Yujiro Suzuki

Increased Red Blood Cell Distribution Width Associates with Cancer Stage and Prognosis in Patients with Lung Cancer

Background Red cell distribution width (RDW), one of many routinely examined parameters, shows the heterogeneity in erythrocyte size. We investigated the association of RDW levels with clinical parameters and prognosis of lung cancer patients. Methods Clinical and laboratory data from 332 patients with lung cancer in a single institution were retrospectively studied by univariate analysis. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. Results The RDW levels were divided into two groups: high RDW (>=15%), n=73 vs. low RDW, n=259 (<15%). Univariate analysis showed that there were significant associations of high RDW values with cancer stage, performance status, presence of other disease, white blood cell count, hemoglobin, mean corpuscular volume, platelet count, albumin level, C-reactive protein level, and cytokeratin 19 fragment level. Kruskal-Wallis tests revealed an association of RDW values with cancer stage in patients irrespective of comorbidity (patient with/without comorbidity: p<0.0001, patient without comorbidity: p<0.0001). Stages I-IV lung cancer patients with higher RDW values had poorer prognoses than those with lower RDW values (Wilcoxon test: p=0.002). In particular, the survival rates of stage I and II patients (n=141) were lower in the high RDW group (n=19) than in the low RDW group (n=122) (Wilcoxon test: p<0.001). Moreover, multivariate analysis showed higher RDW is a significant prognostic factor (p=0.040). Conclusion RDW is associated with several factors that reflect inflammation and malnutrition in lung cancer patients. Moreover, high levels of RDW are associated with poor survival. RDW might be used as a new and convenient marker to determine a patient’s general condition and to predict the mortality risk of lung cancer patients.

Phase II study of carboplatin and pemetrexed in advanced non-squamous, non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial 0902

BackgroundSubgroup analyses of randomized studies have consistently shown that pemetrexed is exclusively effective in non-small-cell lung cancer (NSCLC) other than squamous cell carcinoma and the combination of pemetrexed and platinum agents is recommended for first-line chemotherapy in advanced non-squamous NSCLC; however, there have been few prospective studies of a selected population.Patients and methodsThis was a single-arm phase II study of carboplatin and pemetrexed in Japanese patients with chemo-naive advanced non-squamous NSCLC. Patients received six cycles of pemetrexed (500xa0mg/m2) combined with carboplatin (area under the curve: AUC 6) every 3xa0weeks. Maintenance chemotherapy with pemetrexed was permitted in patients whose disease did not progress after combination chemotherapy. The primary endpoint was the response rate, and secondary endpoints were safety and survival.ResultsFifty-one patients were enrolled between November 2009 and March 2011, and 49 patients were evaluable for both safety and efficacy. All but one patient had adenocarcinoma histology. Forty-four (90xa0%) patients completed four cycles, and 33 (67xa0%) completed six cycles of chemotherapy. Partial response was achieved in 25 patients (response rate: 51xa0%) and stable disease in 18 patients (37xa0%). Median progression-free survival (PFS) and overall survival (OS) were 6.3xa0months and 24.3xa0months, respectively. The median PFS and OS were 7.9xa0months and 24.3xa0months in patients with epidermal growth factor receptor (EGFR) mutation, and 6.3xa0months and 21.0xa0months in patients with EGFR wild type or unknown. There were no statistical differences between EGFR mutants and non-mutants for both PFS (pxa0=xa00.09) and OS (pxa0=xa00.23). Grade 3/4 neutropenia and thrombocytopenia were observed in 16 (33xa0%) and 9 (18xa0%) patients, respectively. Non-hematologic toxicities were generally mild, and there were no treatment-related deaths.ConclusionsThe combination of carboplatin and pemetrexed was safe and effective in advanced non-squamous NSCLC. Although the sample size was small, our results indicate that pemetrexed is a key drug for advanced non-squamous NSCLC, irrespective of the EGFR mutation status (UMIN-CTR number 000002451).

Successful treatment with erlotinib after gefitinib-induced interstitial lung disease: a case report and literature review.

Gefitinib and erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), are widely used anticancer drugs for patients with non-small cell lung cancer (NSCLC), especially for those with EGFR-activating mutations. Both agents are considered to be less toxic compared with cytotoxic drugs; however, serious adverse events including interstitial lung disease (ILD) which can be fatal occur rarely. After such an event, physicians avoid to use another TKI. In such cases, patients and physicians are forced to make difficult decisions or reluctantly choose TKI when there is no other option. Here we report a case of a patient with lung adenocarcinoma who showed good recovery from gefitinib-induced ILD by high-dose corticosteroid therapy. The patient was then administrated erlotinib as second-line chemotherapy and showed tumor shrinkage without ILD after 6 months of treatment. We discuss the common features of the cases in the previous documentations and ours which were successfully retreated with erlotinib after gefitinib-induced ILD had previously developed.

