Utility of serum immunoglobulin A antibody against glycopeptidolipid core antigen in the diagnosis and management of hypersensitivity pneumonitis associated with Mycobacterium avium complex: A case report.

Measurement of the levels of serum immunoglobulin A antibody against glycopeptidolipid (GPL) core antigen, a cell surface antigen found in Mycobacterium avium complex (MAC), has been reported to be useful in the diagnosis and management of pulmonary MAC infection. However, evidence on its utility in hypersensitivity pneumonitis (HP) associated with MAC (i.e., "hot-tub lung") is limited. We herein report a case of HP associated with MAC in which the GPL core antibody levels were serially measured from diagnosis to treatment and thereafter. A 61-year-old man was suspected to have non-fibrotic HP based on the clinical course, laboratory findings, imaging pattern, bronchoalveolar lavage (BAL) lymphocytosis, and histopathological findings. Based on the history of whirlpool bath use, inhalation of aerosolized MAC was suspected as the cause of HP. The GPL core antibody level, measured using an enzyme-linked immunosorbent assay kit, was elevated, suggesting an immunological sensitization to MAC. A provocation test using the patient's whirlpool bath was positive. An identical MAC strain was isolated from the BAL fluid and bathtub. Accordingly, the patient was diagnosed with HP caused by the inhalation of aerosolized MAC from the whirlpool bath. The patient recovered after steroid treatment and discontinuation of the whirlpool bath. The GPL core antibody levels decreased with disease improvement. In conclusion, GPL core antibody levels could be elevated in HP associated with MAC and decrease with disease improvement. Thus, measurement of the GPL core antibody level may be useful for the diagnosis and management of HP associated with MAC.

Propensity score analysis of overall survival between first- and second-generation EGFR-TKIs using real-world data.

We constructed a data set of EGFR-mutant non-small-cell lung carcinoma (NSCLC) patients, and compared the overall survival of first-generation (1G), and second-generation (2G) EGFR-tyrosine kinase inhibitors (TKIs) in clinical practice using a propensity score. We reviewed the clinical data of consecutive EGFR-mutated NSCLC patients who received EGFR-TKI therapy between January 2008 and August 2017 at 11 institutions in Japan. The primary endpoint was overall survival (OS). When comparing OS between 1G and 2G EGFR-TKIs, propensity score analyses were performed using 2 methods: matching and inverse probability of treatment weighting (IPTW). (Clinical Trial information: UMIN000030121) In total, 1400 patients from 11 institutions were enrolled in this study, and the data from the 1366 patients who received only EGFR-TKI therapy were analyzed (gefitinib [GEF], N = 732; erlotinib [ERL], N = 416; afatinib, N = 218). Median OS times (months [95%CI]) were 29.7 [27.5-33.5] in the 1G group (gefitinib, 32.0 [28.1-35.8]; erlotinib, 27.5 [23.9-31.7]), and 38.6 [32.2-NR] in the 2G group (afatinib), respectively. The trend of longer OS for afatinib against 1G EGFR-TKIs remained, even after adjusted by propensity score. (unadjusted, hazard ratio [HR] 0.676, P = .0023; adjusted by IPTW, HR 0.685 P < .0001; adjusted by matching, HR 0.725, P = .0418). Exploratory analysis showed that OS using the 2G EGFR-TKI was superior to that of the 1G EGFR-TKIs, suggesting the potential of sequential therapy of 2G EGFR-TKI followed by osimertinib. (HR 0.419, P = .0519) Real-world data analysis using 1354 data records, using propensity scoring, indicated that 2G EGFR-TKI had a trend of longer OS compared with 1G EGFR-TKIs.

Thrombomodulin Alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis. A Randomized, Double-Blind Placebo-controlled Trial.

