Yasuhiro Chikaishi

Clinical Significance of IGF1R Expression in Non-Small-Cell Lung Cancer

BACKGROUND The purpose of the current study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGF1R) in NSCLC. PATIENTS AND METHODS Tumor specimens were collected from 285 patients who underwent complete resection for adenocarcinoma (AD, n = 182), squamous cell carcinoma (SCC, n = 77), and other histologic types of cancer (n = 26) of the lung. The expression of IGF1R and Ki-67 was evaluated by immunohistochemical (IHC) analysis. RESULTS Positive expression of IGF1R was detected in 87 (30.5%) of 285 cases, of which 43 (23.6%) of 182 cases were AD, 36 (46.8%) of 77 cases were SCC, and 8 (30.8%) of 26 cases were other histologic types (SCC vs. AD, p < .001; SCC vs. non-SCC, p < .001). Positive IGF1R expression was also identified in 20 (44.4%) and 67 (27.9%) of the patients with and without recurrence, respectively (p = .027). Multivariate logistic regression models indicated that positive staining for IGF1R expression was an independent factor in AD associated with tumor recurrence (p = .040) but not in NSCLC, SCC, and other types of cancer. A positive IGF1R expression tended to demonstrate a poor disease-free survival (DFS) in NSCLC according to the Kaplan-Meier DFS curves (p = .053). The tumors showing a positive expression of IGF1R were observed more frequently in tumors with a positive expression of Ki-67 than in the tumors with a negative expression of Ki-67 (p = .010). CONCLUSION IGF1R expression was associated with reduced DFS correlating with postoperative recurrence. In addition, a significant relationship was also observed between IGF1R and Ki-67 expression in NSCLC. However, in subgroup analysis, a significant correlation was not observed. IGF1R expression predicts postoperative recurrence in patients with AD, but not in those with non-AD of NSCLC.

Clinical significance of the frequency of regulatory T cells in regional lymph node lymphocytes as a prognostic factor for non-small-cell lung cancer.

BACKGROUND Regulatory T cells (Tregs) are potent immunosuppressive cells that play a crucial role in tumor immune escape. The purpose of the present study was to evaluate the prognostic significance of the frequency of CD4+CD25+Foxp3+ Tregs in the regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) in patients who underwent surgical resection of non-small cell lung cancer (NSCLC). METHODS The RLNL and PBL in 158 NSCLC patients who underwent complete surgical resection were collected at the time of surgery. The proportions of CD4+CD25+Foxp3+ cells in the RLNL and PBL were determined by flow cytometry. RESULTS The average proportions of Tregs in the RLNL and PBL were 1.28% and 0.76%, respectively. The proportion of Tregs in the RLNL was significantly higher than that in the PBL (p < 0.0001). The 5-year overall survival rates of the patients according to the proportion of Tregs in the RLNL were 84.4% and 63.5% in the lower and higher groups, respectively. A significant difference was observed in the survival rate between the higher and lower groups (p = 0.0056). Among the patients with stage I disease, the 5-year survival rate (91.4%) was significantly higher in patients with the lower proportion of Tregs in RLNL that in the higher group (72.1%) (p = 0.0147). CONCLUSIONS The higher proportion of Tregs in the RLNL was a significant unfavorable prognostic factor, even in patients with node-negative NSCLC. The information about the proportion of Tregs in the RLNL might improve the discriminatory power for assessing the risk of the recurrence of NSCLC.

Serum Level of Osteopontin as a Prognostic Factor in Patients Who Underwent Surgical Resection for Non-Small-Cell Lung Cancer

