may improve risk enrichment for OND and help guide additional staging and treatment sequencing.
Kawashima et al. (2026) studied this question.