Hisashi Oishi

Transbronchial human interleukin-10 gene transfer reduces acute inflammation associated with allograft rejection and intragraft interleukin-2 and tumor necrosis factor-α gene expression in a rat model of lung transplantation

BACKGROUND The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). This study examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on AR and the intragraft cytokine profile in a rat model of lung transplantation. METHODS Left single lung transplants were performed between a highly histoincompatible combination of inbred rats. The donor left lung was extracted and intrabronchially instilled with a plasmid encoding hIL-10 (IL-10 group) or Escherichia coli beta-galactosidase (control group), mixed with a cationic lipid. At 3 and 6 days after transplantation, the degree of AR was graded histologically (stage 1-4) and several pathologic categories of inflammation were scored on a scale of 0 to 4 according to the percentage of involvement. Intragraft cytokine profile was examined by real-time reverse transcription polymerase chain reaction. RESULTS The stage of AR (3.1 +/- 0.4 vs 3.8 +/- 0.4) and the pathologic scores for edema (2.3 +/- 0.8 vs 3.2 +/- 0.4), intraalveolar hemorrhage (0.3 +/- 0.5 vs 2.2 +/- 0.8), and necrosis (0.3 +/- 0.5 vs 1.2 +/- 0.4) in the IL-10 group were significantly decreased compared with the control group at Day 6. IL-2 and tumor necrosis factor-alpha messenger RNA expression levels on Day 3 were significantly decreased in the IL-10 group. CONCLUSIONS Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR, which was related to decreased levels of proinflammatory cytokine gene expression in a rat model of lung transplantation.

Reconstruction of Pulmonary Artery With Donor Aorta and Autopericardium in Lung Transplantation

A 44-year-old man with Eisenmengers syndrome due to ventricular septal defect (VSD) was listed for lung transplantation. The patients condition was complicated by a giant pulmonary artery (PA) aneurysm. Concurrent VSD closure and total reconstruction of the recipient PA with the donor aorta were planned. When the patient underwent bilateral lung transplantation, the aortic graft obtained turned out to be too short to complete the reconstruction. A PA graft made of the recipients pericardium was successfully interposed between the donors PA and the donors aortic graft.

A Case of Successful Therapy by Intrapleural Injection of Fibrin Glue for Chylothorax after Lung Transplantation for Lymphangioleiomyomatosis

A 37-year-old woman underwent bilateral lung transplantation for lymphangioleiomyomatosis. Dense pleural adhesions due to past pleurodesis for chylothorax were observed and dissected in both thoracic cavities. The patient developed chylothorax after transplant. Chylothorax in the right thoracic cavity was successfully treated by conventional pleurodesis; however, pleural effusion from the left thoracic cavity was not reduced. According to fluoroscopic images obtained by injecting a contrast medium through the chest tube, the remaining pleural space in the left thoracic cavity was small and localized in the lower region adjacent to the mediastinum. We opted to fill this space with fibrin glue; we injected fibrinogen and thrombin solution into the space through the chest tube. We performed fibrin glue treatment three times and pleural effusion was dramatically decreased. We removed the chest tube on day 107 post-transplant. No recurrent chylothorax has been recorded for 10 years after lung transplantation.

Contralateral Pulmonary Artery Banding After Single Lobar Lung Transplantation

A 14-year-old female patient underwent right single living-donor lobar lung transplantation for bronchiolitis obliterans after bone marrow transplantation. The patient experienced a complication with severe hypoxemia requiring venovenous extracorporeal membrane oxygenation, which appeared to result from significant ventilation-perfusion mismatch caused by preferential ventilation of the transplanted lobe and relatively preserved perfusion to the native lung. On day 2, we performed left pulmonary artery banding, which significantly improved oxygenation leading to weaning from extracorporeal membrane oxygenation. Our experience indicates that contralateral pulmonary artery banding may be a feasible option to rescue patients from hypoxemia resulting from ventilation-perfusion mismatch after single living-donor lobar lung transplantation.

The intensity of bronchiolar epithelial cell injury caused by an alloimmune response is ameliorated by transbronchial human interleukin-10 gene transfer in a rat model of lung transplantation

The aim of the present study was to determine whether the intensity of bronchiolar epithelial cell injury is ameliorated by transbronchial human IL-10 (hIL-10) gene transfer in a rat model of lung allograft rejection. The left lung was extracted from a donor Brown Norway rat and transbronchially instilled with encoding hIL-10 (IL-10 group) or β-galactosidase (control group). The lung graft was then transplanted into a Lewis rat and harvested on day 6 after transplantation. The allografts were histologically examined and all bronchioles in the slides were assigned one of three grades according to the intensity of epithelial cell loss. The distribution of the grades was significantly different between the two groups, and the epithelial cell injury was significantly improved in the IL-10 group. The present study demonstrated the effect of transbronchial hIL-10 gene transfer on ameliorating bronchiolar epithelial cell injury in a rat model of lung allograft rejection.

Single lung transplantation for lymphangioleiomyomatosis: a single-center experience in Japan

PurposeLung transplantation is accepted as an effective modality for patients with end-stage pulmonary lymphangioleiomyomatosis (LAM). Generally, bilateral lung transplantation is preferred to single lung transplantation (SLT) for LAM because of native lung-related complications, such as pneumothorax and chylothorax. It remains controversial whether SLT is a suitable surgical option for LAM. The objective of this study was to evaluate the morbidity, mortality and outcome after SLT for LAM in a lung transplant center in Japan.MethodsWe reviewed the records of 29 patients who underwent SLT for LAM in our hospital between March, 2000 and November, 2017. The data collected included the pre-transplant demographics of recipients, surgical characteristics, complications, morbidity, mortality and survival after SLT for LAM.ResultsThe most common complication after SLT for LAM was contralateral pneumothorax (n = 7; 24.1%). Six of these recipients were treated successfully with chest-tube placement and none required surgery for the pneumothorax. The second-most common complication was chylous pleural effusion (n = 6; 20.7%) and these recipients were all successfully treated by pleurodesis. The 5-year survival rate after SLT for LAM was 79.5%.ConclusionLAM-related complications after SLT for this disease can be managed. SLT is a treatment option and may improve access to lung transplantation for patients with end-stage LAM.

Surgical treatment for locally advanced lung cancer in a human immunodeficiency virus-infected patient

Highly active antiretroviral therapy (HAART) has changed the most common cause of death among patients infected with the human immunodeficiency virus (HIV). These patients are known to be at increased risk for lung cancer compared with the general population. Recently, HIV-infected patients who need surgical treatment of lung cancers are becoming increasingly common. We present a 60-year-old HIV-infected man with locally advanced lung cancer with a helper T-lymphocyte count of 195 cells/μl at the time of lung cancer diagnosis. HAART was initiated before surgery, and extended resection was performed without discontinuance of HAART. The patient successfully recovered from surgery without complication.