Successful use of bio plugs for delayed bronchial closure after pneumonectomy in experimental settings

OBJECTIVES: Cell therapies, such as stem cell suspension injection, are used to treat bronchopleural fistula. Although it is safe and effective, injected cells cannot remain within the bronchioles of the fistula due to cell leakage into the thoracic cavity. Here, we inserted a ‘bio plug’ into the fistula, produced using cells and a bio-3D printer, to examine the effectiveness of bio plugs for the closure of bronchopleural fistulas, the optimal cell source and the closure mechanism.METHODS: Bio plugs were made with mesenchymal stem (stromal) cells derived from bone marrow (MSCBM), fibroblasts and rat lung micro-vessel endothelial cells using a bio-3D printer with different cell mixing ratios. Six groups, according to the presence or absence and the type of bio plugs, were compared. The plugs were inserted into the bronchi of F344 rats. The obstruction ratio and histological and immunohistochemical findings were evaluated.RESULTS: MSCBM+ rat lung micro-vessel endothelial cell group exhibited a higher obstruction ratio among all groups excluding the MSCBM group (P = 0.039). This group had fibrosis and CD31-positive cells and fewer CD68-positive cells than MSCBM and MSCBM+ fibroblast groups.CONCLUSIONS: Bio plugs with mixed cells, including stem cells, contribute to bronchial closure in the current experimental setting. Endothelial cells effectively maintain the structure in this model. Although bronchial closure for bronchopleural fistula could not be described as clinical conditions were not reproduced, we collected essential data on bronchial closure; however, further experiments are warranted

Video-assisted thoracic surgery attenuates perioperative oxidative stress response in lung cancer patients: a preliminary study

Objectives: Reactive oxygen species (ROS) function as key metabolites that can impair biological processes. The aim of this preliminary study was to assess the perioperative oxidative changes in lung cancer surgery.Methods: We measured the levels of blood hydroperoxides, a type of ROS, as an index of oxidative injury to cellular components, as well as the plasma ferric-reducing ability as an index of total antioxidant potential in 32 lung cancer patients. Hydroperoxides were measured by the levels of diacron reactive oxygen metabolites (d-ROMs). The antioxidant potential was determined by the biological antioxidant potential (BAP), which represents the levels of endogenous antioxidant enzymes.Results: Lung cancer patients had slightly affected oxidative stress before surgery. The d-ROM and BAP levels after surgery and were significantly decreased than before surgery (p< 0.001) and the levels recovered preoperatively at third postoperative day. The d-ROM level in video-assisted surgery group (n=17) was significantly decreased than those in thoracotomy group (n=15) at third and seventh post-operative day (p < 0.001, and < 0.02).Conclusions: Lung cancer patients had already exposed oxidative stress before surgery and surgical intervention also generates large amounts of ROS. Video-assisted thoracic surgery can reduce the ROS compared to the standard thoractomy

Experience of Surgical Resection for Hilar Cholangiocarcinomas at a Japanese Single Cancer Institute

Background/Aims: Surgical resection is a radical treatment option for hilar bile duct carcinoma (HBDC); however, it is still difficult to cure and postoperative morbidity is high at this stage. Methodology: We examined the demographics, surgical records and outcome in 38 patients with hilar cholangiocarcinoma undergoing operation. Results: Five patients (13%) underwent probe laparotomy because of peritoneal dissemination or liver metastasis. Of 33 patients, extended hemi-hepatectomy was performed in 32 patients.Postoperative complications were observed in 46% including hepatic failure in 3 and hospital death was observed in 4 patients. Advanced tumor stage more than stage III was observed in 23 patients. Curability of operation was A in 5 patients, B in 17 and C in 11 and postoperative adjuvant chemotherapy was administered in 24% including photodynamic therapy in 3. Tumor recurrence was observed in 41% of HBDC patients. The 3- and 5-year tumor-free survival was 38% and 10%, respectively and 3- and 5-year overall survival was 48% and 32%, respectively. By comparison with tumor stage or final curability, survival rates were not significantly different between groups.Conclusions: Surgical resection is still the only curative treatment option to improve patient survival even in advanced stage HBDC

Spontaneous pleural aspergillosis in an immunocompetent young adult treated with minimally invasive surgery

Spontaneous cases of pleural aspergillosis in healthy adults are rare, and the optimal therapeutic approach has not been established. Here we report a rare case of spontaneous pleural aspergillosis in an otherwise healthy young adult. Two-stage surgery with decortication and cavernostomy, followed by systemic antifungal therapy, finally resulted in a successful resolution of his empyema without any serious complications. In young patients with good pulmonary compliance, less invasive procedures, such as thoracoscopic decortication and/or carvernotomy, is a potential treatment option

Correction: Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.

[This corrects the article DOI: 10.1371/journal.pone.0211339.]

Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing

Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12- week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents.The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects