Masamichi Yoshida

Prognostic significance of plasma D-dimer levels in patients with lung cancer.

BACKGROUND: The peripheral blood concentrations of several proteases of the clotting system have been shown to predict survival in patients with malignancy. A study was undertaken to investigate the independent value of the plasma levels of the D-dimer degradation product of fibrin before treatment for predicting prognosis in patients with lung cancer. METHODS: The study comprised 70 patients with lung cancer (49 non-small cell lung cancer and 21 small cell lung cancer). Plasma levels of D-dimer were measured using an enzyme immunoassay kit. Multivariate statistical analysis was carried out using the Coxs proportional hazards model. RESULTS: The median value of the plasma level of D-dimer differentiated two groups of patients with different outcomes: a group with a D-dimer level of < 150 ng/ml (low DD group) and those with D-dimer levels of > or = 150 ng/ml (high DD group). Survival time was significantly better in patients in the low DD group than in those in the high DD group in all patients (hazard ratio for high DD group = 4.7; 95% confidence interval (CI) 1.8 to 11.7). The plasma levels of D-dimer predicted survival independently from the clinical stage of disease, histological type, performance status, and tumour size (hazard ratio = 3.9; 95% CI 1.6 to 9.2). CONCLUSIONS: These results suggest that plasma levels of D-dimer might be useful for predicting the clinical outcome in patients with lung cancer. However, further prospective studies are needed in a larger population to confirm these findings.

A New Strategy for Healthcare-Associated Pneumonia: A 2-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-Resistant Pathogens to Select Initial Empiric Therapy

BACKGROUND Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain. METHODS We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321). RESULTS MDR pathogens were more common (15.3% vs 0.8%, P < .001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, P < .001); methicillin-resistant S. aureus (6.9% vs 0%, P = .003); Enterobacteriaceae (7.8% vs 2.4%, P = .037); and Pseudomonas aeruginosa (6.9% vs 0.8%, P = .01). Using the proposed algorithm, HCAP patients with ≥2 MDR risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0-1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P < .001). In total, 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. Thirty-day mortality was significantly higher for HCAP than for CAP (13.7% vs 5.6%, P = .017), but among HCAP patients with 0-1 MDR risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P = .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0). CONCLUSIONS Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy. CLINICAL TRIALS REGISTRATION Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

Arterial endothelin-1 level in pulmonary emphysema and interstitial lung disease. Relation with pulmonary hypertension during exercise.

This study was undertaken to assess the arterial plasma levels of endothelin-1 (ET-1) and their relationship with pulmonary haemodynamic and gas exchange variables during exercise in patients with emphysema and interstitial lung disease (ILD). Incremental cycle ergometry was performed in all patients up to maximal capacity. At rest, arterial ET-1 levels were higher in emphysema (1.86 +/- 0.35 pg.mL-1; p < 0.02) and ILD (1.75 +/- 0.25 pg.mL-1; p < 0.03) patients than in controls (1.35 +/- 0.18 pg.mL-1). Emphysema (2.08 +/- 0.26 versus 1.70 +/- 0.40 pg.mL-1) and ILD (1.98 +/- 0.21 versus 1.67 +/- 0.02 pg.mL-1) patients with pulmonary hypertension (PH) presented significantly (p < 0.05) higher arterial ET-1 levels than those without. At rest, arterial ET-1 levels were significantly correlated with mean pulmonary arterial pressure (Ppa) in both ILD (r = 0.8, p = 0.01) and emphysema (r = 0.5, p = 0.03) patients. During exercise, the arterial ET-1 levels were significantly correlated with arterial oxygen (Pa,O2) (r = -0.6, p = 0.04), alveolar-arterial oxygen difference (r = 0.8, p = 0.01), and Ppa (r = 0.6, p = 0.04) in ILD patients, but not in those with emphysema. In brief, the results of this study suggest that arterial endothelin-1 is markedly increased in interstitial lung disease and emphysema patients, and that, it is related to the exercise-induced exacerbation of pulmonary hypertension in patients with interstitial lung disease, but not in those with emphysema.

