Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products.

INTRODUCTION: Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. METHODS: This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. RESULTS: Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p<0.05). The logistic regression analysis model showed that a younger age and higher education level were associated with the use of HTP (age OR=0.83; higher education level OR=4.63; p<0.05). Many of the current smokers displayed smoking behaviors that are not guaranteed to be safe, such as reducing smoking or switching to lighter cigarettes or HTP. CONCLUSIONS: Patients with COPD who continue smoking tended to have low appetite as well as smoking behaviors that are not guaranteed to be safe. Physicians should provide appropriate guidance to these patients on smoking cessation.

Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) with platinum-irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum-etoposide (Pem+EP), durvalumab plus platinum-etoposide (Dur+EP), atezolizumab plus platinum-etoposide (Atz+EP), platinum-amrubicin (AP), IP, and platinum-etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.

Investigating Patient and Family Satisfaction with the Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease.

The current chronic obstructive pulmonary disease (COPD) management aims to improve the patients' quality of life and healthy life expectancy; however, few studies have evaluated the level of satisfaction with the patients' current respiratory status in COPD patients and their families. This study aimed to examine the level of patient and family satisfaction with the patients' current respiratory status and to identify the clinical factors closely linked to dissatisfaction.This multicenter, cross-sectional study included 454 outpatients with COPD and 296 family members. Patients and families were allocated to the satisfied and dissatisfied groups based on their satisfaction with the patients' current respiratory status. Patients' health status, dyspnoea, appetite, respiratory function, and mood disorders were assessed.Among the participants of this study, 67% of patients and 60% of their families were dissatisfied with the patients' current respiratory status. The COPD assessment test (CAT) was the most sensitive marker of dissatisfaction compared to other clinical factors (p < 0.01). The statistical cut-off value of CAT for predicting patient dissatisfaction was 11. CAT reflected patient dissatisfaction independent of age, sex, dyspnoea, appetite, mood disorders, body mass index, and respiratory function (odds ratio: CAT; 1.12 (1.07-1.19): p < 0.01).Many patients and families are dissatisfied with the patients' respiratory status, and the patients' CAT score is useful to predict dissatisfaction. Our findings are consistent with the Global Initiative for Chronic Obstructive Lung Disease indicating that treatment should be enhanced in patients with a CAT score ≥10. Furthermore, treatment strategies targeting CAT may contribute to an improved patient satisfaction.

Nivolumab plus Ipilimumab versus Existing Immunotherapies in Patients with PD-L1-Positive Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

No head-to-head trials have compared the efficacy and safety of nivolumab (Niv) plus ipilimumab (Ipi) combination therapy (Niv+Ipi) and existing regimens with immunotherapies approved as first-line treatment in patients with programmed cell death ligand 1 (PD-L1)-positive previously untreated advanced non-small cell lung cancer (NSCLC). We conducted a network meta-analysis of four relevant Phase Ⅲ trials to compare the efficacy and safety of Niv+Ipi, pembrolizumab (Pem) plus platinum-based chemotherapy (PBC) (Pem+PBC), Pem, Niv, or PBC using Bayesian analysis. The primary efficacy endpoint was progression-free survival (PFS) in patients with advanced NSCLC with PD-L1 expression ≥1%. The primary safety endpoint was the incidence of Grade 3-5 drug-related adverse events (G3-5AEs). Efficacy and safety were ranked using surface under the cumulative ranking curve (SUCRA). With regard to PFS, Niv+Ipi was inferior to Pem+PBC, and superior to Pem, Niv, or PBC alone. SUCRA ranking showed Pem+PBC had the highest efficacy for PFS, followed by Niv+Ipi, Niv, PBC, and Pem. The safety outcome analysis revealed Niv+Ipi was generally well tolerated compared to existing immunotherapy regimens. These results provide clinical information regarding the efficacy and safety of Niv+Ipi and indicate the possibility of the Niv+Ipi combination as a new therapeutic option in PD-L1-positive advanced NSCLC.

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 Immune Checkpoint Inhibitors for Refractory or Relapsed Advanced Non-Small-Cell Lung Cancer-A Systematic Review and Network Meta-Analysis.