Rationale: Acute exacerbation during the course of idiopathic pulmonary fibrosis causes a poor prognosis. Coagulation abnormalities and endothelial damage are involved in its pathogenesis. Thrombomodulin alfa, a recombinant human soluble thrombomodulin, has anticoagulant and antiinflammatory effects. Several clinical studies have shown that thrombomodulin alfa may improve survival of acute exacerbation.Objectives: To determine the efficacy and safety of thrombomodulin alfa compared with placebo in acute exacerbation of idiopathic pulmonary fibrosis.Methods: This randomized, double-blind placebo-controlled phase 3 study conducted at 27 sites in Japan involved patients with an acute exacerbation of idiopathic pulmonary fibrosis. Subjects were randomized 1:1 to receive placebo or thrombomodulin alfa (380 U/kg/d for 14 d by intravenous drip infusion). All subjects were treated with high-dose corticosteroid therapy. The primary endpoint was the survival proportion on Day 90.Measurements and Main Results: Of the 82 randomized subjects, 77 completed the study and were included in the full analysis set (thrombomodulin alfa, n = 40; placebo, n = 37). The survival proportions on Day 90 were 72.5% (29 of 40) in the thrombomodulin alfa group and 89.2% (33 of 37) in the placebo group, a difference of -16.7 percentage points (95% confidence interval, -33.8 to 0.4%; P = 0.0863). In the safety population (n = 80), bleeding adverse events occurred in the thrombomodulin alfa group (10 of 42; 23.8%) and the placebo group (4 of 38; 10.5%).Conclusions: Thrombomodulin alfa did not improve the 90-day survival proportion. The present results suggest that the use of thrombomodulin alfa for the treatment of acute exacerbation of idiopathic pulmonary fibrosis not be recommended.Clinical trial registered with www.clinicaltrials.gov (NCT02739165).

Evaluation of treatment outcomes of patients with MRSA bacteremia following antimicrobial stewardship programs with pharmacist intervention.

BACKGROUND: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) is associated with high mortality and implementing an appropriate antimicrobial stewardship (AS) program with treatment intervention is essential. The aim of this study was to evaluate the impact of AS with pharmacist intervention on patients with MRSA-B. METHODS: Patients who were diagnosed with MRSA-B between January 2012 and April 2013 were defined as the pre-intervention group, while those diagnosed between May 2013 and December 2015 were defined as the intervention group (ie, AS with pharmacist intervention). The factors affecting bundle compliance rates and mortality were analysed. RESULT: The pre-intervention group comprised 43 patients and the intervention group comprised 51 patients. Bundle compliance rates were estimated as follows in the intervention group: an increase was observed in the appropriate duration of therapy (from 44.8% to 72.1%, P = .027), incidences of the early use of anti-MRSA drugs (from 62.3% to 82.4%, P = .038), and the number of negative follow-up blood cultures (from 40.0% to 80.0%, P < .001), and a decrease was observed for 30-day mortality (from 41.8% to 21.6%, P = .044) and hospital mortality (from 58.1% to 27.5%, P = .003). In multivariate analysis, the intervention group was independent of 30-day mortality and hospital mortality risk reduction factors (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.12-0.86, and OR, 0.20; 95% CI, 0.07-0.53). CONCLUSIONS: AS programs with pharmacist intervention improve mortality in patients with MRSA-B.

Can we predict the development of serious adverse events (SAEs) and early treatment termination in elderly non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy?

PURPOSE: Predicting the feasibility of platinum-based chemotherapy remains an important issue in elderly (over 70 years) patients with non-small cell lung cancer (NSCLC). The aim of this study was to identify the risk factors for the early serious adverse events (SAEs) (during cycles 1-2) in elderly receiving platinum-based chemotherapy, and to explore the clinical characteristics of patients who require early treatment termination without progressive disease (PD). METHODS: One hundred and ninety-eight consecutive elderly NSCLC patients receiving platinum-based chemotherapy were retrospectively reviewed. RESULTS: The median age was 73 years (range 70-83). 161 (81 %) were males, and 190 (95 %) were PS 0-1. Fifty-one (29 %) and 39 (19 %) patients developed early non-hematological SAEs and hematological SAEs, respectively. Multivariate analysis identified low serum albumin (<3.0 g/dl) as an independent risk factor for non-hematological SAEs, while low creatinine clearance (<45 ml/min) for hematological SAEs. In all, 24 (12 %) patients needed early treatment termination without PD. The major reason for this event was the development of non-hematological SAEs (4.5 %), followed by grade 2 non-hematological adverse events (AEs) (3 %). In multivariate analysis, age over 75 years and low serum albumin were associated with this event. The median overall survival (OS) in patients with this event was only 6.0 months, while the development of early SAE was not associated with poor OS. CONCLUSION: Baseline serum albumin might be useful for predicting the feasibility of platinum-based chemotherapy, and the risk estimation of early treatment termination without PD might be beneficial for the treatment selection in elderly NSCLC patients.

Risk factors for 30-day mortality in patients with pneumonia who receive appropriate initial antibiotics: an observational cohort study.

