Prognostic value and risk stratification of residual disease in patients with incidental gallbladder cancer

Abstract

Background and aim: Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than Tstage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. Material and methods: A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher's exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. Results: RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). Conclusion: RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD.

The Significance of Tumor Budding and Immunohistochemical Axl Expression in Gallbladder Adenocarcinomas

“…Therefore, resection margin positivity is a common histopathological finding in GBC since they cannot be operated curatively. The ratio of resection margin 1 patients is 36.8% and is compatible with the literature 1 , 6 , 7 , 35 . The statistically significant distinction in the short overall survival time in this group of patients underlines the need for a complete resection during the operation.…”

“…Practical clinical diagnostic tools for early diagnosis do not yet exist, sometimes discovered accidentally after cholecystectomy. The light of the literature shows that GBC’s prognostic characteristics have been almost the same for many years 1 , 3 , 4 , 7 , 35 . Tumor size, pT staging, lymph node metastasis, perineural invasion, histological grading, RM, and liver invasion play decisive roles in the prognosis of GBC patients 1 , 4 , 6 , 7 , 35 .…”

“…The light of the literature shows that GBC’s prognostic characteristics have been almost the same for many years 1 , 3 , 4 , 7 , 35 . Tumor size, pT staging, lymph node metastasis, perineural invasion, histological grading, RM, and liver invasion play decisive roles in the prognosis of GBC patients 1 , 4 , 6 , 7 , 35 . The present study found that the relationship between poor tumor differentiation, advanced pT, positive resection margin, the presence of perineural invasion, lymphovascular invasion, and serosal invasion with a short OS time is in agreement with the literature 1 , 3 , 6 , 7 .…”

Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

“…Mochizuki et al [87] evaluated the prognostic ability of the GBRS in a single-center cohort of 56 GBC patients following curative surgery and determined that higher GBRS associated with poor long-term prognosis and high rate of tumor recurrence in incidental and non-incidental GBC [87]. Similarly, the GBRS was useful to predict the presence of regional or distant residual disease in a subgroup of 25 patients with incidental GBC, which was significantly higher in high-risk patients than in intermediate-risk patients (80% vs 30%, p = 0.041) [80]. Those studies underline the potential value of this novel predictive risk-score to guide treatment strategies regarding the selection of patients for reoperation and adjuvant therapy.…”

“…Therefore, re-exploration and definitive resection are recommended for selected patients with invasive tumors without evidence of disseminated disease. Single and multicenter studies have shown that residual disease is found in over 50% of incidental GBC, involving mainly lymph nodes, common bile duct, and the liver [65,[77][78][79][80]. The presence of residual disease is significantly associated with a higher T, TNM stage [78,79,81], and disease recurrence [78].…”