Hirofumi Matsuoka

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.

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.

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.

Plasmablastic lymphoma with unfavorable chromosomal abnormalities related to plasma cell myeloma: A borderline case between plasmablastic lymphoma and plasmablastic plasma cell myeloma

Plasmablastic lymphoma (PBL) is an aggressive subtype of DLBCL, first reported in HIV-infected patients1 and subsequently recognized in the WHO 2008 classification.2 PBL often arises in the oral cavity, but other sites include the nasal cavity, GI tract, skin, bone, and lungs.3-5 PBL mainly affects those with immunodeficiency,3-5 but can affect some immunocompetent individuals.6 Histologically, PBL presents as dense proliferation of immature cells like Burkitt’s lymphoma.2,5,7 The immunophenotype of PBL, however, resembles myeloma cells: CD38+, CD138+, cyIg+, MUM1+, CD45-, CD20-, and smIg-.3-5 EBV is mostly positive.3-5,7 A 53-year-old HIV-negative and immunocompetent woman was admitted because of chest pain and dyspnea. CT scanning revealed a large tumor in the right chest wall (Figure 1A), pleural effusion, para-aortic lymph node swelling, and a tumor in the sacral bone (Figure 1B and 1C, respectively). Laboratory findings are shown in Table 1. Serum IgG was 7,633 mg/dL, and revealed to be IgG-λ monoclonal protein. Many atypical plasma cell-like cells with CD38+, CD56+, CD138+, cyIgG+, and cyλ+ phenotype were observed in the pleural effusion (Figure 2). The karyotype was abnormal, with a complex involving chromosomes 1 and 3 (Table 1).8-10 Furthermore, FISH analysis demonstrated t(4;14).11 The chest tumor histologically exhibited dense proliferation of large immature cells (Figure 3A, B), and these cells were positive for CD138 and λ light chain (Figure 3C and 3D, respectively). A tentative diagnosis of multiple myeloma was made. She refused treatment with conventional anti-cancer agents. We therefore treated her with novel agents for myeloma, which were available in 2015 without any obvious response. Then, we performed radiotherapy for the chest tumor and other tumoral lesions. However, she died four months after admission. Histopathological re-examination of the chest tumor revealed it to be PBL. Immunostaining for myc was strongly positive as reported in PBL, and FISH split signal analyses for c-myc, but not for Bcl-2 or Bcl6, yielded split signals and amplification of this gene (Figure 3F). Serum virus genomes for EBV and HHV-8 were not detected by PCR. This patient appeared to have a borderline feature between plasmablastic plasma cell myeloma (PBPCM)12 because the tumor-involvement site was atypical for PBL3-5 and this patient carried multiple chromosomal abnormalities related with aggressive multiple myeloma.8-11 The genetic background of PBL has not yet fully understood5; therefore, accumulation of PBL cases and further molecular studies are required regarding clinical features and molecular profiles of PBPCM.

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.