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Release of Circulating Tumor Cells during Surgery for Non-Small Cell Lung Cancer: Are They What They Appear to Be?
Clinical Cancer Research ( IF 10.0 ) Pub Date : 2020-04-01 , DOI: 10.1158/1078-0432.ccr-19-2541
Menno Tamminga 1 , Sanne de Wit 2 , Caroline van de Wauwer 3 , Hilda van den Bos 4 , Joost F Swennenhuis 2 , Theo J Klinkenberg 3 , T Jeroen N Hiltermann 1 , Kiki C Andree 2 , Diana C J Spierings 4 , Peter M Lansdorp 4, 5, 6 , Anke van den Berg 7 , Wim Timens 7 , Leon W M M Terstappen 2 , Harry J M Groen 1
Affiliation  

PURPOSE Tumor cells from patients with lung cancer are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTCs) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. EXPERIMENTAL DESIGN Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTCs were enumerated using the CellSearch system. Single-cell whole-genome sequencing was performed on isolated CTCs for aneuploidy. RESULTS CTCs were detected in 58 of 138 samples (42%) of 31 patients. CTCs were more often detected in the PV (70%) compared with the RA (22%, P < 0.01) and in higher counts (P < 0.01). After surgery, the RA but not the PV showed less often CTCs (P = 0.02). Type of surgery did not influence CTC release. Only six of 496 isolated CTCs showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTCs had a different morphology than aneuploid. CONCLUSIONS CTCs defined by CellSearch were identified more often and in higher numbers in the PV compared with the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTCs. Release of CTCs was not influenced by surgical approach.

中文翻译:

非小细胞肺癌手术过程中循环肿瘤细胞的释放:它们看起来像是什么吗?

目的肺癌患者的肿瘤细胞从原发肿瘤排出到血液中,但在外周循环中很难检测到。我们研究了手术期间循环肿瘤细胞(CTC)的释放,以检验以下假设:CTC计数受血液动力学变化(由手术方法引起)和操作的影响。实验设计包括接受电视胸腔手术(VATS)或开放手术(疑似)原发性肺癌的患者。手术前(T0)从the动脉(RA),RA和肺静脉(PV)在定位PV(T1)以及肺动脉(T2打开)或PV(T2)时采集血样解剖)。使用CellSearch系统枚举了四氯化碳。对非整倍性在分离的CTC上进行单细胞全基因组测序。结果31例患者的138例样本中有58例(42%)检测到四氯化碳。与RA(22%,P <0.01)相比,PV中检出CTC的频率更高(70%),且计数更高(P <0.01)。手术后,RA而非PV表现出较少的CTCs(P = 0.02)。手术类型不影响CTC释放。尽管匹配的原发肿瘤组织为非整倍体,但在496个分离的CTC中只有6个显示非整倍体。整倍体所谓的CTC具有与非整倍体不同的形态。结论与RA相比,由CellSearch定义的CTC在PV中的识别率更高,且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。结果31例患者的138例样本中有58例(42%)检测到四氯化碳。与RA(22%,P <0.01)相比,PV中检出CTC的频率更高(70%),且计数更高(P <0.01)。手术后,RA而非PV表现出较少的CTCs(P = 0.02)。手术类型不影响CTC释放。尽管匹配的原发肿瘤组织为非整倍体,但在496个分离的CTC中只有6个显示非整倍体。整倍体所谓的CTC具有与非整倍体不同的形态。结论与RA相比,CellSearch定义的PV中发现的CTC更为频繁且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。结果31例患者的138例样本中有58例(42%)检测到四氯化碳。与RA(22%,P <0.01)相比,PV中检出CTC的频率更高(70%),且计数更高(P <0.01)。手术后,RA而非PV表现出较少的CTCs(P = 0.02)。手术类型不影响CTC释放。尽管匹配的原发肿瘤组织为非整倍体,但在496个分离的CTC中只有6个显示非整倍体。整倍体所谓的CTC具有与非整倍体不同的形态。结论与RA相比,由CellSearch定义的CTC在PV中的识别率更高,且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。与RA(22%,P <0.01)相比,PV中检出CTC的频率更高(70%),且计数更高(P <0.01)。手术后,RA而非PV表现出较少的CTCs(P = 0.02)。手术类型不影响CTC释放。尽管匹配的原发肿瘤组织为非整倍体,但在496个分离的CTC中只有6个显示非整倍体。整倍体所谓的CTC具有与非整倍体不同的形态。结论与RA相比,由CellSearch定义的CTC在PV中的识别率更高,且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。与RA(22%,P <0.01)相比,PV中检出CTC的频率更高(70%),计数更高(P <0.01)。手术后,RA而非PV表现出较少的CTCs(P = 0.02)。手术类型不影响CTC释放。尽管匹配的原发肿瘤组织为非整倍体,但在496个分离的CTC中只有6个显示非整倍体。整倍体所谓的CTC具有与非整倍体不同的形态。结论与RA相比,CellSearch定义的PV中发现的CTC更为频繁且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。RA而非PV显示出较少的CTC(P = 0.02)。手术类型不影响CTC释放。尽管匹配的原发肿瘤组织为非整倍体,但在496个分离的CTC中只有6个显示非整倍体。整倍体所谓的CTC具有与非整倍体不同的形态。结论与RA相比,由CellSearch定义的CTC在PV中的识别率更高,且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。RA而非PV显示出较少的CTC(P = 0.02)。手术类型不影响CTC释放。尽管匹配的原发肿瘤组织为非整倍体,但在496个分离的CTC中只有6个显示非整倍体。整倍体所谓的CTC具有与非整倍体不同的形态。结论与RA相比,CellSearch定义的PV中发现的CTC更为频繁且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。结论与RA相比,CellSearch定义的PV中发现的CTC更为频繁且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。结论与RA相比,由CellSearch定义的CTC在PV中的识别率更高,且数量更高,提示中心清除。PV中的大多数细胞是正常上皮细胞,并且数量超过CTC。四氯化碳的释放不受手术方式的影响。
更新日期:2020-04-01
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