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.

Outcomes of Surgical Treatment for Mycobacterium abscessus Complex Pulmonary Disease.

BACKGROUND: Mycobacterium abscessus complex pulmonary disease is notoriously difficult to treat by medication alone. We report our experience with resectional surgery combined with preoperative and postoperative multidrug chemotherapy for the treatment of patients with M. abscessus complex pulmonary disease. METHODS: This is a retrospective review of 33 patients undergoing lung resection for M. abscessus complex pulmonary disease at a single center in Japan between January 2008 and December 2019. RESULTS: The median age of patients was 54.0 (interquartile range [IQR], 49.0-66.0) years; 27 (81.8%) were female. Nodular-bronchiectatic was the most common disease type (n = 24, 72.7%). Disease was limited in 18 (54.5%) patients and extensive in 15 (45.5%). The median duration of preoperative multidrug chemotherapy employing oral and parenteral antibiotics was 10.0 (IQR, 3.0-18.0) months. A total of 34 anatomical lung resections were performed as follows: 22 lobectomies, 5 segmentectomies, 4 combined resections, 2 bilobectomies, and 1 pneumonectomy. No operative mortalities and 4 (13.3%) morbidities occurred. The median duration of multidrug chemotherapy after the surgery was 18.0 (IQR, 12.0-31.0) months. Postoperative sputum-negative status was achieved in 31 (93.9%) patients; all 23 patients obtaining preoperative negative conversion remained negative, and 8 (80.0%) of 10 patients with preoperative positive sputum became negative postoperatively. Recurrence was observed in 2 (6.5%) patients. The recurrence-free probabilities were 96.3%, 96.3%, and 80.2% at 1 year, 3 years, and 5 years, respectively. CONCLUSIONS: Combined with preoperative and postoperative multidrug chemotherapy, resectional surgery can be performed safely and achieve favorable outcomes for patients with M. abscessus complex pulmonary disease.

A Novel Approach to Extensive Clarithromycin-Resistant Mycobacterium avium Complex Pulmonary Disease.

A 48-year-old woman with extensive clarithromycin-resistant Mycobacterium avium complex pulmonary disease (MAC-PD) was successfully treated by left lower lobectomy and lingulectomy following combination treatment of intravenous/inhaled amikacin plus bronchial occlusion by Endobronchial Watanabe Spigots (EWSs). A left pneumonectomy was initially indicated for removing all the lesions, but the procedure would have been barely tolerated by the patient. However, her preoperative combination treatment sufficiently reduced the lesions requiring resection to allow surgical preservation of the left upper division. This novel approach might be promising for patients with Mycobacterium avium complex lung disease whose pulmonary reserve will not allow an extensive parenchymal resection.

Residual Destructive Lesions and Surgical Outcome in Mycobacterium avium Complex Pulmonary Disease.

BACKGROUND: Successful surgical treatment of patients with Mycobacterium avium complex pulmonary disease is thought to require complete removal of parenchymal destructive lesions. This study aimed to evaluate the short-term and long-term outcomes and the predictors of microbiological recurrence after surgery for M avium complex pulmonary disease. METHODS: We conducted a retrospective review of 184 patients undergoing unilateral lung resection for M avium complex pulmonary disease at a single center in Japan between January 2008 and December 2017. RESULTS: Median age of the 184 patients was 55.5 years; 133 were female (72.3%). All but 2 patients had anatomical lung resection. A total of 116 patients had limited disease and underwent complete resection (63.0%); the remaining 68 patients had extensive disease and underwent debulking surgery (37.0%). No operative mortalities occurred. In 18 of 184 patients, 21 morbidities occurred (9.8%), including 3 bronchopleural fistulas (1.6%). Postoperative sputum-negative status was achieved in 183 patients (99.5%). Microbiological recurrences occurred in 15 patients (8.2%). By multivariate analysis, extensive disease was an independent risk factor for recurrence (hazard ratio, 5.432; 95% confidence interval, 1.372-21.50; P = .016). Recurrence-free rates were significantly higher in patients with limited disease compared with those with extensive disease (99.0%, 97.4%, and 95.0% versus 93.0%, 89.2%, and 75.1% at 1, 3, and 5 years, respectively; P < .001). CONCLUSIONS: Complete resection of parenchymal destructive lesions can achieve excellent microbiological control for patients with limited M avium complex pulmonary disease. The efficacy of debulking surgery in patients with extensive disease needs further investigation.

