Mantel Hendrik T J, Wiggers Jim K, Verheij Joanne, Doff Jan J, Sieders Egbert, van Gulik Thomas M, Gouw Annette S H, Porte Robert J
Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Hepato-Pancreatico-Biliary Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1107-15. doi: 10.1245/s10434-015-4723-9. Epub 2015 Jul 16.
Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology.
Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months.
Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02).
Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.
常规组织学检查发现的淋巴结转移是肝门部胆管癌切除术后生存的强烈负性预测指标。额外的免疫组化可在其他方面淋巴结阴性的患者中检测到淋巴结微转移，但预后价值尚不确定。本研究的目的是评估免疫组化检测到的淋巴结微转移对常规组织学检查淋巴结阴性（pN0）的肝门部胆管癌患者生存的影响。
1990年至2010年期间，荷兰两家大学医学中心共有146例患者接受了肝门部胆管癌根治性切除及区域淋巴结清扫术。纳入91例（62%）常规组织学检查无淋巴结转移的患者。通过对所有淋巴结进行多切片及使用细胞角蛋白19（K19）抗体进行额外免疫染色来识别微转移。在单变量和多变量分析中评估其与总生存的相关性。中位随访时间为48个月。
在324个淋巴结中的16个（5%）发现微转移，对应91例患者中的11例（12%）。K19淋巴结阳性和阴性患者的临床变量无差异。有淋巴结微转移的患者5年生存率显著低于无微转移的患者（27%对54%，P = 0.01）。多变量分析证实微转移是生存的独立预后因素（调整后风险比2.4，P = 0.02）。
淋巴结微转移与肝门部胆管癌切除术后较差的生存相关。免疫组化检测淋巴结微转移可使最初在常规组织学检查中被诊断为淋巴结阴性（pN0）的肝门部胆管癌患者分期更准确。