Clinical characteristics and outcomes of patients with community-acquired, health care-associated, and hospital-acquired empyema.

Patients with pneumonia, a common cause of empyema, are stratified based on their risk factors, and the treatment of empyema might benefit from this risk stratification.

Orbital metastasis secondary to pulmonary adenocarcinoma treated with gefitinib: a case report

IntroductionOrbital metastases of lung cancer are rare. However, because the number of patients diagnosed with lung cancer is increasing, the probability that a physician will see a patient with an orbital metastasis is also increasing. Unfortunately, the clinical course and response of these patients to cytotoxic chemotherapy are generally poor and keeping a patient’s quality of vision is difficult. In recent years, gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has brightened the outlook for patients with advanced non-small cell lung cancer, especially for those who carry epidermal growth factor receptor-activating mutations.Case presentationA 62-year-old Japanese man presented with swelling of the eyelid margin and ptosis of his right eye. A physical examination revealed double vision in his right eye and an alteration in elevator muscle mobility. A magnetic resonance image demonstrated a right intra-orbital mass (18 × 16mm). Screening examinations were carried out because this mass was suspected to be a metastasis from another organ. Chest computed tomography revealed a 42 × 37mm mass shadow on the left side of the hilum with mediastinal lymph node metastases. Adenocarcinoma with an epidermal growth factor receptor gene mutation (exon 19 deletion L747-E749; A750P) was detected in a transbronchial biopsy specimen; the patient was diagnosed with stage IV (T2N2M1) non-small cell lung cancer.Gefitinib (250mg/day) was chosen as first-line chemotherapy because there was no pre-existing interstitial shadow. After two months of treatment, the patient’s right eye opened completely and follow-up magnetic resonance imaging revealed a marked reduction of the intra-orbital mass to 14 × 13mm. Three months after treatment initiation, a follow-up computed tomography showed a marked reduction in the size of the primary lesion to 23 × 20mm. The patient is continuing gefitinib treatment without any adverse effects noted on computed tomography, physical, or laboratory examination.ConclusionsWe report the case of a patient with an orbital non-small cell lung cancer metastasis with epidermal growth factor receptor-activating mutations. This metastasis, as well as the primary lesion, showed a marked response to the molecular targeting drug gefitinib, and the patient’s vision was kept without an invasive procedure. Gefitinib may be a good first choice for patients with orbital non-small cell lung cancer metastasis harboring epidermal growth factor receptor-activating mutations.

Primary Bronchopulmonary Fibrosarcoma: Report of a Case

We herein report a case of primary bronchopulmonary fibrosarcoma in a 70-year-old man. The patient was referred to our hospital for investigation of hemosputum and an abnormal shadow. On admission, chest radiograph and computed tomography scan showed a mass lesion in right S3 and an infiltrative shadow in the right upper lobe. Transbronchial biopsy specimens showed findings of malignancy, and adenocarcinoma was suspected. A right pneumonectomy was performed, and pathologic examination confirmed a diagnosis of fibrosarcoma. The patient had an uneventful recovery and no sign of recurrence has been found in the year since his operation, although strict follow-up is essential.

Autoantibody profiles and their association with blood eosinophils in asthma and COPD

BACKGROUNDnAutoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of autoimmunity. This study aimed to compare the autoantibody profiles of asthma and COPD, and the relationship between autoantibodies and features of these diseases.nnnMETHODSnWe recruited 110 asthma patients and 92 COPD patients for a prospective study. Six autoantibody types were evaluated: antinuclear antibody, anti-cytoplasmic antibodies, rheumatoid factor, anti-cyclic citrullinated peptide antibody, myeloperoxidase-anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and proteinase 3-ANCA. Other clinical data were also recorded concurrently.nnnRESULTSnAn antinuclear antibody titre of ≥1:160 presented only in asthma but not in COPD (10% vs. 0%, pxa0=xa00.0002). Eosinophil counts in blood were negative predictors of antinuclear antibody in asthma. Conversely, eosinophil counts in blood and immunoglobulin-E levels of ≥100xa0IU/mL were positively associated with rheumatoid factor in asthma but not in COPD. There was no relationship between antinuclear antibody or rheumatoid factor and disease severity.nnnCONCLUSIONSnIt is possible that asthma tends to involve autoimmunity associated with antinuclear antibody more frequently than COPD because asthma is the more robust factor for antinuclear antibody positivity. Antinuclear antibody and rheumatoid factor are associated with eosinophilic responses, but they do not work as biomarkers for disease severity.

