Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with pulmonary vascular remodeling. Because hypoxia might promote generation of oxidative stress in vivo, we hypothesized that oxidative stress may play a role in the hypoxia-induced cardiopulmonary changes and examined the effect of treatment with the antioxidant N-acetylcysteine (NAC) in rats. NAC reduced hypoxia-induced cardiopulmonary alterations at 3 wk of hypoxia. Lung phosphatidylcholine hydroperoxide (PCOOH) increased at days 1 and 7 of the hypoxic exposure, and NAC attenuated the increase in lung PCOOH. Lung xanthine oxidase (XO) activity was elevated from day 1 through day 21, especially during the initial 3 days of the hypoxic exposure. The XO inhibitor allopurinol significantly inhibited the hypoxia-induced increase in lung PCOOH and pulmonary hypertension, and allopurinol treatment only for the initial 3 days also reduced the hypoxia-induced right ventricular hypertrophy and pulmonary vascular thickening. These results suggest that oxidative stress produced by activated XO in the induction phase of hypoxic exposure contributes to the development of chronic hypoxic pulmonary hypertension.
Background: Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer.
The number of organ donations after brain death has significantly increased since the revised Japanese Organ Transplant Law took effect in July 2010. Sixty-one lung transplantations were conducted throughout Japan in 2013, including 20 living-donor lung transplantations and 41 brain-dead-donor lung transplantations (23 bilateral lungs, 17 single lungs, and 1 heart-lung transplantation). The number of lung transplant candidates newly registered at the Japan Organ Transplantation Network also increased to 126 in 2013, suggesting a severe donor shortage in Japan. More than 60 % of offered brain-dead-donor, lungs were used for transplantation, indicating the effort of Japanese lung transplant centers to overcome the challenge of donor shortage. After lung transplantation, patients generally enjoyed a good quality of life with excellent survival of 86.2 % at 1 year, 79.6 % at 3 years, and 73.7 % at 5 years post-transplantation. There was no significant difference in patient survival between living-donor and brain-dead-donor lung transplantation. Early mortality of lung transplant recipients within 90 days was attributable to graft failure followed by infection, while long-term mortality was mostly explained by chronic lung allograft dysfunction (chronic rejection), infection, and malignancy. Eight lung transplant centers are currently approved to conduct lung transplantation in Japan (Tohoku, Dokkyo, Chiba, Kyoto, Osaka, Okayama, Fukuoka, and Nagasaki Universities). These centers are expected to continue to make a special effort to save critically ill patients waiting for lung transplantation.
With these criteria, limited resection was performed safely without any recurrence, and the postoperative pulmonary function was well preserved. The outcomes of limited resection for small-sized lung cancer with GGOs that met the criteria of this study were satisfactory.
OBJECTIVESUsing data obtained from a Japanese nationwide annual database with web-based data entry, we developed a risk model of mortality and morbidity after lung cancer surgery.METHODSThe characteristics and operative and postoperative data from 80 095 patients who underwent lung cancer surgery were entered into the annual National Clinical Database of Japan data sets for 2014 and 2015. After excluding 1501 patients, the development data set for risk models included 38 277 patients entering in 2014 and the validation data set included 40 317 patients entering in 2015. Receiver–operating characteristic curves were generated for the outcomes of mortality and composite mortality/major morbidity. The concordance index was used to assess the discriminatory ability and validity of the model.RESULTSThe 30-day mortality and overall mortality rates, including in-hospital deaths, were 0.4% and 0.8%, respectively, in 2014, and 0.4% and 0.8%, respectively, in 2015. The rate of major morbidity was 5.6% in 2014 and 5.6% in 2015. Several risk factors were significantly associated with mortality, namely, male sex, performance status, comorbidities of interstitial pneumonia and liver cirrhosis, haemodialysis and the surgical procedure pneumonectomy. The concordance index for mortality and composite mortality/major morbidity was 0.854 (P < 0.001) and 0.718 (P < 0.001), respectively, for the development data set and 0.849 (P < 0.001) and 0.723 (P < 0.001), respectively, for the validation data set.CONCLUSIONSThis model was satisfactory for predicting surgical outcomes after pulmonary resection for lung cancer in Japan and will aid preoperative assessment and improve clinical outcomes for lung cancer surgery.
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