The efficacy and safety of immune checkpoint inhibitors (ICIs) in refractory or relapsed advanced non-small-cell lung cancer (NSCLC) have not yet been compared with those of ramucirumab (Ram) plus docetaxel (Doc). Furthermore, comprehensive comparisons between ICIs have not been conducted to date. In the current study, a Bayesian network meta-analysis of related phase III clinical trials was performed to compare the efficacy and safety of Ram+Doc, Niv, Atz, and Doc treatments in patient groups lacking the PD-L1 constraint. Surface under the cumulative ranking area (SUCRA) revealed that the overall survival (OS) of patients treated with Niv was the highest, followed by Atz, Ram+Doc, and Doc. Regarding grades 3-5 treatment-related adverse events (G3-5AEs), the use of Niv was ranked the safest, followed by Atz, Doc, and Ram+Doc. Significant differences in OS were observed between Niv and Ram+Doc, while significant differences in G3-5AEs were observed between Ram+Doc and Niv or Atz. In the PD-L1 positive (≥1%) patient subgroup, Pem (10 mg/kg) ranked the highest in efficacy for OS, followed by Niv, Pem (2 mg/kg), Atz, and Doc. These findings may expectedly provide oncologists with useful insights into therapeutic selection for refractory or relapsed advanced NSCLC.

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. OBJECTIVE: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. METHOD: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). RESULTS: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. CONCLUSION: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

Acute exacerbation of idiopathic pulmonary fibrosis induced by pertussis: the first case report.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe condition with limited treatment strategies. Although respiratory infection is a major cause of AE-IPF, no reports have indicated pertussis infection as a cause. Here we report two cases of pertussis infection-induced AE-IPF. CASE PRESENTATION: Both patients presented with a chief complaint of acute respiratory distress and were previously diagnosed with idiopathic pulmonary fibrosis (IPF). Neither patient had received any pertussis vaccination since adolescence. Both patients were diagnosed with AE-IPF accompanying acute pertussis infection based on chest computed tomography and serum pertussis toxin antibody > 100 EU/mL. Both patients were treated with macrolide antibiotics and systemic corticosteroids. Both patients were able to be discharged and return home. CONCLUSIONS: The presence of pertussis infection in AE-IPF can present a diagnostic challenge, as coughing accompanying pertussis may be difficult to distinguish from IPF-associated coughing. Pertussis infection should be assayed in AE-IPF patients. Since pertussis can be prevented with vaccination and is expected to be affected by antibiotics, consideration of pertussis infection as a causative virulent factor of AE-IPF may be important for management of subjects with IPF.

High burden of Aspergillus fumigatus infection among chronic respiratory diseases.

Aspergillus fumigatus (AF) is a ubiquitous fungus in our environment and causes severe airway disorders. Chronic respiratory diseases (CRDs) are a series of chronic airway and lung diseases. Although both are chronic disorders, however, the relationships between AF and CRDs are still unclear. Therefore, we examined 104 Aspergillus species (spp.) isolated samples in our hospital during three consecutive years to further elucidate the relationships between Aspergillus spp. and CRDs. Based on sample isolates, we then grouped these into two groups, AF and non-AF, to retrospectively analyse the clinical features and to clarify the relationships between AF and CRDs. Importantly, the manifestation of CRD was more frequent in the AF group than in the non-AF group ( p = 0.035). Among CRDs, lung fibrosis was more evident in the AF group ( p = 0.025). Moreover, diabetes mellitus was tended to be evident in AF group than non-AF group ( p = 0.035). In conclusion, CRDs, especially lung fibrosis, were highly prevalent in AF group than non-AF group.

Association between respiratory impedance measured by forced oscillation technique and exacerbations in patients with COPD.

