Background: Surgical manipulation of a tumor can lead to shedding of tumor cells that can enter the circulation and lead to metastasis. The present study evaluated the clinical relevance of circulating tumor cells (CTCs) that were identified immediately after non-small cell lung cancer resection in patients without preoperative CTCs, and whether postoperative CTC detection was associated with recurrence. Methods: Immediate preoperative testing for CTCs was performed for 147 patients with pulmonary nodules. This study included 81 lung cancer patients (55.1%) with negative preoperative results for CTCs and who completed postoperative testing for CTCs. The clinical relevance of postoperative CTC detection was evaluated based on the clinicopathological characteristics and recurrence patterns. Results: Among the eligible patients, the postoperative CTC results were none detected in 58 patients (71.6%, “Group N”), only a single CTC detected in 6 patients (7.4%, “Group S”), and CTC clusters detected in 17 patients (21.0%, “Group C”). The presence of postoperative CTCs was associated with tumor vessel invasion, lymph duct invasion, and pleural invasion. Distant metastasis was very common in cases with postoperatively detected CTC clusters. The 2-year recurrence-free survival rates were 94.6% for Group N, 62.5% for Group S, and 52.9% for Group C (P<0.01). Multivariate analysis revealed that recurrence was independently related to the postoperative detection of single CTCs and CTC clusters. Conclusions: In cases without preoperative CTCs, we postoperatively detected CTCs and the postoperative CTC results were an independent predictor of recurrence.

The existence of clustered isolated tumour cells (ITCs) in the pulmonary vein (PV) of the lungs of patients with lung cancer has been reported to be a prognostic factor. However, the clinical–pathological characteristics related to their presence in the PV remain unclear. We analysed the surgical results and clinical–pathological findings of 130 patients who underwent surgery for non-small-cell lung cancer in regard to blood vessel invasion (BVI), serum carcinoembryonic antigen (CEA) level, maximum standardized uptake value (SUV-max), size of the solid region in computed tomography findings and pathological stage according to an ITC type, i.e. no tumour (N), singular tumour cells (S) and clustered tumour cells (C). ITCs were detected in 96 (74%) of the patients, with C observed in 43, S in 53 and N in 34. Recurrence was seen in 33 (26%) cases, 21 of which were classified as C, 9 as S and 3 as N. The disease-free survival rate was significantly worse in C cases when compared with the others (P < 0.01). The rate of C was high in cases with high serum CEA, advanced p-staging and positive BVI ratio. Furthermore, BVI positive and ITC morphology were strongly related (BVI positive; 79 in C, 40 in S, 9% in N; P < 0.01). Clustered ITCs were shown to be a prognostic indicator and strongly related to BVI. Our results suggest that determination of BVI has prognostic value, as clustered ITCs with metastatic potential are disseminated from the invaded vein.