BACKGROUND: Appropriate initial antibiotics are essential for the treatment of infectious diseases. However, some patients with pneumonia might develop adverse outcomes, despite receiving appropriate initial antibiotics. We aimed to clarify the risk factors for 30-day mortality in patients who received appropriate initial antibiotics and to identify potential candidates who would benefit from adjunctive therapy. METHODS: From March 15, to Dec 22, 2010, we did a prospective, observational study at ten medical institutions in hospitalised patients (aged ≥20 years) with pneumonia. We did a multivariable logistic regression analysis to calculate odds ratios (ORs) and 95% CI to assess the risk factors for 30-day mortality. This study was registered with the University Medical Information Network in Japan, number UMIN000003306. FINDINGS: The 30-day mortality was 11% (61 of 579 patients) in the appropriate initial antibiotic treatment group and 17% (29 of 168) in the inappropriate initial antibiotic treatment group. Albumin concentration of less than 30 mg/L (adjusted OR 3·39, 95% CI 1·83-6·28), non-ambulatory status (3·34, 1·84-6·05), pH of less than 7·35 (3·13, 1·52-6·42), respiration rate of at least 30 breaths per min (2·33, 1·28-4·24), and blood urea nitrogen of at least 7·14 mmol/L (2·20, 1·13-4·30) were independent risk factors in patients given appropriate initial antibiotic treatment. The 30-day mortality was 1% (one of 126 patients), 1% (two of 168), 17% (23 of 137), 22% (20 of 89), and 44% (14 of 32) for patients with no, one, two, three, and four or five risk factors, respectively. INTERPRETATION: Patients with two or more risk factors were at a higher risk of death during the 30 days assessed than were individuals with no or one risk factor, despite appropriate initial antibiotic treatment. Therefore, adjunctive therapy might be important for improving outcomes in patients with two or more risk factors. FUNDING: Central Japan Lung Study Group.

Phase II study of erlotinib for previously treated patients with EGFR wild-type non-small-cell lung cancer, following EGFR mutation status reevaluation with the Scorpion Amplified Refractory Mutation System.

While assessing the efficacy of erlotinib in patients with epidermal growth factor receptor (EGFR) wild-type (WT) non-small-cell lung cancer (NSCLC), the sensitivity of the method used for the EGFR mutation analysis may affect the evaluation of the efficacy. We conducted a phase II study of erlotinib for previously treated patients with EGFR WT NSCLC screened by the peptide nucleic acid-locked nucleic acid (PNA-LNA) polymerase chain reaction (PCR) clamp method, which is known to be highly sensitive. The primary endpoint was the objective response rate (ORR). Preplanned reevaluation of the EGFR genotype as an exploratory endpoint was performed using the Scorpion Amplification Refractory Mutation System (S-ARMS) assay. Erlotinib was administered daily until disease progression or development of unacceptable toxicity. A total of 53 evaluable patients were enrolled. The histological subtypes were adenocarcinoma in 40 patients, squamous cell carcinoma in 9 patients and not otherwise specified NSCLC in 4 patients. Partial response (PR) was achieved in 6 patients (4 with adenocarcinoma and 2 with squamous cell carcinoma). The ORR was 11.3% [95% confidence interval (CI): 4.3-23.0]. The median progression-free survival (PFS) was 1.8 months (95% CI: 1.2-2.3). Samples from 26 of the 53 patients (49.0%) were available for EGFR mutation reanalysis with the S-ARMS assay. Of these 26 samples, only 1 sample of adenocarcinoma was found to be EGFR mutation-positive (exon 19 deletion) and the patient achieved a PR. The EGFR WT genotype was reconfirmed by the S-ARMS assay in the remaining 25 patients and 2 of these patients exhibited a PR. This study did not meet the primary endpoint, although erlotinib was found to be moderately effective in pretreated patients with EGFR WT NSCLC, even when the EGFR mutational status was confirmed by the highly sensitive PNA-LNA clamp PCR method.

First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901.

