Beyond station 16: A pathway-aware framework for gallbladder cancer lymphadenectomy after neoadjuvant therapy

Table 1 Pathway-oriented interpretation of gallbladder cancer lymphadenectomy

Pathway	Main stations	Meaning	Proposed surgical consideration	Key caution
Cholecysto-celiac	12 → 8 → 9 → 16	Spread through the hepatoduodenal ligament toward the common hepatic artery and celiac axis	Consider stations 8 and 9 when stage, imaging or intraoperative findings suggest celiac-route risk	Schematic pathway based on anatomical literature; not a universal sequence
Cholecysto-retropancreatic	12 → 13 → 17 → 16	Main route described in anatomical studies; involves posterior pancreatic head and inferior pancreatic border	Consider retropancreatic exposure and station 13/17 assessment when suspicious or high-risk	Station 13/17 relevance does not automatically imply pancreaticoduodenectomy
Cholecysto-mesenteric	12 → 14 → 16	Drainage toward the superior mesenteric root and vessels	Consider station 14 around both SMA and SMV when mesenteric-route risk is present	Apparent skip disease may reflect a recognized route but remains variably reported
Para-aortic/interaortocaval convergence	16a2/16b1	Terminal convergence near the left renal vein and interaortocaval space	Sampling may avoid futile surgery; clearance is investigational in selected responders	Do not infer therapeutic benefit from anatomy alone

The station sequences are schematic and based on classical anatomical studies and Japanese Society of Biliary Surgery nomenclature[4-6]. They do not exclude anatomical variability or alternative drainage. Surgical implications are proposed considerations, not uniform requirements. SMA: Superior mesenteric artery; SMV: Superior mesenteric vein.

Table 2 Source-specific lymph-node metrics and interpretation

Ref.	Reported metric	Metric type	Interpretation for this review
AJCC 8th edition[11]	Number-based pN classification	Staging framework	Supports quantitative nodal staging; does not define an extended operative field
Ito et al[24] and Widmann et al[32]	At least six examined nodes	Staging/adequacy threshold	Useful quantitative floor for staging, not proof of therapeutic benefit
Yoon et al[27]	11-node cutoff proposed to reduce false N0 staging	Staging-accuracy reference	Supports careful nodal evaluation; survival association should not be read as causation
Tang et al[28]	Fusion LND increased mean yield vs standard dissection	Technical yield comparison	Demonstrates feasibility and detection gain; not definitive survival evidence
Vega et al[30]	At least four nodes as an international benchmark	Pragmatic quality benchmark	Shows real-world heterogeneity and difficulty achieving higher thresholds
Giehl-Brown et al[31]	Extended LND ≥ 6 associated with morbidity in major resections without independent OS/RFS benefit	Retrospective comparative caution	Reinforces separation of staging value from unproven therapeutic value

LND: Lymph-node dissection; OS: Overall survival; RFS: Recurrence-free survival.

Table 3 Evidence hierarchy underlying the pathway-aware framework

Evidence domain	What is established	What remains uncertain	Implication for this review
Anatomical studies	Three lymphatic routes and variable convergence toward para-aortic/interaortocaval nodes are described[4-6]	Anatomy alone does not prove survival benefit from extended dissection	Provides the map, not the indication
Guidelines and consensus	Regional lymphadenectomy, adequate staging and avoidance of futile radical surgery are emphasized[11-19]	Guidelines do not validate routine pathway-oriented extended clearance after neoadjuvant therapy	Current standards remain the baseline
Retrospective station-specific series	Station 13 and interaortocaval disease may not behave uniformly as distant disease in selected patients[20,23]	Selection bias is substantial and therapeutic benefit is unproven	Supports hypothesis generation only
Nodal-yield studies	Node count, positive-node count and lymph-node ratio have prognostic value[24-26,28-30,32,44]	The independent value of station distribution requires validation	Report both number and map
Neoadjuvant selection	Response or stability can identify more favorable biology[36,37]	Response does not prove benefit from extended nodal clearance	Use as a filter, not proof

Table 4 Practical station-specific decision criteria in selected patients

Station/region	Primary purpose	When to consider	When to avoid
12	Regional staging and gateway assessment	Radical/re-resection intended to stage beyond simple cholecystectomy[11,17-19,24]	Frailty, nonoperative intent or disseminated disease
8/9	Celiac pathway mapping and selected sampling/clearance	Suspicious nodes, T2/T3 or more advanced disease, or celiac-route concern[4,7,8]	Low-risk early disease without suspicion; no evidence supports routine use
13/17	Retropancreatic pathway mapping and selected assessment	Suspicious retropancreatic nodes, high-risk biology or expert HPB exposure available[4,5,7,20]	If clearance would require disproportionate morbidity or if no R0 operation is possible
14	Mesenteric pathway assessment	Superior mesenteric-root suspicion or disease pattern compatible with this route[4-6]	Routine use without pathway risk or when systemic progression is present
16a2/16b1	Futility assessment by sampling; exceptional investigational clearance	Suspicious convergence-basin disease after response/stability and no occult spread[9,10,21-23]	Progression, new metastases, poor reserve or no realistic R0 resection[9,12-18,23]

The table separates anatomical mapping, staging/sampling and therapeutic clearance. The latter remains investigational and should be discussed only in expert-center multidisciplinary settings. Citations in the table indicate the anatomical, staging or retrospective literature informing each station-specific consideration; they do not establish a therapeutic standard.