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.

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.

Increased serum human epidermal growth factor receptor 2 levels have been found in metastatic breast cancer patients and are correlated with human epidermal growth factor receptor 2 overexpression in tumor cells. However, the prevalence of serum human epidermal growth factor receptor 2 in gastric cancer patients has not been elucidated. We retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues and serum samples from 96 advanced gastric cancer patients. Human epidermal growth factor receptor 2 expression and gene amplification in tumor cells were determined by immunohistochemistry and fluorescence in situ hybridization. Serum human epidermal growth factor receptor 2 levels were measured using a chemiluminescent immunoassay. Human epidermal growth factor receptor 2 positivity in tumor cells was defined as immunohistochemistry 2+ with fluorescence in situ hybridization positive or immunohistochemistry 3+ with any fluorescence in situ hybridization results. All tissue samples and serum samples were successfully measured. Nineteen patients (20%) were human epidermal growth factor receptor 2-positive in tumor cells. The median serum human epidermal growth factor receptor 2 level was 9.3 ng/ml (range, 5.0–332.4 ng/ml), and serum human epidermal growth factor receptor 2 levels were significantly separated according to human epidermal growth factor receptor 2 status in tumor cells (P < 0.0001, Wilcoxon's rank sum test); median serum human epidermal growth factor receptor 2 levels in human epidermal growth factor receptor 2-negative patients and -positive patients were 8.9 (range, 5.0–20.5) and 24.0 (range, 9.7–332.4), respectively. There were 15 serum human epidermal growth factor receptor 2-positive patients (16%) using a cutoff value of 15 ng/ml. The sensitivity and the specificity of serum human epidermal growth factor receptor 2 with respect to human epidermal growth factor receptor 2 positivity in tumor cells were 53 and 94%, respectively. Serum human epidermal growth factor receptor 2 measurements cannot be substituted for tissue human epidermal growth factor receptor 2 diagnosis in advanced gastric cancer patients. However, serum human epidermal growth factor receptor 2 levels are associated with human epidermal growth factor receptor 2 overexpression in tumor cells. Further investigations of clinical significance of serum human epidermal growth factor receptor 2 as a predictive marker and a therapy-monitoring marker are warranted.

Background: The detection of extremely small lung tumors has increased with the development of computed tomography. Resection of such tumors by thoracoscopy is often hindered due to the unclear location of the tumor. Various methods of preoperative determination of such lesions have been attempted, but without marked success. Here we used virtual-assisted lung mapping (VAL-MAP) to perform surgical resection of small lung lesions. Methods: We selected patients with pulmonary tumors that we anticipated to be difficult to identify during thoracoscopy and/or decide the resection line for sub-lobar lung resection. The wedge resections in the VAL-MAP group were compared to a group of patients who underwent wedge resection without VAL-MAP in 2013. Results: Surgery duration was significantly shorter in the VAL-MAP group (average: 76.4 min) than in the 2013 group (average: 108.6 min; P=0.000451), although the VAL-MAP group (average major axis: 9.6 mm) had smaller tumors (P=0.000032) and more pure ground-glass opacities (GGOs) (P=0.0000919) than the 2013 group (average major axis: 16.6 mm). Conclusions: The findings of this study indicate that VAL-MAP is efficacious. In particular, VAL-MAP resulted in a shorter surgery duration and has expanded the indications of resectable lesions.