[Fetal Adenocarcinoma of the Lung].

We report a resected case of fetal adenocarcinoma. Fetal adenocarcinoma is a rare type of malignant lung tumor. A 53-year-old man had a 25 mm tumor in the right upper lobe on chest computed tomography. On fluorodeoxyglucose-positron emission tomography( FDG-PET), the tumor showed the accumulation of FDG with a standardized uptake value( SUV) max of 5.63. He underwent bronchoscopic examination, but a diagnosis was not established. We suspected that the tumor was primary lung cancer or metastatic lung tumor of rectal cancer which was resected prior to the treatment for pulmonary lesion. A right upper lobectomy with lymph node dissection was performed and the pathological diagnosis was high-grade fetal adenocarcinoma, stage IB (pT2aN0M0). The patient was treated with postoperative adjuvant chemotherapy. There has been no recurrence after surgery resection for 9 months.

Autoantibody profiles and their association 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. This study aimed to compare the autoantibody profiles of asthma and COPD, and the relationship between autoantibodies and features of these diseases. METHODS: We 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. RESULTS: An antinuclear antibody titre of ≥1:160 presented only in asthma but not in COPD (10% vs. 0%, p = 0.0002). Eosinophil counts in blood were negative predictors of antinuclear antibody in asthma. Conversely, eosinophil counts in blood and immunoglobulin-E levels of ≥100 IU/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. CONCLUSIONS: It 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.

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

BACKGROUND AND AIMS: 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. METHODS: The etiology, bacteriologic profile and outcome of patients diagnosed with empyema in Shinko Hospital between May 2005 and October 2013 were retrospectively studied. The patients were stratified according to whether they had community-acquired empyema (CAE), health-care-associated empyema (HCAE) or hospital-acquired empyema (HAE). RESULTS: The study included 81 patients, 25 CAE, 40 HCAE and 16 HAE. The comorbidity rate was highest among HAE patients (100%), followed by 95% of HCAE and 72% of CAE patients (P = 0.005). The rates of cancer and central nervous system (CNS) disease were higher in patients with HCAE and HAE than in patients with CAE (P = 0.030, P = 0.018, respectively). Pleural fluid cultures were positive in 58/81 patients. Streptococcus species were the most common organisms cultured from CAE (12/15) and HCAE patients (17/30), but not from HAE patients (3/13). Anaerobic organisms were cultured from 3 CAE, 5 HCAE and 3 HAE patients. Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were only cultured from HCAE and HAE patients. The mortality rates were higher in HCAE (18%) and HAE (50%) than in CAE (4%) patients (log-rank test: P = 0.0012). CONCLUSIONS: Half of patients with empyema were HCAE patients, who had comorbidities, bacteriological profile and outcome different from CAE patients. The patient with HCAE should be differentiated from CAE patient, and the stratification of patients based on risk factors may be useful for treatment strategy.

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

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/m(2). 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.

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

INTRODUCTION: Pulmonary 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 PRESENTATION: A 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. CONCLUSIONS: Although 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.

[Two cases of recurrent invasive mucinous adenocarcinoma of the lung showing marked responses to platinum-based chemotherapyregimens with pemetrexed and bevacizumab].

Here, we report 2 cases of recurrent invasive mucinous adenocarcinoma of the lung after surgery, which showed marked responses to platinum-based regimens with pemetrexed(PEM)and bevacizumab(BEV). The first patient was diagnosed with stage I B(p-T2N0M0)invasive mucinous adenocarcinoma, and new nodules were detected on computed tomography (CT)after 24 months of adjuvant chemotherapy with uracil/tegafur(UFT). Therefore, the patient was administered carboplatin(CBDCA; AUC 5.0), PEM(500mg/m2), and BEV(15mg/kg)for 6 courses followed by BEV(15mg/kg)for 3 courses, resulting in a complete response. The second patient was diagnosed with stage IV(p-T3N0M1)invasive mucinous adenocarcinoma, and metastases appeared after the surgery. The patient was treated with S-1 for 18 weeks, but the tumor recurred 18weeks after surgery. Therefore, the patient was administered 4 courses of cisplatin(CDDP 60mg/m2), PEM(500mg/m2), and BEV(15mg/kg)followed by 5 courses of PEM(15mg/kg)as maintenance therapy. This resulted in a good response. The first patient had grade 3 toxicities at the sixth course of combined CBDCA-PEM-BEV therapy, while the second patient did not have any adverse events throughout chemotherapy. These 2 cases showed that platinum-based regimens with PEM and BEV may be a good choice for patients with invasive mucinous adenocarcinoma of the lung.