Community-acquired pneumonia and nursing home-acquired pneumonia in the very elderly patients

The rapid increase in the elderly population is leading to a corresponding increase in the number of people requiring medical care. To date no comparative study between community-acquired pneumonia (CAP) and nursing home-acquired pneumonia (NHAP) has been reported in the very elderly non-intubated patients. The present study was undertaken to compare the clinical characteristics and microbial etiology between CAP and NHAP in elderly patients >/=85-years old. There were 54 patients with NHAP and 47 with CAP. Performance status was significantly worse in the NHAP than in the CAP group. Among all patients, the most frequent pathogens were Chlamydophilia pneumoniae followed by Streptococcus pneumoniae, Mycoplasma pneumoniae influenza virus and Staphylococcus aureus. The frequency of S. peumoniae was significantly higher in NHAP patients than in CAP patients after adjusting for age and sex. Physical activity, nutrition status and dehydration were significant prognostic factors of pneumonia among all patients. In-hospital mortality was significantly higher in NHAP than in CAP after adjusting for age and sex. This study demonstrated that the etiology and clinical outcome differ between CAP and NHAP patients in the very elderly non-intubated population.

The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis

The aim of this study was to determine whether low-dose inhalation of nitric oxide (NO) improves pulmonary haemodynamics and gas exchange in patients with stable idiopathic pulmonary fibrosis (IPF). The investigation included 10 IPF patients breathing spontaneously. Haemodynamic and blood gas parameters were measured under the following conditions: 1) breathing room air; 2) during inhalation of 2 parts per million (ppm) NO with room air; 3) whilst breathing O2 alone (1 L.min-1); and 4) during combined inhalation of 2 ppm NO and O2 (1 L.min-1). During inhalation of 2 ppm NO with room air the mean pulmonary arterial pressure (Ppa 25 +/- 3 vs 30 +/- 4 mmHg) and the pulmonary vascular resistance (PVR 529 +/- 80 vs 699 +/- 110 dyn.s.cm-5) were significantly (p < 0.01) lower than levels measured whilst breathing room air alone. However the arterial oxygen tension (Pa,O2) did not improve. The combined inhalation of NO and O2 produced not only a significant (p < 0.01) decrease of Ppa (23 +/- 2 vs 28 +/- 3 mmHg) but also, a remarkable improvement (p < 0.05) in Pa,O2 (14.2 +/- 1.2 vs 11.7 +/- 1.0 kPa) (107 +/- 9 vs 88 +/- 7 mmHg)) as compared with the values observed during the inhalation of O2 alone. These findings suggest that the combined use of nitric oxide and oxygen might constitute an alternative therapeutic approach for treating idiopathic pulmonary fibrosis patients with pulmonary hypertension. However, further studies must first be carried out to demonstrate the beneficial effect of oxygen therapy on pulmonary haemodynamics and prognosis in patients with idiopathic pulmonary fibrosis and to rule out the potential toxicity of inhaled nitric oxide, particularly when used in combination with oxygen.

High plasma level of plasmin-α2-plasmin inhibitor complex is predictor of poor prognosis in patients with lung cancer

The occurrence of thrombotic complications is commonly associated with poor prognosis in patients with malignancy. However, the prognostic significance of the subclinical activation of the clotting system, frequently observed in cancer patients, is unknown. The purpose of the present study was to evaluate the value of the pre-thrombotic state for predicting survival of lung cancer patients. This investigation comprised 70 lung cancer patients without clinical or laboratory diagnosis of intravascular coagulation. There were 49 cases with non-small and 21 with small cell carcinomas. Samples taken in controls were available for comparison. The clotting system was assessed measuring thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP). The independent value of these clotting markers to predict survival was evaluated in relation with previously well-established prognostic factors for lung cancer patients. Plasma concentration of each parameter was significantly higher in cancer patients as compared to that of controls. The plasma level of PAP was a predictor of survival independently from the stage of disease, sex, age, histological type, performance status, tumor size and the presence of distant metastasis. Discriminant analysis of PAP plasma concentration identified 2 groups with significant difference in survival rate in all patients, cases in advanced stages of disease and in those with small and non-small cell lung cancer. The results of the present study showed prognostic significance of the subclinical activation of the clotting system, particularly of the fibrinolytic pathway, in lung cancer. Newly developed markers of fibrinolysis might be potentially applicable for predicting outcome in malignancy.

Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non–Small Cell Lung Cancer—A Multicenter Retrospective Study