Marked improvement in autoimmune pulmonary alveolar proteinosis with severe hypoxemia in a patient treated with ambroxol: a case report

IntroductionPulmonary alveolar proteinosis is characterized by accumulation of surfactant and phospholipids in the pulmonary alveoli. Whole lung lavage is considered the first-line therapy, which requires special techniques. To the best of our knowledge, there have only been limited reports that have demonstrated the effectiveness of ambroxol on a mild case of pulmonary alveolar proteinosis.Case presentationA 72-year-old Japanese woman presented to our hospital with a one-year history of productive cough and progressive dyspnea. Her chest computed tomography scan showed a bilateral crazy-paving pattern in both of her lungs. She was diagnosed with autoimmune pulmonary alveolar proteinosis based on bronchoalveolar lavage findings and the presence of serum anti-granulocyte macrophage colony-stimulating factor antibodies. She was severely hypoxemic, so we recommended whole lung lavage or inhaled granulocyte macrophage colony-stimulating factor treatment, which she refused. We initiated treatment with ambroxol and her symptoms markedly improved.ConclusionsAlthough whole lung lavage is the first-line therapy for pulmonary alveolar proteinosis, oral ambroxol could be an alternative treatment option, even in patients with severe respiratory compromise.

Antinuclear antibodies and rheumatoid factor are associated with blood eosinophils in asthma and COPD

Background: Autoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of autoimmunity. Autoantibody assessment may help to better characterize asthma and COPD. Aims: Determine autoantibody profiles, and the relationship between autoantibodies and features of asthma and COPD. Methods: We recruited 102 asthma patients and 88 COPD patients prospectively. Six autoantibody types were evaluated: antinuclear antibody (ANA), anti-cytoplasmic antibodies, rheumatoid factor (RF); anti-cyclic citrullinated peptide (CCP) antibody; myeloperoxidase-anti-neutrophil cytoplasmic autoantibody (ANCA); proteinase 3–ANCA. Results: ANA prevalence was significantly higher in asthma than in COPD (24% vs . 10%, p=0.01). Low eosinophil counts in blood (ECB) were related to positive ANA in asthma and COPD. Conversely, high ECB and high levels of immunoglobulin-E were associated with RF in asthma but not in COPD. There was no relationship between ANA or RF and disease severity, including asthma control test, COPD assessment test, exacerbations in 1 % predicted. Prevalence of anti-cytoplasmic antibodies and anti-CCP antibody was low, and no patient harbored ANCA. Conclusions: It is possible asthma tends to involve autoimmunity more frequently than COPD because the prevalence of ANA is higher in asthma than in COPD. ANA and RF are associated with eosinophilic responses, but they do not work as biomarkers for disease severity.

Nocturnal Oxygen Desaturation Index is Inversely Correlated with Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

Abstract The concurrent diagnosis of chronic obstructive pulmonary disease (COPD) and sleep apnoea–hypopnoea syndrome (SAHS) (overlap syndrome), can contribute to worsening respiratory symptoms, but whether the severity of COPD is associated with co-morbid SAHS is unknown. We investigated whether the severity of COPD is associated with the complication of SAHS by examination of nocturnal oximetry as an alternative to polysomnography. Patients with COPD concurrently completed nocturnal oximetry, pulmonary function tests, a COPD assessment test, an Epworth sleepiness scale and a hospital anxiety and depression scale to evaluate the severity of COPD and possible concurrent presence of SAHS. We retrospectively analysed the data to assess correlation between the oxygen desaturation index (ODI) and each clinical variables and evaluated the predictors of ODI ≥ 15. This study included 103 patients (91 males, 88%) with a mean age of 72 ± 8 years and body mass index of 22 ± 3 kg/m2. ODI was positively correlated with FEV1, FEV1/FVC and FEV1% predicted, which meant that ODI was inversely correlated with airflow limitation. Univariate logistic regression analysis revealed that FEV1% predicted and FEV1/FVC were predictors of ODI ≥ 15. ODI is inversely correlated with airflow limitation and milder COPD patients may have co-morbid SAHS.