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.

Pneumonitis induced by rifampicin: a case report and literature review.

An 84-year-old woman being treated for miliary tuberculosis (TB) with rifampicin (RFP), isoniazid (INH), ethambutol (EB) and corticosteroids suffered from a persistent fever for five months. While tapering the dose of prednisolone, chest computed tomography (CT) revealed diffuse ground glass opacities (GGO) and bronchoalveolar lavage fluid (BALF) showed an increase in lymphocytes. After the anti-TB drugs were discontinued and the dose of the corticosteroids was increased, the CT findings and fever improved considerably. However, readministration of RFP provoked an inflammatory reaction, leading to a diagnosis of RFP-induced pneumonitis. This condition is very rare. This is the first report of RFP-induced pneumonitis occurring during adjunct steroid therapy.

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

INTRODUCTION: Orbital 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 PRESENTATION: A 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. CONCLUSIONS: We 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.

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.

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

BACKGROUND: Subgroup 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 METHODS: This 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 (500 mg/m(2)) combined with carboplatin (area under the curve: AUC 6) every 3 weeks. 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. RESULTS: Fifty-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 (90 %) patients completed four cycles, and 33 (67 %) completed six cycles of chemotherapy. Partial response was achieved in 25 patients (response rate: 51 %) and stable disease in 18 patients (37 %). Median progression-free survival (PFS) and overall survival (OS) were 6.3 months and 24.3 months, respectively. The median PFS and OS were 7.9 months and 24.3 months in patients with epidermal growth factor receptor (EGFR) mutation, and 6.3 months and 21.0 months in patients with EGFR wild type or unknown. There were no statistical differences between EGFR mutants and non-mutants for both PFS (p = 0.09) and OS (p = 0.23). Grade 3/4 neutropenia and thrombocytopenia were observed in 16 (33 %) and 9 (18 %) patients, respectively. Non-hematologic toxicities were generally mild, and there were no treatment-related deaths. CONCLUSIONS: The 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).

[A case of pulmonary carcinomatous lymphangitis and multiple pulmonary infarctions from gastric cancer].

We report a case of pulmonary carcinomatous lymphangitis and multiple pulmonary infarctions from gastric cancer. A 58-year-old housewife presented with a complaint of a worsening cough over the previous 6 weeks. Chest radiography and CT scans revealed infiltration and diffuse ground-glass opacities in both lung fields, and she was hospitalized for further examination. No specific findings were found upon screening examination, including bronchoscopy with bronchoalveolar lavage (BAL). However, a CT scan showed mediastinal, hilar and paraaortic lymph node swelling, and therefore we suspected the presence of a malignant tumor. On the 11th hospital day, she suddenly developed severe hypoxia and went into cardiogenic shock. Although there was no sign of a filling defect in the vessels on CT with an intravenous contrast, we diagnosed pulmonary thromboembolism based on other examination findings and began thrombolysis and anticoagulant therapy. Treatment with heparin and urokinase did not improve her condition, and she died on the 14th hospital day. The autopsy findings revealed widespread gastric cancer with pulmonary lymphangitis carcinomatosa and thrombus formation in arterioles throughout the pulmonary lobes: 'Trousseau syndrome'.