Kei Nakashima

Efficacy and safety of amurubicin for the elderly patients with refractory relapsed small cell lung cancer as third-line chemotherapy

BACKGROUND While more elderly patients are being diagnosed with lung cancer every year, no anti-lung cancer therapy designed specifically for the elderly has been established yet. This is the first retrospective study to examine the efficacy and safety of amurubicin (AMR) for elderly patients with refractory relapsed small cell lung cancer (SCLC) as second or third-line chemotherapy. MATERIALS AND METHODS Thirty-six patients were eligible for analyzing the frequency of hematologic and non-hematologic toxicities and effectiveness of AMR for refractory relapsed SCLC in both elderly (≥ 70 years) and non-elderly (<70 years) groups. RESULTS Among these patients as third-line chemotherapy, the response rate and the disease control rate of refractory relapsed cases were 44.4 and 55.6%, respectively. The median of progression-free survival time was 3.0 months and the median of overall survival time was 5.1 months. There were no significant differences in the frequency of the grade 3-5 hematologic or non-hematologic toxicity between the elderly (≥ 70 years) and non-elderly (<70 years) patients or second and third-line chemotherapies. CONCLUSIONS AMR could be one of the effective tools in the treatment of elderly patients with refractory relapsed SCLC as third-line chemotherapy, and the recommended dose is 30 mg/m 2 for three consecutive days.

Loop-mediated isothermal amplification method for diagnosing Pneumocystis pneumonia in HIV-uninfected immunocompromised patients with pulmonary infiltrates

Loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We retrospectively evaluated 78 consecutive HIV-uninfected patients who underwent LAMP method for diagnosing Pneumocystis pneumonia (PCP). Diagnosis of PCP was made by the detection of Pneumocystis jirovecii (P. jirovecii) with positive LAMP or conventional staining (CS) (Grocott methenamine silver staining or Diff-Quick™) on the basis of compatible clinical symptoms and radiologic findings. Additionally, we reviewed HIV-uninfected immunocompromised patients who underwent subcontract PCR as a historical control. LAMP was positive in 10 (90.9%) of 11 positive-CS patients. Among 13 negative-CS patients with positive LAMP, 11 (84.6%) had PCP, and the remaining 2 were categorized as having P. jirovecii colonization. LDH levels in negative-CS PCP were higher than in positive-CS PCP (p = 0.026). (1 → 3)-β-D-glucan levels in negative-CS PCP were lower than in positive-CS PCP (p = 0.011). The interval from symptom onset to diagnosis as PCP in LAMP group (3.45 ± 1.77 days; n = 22) was shorter than in subcontract PCR group (6.90 ± 2.28 days; n = 10; p < 0.001). As for patients without PCP, duration of unnecessary PCP treatment in LAMP group (2; 2-3 days; n = 10) was shorter than in subcontract PCR group (7; 7-12.25 days; n = 6; p = 0.003). LAMP showed higher sensitivity (95.4%) and positive predictive value (91.3%) than subcontract PCR did. Pneumocystis LAMP method is a sensitive and cost-effective diagnostic method and is easy to administer in general hospitals. In-house LAMP method would realize early diagnosis of PCP, resulting in improving PCP prognosis and reducing unnecessary PCP-specific treatment.

A successful diagnostic case of Pneumocystis pneumonia by the loop-mediated isothermal amplification method in a patient with dermatomyositis

Pneumocystis pneumonia (PCP) can occur in patients with many causes of the immunocompromised state other than human immunodeficiency virus (HIV). It is quite difficult to diagnose PCP without HIV because there is no method for detecting Pneumocystis jirovecii. Thus, non-HIV PCP continues to have high mortality. Recently, loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We report a non-HIV PCP case successfully diagnosed by the LAMP method. It was previously reported that PCR in BALF specimens had been the most sensitive method in the diagnosis of PCP without HIV. The LAMP method would be more sensitive than conventional PCR and an effective tool in the early diagnosis of PCP.

A case of asthma-complicated influenza myocarditis

A 36-year-old man with a history of asthma visited an outpatient clinic complaining of high fever and general fatigue, and was diagnosed as having influenza type A by influenza antigen test. Laboratory findings revealed mild inflammation, mild acidemia, and hypercapnea with radiologic infiltrations in the right lung, and remarkable wheezes in both lungs were heard on auscultation. He was diagnosed with asthma exacerbation and having influenza pneumonia, and was referred to us. Therapy was begun with oseltamivir for influenza infection and intravenous infusions of betamethasone and aminophylline with non-invasive pulmonary ventilation for asthma exacerbation and acute respiratory failure. Although he was weaned from mechanical ventilation and his general condition became good, electrocardiogram showed sinus bradycardia and negative T waves in V1-4 without any symptoms. Blood test and echocardiography showed almost normal findings except for slight elevation of LDH and AST. Influenza A antigen was already confirmed and he was diagnosed as having influenza myocarditis clinically. Although it is well known that influenza can cause asthma exacerbation and encephalopathy, influenza myocarditis is regarded as rare by physicians. In fact, the number of case reports about influenza myocarditis is few. Myocarditis may not appear to be serious, but could cause fatal arrhythmia and heart failure. All clinicians should be aware of the overall clinical picture and the possibility of severe complications of myocarditis caused by flu infection.

Immunogenicity of trivalent influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy

ABSTRACT Lung cancer is a leading cause of cancer-related death, and patients with lung cancer are a priority group for influenza vaccination. However, few studies have assessed the immunogenicity of the influenza vaccine in these patients. Here, we performed a prospective study to evaluate the immunogenicity of the influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy. Twenty-five patients with lung cancer undergoing anticancer chemotherapy and 26 patients with chronic obstructive pulmonary disease (COPD) as controls were enrolled. A trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 was administered as a single subcutaneous injection. Serum samples were collected before vaccination, and at 4–6 weeks after vaccination. Levels of serum antibody to hemagglutinin were measured. Among patients with lung cancer, the seroprotection rate (postvaccination titer > 1:40) was 84% for both A(H1N1) and A(H3N2), similar to the levels observed in patients with COPD. However, the seroprotection rate for the B strain was significantly lower in patients with lung cancer than in patients with COPD (64% versus 92%). Even after adjustment for potential confounders, patients with lung cancer had a significantly lower odds ratio for seroprotection against the B strain than patients with COPD. Moreover, in patients with lung cancer, those receiving the platinum doublet treatment tended to exhibit a lower seroprotection rate than those receiving a single agent. Thus, patients with lung cancer undergoing anticancer chemotherapy showed acceptable immune responses to a trivalent influenza vaccine, supporting the recommendation for annual influenza vaccination in these patients.

Asma persistente grave com resposta ao uso off label de omalizumabe, não obstante a IgE sérica total ser alta ou baixa

Here, we present two cases of patients with severe persistent asthma. The two patients differed in terms of the total serum IgE level, which was quite high in one and quite low in the other. Despite the fact that the level of total serum IgE was not within the recommended range in either case, we opted to treat both with omalizumab. The treatment responses were favorable, and neither patient experienced any omalizumab-related side effects. The first case (Case 1) was in a 75-year-old woman who visited our hospital for an asthma evaluation. Her asthma had been poorly controlled despite multi-drug therapy with salmeterol (100 µg/day), fluticasone (1,000 µg/ day), ciclesonide (200 µg/day), tiotropium (18 µg/day), montelukast (10 mg/day), fexofenadine (60 mg/day), and theophylline (200 mg/day). As can be seen in Table 1, she had an asthma control test (ACT) score of 7 at the initial evaluation. The total serum IgE level was 1,149 IU/mL, and she tested positive for specific IgE to house dust and mites. In the previous year, she had had numerous asthma exacerbations, resulting in 7 emergency room visits and 6 hospitalizations. With the consent of the patient, we decided to initiate treatment with omalizumab, despite the fact that her total serum IgE level was well above the recommended cut-off value of 700. Omalizumab (300 mg/kg of body weight) was administered every two weeks for 16 weeks. The dose was determined to be identical to that which would be given based on the high IgE level. The patient reported an improvement in her quality of life immediately (after the first dose), and her ACT score rose to 25 (the maximum score). There were also improvements in PEF and FEV 1 (Table 2). We therefore classified the patient as an omalizumab responder, and the treatment was characterized as definitely effective. Thereafter, we maintained her on omalizumab (150 mg/ kg every 4 weeks). While under treatment with

