Orthotopic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells.

Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using box-counting analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering.

Prognostic impact of LILRB4 expression on tumor-infiltrating cells in resected non-small cell lung cancer.

BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4/ILT3) is an up-and-coming molecule that promotes immune evasion. We have previously reported that LILRB4 facilitates myeloid-derived suppressor cells (MDSCs)-mediated tumor metastasis in mice. This study aimed to investigate the impact of the LILRB4 expression levels on tumor-infiltrating cells on the prognosis of non-small cell lung cancer (NSCLC) patients. METHODS: We immunohistochemically evaluated the LILRB4 expression levels of completely resected 239 NSCLC specimens. Whether the blocking of LILRB4 on human PBMC-derived CD33+ MDSCs inhibited the migration ability of lung cancer cells was also examined using transwell migration assay. RESULTS: The LILRB4 high group, in which patients with a high LILRB4 expression level on tumor-infiltrating cells, showed a shorter overall survival (OS) (p = 0.013) and relapse-free survival (RFS) (p = 0.0017) compared to the LILRB4 low group. Multivariate analyses revealed that a high LILRB4 expression was an independent factor for postoperative recurrence, poor OS and RFS. Even in the cohort background aligned by propensity score matching, OS (p = 0.023) and RFS (p = 0.0046) in the LILRB4 high group were shorter than in the LILRB4 low group. Some of the LILRB4 positive cells were positive for MDSC markers, CD33 and CD14. Transwell migration assay demonstrated that blocking LILRB4 significantly inhibited the migration of human lung cancer cells cocultured with CD33+ MDSCs. CONCLUSION: Together, signals through LILRB4 on tumor-infiltrating cells, including MDSCs, play an essential role in promoting tumor evasion and cancer progression, impacting the recurrence and poor prognosis of patients with resected NSCLC.

Single-center evaluation of prognostic factors for thymoma treated by surgery: a retrospective study.

BACKGROUND: This study aimed to retrospectively evaluate the clinical, pathological, and treatment-related factors associated with survival in patients with surgically treated thymomas. METHODS: Sixty patients with thymomas who underwent treatment at our institution between 2004 and 2015 were included. Survival analysis was performed based on curves that were obtained using the Kaplan-Meier method. The Wilcoxon test was used for all comparisons, and p < 0.05 was considered statistically significant. RESULTS: Forty-seven, four, three, four, and two patients presented tumor stages I, II, III, IVa, and IVb (according to the Masaoka classification), respectively, while six, 14, 11, 22, and seven patients had type A, AB, B1, B2, and B3 thymomas, respectively. Furthermore, 53 and eight patients underwent complete resection and required additional resection of adjacent organs, respectively, and no patients died from surgery-related complications. The five-year survival and recurrence-free survival (RFS) rates were 96 and 86%, respectively. The five-year survival rate for all stages was 100% except for those with stage IVb tumors (Masaoka classification); the survival rate for those patients was 0%. Separately, the five-year RFS rates for tumor stages I, II, III, IVa, and IVb were 100, 91, 91, 81, and 71%, respectively. Finally, the five-year survival rates in cases with complete and incomplete resections were 100 and 71%, respectively, indicating that the latter group had a significantly poorer prognosis (p < 0.001). CONCLUSIONS: These findings suggest that complete resection and the Masaoka pathological stage are significant predictors of prognosis in patients with thymomas. Surgery should aim to achieve complete resection; however, advanced cases may require multimodality therapy.

Intrathoracic fibrolipoma resected using complete thoracoscopic surgery: a case report.

BACKGROUND: Other than adipocytes, lipomas may contain mesodermal components such as varying proportions of fibrous tissues and blood vessels. Fibrolipoma is an uncommon variant of lipoma and comprises a high proportion of fibrous components. An intrathoracic fibrolipoma is extremely rare; to the best of our knowledge, only three such cases have been reported till date. CASE PRESENTATION: A 51-year-old female presented with a left intrathoracic mass, which was confirmed to be a lipomatous tumor using computed tomography. A pedunculated tumor originating from the parietal pleura was resected using complete thoracoscopic surgery. Pathological examination indicated a diagnosis of fibrolipoma. Intrathoracic fibrolipomas are extremely rare; this is one of the first reported cases of successfully resecting an intrathoracic fibrolipoma using complete thoracoscopic surgery. CONCLUSIONS: The tumor was asymptomatic and relatively small when detected during a medical checkup. This enabled the successful resection of the tumor via complete thoracoscopic surgery. Although fibrolipomas are histologically benign, careful observation and follow-up are essential owing to the possibility of recurrence.