Introduction: Alectinib and crizotinib have been approved for the therapy of NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement. The effect of alectinib or crizotinib on overall survival (OS) in patients with ALK‐rearranged NSCLC remains unknown. Methods: A multicenter retrospective study was conducted to compare OS between patients receiving alectinib and crizotinib and between patients treated with alectinib and those treated sequentially with crizotinib and then alectinib after crizotinib failure. The time to treatment failure (TTF), progression‐free survival (PFS), and OS were compared. Results: Sixty‐one patients with ALK‐rearranged NSCLC were enrolled. Forty‐six patients were treated with anaplastic lymphoma kinase (ALK) inhibitors (31 with crizotinib, 28 with alectinib, and 13 with both ALK inhibitors). The response rate was 66.7% for the crizotinib‐treated group and 80.8% for the alectinib‐treated group. Among all patients, TTF and PFS were significantly prolonged in the alectinib‐treated group compared with in the crizotinib‐treated group. Subgroup analyses revealed significantly prolonged TTF for alectinib compared with crizotinib therapy in the ALK inhibitor–naive population. OS was significantly longer in the alectinib‐treated group than in the crizotinib‐treated group. The TTF and OS of patients treated sequentially with crizotinib and then with alectinib after crizotinib failure tended to be longer than those of patients treated with alectinib alone. Conclusions: Therapy with alectinib alone was significantly superior to therapy with crizotinib alone in terms of TTF, PFS, and OS, and sequential therapy with crizotinib and alectinib after crizotinib failure tended to provide a better OS benefit than did therapy with alectinib alone in patients with ALK‐positive NSCLC. However, large‐scale prospective studies are needed to confirm these observations.

Role of Thrombin-Activatable Fibrinolysis Inhibitor in Allergic Bronchial Asthma

BackgroundBronchial asthma is an inflammatory disease of the airways. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase that besides inhibiting fibrinolysis, also regulates inflammatory processes. The only validated substrate known for TAFI is fibrin. In the present study we evaluated the role of TAFI in bronchial asthma by comparing the development of allergic bronchial asthma between wild-type (WT) and TAFI-deficient mice (KO).MethodsAsthmatic inflammation was induced by sensitization and challenge with ovalbumin in WT (WT/OVA) and TAFI KO (KO/OVA) mice. WT mice (WT/SAL) and TAFI KO (KO/SAL) were used as controls. Cytokines, markers of inflammation, and coagulation were measured in bronchoalveolar lavage fluid (BALF).ResultsAirway hyperresponsiveness was worse in KO/OVA mice than in WT/OVA mice or control mice. Markers of lung injury were significantly increased in BALF from KO/OVA mice compared to WT/OVA mice. Airway hyperresponsiveness and the BALF concentrations of IL-5 and osteopontin were significantly increased in KO/OVA mice compared to WT/OVA mice. Treatment of WT/OVA and KO/OVA mice with a C5a receptor antagonist significantly decreased hyperresponsiveness along with the BALF concentrations of total protein and C5a compared to untreated asthmatic mice.ConclusionThe results of this study suggest that TAFI plays a protective role in the pathogenesis of allergic inflammation probably by inhibiting the complement system.

Ct Scores of Emphysema and Oxygen Desaturation During Low-Grade Exercise in Patients with Emphysema

PURPOSE We evaluated the usefulness of CT for assessing oxygen desaturation during walking in patients with emphysema. MATERIAL AND METHODS The study comprised 32 patients with emphysema (mean age 67+/-6 years). Serial CT images of 5 mm were obtained from the apex to the basal regions of the lung during deep inspiration. The severity of emphysema was scored by four physicians according to a visual method. A six-minute walking test and oxygen desaturation (pSO2) measurements were performed. RESULTS AND CONCLUSION The mean CT score of the four observers was significantly correlated with the nadir pSO2 and deltapSO2, but did not correlate with the total distance walked. These results suggest that CT may be used for the assessment of oxygen desaturation during low-grade exercise in patients with emphysema.

Solitary pulmonary nodule of benign metastasizing leiomyoma associated with primary lung cancer: a case report

IntroductionBenign metastasizing leiomyoma in the lung is a very rare disease characterized by the growth of uterine leiomyoma tissue. In most cases there is a previous history of hysterectomy for uterine leiomyoma.Case presentationA 50-year-old Asian woman underwent a total abdominal hysterectomy for uterine leiomyoma at the age of 37 years old. She was referred to our hospital because of sudden anterior chest pain. A chest computed tomography scan revealed a ground-glass opacity in her left S10 lung segment and a solitary small nodule in her left bronchial segment, S4. We performed a left lower lobectomy and an upper lung partial resection in order to make a definitive diagnosis and to enable us to determine a further therapeutic strategy. The ground-glass opacity in her left S10 was a primary lung adenocarcinoma, while the small nodule in her left S4 was diagnosed as a benign metastasizing leiomyoma. No additional therapy was done and our patient was followed up with chest computed tomography. Up to date, repetitive evaluation by chest computed tomography has shown no sign of benign metastasizing leiomyoma or lung cancer recurrence.ConclusionThis is a very rare case of benign metastasizing leiomyoma of the lung associated with primary lung cancer. This comorbid association should be considered in the differential diagnosis when a solitary lung nodule is detected in a patient with a history of uterine leiomyoma.