BACKGROUND OPN is a multifunctional glycophosphoprotein originally described as a secreted protein from malignant epithelial cells. This study focused on the clinical significance of preoperative serum level of OPN in NSCLC patients who underwent a complete resection. PATIENTS AND METHODS The serum OPN level was assayed in 244 patients who underwent a complete resection of NSCLC by commercially available sandwich enzyme-linked immunosorbent assay kits. The patients were considered as a higher group, when the serum OPN levels exceeded 81.3 ng/mL. RESULTS The patients included 166 male and 78 female subjects. The histologic types included 172 adenocarcinomas, 49 squamous cell carcinomas, and 23 other types of carcinoma. The serum level of OPN in male patients (92.6 ng/mL) was significantly higher than that of female patients (76.9 ng/mL). The OPN level of squamous cell carcinoma was significantly higher than that of adenocarcinoma. The OPN level was significantly elevated in patients with the pleural invasion or microvascular invasion than those without the invasion. The 5-year survival rate after surgery in the lower OPN group (82.0%) was a significant favorable prognosis than that in the higher OPN group (63.7%) (P < .0001). The 5-year survival rates in the lower OPN group at stage I NSCLC (88.1%) was significantly better than that in the higher OPN group (80.5%) (P = .0321). CONCLUSION The preoperative serum OPN level was a useful predictor of an unfavorable prognosis, and it was found to be an independent prognostic determinant of outcome in patients who underwent surgery for NSCLC.

Evaluation of undiagnosed solitary lung nodules according to the probability of malignancy in the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines

Abstract Background. This study retrospectively investigated the clinical significance of undiagnosed solitary lung nodules removed by surgical resection. Patients and methods. We retrospectively collected data on the age, smoking, cancer history, nodule size, location and spiculation of 241 patients who had nodules measuring 7 mm to 30 mm and a final diagnosis established by histopathology. We compared the final diagnosis of each patient with the probability of malignancy (POM) which was proposed by the American College of Chest Physicians (ACCP) guidelines. Results. Of the 241 patients, 203 patients were diagnosed to have a malignant lung tumor, while 38 patients were diagnosed with benign disease. There were significant differences in the patients with malignant and benign disease in terms of their age, smoking history, nodule size and spiculation. The mean value and the standard deviation of the POM in patients with malignant tumors were 51.7 + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best cut-off value provided from the ROC curve was 22.6. When the cut-off value was set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value 90%, negative predictive value 36% and accuracy 77%, respectively. Conclusions. The clinical prediction model proposed in the ACCP guidelines showed unsatisfactory results in terms of the differential diagnosis between malignant disease and benign disease of solitary lung nodules in our study, because the specificity, negative predictive value and AUC were relatively low.

The impact of covering the bulla with an absorbable polyglycolic acid (PGA) sheet during pneumothorax surgery

We herein present the pathological findings of a bulla covered using an absorbable polyglycolic acid sheet applied with fibrin glue. These findings indicated that the membrane of the bulla was reinforced. Covering the bulla with an absorbable polyglycolic acid sheet (Neoveil, Gunze Ltd, Kyoto, Japan) and applying fibrin glue was effective to prevent the recurrence of the pneumothorax. Moreover, this report is the first case report showing the pathological findings of a bulla which was covered with an absorbable polyglycolic acid sheet and fibrin glue.

Complete Resection of Thymic Sarcomatoid Carcinoma Through Total Aortic Arch Replacement.

Sarcomatoid carcinoma of the thymus is extremely rare. An operation remains the only effective treatment for this disease. We report a case of complete resection of thymic sarcomatoid carcinoma through a total aortic arch replacement and left upper lobectomy at our institution. Our aggressive operation was very effective, and the patient has experienced no recurrence in the 3 years since his operation.

Primary Adenoid Cystic Carcinoma of the Peripheral Lungs

We herein report a very rare case of adenoid cystic carcinoma of the peripheral lungs. A 77-year-old female visited a family physician for aortitis syndrome, diabetes mellitus and hyperlipidemia. A follow-up chest computed tomography scan for aortitis syndrome revealed a nodule in the middle lobe of the right lung. Although a transbronchial lung biopsy was attempted, a definitive diagnosis could not be made. Because the possibility of lung malignancy could not be ruled out, thoracoscopic wedge resection of the middle lobe was performed. The intraoperative pathological diagnosis revealed carcinoma of the lungs and we performed middle lobectomy under complete video-assisted thoracoscopic surgery. A histopathological examination demonstrated an adenoid cystic carcinoma with a characteristic cribriform structure.