Background: It is well known that increased airflow limitation as measured by spirometry is associated with the risk of exacerbation in patients with COPD. The forced oscillation technique (FOT) is a noninvasive method used to assess respiratory impedance (resistance and reactance) with minimal patient cooperation required. The clinical utility of the FOT in assessing the risk of exacerbations of COPD is yet to be determined. We examined the relationship between respiratory impedance as measured by FOT and exacerbations in patients with COPD. Materials and methods: Among 310 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages I-IV) who presented at the outpatient clinic of the Showa University Hospital from September 2014 through January 2015, 119 were collected and assigned into 2 groups according to their history of exacerbation: exacerbators and nonexacerbators. Respiratory resistance components and respiratory reactance components, as measured by FOT, were compared between the two groups. Results: Exacerbators were significantly older and had a higher white blood cell count than nonexacerbators. Resistance at 20 Hz, reactance at 5 Hz (X5), resonant frequency (Fres), and area of low reactance (ALX) differed significantly between the two groups. In addition, among patients with stage II COPD, there were significant differences in X5, Fres, and ALX between the two groups despite no significant differences in respiratory function as assessed by spirometry. Finally, receiver operating characteristic curve analysis revealed that the reactance components rather than the resistance components were associated with the risk of exacerbation. Conclusion: There were significant differences in respiratory impedance between exacerbators and nonexacerbators in patients with moderate COPD. FOT is a promising tool for assessing future exacerbations in patients with COPD.

AN ADULT CASE OF ANAPHYLAXIS CAUSED BY ALLERGY TO JELLYFISH.

A 35-year-old female, professional diver, reported nausea, vomiting, and systemic hives 20 to 30 minutes after ingestion of antipasto made with jellyfish. Patient reported prior episodes of swelling after stings from several different creatures, including jelly fish. She also developed a systemic allergic reaction after sting from an unknown creature while diving. On the initial visit to our hospital, serum total IgE level was 545IU/ml. We extracted crude allergen from jellyfish and evaluated allergen specific IgE antibody levels using ELISA. Patient samples showed higher levels of jellyfish-derived allergen specific IgE than healthy control samples. Basophils were isolated from the peripheral blood of patient. Stimulation with jellyfish-derived allergen showed expression of surface antigens on basophils increased in a concentration-dependent manner. Methods using sodium dodecyl sulfate poly acrylamide gel electrophoresis and immunoblotting showed acid-soluble collagen fraction from jellyfish contained above 250kDa weighed protein that may have caused this current event. A provocation test using jellyfish samples was not performed due to risk of anaphylactic shock. The patient was diagnosed with a jellyfish allergy due to IgE mediated anaphylaxis after ingestion. She was asked to refrain from consuming any food containing jellyfish. IgE-mediated food allergy caused by jellyfish is rare worldwide. Collagen was speculated to be an allergen in this study. Additional study to detect specific allergens related to jellyfish allergy would be particularly useful to specify disease phenotypes and individual care in future.

Distinct Afatinib Resistance Mechanisms Identified in Lung Adenocarcinoma Harboring an EGFR Mutation.

EGFR tyrosine kinase inhibitors (TKI) are associated with significant responses in non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations. However, acquired resistance to reversible EGFR-TKIs remains a major obstacle. In particular, although the second-generation irreversible EGFR-TKI afatinib is currently used for treating NSCLC patients, the mechanisms underlying acquired afatinib resistance remain poorly understood. Here, heterogeneous mechanisms of acquired resistance were identified following long-term exposure to increasing doses of afatinib in EGFR-mutant lung adenocarcinoma PC-9 cells. Notably, three resistant cell lines, PC-9AFR1, PC-9AFR2, and PC-9AFR3 (AFR1, AFR2, and AFR3, respectively) employed distinct mechanisms for avoiding EGFR inhibition, with increased EGFR expression being detected in all resistant cell lines. Moreover, an activating EGFR mutation was partially lost in AFR1 and AFR2 cells. AFR1 cells exhibited afatinib resistance as a result of wild-type KRAS amplification and overexpression; however, these cells showed a progressive decrease and eventual loss of the acquired KRAS dependence, as well as resensitization to afatinib, following a drug holiday. Meanwhile, AFR2 cells exhibited increased expression of insulin-like growth factor-binding protein 3 (IGFBP3), which promoted insulin-like growth factor 1 receptor (IGF1R) activity and subsequent AKT phosphorylation, thereby indicating a potential bypass signaling pathway associated with IGFR1. Finally, AFR3 cells harbored the secondary EGFR mutation T790M. Our findings constitute the first report showing acquired wild-type KRAS overexpression and attenuation of afatinib resistance following a drug holiday.Implications: The heterogeneous mechanisms of afatinib resistance should facilitate the development of more effective therapeutic strategies for NSCLC patients. Mol Cancer Res; 15(7); 915-28. ©2017 AACR.

Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI-Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation.

Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition of EGFR and Met tyrosine kinase activities. PC-9 lung adenocarcinoma cells harboring 15-bp deletions (Del E746_A750) in EGFR exon 19 were treated with increasing concentrations of the Met-TKI PHA665752 and 1 µmol/L gefitinib for 1 year; three resistant clones were established via Met amplification. The three dual-resistance cell lines (PC-9DR2, PC-9DR4, and PC-9DR6, designated as DR2, DR4, and DR6, respectively) exhibited different mechanisms for evading both EGFR and Met inhibition. None of the clones harbored a secondary mutation of EGFR T790M or a Met mutation. Insulin-like growth factor (IGF)/IGF1 receptor activation in DR2 and DR4 cells acted as a bypass signaling pathway. Met expression was attenuated to a greater extent in DR2 than in PC-9 cells, but was maintained in DR4 cells by overexpression of IGF-binding protein 3. In DR6 cells, Met was further amplified by association with HSP90, which protected Met from degradation and induced SET and MYND domain-containing 3 (SMYD3)-mediated Met transcription. This is the first report describing the acquisition of dual resistance mechanisms in NSCLC harboring an activating EGFR mutation to Met-TKI and EGFR-TKI following previous EGFR-TKI treatment. These results might inform the development of more effective therapeutic strategies for NSCLC treatment. Mol Cancer Ther; 15(12); 3040-54. ©2016 AACR.

[Successful Treatment of Seasonal Influenza A (H3N2) infection-related Hemophagocytic Lymphocytosis in an Elderly Man].

A 79-year-old man experienced severe chronic obstructive pulmonary disease (COPD) and was receiving treatment for ischemic heart disease. Starting from dizziness and chilliness, he lost consciousness after few days. He was taken to our emergency department. On initial evaluation, he complained of dyspnea and was afebrile with a pulse rate, blood pressure, and respiratory rate of 105 beats/min, 112/98mmHg, and 28 breath/min, respectively. His respiratory sounds were clear and chest radiography did not show any abnormal shadows, but his arterial blood gas examination showed type II respiratory failure. Because the nasopharyngeal seasonal influenza A virus (IAV) test was positive, the patient was admitted with the diagnosis of acute exacerbation of COPD due to IAV. We administered peramivir, a specific anti-influenza drug, and started mechanical ventilation. Over time, he started to show signs of disseminated intravascular coagulation, such as multiple organ failure and thrombocytopenia. Subsequently, blood tests showed elevation of ferritin and soluble interleukin 2 receptor (sIL2R); microscopic examination of the peripheral blood revealed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis (HLH) due to IAV was diagnosed and together with corticosteroid therapy, intravenous gamma globulin was administered from the 3rd clinical day. The patint was saved with our early diagnosis and treatment of HLH and was discharged on the 92nd clinical day. Viral-induced HLH, formerly known as virus-associated hemophagocytic syndrome (VAHS), leads to multiple organ failure due to a cytokine storm scattered by viral-infected pathogenic inflammatory cells. It is well known that pandemic swine flu causes secondary HLH leading to poor outcomes. Currently, not much is known about HLH due to seasonal flu; particularly, IAV (H3N2)-related HLH cases are rare and reported cases showed poor outcomes as well. With an early diagnosis and minimum immunotherapy, we report herein on a case of IAV (H3N2)-related HLH which was treated successfully.

Phase II study of concurrent chemoradiotherapy with carboplatin and vinorelbine for locally advanced non-small-cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) have locally advanced disease with poor prognosis. Although concurrent chemoradiotherapy is the standard treatment, more effective regimens are required. The aim of this study was to assess the safety and efficacy of concurrent chemoradiotherapy with a divided schedule of carboplatin and vinorelbine in patients with locally advanced NSCLC. Patients with unresectable, stage IIIA or IIIB NSCLC were eligible for enrollment if they exhibited a performance status of 0-2 and were ≤75 years of age. Patients were treated with carboplatin at an area under the plasma concentration vs. time curve of 2.5 mg/ml/min and vinorelbine at 20 mg/m2 on days 1 and 8 every 3 weeks. Thoracic radiotherapy at a total dose of 60 Gy was concurrently administered (2 Gy per fraction). Twenty-eight patients (23 men and 5 women; median age, 67 years; range 47-75 years) were enrolled in the present study. The overall response rate was 85.7% [95% confidence interval (CI), 67.3-96.0%] and the disease control rate was 96.4% (95% CI, 81.7-99.9%). The median survival time (MST) was 23 months and the median progression-free survival (PFS) time was 8 months. Grade 3-4 toxicities included neutropenia, thrombocytopenia, anemia and infection in 100, 14, 46 and 36% of patients, respectively. One patient (4%) developed grade 3 radiation esophagitis that resolved completely without residual dilation. Grade 3 radiation pneumonitis occurred in 2 patients (7%); however, the symptoms and radiographic abnormalities subsided with corticosteroid therapy. In conclusion, concurrent chemoradiotherapy with a divided schedule of carboplatin and vinorelbine is well-tolerated and effective in patients with locally advanced NSCLC.

Evaluation of the safety and efficacy of combination chemotherapy with vinorelbine and platinum agents for patients with non-small cell lung cancer with interstitial lung disease.

BACKGROUND: Acute chemotherapy-associated exacerbation of interstitial lung disease (ILD) can occur in patients with non-small cell lung cancer (NSCLC). The safety and efficacy of cytotoxic chemotherapy has not yet been established for NSCLC with ILD. Thus, patients with advanced NSCLC with ILD usually receive only best supportive care. The aim of this study was to assess the safety and efficacy profiles of the combination chemotherapy of vinorelbine and a platinum agent in patients with advanced NSCLC with ILD. PATIENTS AND METHODS: Nineteen patients with advanced NSCLC with ILD treated with vinorelbine and a platinum agent, either cisplatin or carboplatin, were retrospectively reviewed to examine acute exacerbation of ILD, toxicity, response rate, and survival time. Additionally, possible predictive factors for acute chemotherapy-associated exacerbation of ILD were analyzed. RESULTS: The response rate was 42.1%, the progression-free survival time was 4.4 months, the median survival time was 7.4 months, and the one-year survival rate was 36.8%. Neutropenia was the most frequent grade 3 to 4 toxicity and it occurred in 63.2% of patients. Acute chemotherapy-associated exacerbation of ILD occurred in three patients (15.8%) and caused the death of one of these patients (5.3%). No variables were identified as being predictive factors for acute chemotherapy-associated exacerbation of ILD. CONCLUSION: The combination chemotherapy with vinorelbine and a platinum agent can be considered as a treatment option for patients with advanced NSCLC with ILD, with careful management after sufficient evaluation of the risks and the benefits.

Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer.

The aim of this study was to investigate the relationship of the number of circulating tumor cells (CTCs) with the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We prospectively evaluated CTCs in the peripheral blood of patients with previously untreated metastatic NSCLC. From May 2008 through August 2010, 33 patients (23 men and 10 women; median age, 64 years; range, 46-74 years) were enrolled. All patients received combination chemotherapy with gemcitabine and carboplatin. The CTCs were captured from samples of peripheral blood with a semiautomated system using an antibody against epithelial cell adhesion molecule. Blood samples with one or more CTC per 7.5 ml were defined as positive. Of total 33 patients, 12 (36.4%) had positive CTCs and 5 (15.2%) had five or more CTCs before chemotherapy. There were no differences in response rates to cytotoxic chemotherapy between CTC-positive patients and CTC-negative patients. On the other hand, the rate of progressive disease in cytotoxic chemotherapy was significantly higher in CTC-positive patients (66.7%) than in CTC-negative patients (23.8%, p = 0.02). In conclusion, the number of CTCs could be a useful predictive factor for the effectiveness of cytotoxic chemotherapy in patients with metastatic NSCLC.