BACKGROUND: The population of elderly patients with lung cancer is increasing worldwide. Although first-line gefitinib is one of the standard treatments for advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, few data have been reported regarding gefitinib and elderly patients. PATIENTS AND METHODS: Chemotherapy-naïve patients aged 70 years or older with stage IIIB or IV NSCLC harboring EGFR-activating mutation were enrolled and treated with 250 mg of gefitinib daily until disease progression. The primary end point was response rate, and secondary end points were survival, safety, and quality of life. RESULTS: Twenty patients were enrolled, and the median age was 79.5 years (range 72-90). Overall response rate was 70% (95% CI 45.7-88.1%), and the disease control rate was 90% (95% CI 68.3-98.7%). The median progression-free survival and overall survival time were 10.0 and 26.4 months, respectively. The Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) scores improved significantly 4 weeks after the initiation of gefitinib (P = 0.037) and maintained favorably over a 12-week assessment period. Among the seven items of FACT-LCS, shortness of breath and cough improved significantly after 4 weeks of treatment (P = 0.046 and P = 0.008, respectively). The most common adverse events were rash and liver dysfunction. Although Grade 1 pneumonitis developed in one patient, no treatment-related death was observed. CONCLUSION: First-line gefitinib therapy is effective and feasible for elderly patients harboring EGFR mutation, and improves disease-related symptoms, especially pulmonary symptoms like shortness of breath and cough.

Cefepime monotherapy for febrile neutropenia in patients with lung cancer.

UNLABELLED: We assessed the efficacy and safety of cefepime monotherapy (1 g intravenously every 8 h) for febrile neutropenia in patients with lung cancer in a multi-institutional phase II study. Patients treated with chemotherapy with or without radiotherapy for lung cancer were eligible for this study. Other eligibility criteria included fever (temperature of ≥38.0 °C) and an absolute neutrophil count of <500/mm(3) or <1000/mm(3) with an expected decline to <500/mm(3) within the next 48 h. Risk assessment was performed using the Multinational Association of Supportive Care in Cancer risk-index score. Cefepime 1 g was given intravenously every 8 h. The primary endpoint was the response rate at the end of cefepime therapy. Co-administration of granulocyte-colony-stimulating factor was permitted. Of 54 patients enrolled, 39 were classified in the low-risk group and 15 in the high-risk group. Overall response rate was 78% (95% CI: 64.4-88.0%). The response rates were 85% (95% CI: 69.5-94.1%) in the low-risk group and 60% (95% CI: 32.3-83.7%) in the high-risk group, respectively. One patient died from septic shock due to Enterobacter cloacae bacteremia. There was no significant adverse event. Cefepime 1 g intravenously every 8 h appears to be effective for febrile neutropenia in patients with lung cancer, especially in those with low-risk febrile neutropenia, and is well tolerated. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000006157.

Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia.

RATIONALE: Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia. OBJECTIVES: To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patients with CAP and HCAP. METHODS: A prospective observational study was conducted in hospitalized patients with pneumonia at 10 institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant pathogens (CAP-DRPs). MEASUREMENTS AND MAIN RESULTS: In total, 1,413 patients (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11), previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid-suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95% CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the combined patients with CAP and HCAP. The area under the receiver operating characteristic curve for counting the number of risk factors was 0.79 (95% CI, 0.74-0.84). CONCLUSIONS: The clinical profile of HCAP was different from that of CAP. However, physicians can predict drug resistance in patients with either CAP or HCAP by taking account of the cumulative number of the risk factors. Clinical trial registered with https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004001&language=E ; number UMIN000003306.

Virtual bronchoscopic navigation combined with ultrathin bronchoscopy. A randomized clinical trial.

RATIONALE: In bronchoscopy, an ultrathin bronchoscope can be advanced to more peripheral bronchi. Because virtual bronchoscopic navigation (VBN) is a method to guide a bronchoscope under direct observation using VB images, VBN may be particularly useful when combined with ultrathin bronchoscopy. OBJECTIVES: This prospective multicenter study evaluated the value of VBN-assisted ultrathin bronchoscopy for diagnosing peripheral pulmonary lesions. METHODS: We randomly assigned 350 patients with peripheral pulmonary lesions (diameter, ≤30 mm) to VBN-assisted or non-VBN-assisted groups. An ultrathin bronchoscope (outer diameter, 2.8 mm) was introduced to the target bronchus using a VBN system in the VBN-assisted group, whereas only computed tomography axial images were referred to in the non-VBN-assisted group. Specimen sampling sites were verified using X-ray fluoroscopy. MEASUREMENTS AND MAIN RESULTS: Subjects for analysis included 334 patients. There was no significant difference in the diagnostic yield between the VBN-assisted group (67.1%) and the non-VBN-assisted group (59.9%; P = 0.173). The subgroup analysis showed that the diagnostic yield was significantly higher in the VBN-assisted group than in the non-VBN-assisted group for right upper lobe lesions (81.3% vs. 53.2%; P = 0.004); lesions invisible on posterior-anterior radiographs (63.2% vs. 40.5%; P = 0.043); and lesions in the peripheral third of the lung field (64.7% vs. 52.1%; P = 0.047). CONCLUSIONS: VBN-assisted ultrathin bronchoscopy does not improve the diagnostic yield for peripheral pulmonary lesions. However, the method improves the diagnostic yield for lesions in the subcategories (right upper lobe, invisible, peripheral third), warranting further study. Clinical trial registered with www.umin.ac.jp/ctr/ (UMIN 000001536).

