Clinical significance of wall invasion pattern of subserosa-invasive gallbladder carcinoma

We have previously classified wall invasion patterns of gallbladder carcinoma (GBC) cases into two groups, i.e., the infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor differentiation, aggressive infiltration and decreased postoperative survival in terms of its histological differentiation, lymphatic invasion, venous invasion, lymph node status, neural invasion and mode of subserosal infiltration. In the present study, we analyzed 42 surgically-resected subserosal invasive gallbladder adenocarcinomas, invading the perimuscular connective tissue (pT2). The cumulative 5-year survival rate in the series was 48.7%. Lymphatic invasion (p=0.021), venous invasion (p=0.020), mode of subserosal infiltration (p<0.001), histological differentiation (p=0.030) and biliary infiltration (p=0.007) were noted, respectively, at a significantly higher incidence in more aggressive infiltration or poor differentiation in the DG type. The cumulative 5-year survival rate of curative resection cases was lower in patients with the DG type than in those with the IG type (68.9 versus 20.2%, respectively, p=0.006, log-rank test). On Cox's proportional hazard regression modeling, the low degree of venous/perineural invasion and IG type of wall invasion pattern were associated with a significant improvement in overall survival. Our data suggest that the wall invasion pattern is an independent predictor of survival in subserosal invasive GBC. Regarding the clinical application of our concept, on the classification of patients with subserosal invasive GBC based on a combination of the wall invasion pattern and lymph node status, the overall survival rate in patients with the DG type and/or N2 metastasis (n=21) was lower than in patients with the IG type and N0, 1 metastasis (n=21) (p=0.0023, log-rank test). The wall invasion pattern could contribute to decision-making concerning curative resection for subserosal invasive GBC.