Circulating tumor cell (CTC) is a potentially useful surrogate of micro-metastasis, but detection of rare tumor cells contaminated in a vast majority of normal hematologic cells remains technical challenges. To achieve effective detection of a variety of CTCs, we have developed a novel microfluidic system (CTC-chip) in which any antibody to capture CTCs is easily conjugated. In previous studies, we employed an antibody (clone E-1) against podoplanin that was strongly expressed on mesothelioma cells. The CTC-chip coated by the E-1 antibody (E1-chip) provided a modest sensitivity in detection of CTCs in malignant pleural mesothelioma (MPM). Here, to achieve a higher sensitivity, we employed a novel anti-podoplanin antibody (clone NZ-1.2). In an experimental model, MPM cells with high podoplanin expression were effectively captured with the CTC-chip coated by the NZ-1.2 antibody (NZ1.2-chip). Next, we evaluated CTCs in the peripheral blood sampled from 22 MPM patients using the NZ1.2-chip and the E1-chip. One or more CTCs were detected in 15 patients (68.2%) with the NZ1.2-chip, whereas only in 10 patients (45.5%) with the E1-chip. Of noted, in most (92.3%, 12/13) patients with epithelioid MPM subtype, CTCs were positive with the NZ1.2-chip. The CTC-count detected with the NZ1.2-chip was significantly higher than that with the E1-chip (p = 0.034). The clinical implications of CTCs detected with the NZ1.2-chip will be examined in a future study.

The prognostic impact of tumoral programmed death-ligand 1 (PD-L1) expression in correlation with neutrophil-to-lymphocyte ratio (NLR) was retrospectively assessed in 83 patients with completely resected stage I squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Forty-three patients (51.8%) had tumor with positive PD-L1 expression. There was no significant correlation between PD-L1 expression and NLR. PD-L1-positivity failed to provide a significant prognostic impact (overall survival [OS] rate at 5 years, 53.0% in PD-L1-positive patients versus 70.1% in PD-L1-negative patients; P = 0.117). Among NLR-low (<2.2) patients, however, PD-L1-positivity was significantly correlated with a poor prognosis (OS rate at 5 years, 46.1% versus 86.0%; P = 0.020). In contrast, among NLR-high (≥2.2) patients, PD-L1-positivity provided no prognostic impact (P = 0.680). When NLR status and tumoral PD-L1 status were combined, “NLR-low and PD-L1-negative” was a significant and independent factor to predict a favorable recurrence-free survival (hazard ratio, 0.237 [95% confidence interval, 0.083 to 0.674]; P = 0.007) and OS (hazard ratio, 0.260 [0.091 to 0.745]; P = 0.012). These results suggest the prognostic impact of tumoral PD-L1 expression might be influenced by the status of NLR.

Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, “CTC‐chip,” for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM‐chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression‐free survival (P = .037) and cancer‐specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression‐free survival was worse in CTC‐positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM‐chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.

Background: The artery of Adamkiewicz (AKA) provides the major blood supply to the lower two-thirds of the spinal cord. As the AKA typically arises from a left posterior intercostal artery at the levels between 9 and 12th thoracic vertebrae, injury of the AKA during thoracic surgery such as resection of a lower paravertebral tumor may cause serious neurological complications. Robot-assisted thoracic surgery (RATS) has several advantages over video-assisted thoracic surgery including three-dimensional and high-definition view with high image magnification and reduced restriction in movement of surgical instruments. Here, we present a case of a left paravertebral ganglioneuroma originating from the sympathetic trunk. Whereas both tumor-feeding arteries and the AKA arose from the 9^th intercostal artery, complete tumor resection with preserving the AKA was achieved by RATS. Case presentation: A 15-year-old girl admitted for surgery for a posterior mediastinal tumor. Chest computed tomography showed a well-circumscribed 8.0 cm tumor adjacent to 8–11th thoracic vertebrae and the descending aorta. Contrast-enhanced CT and angiography revealed that the AKA arose from the left 9^th intercostal artery that ran between the tumor and the vertebrae and that tumor-feeding arteries also arose from the same intercostal artery. RATS was performed with the left intercostal approach using the da Vinci Xi system (Intuitive Surgical, Mountain View, CA). The tumor originating from the sympathetic trunk was completely resected with preserving the sympathetic trunk and the AKA. Postoperative course was uneventful without any adverse event, such as neurological complications. The final pathological diagnosis of the tumor was ganglioneuroma. Conclusions: RATS is a useful surgical approach for removal of a mediastinal tumor with preserving surrounding organs or tissues, such as the AKA.

Lung cancer patients with interstitial lung disease often develop acute exacerbation of their interstitial lung disease after lung resection. Special care is needed in selection of the surgical procedure to reduce acute exacerbation and provide long-term survival. The Japanese Association for Chest Surgery devised a risk scoring system based on 7 risk factors to predict the probability of postoperative acute exacerbation. We excluded surgical procedures and used a modified system categorizing 4 groups: group A (risk score 0–6), group B (risk score 7–10), group C (risk score 11–14), and group D (risk score 15–18). We retrospectively examined 60 lung cancer patients with interstitial lung disease to determine whether the modified risk scoring system is useful for selecting the optimal surgical procedure in anticipation of curability and risk of postoperative acute exacerbation. Eight (13.3%) patients experienced postoperative acute exacerbation. In group A (n = 20), there was no difference in the incidence of acute exacerbation between wedge (0%) and anatomic resection (6.3%, p = 0.800). In group B (n = 40), the incidence was significantly higher after anatomic resection (5.0% vs. 30.0%, p = 0.046). Thus group A had high-quality outcomes with anatomic resection, and in group B, the incidence of postoperative acute exacerbation can be reduced if wedge resection is performed. Our modified risk scoring can be useful for selecting the optimal surgical procedure in anticipation of curability and the risk of acute exacerbation of interstitial lung disease after lung cancer surgery.