CT-guided ultrathin bronchoscopy: bioptic approach and factors in predicting diagnosis.

BACKGROUND: The diagnostic sensitivity of current bronchoscopy for peripheral lung cancer is inadequate because the bronchoscope insertion range is limited and confirmation of the position of the biopsy apparatus at the lesion under X-ray fluoroscopy is inaccurate. The combination of ultrathin bronchoscopy and computed tomography (CT) is effective for solving these problems. OBJECTIVE: This study was a retrospective study analyzing prospectively collected data to identify factors contributing to the diagnosis and the appropriate biopsy method in CT-guided ultrathin bronchoscopy for peripheral lung cancer. METHODS: The subjects comprised 86 patients (88 lesions) who underwent CT-guided ultrathin bronchoscopy and were finally diagnosed with peripheral lung cancer. We evaluated the diagnostic yield according to specific factors and also according to the sample collection method. RESULTS: Sixty-nine lesions were diagnosed as lung cancer, and the diagnostic yield was 78.4% (80.3% in lesions ≤2 cm in diameter). Multivariate analysis showed that the factors contributing to the diagnosis were the observation range by ultrathin bronchoscopy and the presence/absence of the involved bronchus or pulmonary artery. Pathological evaluation facilitated histological diagnoses in 53 (65.4%) of 81 lesions. In 16 lesions, only the cytological diagnosis was positive. CONCLUSION: CT-guided ultrathin bronchoscopy may be particularly useful for lesions for which the involved bronchus or pulmonary artery can be confirmed, and observation of bronchi of the 6th generation or more is possible. Since the specimen preparation rate is low, the combination of histopathological diagnosis with cytological diagnosis particularly that of the discharge attached to the forceps, is optimal.

Second-line weekly paclitaxel in resistant or relapsed non-small cell lung cancer treated with docetaxel and carboplatin: a multi-center phase II study.

We conducted a phase II trial to evaluate the safety and efficacy of weekly paclitaxel in patients with resistant or relapsed non-small cell lung cancer (NSCLC) treated with docetaxel and carboplatin. Thirty-two NSCLC patients at a median age of 58.0 years (range 33-75) were enrolled. The Eastern Cooperative Oncology Group performance status scores (0/1/2) were 18/9/5, respectively. The majority of patients had adenocarcinoma (84%) and stage IV disease (81%). The response rate for the first-line chemotherapy was 28%. Paclitaxel was administered at a dose of 80 mg/m(2) as an intravenous infusion 60 min weekly for 6 consecutive weeks of an 8-week cycle. All patients were assessable for response and toxicity. The median number of cycles administered was two (range 1-8), and the overall response rate was 15.6%. The median survival time (MST) was 10.6 months (95% CI=8.2-12.5), while the 1-year survival rate was 37.5%, and the median progression-free survival was 4.9 months (95% CI=3.0-7.1). Hematological toxicities (grade 3 or 4) were observed in 15 patients (46.9%) with leukopenia, and in 4 (12.5%) with anemia. Non-hematological toxicity was generally mild, though grade 3 anorexia was observed in 3 patients (9.3%). No treatment-related deaths were observed. In conclusion, second-line weekly paclitaxel is effective in NSCLC patients treated with docetaxel plus carboplatin and is associated with a tolerable toxicity profile.

A phase II study of carboplatin and paclitacel with meloxicam.

