Perineural invasion has a negative impact on survival of patients with gallbladder carcinoma

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Abstract
Background The clinical significance of perineural invasion of gallbladder carcinoma remains unclear. The aim of this study was to elucidate the incidence and mode of perineural invasion of gallbladder carcinoma and clarify its prognostic significance. Methods A clinicopathological study was conducted on 68 patients who underwent attempted curative resection for gallbladder carcinoma. According to the pathological tumour node metastasis (pTNM) classification of the Union Internacional Contra la Cancrum, there were five (7 per cent), nine (13 per cent), 20 (29 per cent) and 34 (50 per cent) patients with pT1, pT2, pT3 and pT4 disease respectively. Twenty patients (29 per cent) had pM1 disease, including involved para-aortic nodes, liver metastases and localized dissemination. Results The overall incidence of perineural invasion was 71 per cent (48 of 68 patients). Forty-four (96 per cent) of 46 patients with extrahepatic bile duct invasion had perineural invasion. Although several histological factors were associated with perineural invasion, multivariate analysis demonstrated that extrahepatic bile duct invasion was the only significant factor correlated with perineural invasion (odds ratio 99·0, P < 0·001). The perineural invasion index, defined as the ratio of the number of involved nerves to the total number of nerves examined, was significantly higher at the centre than in the proximal and distal parts of the tumour in the 46 patients with extrahepatic bile duct invasion (P < 0·001). The 5-year survival rate for patients with perineural invasion was significantly lower than that for patients with no invasion (7 versus 72 per cent; P < 0·001). Cox proportional hazard analysis identified perineural invasion (relative risk (RR) 5·3, P < 0·001) and lymph node metastasis (RR 2·5, P = 0·008) as significant independent prognostic factors. Conclusion Perineural invasion is common in advanced gallbladder carcinoma and has a significant negative impact on patient survival.