[Three cases of Mycobacterium kansasii pulmonary diseases in previously healthy young women].

Mycobacterium kansasii pulmonary diseases account for 20% of cases of non-tuberculous mycobacteria. Most patients are male. However, a recent study has found that radiological examinations in female patients often reveal nodular, bronchiectatic opacities. We describe 3 young women with cavitary opacities. Patient 1 was a 35-year-old woman in whom thin-walled cavitary opacities were detected in the upper lobe during a routine checkup. Sputum examination and fiberoptic bronchoscopy led to a diagnosis of M. kansasii pulmonary disease. Patient 2 was a 23-year-old woman who presented with hemoptysis. Thin-walled cavitary opacities were detected in the right upper lobe. Infection with M. kansasii was diagnosed after a sputum examination. Patient 3 was a 43-year-old woman in whom thin-walled cavitary opacities were detected in the left upper lobe during a routine checkup. Infection with M. kansasii was diagnosed after a fiberoptic bronchoscopic examination. Patient 1 was successfully treated with rifampicin, ethambutol, and levofloxacin, and patients 2 and 3 were successfully treated with isoniazid, rifampicin, and ethambutol. The possibility of M. kansasii pulmonary diseases should be considered in a previously healthy young woman with thin-walled cavitary opacities in the upper lobe.

[A case of pulmonary aspergilloma concomitant with allergic bronchopulmonary aspergillosis].

A 69-year-old man with pulmonary aspergilloma was admitted to the hospital because of persistent cough and slight fever. Antifungal agents were administered on a diagnosis of chronic necrotizing pulmonary aspergillosis or symptomatic aspergilloma. Despite the antifungal treatment, wheezing developed, suggesting a complication of allergic bronchopulmonary aspergillosis (ABPA). Finally, a definitive diagnosis of ABPA was made using the Rosenberg-Patterson criteria. Inhaled corticosteroid therapy reduced his wheezing. This case study indicates that there is a possibility that aspergilloma might coexist with ABPA. Therefore, we should pay attention to the possible complication of ABPA when treating pulmonary aspergilloma.

Phase II trial of amrubicin and carboplatin in patients with sensitive or refractory relapsed small-cell lung cancer.

Amrubicin is a novel, totally synthesized anthracycline derivative, and has antitumor activity against several human tumor xenografts. The combination of amrubicin with platinum derivative showed additive effect against a human small-cell lung cancer (SCLC) cell line. Until now, the combination of amrubicin plus carboplatin has not been studied in patients with previously treated SCLC. Therefore, we examined the safety and efficacy of the combination of amrubicin plus carboplatin in patients with sensitive or refractory relapsed SCLC. Patients with previously treated SCLC were eligible if they had a performance status of 2 or less, were 75 years or younger, and had adequate organ function. Twenty-five patients were enrolled (21 men and 4 women; median age, 65 years; age range 55-73 years). Patients received the combination of amrubicin (30 mg/m(2) on days 1-3) plus carboplatin (with a target area under the concentration-versus-time curve of 4 mg min/ml using the Calvert formula on day 1) every 3 weeks. The overall response rate was 36.0% (95% confidence interval [CI], 18.0-57.5%). Response rates differed significantly between patients with sensitive relapse (58.3%; 95% CI, 27.7-84.8%) and those with refractory relapse (15.4%; 95% CI, 1.9-15.4%; p=0.03). The median survival time (MST) from the start of this treatment was 7 months (range: 1-42 months); the MST of patients with sensitive relapse (10 months) was significantly longer than that of patients with refractory relapse (5 months: p=0.004). The median progression-free survival (PFS) time was 3 months (range: 1-14 months): the median PFS time of patients with sensitive relapse (5 months) was significantly longer than that of patients with refractory relapse (2 months; p=0.01). The most frequent grade 3-4 toxicity was myelosuppression, especially neutropenia, which developed in 88% of patients. Grade 3-4 thrombocytopenia developed in 44% of patients, and anemia developed in 56%. Nonhematologic toxicities were generally mild to moderately severe and temporary. None of the patients had cardiotoxicity. In conclusion, this therapy is effective and well tolerated for previously treated SCLC.