[Oral Rehydration Therapy in Thoracic Surgery].

The purpose of this study is to evaluate the safety and the efficacy of preoperative oral rehydration therapy comparison with infusion therapy in thoracic surgery. Eighty-four patients scheduled for thoracic surgery were assigned to an oral rehydration group or an infusion group. We checked the amount of their urine and performed blood and urine test. And we carried out questionnaire concerning preoperative therapies to these patients. No morbidity concerned with preoperative therapies was encountered. There was no significant difference in blood and urine test in 2 groups. The answer of questionnaire showed more difficulties in the preoperative period in the infusion therapy group. Present study showed that the preoperative oral rehydration therapy could be done as safely as the infusion therapy with less difficulties compared to the infusion therapy even in the field of thoracic surgery.

[Nontuberculous Mycobacteriosis Resistant for Chemotherapy which was Suspected to Coexist with Lung Cancer].

Nontuberculous mycobacteriosis (NTM) has been increasing recently. The treatment of choice of NTM is chemotherapy. Surgical treatment is sometimes indicated for patients with refractory NTM. When NTM lesion is enlarging despite of chemotherapy, there are 2 possibilities:intractable NTM and co-existing lung cancer. A 67-year-old male had been treated for fibro-cavitary NTM in the right upper lobe with chemotherapy. The cavitary lesion, however, was growing in spite of 6 months treatment. We suspected of a co-existing lung cancer because SCC level and standardized uptake value (SUV) in positron emission tomography (PET)-computed tomography (CT) were high. Bronchoscopy was performed but revealed no malignancy. He underwent a right upper lobectomy and the intraoperative pathology indicated NTM with no malignancy. After the operation, SCC levels decreased. This is a rare case with preoperative high SCC level which seemed to be related to NTM lesion.

[Vacuum-assisted Closure Therapy for Residual Space after Open Window Thoracotomy for Pleural Empyema due to Bronchopleural Fistula].

A 73-year-old man underwent right middle-lower bilobectomy for lung adenocarcinoma. He suffered from pneumonia followed by empyema due to bronchopleural fistula. On day 19 after the operation, an open window thoracostomy was created. Then the pleural space was treated conservatively with saline irrigation and petrolatum gauze packing. Progressive formation of healthy granulation tissue was observed around the bronchopleural fistula and the adjacent pulmonary artery, resulting in a complete closure of the bronchopleural fistula. And then we applied vacuum-assisted closure (VAC) therapy to the residual pleural cavity. At 4 weeks after the initiation of VAC therapy, the pleural cavity was completely filled with granulation tissue and re-expanded residual lung. In conclusion, VAC therapy is a safe and effective treatment for residual space after open window thoracostomy for empyema due to bronchopleural fistula, if it is applied after closure of bronchopleural fistula and adequate granulation tissue formation on the great vessels.

[Middle mediastinal schwannoma originating from the intrathoracic vagal nerve with difficulty in swallowing; report of a case].

A 41-year-old male complaining of difficulty in swallowing was referred to our hospital. Chest computed tomography( CT) demonstrated 34×25×36 mm tumors in the subcarinal region. Gadolinium( Gd)-diethylenetriamine pentaacetic acid( DTPA) enhanced magnetic resonance imaging (MRI) showed the tumor with the target appearance sign, i.e., signal intensity of the mass was low on T1-weighted MRI, and the center of the mass was enhanced by Gd-DTPA. A neurogenic tumor was suspected on radiological findings. Resection of the tumor by video-assisted thoracoscopic surgery was performed. The tumor was found to originate from the left vagus nerve by operative findings and was diagnosed as schwannoma by pathological examination.

[Air embolism at the pleurodesis for air leakage after pulmonary resection].

A 61-year-old female who was diagnosed with right lung cancer had right lower lobectomy by videoassisted thoracic surgery in June 2010. At the 7th post operative day( 7POD), the patient complained of dyspnea and chest X-ray showed right pneumothorax which was successfully treated by closed drainage and pleurodesis. Since then repeated right pneumothorax appeared and the same procedures were chosen for treatment. In September 2010, just after the pleurodesis for the 3rd time event, she lost consciousness. Brain computed tomography (CT) demonstrated air density area in bilateral internal carotid arteries and right parietal lobe, establishing the diagnosis of air embolism which was successfully treated by hyperbaric oxygen treatment.