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Accurate Staging for Gallbladder Cancer: Implications for Surgical Therapy and Pathological Assessment

Background: This study evaluates the significance of tumor involvement of the liver in early T-stage tumors and lymph node (LN) metastases on outcome after R0 resection of gallbladder cancer (GBCA). Methods: A prospectively maintained database, supplemented with review of the medical record, was used to identify patients who underwent a complete (R0) resection for GBCA. All patients underwent definitive surgical treatment at the initial operation (1 stage) or after initial noncurative cholecystectomy (incidental tumors, 2 stage), including partial hepatectomy and portal LN dissection, with or without bile duct and/or adjacent organ resection. Clinicopathological variables, including TNM stage, histologic tumor involvement of liver (residual or direct extension in the GB fossa or discontiguous disease), and the total number of regional LNs assessed were analyzed for their association with outcome. Results: One hundred twenty-two patients were identified and analyzed. The median follow up period was 23 months. Liver and nodal involvement by GBCA were observed in 61 (50%) and 41(34%) patients, respectively. Among patients with T2 tumors (n = 53), 48 (91%) were incidental. Liver involvement was present in 26%, and this factor was associated with decreased recurrence-free (RFS) and disease-specific survival (DSS) compared with patients with T2 tumors without liver involvement (median RFS, 12 months vs. not reached, P = 0.004, median DSS 25 months versus not reached, P = 0.003); T1b tumors (n = 10) were not associated with liver involvement. The median total lymph node count (TLNC) was 3 (range 0–20). For the entire cohort, survival of patients classified as N0 based on TLNC < 6 was significantly worse than that of N0 patients based on TLNC ≥ 6 (median RFS, 22 months versus not reached, P < 0.001, median DSS 41 months versus not reached, P < 0.001). Liver involvement and TLNC remained significant prognostic factors in a multivariate model that included TNM stage. Conclusion: Resection and histologic evaluation of at least 6 lymph nodes improves risk-stratification after resection of GBCA. Incidental T2 tumors are often associated with residual liver disease and should be reclassified to reflect the adverse outcome. The data suggests a need for standardized minimum requirements for adequate surgical treatment and pathological examination.