鈴木 秀海

BACKGROUND: This study aimed to investigate the benefits of administering perioperative high-dose prednisolone in conjunction with thymectomy in patients with myasthenia gravis. METHODS: We retrospectively reviewed data from patients with Myasthenia Gravis Foundation of America Clinical Class I to IIIB who had undergone an extended thymectomy between 1992 and 2009. Perioperative high-dose prednisolone was administered at starting doses of 10 to 20 mg and escalated up to 100 mg on alternate days. The treatment group comprised 70 patients receiving perioperative high-dose prednisolone, whereas the control group included 61 patients not treated with preoperative steroids. The two groups were compared with respect to baseline clinical characteristics, incidence of postoperative complications, and follow-up disease status. RESULTS: Prednisolone-treated patients presented with more advanced disease compared to controls (Class IIB or greater, 42 [60.0%] versus 7 [11.3%], respectively; P < 0.001). Mean preoperative%FVC was lower and FEV1.0% was higher in treated patients than in controls (%FVC: 92.4 ± 2.3% versus 99.5 ± 2.4%, respectively; P = 0.037, FEV1.0%: 85.2 ± 1.3% versus 81.4 ± 0.9%, respectively; P = 0.017). The groups were similar in other variables including presence of thymoma, and operative procedure. In the treatment group, disease status was significantly improved only by the induction of high-dose prednisolone before the surgery (P < 0.001), and these patients discontinued anti-cholinesterase therapy more frequently than controls (P < 0.001). Moreover, the treatment group demonstrated markedly lower rates of postoperative crisis (12.2% versus 2.9%, respectively; P = 0.045). The incidence of infection, wound dehiscence, and diabetes mellitus were comparable between groups. Survival analysis demonstrated higher rates of treated patients with improved disease status at three and five years (92% and 96%, respectively) compared to controls (57% and 76%, respectively; P < 0.001). Likewise, significantly greater proportions of treated patients achieved complete stable remission or pharmacologic remission at three, five, and ten years (23%, 42%, and 72%, respectively) compared to controls (10%, 20%, and 44%, respectively; P = 0.002). CONCLUSIONS: Perioperative high-dose prednisolone therapy is a safe, promising strategy for managing patients with myasthenia gravis and may reduce the incidence of postoperative crisis while improving disease status.

Obliterative bronchiolitis (OB) post-lung transplantation involves IL-17-regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the specific role of complement activation in lung allograft pathology, IL-17 production, and OB is unknown. The current study examines the role of complement activation in OB. Complement-regulatory protein (CRP) (CD55, CD46, complement receptor 1-related protein y/CD46) expression was downregulated in human and murine OB; and C3a, a marker of complement activation, was upregulated locally. IL-17 differentially suppressed complement receptor 1-related protein y expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen- or autoantigen (type V collagen)-reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17-mediated downregulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed-forward loop that may enhance CRP downregulation, suggesting that complement blockade could be a therapeutic strategy for OB.

OBJECTIVE: The purpose was to determine the rates of postoperative pulmonary complications, and to clarify the impact of COPD on long-term survival in lung cancer patients after surgical resection. METHODS: A retrospective chart review was performed on 1,461 patients who had undergone pulmonary resection for lung cancer from 1990 to 2005. Classification of COPD severity was based on spirometric guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Postoperative complication rates among the four COPD groups were compared and long-term overall and disease-specific survivals were analyzed. RESULTS: The frequencies of all pulmonary complications in three COPD groups were higher than in the non-COPD group (all p < 0.05). Overall and disease-specific survivals were significantly worse in relation to higher COPD grades (all p ≤ 0.05). Significant prognostic factors were age, body mass index, positive smoking history, tumor size, pneumonectomy, pathologic stage, and COPD grade (p < 0.05). CONCLUSION: Higher COPD grades had higher rates of postoperative pulmonary complications and poorer long-term survivals because of higher rates of cancer-related deaths.

目的．本研究の目的は，COPD合併肺癌患者における肺癌手術後合併症および長期予後に与える肺線維症の影響を調べることにある．方法．1990～2005年に千葉大学病院にて施行された肺癌手術症例のうちCOPD合併例380例を対象とした．慢性閉塞性肺疾患（COPD）および肺線維症（PF）の診断基準は，術前肺機能1秒率<70％，胸部CTで両側肺底区域の線維化とした．41例（10.8％）がPF/COPD群，339例（89.2％）がCOPD alone群であった．結果．術前肺機能検査では，％FVCおよび％FEV_1.0はPF/COPD群で有意に低かった．術後合併症では，術後急性肺傷害（ALI）および在宅酸素療法（HOT）がPF/COPD群で有意に高かったが，30日死亡に有意差はなかった．3，5年生存率ではPF/COPD群で53.6％，36.9％に対し，COPD alone群で71.4％，66.1％と，COPD alone群で有意に良好であった（p=0.0009）．肺癌の無再発生存率もCOPD alone群で有意に高かった．多変量解析の結果，男性，BMI,病理病期，PFが予後不良因子として挙がった．結論．PFはCOPD合併肺癌患者においてその予後をさらに低下させる危険因子であった．<br>