Lv Chao, Zhao Bingtian, Wang Limin, Zhang Panpan, Ma Yuanyuan, Wang Yuzhao, Wu Nan, Wu Ying, Yang Yue
Second Department of Thoracic Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Laboratory of Clinical Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Oncol Lett. 2018 Jan;15(1):1103-1112. doi: 10.3892/ol.2017.7405. Epub 2017 Nov 14.
Intraoperative manipulation causes circulating tumor cell (CTC) shedding into the blood and accelerates metastasis in non-small cell lung cancer (NSCLC). The present study was conducted to assess the degree of dissemination resulting from surgery and to explore the biological features of CTCs. In patients with NSCLC who underwent complete resection, the pulmonary vein (PV) was isolated and stapled following thoracotomy. The number of CTCs retained per 7.5 ml PV blood (CTC-PV) and peripheral blood were detected. Following hematopoietic cell depletion, a xenograft assay was performed using the CTC-PV. A total of 32 consecutive patients were enrolled in the study, the majority of whom had CTCs in their PV blood (n=29, 90.6%). Circulating tumor microemboli (CTM) were identified in 12 patients (37.5%). The CTC-PV and CTM-PV counts were positively correlated with tumor size (P=0.012 and P=0.028, respectively). Patients with small tumors (<3.0 cm) also had considerable CTC-PV and CTM-PV. A total of 8 patients received platinum-based chemotherapy prior to surgery. The CTC-PV and CTM-PV counts in patients with partial response were significantly lower than those in patients with stable disease or who did not receive induction therapy (P=0.025 and P=0.044, respectively). The enriched CTC-PV from 3 patients were injected into 3 immunodeficient mice, and 1 mouse developed a xenograft tumor. To conclude, the present study indicates that intraoperative manipulation contributes to the hematogenous dissemination of tumorigenic CTCs and CTM. Lobectomy is recommended for lung cancer of any tumor size and stage according to oncological principles, in addition to ligating the PV, if possible, prior to any other treatment.
术中操作会导致循环肿瘤细胞(CTC)脱落至血液中,并加速非小细胞肺癌(NSCLC)的转移。本研究旨在评估手术造成的播散程度,并探究CTC的生物学特性。在接受根治性切除的NSCLC患者中,开胸后分离并结扎肺静脉(PV)。检测每7.5 ml PV血液(CTC-PV)和外周血中留存的CTC数量。在清除造血细胞后,使用CTC-PV进行异种移植试验。共有32例连续患者纳入本研究,其中大多数患者的PV血液中存在CTC(n = 29,90.6%)。12例患者(37.5%)中发现循环肿瘤微栓子(CTM)。CTC-PV和CTM-PV计数与肿瘤大小呈正相关(分别为P = 0.012和P = 0.028)。肿瘤较小(<3.0 cm)的患者也有相当数量的CTC-PV和CTM-PV。共有8例患者在手术前接受了铂类化疗。部分缓解患者的CTC-PV和CTM-PV计数显著低于病情稳定或未接受诱导治疗的患者(分别为P = 0.025和P = 0.044)。将3例患者富集的CTC-PV注入3只免疫缺陷小鼠体内,1只小鼠发生了异种移植瘤。总之,本研究表明术中操作有助于致瘤性CTC和CTM的血行播散。根据肿瘤学原则,建议对任何肿瘤大小和分期的肺癌行肺叶切除术,此外,如有可能,在任何其他治疗之前先结扎PV。