Clinical significance of lymph node micrometastasis in gallbladder carcinoma

背景。本研究旨在探讨胆囊癌（GBC）淋巴结微转移的临床意义。对63例连续行根治性切除的患者共1136个区域淋巴结进行组织学检查。微转移是指在苏木精和伊红常规组织学检查中未发现，但免疫组织化学检查中抗细胞角蛋白8和18抗体检测到的转移。9例pTl患者（0%）和54例pT2-4患者中19例（35%）无淋巴结微转移。单因素分析发现，淋巴结微转移、根治性切除类型、M分型、pT分型、神经周围浸润、pTNM分期、根治性切除时间、淋巴管浸润和pN分型是显著变量。多因素分析显示，淋巴结微转移（P=.0003）和根治性切除类型（P=.0044）是独立的预后因素。尽管没有（P= 0.0002）或存在（P< 0.0001）明显的淋巴结转移，但淋巴结微转移对生存率有不利影响。淋巴结微转移与浸润性特征有显著相关性：淋巴管浸润、神经周围浸润和远处转移。结论：淋巴结微转移是预后较差的最强独立预测因子，与显性淋巴结状态无关，可能表明行根治性切除的GBC患者肿瘤具有侵袭性。

BACKGROUND.This retrospective study was intended to define the clinical significance of lymph node micrometastasis in gallbladder carcinoma(GBC).METHODS.A total of 1136 regional lymph nodes taken from 63 consecutive patients undergoing radical resection were examined histologically. Micrometastasis was defined as a metastasis missed on routine histologic examination with hematoxylin and eosin but detected by immunohistochemical examination with an antibody against cytokeratins 8 and 18.RESULTS.None of 9 patients(0%)with pTl disease and 19 of 54 patients(35%)with pT2-4 disease had nodal micrometastasis. Univariate analysis identified nodal micrometastasis, type of radical resection, M classification, pT classification, perineural invasion, pTNM stage, timing of radical resection, lymphatic vessel invasion, and pN classification as significant variables. Multivariate analysis revealed that nodal micrometastasis(P=.0003)and type of radical resection(P=.0044)were independent prognostic factors. Nodal micrometastasis affected survival adversely, despite the absence(P=.0002)or presence(P<.0001)of overt nodal metastasis. Nodal micrometastasis correlated significantly with invasive characteristics : lymphatic vessel invasion, perineural invasion, and distant metastasis.CONCLUSIONS.Lymph node micrometastasis is the strongest independent predictor of worse survival regardless of the overt nodal status and may indicate aggressive tumor biology among patients undergoing curative resection for GBC.