Bolha gigante infecciosa associada a câncer de pulmão

Abstract A 79 year-old man sought treatment in the emergency room complaining of persistent fever, chest pain, and general fatigue. A chest X-ray showed a giant infectious bulla (24 cm in diameter) in the left lung. The patient had no history of abnormalities on X-rays, and his latest medical check-up, conducted in the preceding year, had produced no abnormal findings. Diagnostic procedures, including bronchoscopy, revealed lung cancer (large cell carcinoma) in the left lower bronchus. The tumor obstructed the airway. Although there have been various reports of giant bullae, their etiology remains unknown. We suggest that an obstruction, such as that caused by the tumor in this case, can lead to air trapping, resulting in the formation of a bulla. In the case of a giant bulla that rapidly increases in size, lung cancer should be included in the differential diagnosis. Keywords: Lung neoplasms/complications; Infection; Drainage. Resumo Um homem de 79 anos procurou tratamento no pronto-socorro com queixas de febre persistente, dor toracica e fadiga geral. A radiografia de torax mostrou uma bolha gigante infecciosa (24 cm de diâmetro) no pulmao esquerdo. O paciente nao tinha historico de anormalidades em radiografias, e seu ultimo check-up medico no ano anterior nao revelou anormalidades. Os procedimentos diagnosticos, incluindo broncoscopia, revelaram câncer de pulmao (carcinoma de pulmao de celulas grandes) no bronquio inferior esquerdo. O tumor obstruia a via aerea. Apesar de varios relatos de bolhas gigantes, a sua etiologia ainda e desconhecida. Nos sugerimos que uma obstrucao, como a causada pelo tumor neste caso, pode causar aprisionamento aereo, resultando na formacao de uma bolha. No caso de uma bolha gigante que cresce rapidamente de tamanho, o câncer de pulmao deve ser incluido no diagnostico diferencial.

Severe Community-acquired Pneumonia Caused by Acinetobacter baumannii Successfully Treated with the Initial Administration of Meropenem Based on the Sputum Gram Staining Findings: A Case Report

A 62-year-old man with diabetes mellitus and a two-day history of fever and dyspnea presented at our hospital. He was diagnosed with community-acquired pneumonia (CAP), septic shock, and respiratory failure. Sputum Gram staining revealed Gram-negative coccobacilli. Based on the Gram staining findings and history, Acinetobacter baumannii was considered as one of the causative organisms of his CAP. Consequently, he was successfully treated with the initial administration of meropenem. We suggest that A. baumannii should be considered as one of the possible causative organisms of CAP based on a fulminant clinical course, and the presence of Gram-negative coccobacilli.

Disseminated varicella-zoster virus infection with abdominal pain possibly caused by pirfenidone: A case report

We report a case of chronic hypersensitivity pneumonitis treated with pirfenidone in a 76-year-old woman who complained of acute-onset abdominal pain and rashes. The patient was diagnosed with disseminated varicella-zoster virus (VZV) infection, and pirfenidone was discontinued. Her condition improved in one month. Pirfenidone may induce disseminated VZV infection.

Combined pulmonary fibrosis and emphysema with myeloperoxidase-antineutrophil cytoplasmic antibody positivity that resolved upon smoking cessation

Myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) is well-known as a serological marker for small-vessel vasculitis. However, when a smoker with interstitial lung disease (ILD) exhibits serum ANCA positivity without systemic vasculitis, diagnosis is a matter of debate; the relationship between smoking and ANCA is unknown. We report a case of combined pulmonary fibrosis and emphysema (CPFE) with elevated MPO-ANCA. Surgical lung biopsy showed emphysema and fibrotic interstitial pneumonia without vasculitis. The MPO-ANCA level decreased after smoking cessation, and no vasculitis or progression was observed during 3 years of follow-up. This suggested that smoking cessation was related to normalization of MPO-ANCA and corresponding disease activity.