Clinical significance of lymph node micrometastasis in gallbladder carcinoma

目的：探讨胆囊癌(GBC)淋巴结微转移的临床意义。方法：对63例胆囊癌根治术患者的1136个区域淋巴结进行组织学检查。微转移定义为常规组织学检查中苏木精-伊红染色漏诊，而免疫组织化学检测细胞角蛋白8和18抗体发现的转移。结果9例(0%)PTL患者和19例(35%)PT2-4患者均无结节微转移。单因素分析显示，淋巴结微转移、根治性切除类型、M分期、PT分期、神经周围侵犯、pTNM分期、根治性切除时机、淋巴管侵犯和PN分类是有意义的变量。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)是影响预后的独立因素。尽管没有(P=.0002)或存在(P&lt；.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。淋巴结微转移与淋巴管侵袭、神经侵袭和远处转移显著相关。结论：淋巴微转移是预后较差的独立预测因子，与淋巴结状态无关，可能提示根治性切除患者具有侵袭性的肿瘤生物学行为。

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.