Abstract 380: Capture of EpCAM-negative circulating tumor cells (CTCs) with a “Universal CTC-Chip”

Background: Circulating tumor cell (CTC) can be a potentially useful clinical marker in early diagnosis and monitoring therapeutic effects for patients with malignant tumors. Our previous study showed that CTC detected by an EpCAM (epithelial cell adhesion molecule) based immuno-magnetic separation system “CellSearch” was useful in the diagnosis of malignant pleural mesothelioma (MPM), and also useful in the prognosis of epithelioid type MPM (Yoneda K, et al. Ann Surg Oncol. 2013). However, EpCAM-negative tumor cells cannot be principally captured with the system. Therefore, we have developed EpCAM-independent “Universal CTC-Chip System”, and assessed its capture capability. Methods: PC-9 (lung cancer cell line) was employed as EpCAM-positive cells, ACC-MESO-1 and ACC-MESO-4 (mesothelioma cell lines) were employed as EpCAM-negative cells. The expression of cell surface antigen was confirmed by flow cytometry. A microfluidic devices made of resin was coated in two steps with bridging antibody and capture antibody. It is possible to use any antibody to capture. In this study, we use anti-EpCAM antibody, anti-podoplain antibody, anti-mesothelin antibody, and isotype control. First, we verified capture capability of this system using samples which were spiked tumor cells labeled with CFSE in PBS containing 5% BSA. Then, we measured in the same manner by adding the cells to the blood of healthy donor, and calculated capture rate. Results: The expression analysis of cell surface antigens, PC-9 was EpCAM-positive, podoplanin, mesothelin were negative. On the other hand, MESO-1, 4 was EpCAM negative, podoplanin, mesothelin were positive. The capture efficiency in PBS containing 5% BSA with each cell using anti-EpCAM antibody, anti-podoplanin antibody and anti-mesothelin were PC-9: 101.1% / 2.3% / 2.9%, MESO-1: 3.5% / 52.7% / 4.3%, MESO-4: 3.0% / 78.3% / 5.4%, respectively. In the study of blood, each of the capture rate using anti-EpCAM antibody and anti-podoplanin antibody were PC-9: 88.0/ 6.9%, MESO-1: 4.0%/ 12.7%, MESO-4: 2.2%/ 38.4%, respectively. Conclusions: The capture efficiency using this device depends on the expression intensity of cell surface antigens. In experiments with PBS samples, it was possible to capture targeting specific cell surface antigen. Mesothelioma cells in the blood ware captured with combination of this CTC-Chip system and anti-podoplanin antibody. Citation Format: Kazue Yoneda, Yasuhiro Chikaishi, Eri Kawashima, Tomoko So, Hidetaka Uramoto, Takashi Ohnaga, Fumihiro Tanaka. Capture of EpCAM-negative circulating tumor cells (CTCs) with a “Universal CTC-Chip”. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2015-380

Immunohistochemical Expression and Serum Levels of CD44 as Prognostic Indicators in Patients with Non-Small Cell Lung Cancer

Background/Objectives: CD44 is often expressed in various types of tumor cells and involved in a number of biological behaviors of malignancy. The present study focused on the clinical significance of the expression of CD44st and CD44v6 in non-small cell lung cancer (NSCLC). Methods: The cohort consisted of 261 consecutive patients who had undergone complete resection of NSCLC. CD44 expression was evaluated in surgical specimens by immunohistochemical staining. Serum CD44 levels were determined using a sandwich ELISA (enzyme-linked immunosorbent assay). Results: In the immunohistochemical analysis, significant correlations were observed between CD44 expression and clinicopathological factors such as the T factor, N factor, pathological stage, and histological type. The 5-year survival rates according to CD44v6 expression were 65.8 and 80.6% in the higher and lower expression groups, respectively (p = 0.0053). According to ELISA, the group with higher expression of serum CD44v6 also showed a significantly more unfavorable prognosis than the lower expression group (p = 0.014). According to multivariate analysis using these significant variables, serum CD44v6 level was found to be an independent prognostic factor (p = 0.048). Conclusions: CD44v6 overexpression and higher serum CD44v6 levels were found to be significantly unfavorable prognostic factors.

Total vertebrectomy (Th2) and dissection of the subclavian artery for a superior sulcus tumor invading the spine: A case report

Highlights • The treatment of patients for lung cancer with vertebral body invasion remains challenging.• We reported a case that total vertebrectomy (Th2) and dissection subclavian artery for lung cancer invading spine and subclavian artery.• We experienced complete resected one case that tumor location and invading was very complicated.