BACKGROUND: Cyclooxygenase (COX-2) overexpression is seen in many malignancies including lung cancer. Recent pre-clinical studies have shown that selective COX-2 inhibitors have demonstrated promising results when used with chemotherapy. Based on these observations, we assessed the efficacy and tolerability of the combination chemotherapy consisting of carboplatin and paclitaxel with meloxicam, a selective COX-2 inhibitor. METHODS: Forty-four patients with stage IIIB or IV non-small cell lung cancer (NSCLC), Eastern Cooperative Oncology Group performance status (PS) 0 or 1, who had adequate organ function, were eligible. Patients received paclitaxel 70 mg/m(2) weekly for 3 of 4 weeks with carbopltin (AUC 6) on day 1, as well as daily meloxicam (10 mg/day). The response rate was the primary endpoint. Secondary endpoints were overall survival, toxicity profile and quality of life (using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and LC13). RESULTS: From March 2005 to September 2006, 44 patients were evaluated in this study. Gender M/F, 31/13; median age, 64 years (range, 34-75); stage IIIB/IV, 11/33; PS0/1, 22/22; histology Ad/Sq/Other, 29/6/9. Partial response was observed in 19 patients (43%) with stable disease, and there was no complete response, for an overall response rate of 43% (95% confidence interval, 28.5-57.8%). Ten patients (23%) had grade (G) 3 and three (7%) had G4 neutropenia. Three patients (7%) had G3 thrombocytopenia. As for non-hematological toxicities, one case of G4 toxicity (perforation of jejunum) was observed, but other toxicities were mild (one muscle pain, two liver dysfunction, one fatigue and one nausea G3). Grade 2 peripheral neuropathy was observed in only one patient. Using the EORTC QLQ questionnaire, the global health status did not change significantly during this therapy (before and 4 and 8 weeks later). Median follow-up was 13.6 months (range, 1.8-31.3 months). By the time of the final analysis (October 2007), 26 of the initial 44 patients had died. The 1-year survival rate was 64% and median survival time was 15.9 months. CONCLUSIONS: Meloxicam in combination with carboplatin and weekly paclitaxel chemotherapy showed promising activity with encouraging survival. This therapy is relatively well tolerated in advanced NSCLC.

[Prevalence of myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) in patients with interstitial pneumonia].

Myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) is an autoantibody that is frequently found in patients with vasculitides. We encountered some MPO-ANCA positive patients with interstitial pneumonia who lacked vasculitides, but its meaning remains unclear. We measured MPO-ANCA titers in 69 patients with interstitial pneumonia (IP) who did not have collagen vascular diseases and observed their outcome. MPO-ANCA was positive in 5 patients and its prevalence was 7.2%. Patients with MPO-ANCA positive showed higher positivity in rheumatoid factor (RF) than patients with MPO-ANCA negative. The sensitivity and specificity of a combination of anti-nuclear antibody-negative and RF-positive were 80.0% and 87.7%, respectively. Two patients were accompanied by microscopic polyangiitis and the 3-year survival rate was 40% in all patients with MPO-ANCA. Measurement of MPO-ANCA titers in patients with IPs is meaningful for determining therapeutic strategy.

Phase I/II trial of docetaxel and carboplatin as a first-line therapy in patients with stage IV non-small-cell lung cancer.

A phase I/II study was conducted to determine the maximum-tolerated dose, the safety and tolerability, and the clinical efficacy of carboplatin and docetaxel in combination in patients with stage IV non-small-cell lung cancer. Patients with measurable, previously untreated, good performance status, and stage IV non-small-cell lung cancer were eligible. Increasing doses of docetaxel were given in combination with a fixed dose of carboplatin except at level 5. Cycles were repeated every four weeks. Seventy-seven patients were registered. In phase I, 27 patients were entered at five different dose levels. A docetaxel dose of 60 mg/m(2) and carboplatin area under the concentration time curve 6 was recommended for phase II, and an additional 50 patients were entered at this level for a total of 56 patients. Grade 3/4 neutropenia was the most common adverse event and occurred in 70% of the patients. Two patients had febrile neutropenia. Fifty-six patients were assessable for response; 21 partial responses were observed for an overall response rate of 37.5%. The median time to tumor progression was 4.0 months (range, 1.0-21.0 months), and the median survival was 12.9 months (range, 0.4-51.3 months). The one-year survival rate was 46.4%. The combination of docetaxel 60 mg/m(2) and carboplatin area under the concentration time curve 6 is feasible and effective in patients with stage IV non-small-cell lung cancer.

Ultrathin bronchoscopic barium marking with virtual bronchoscopic navigation for fluoroscopy-assisted thoracoscopic surgery.

STUDY OBJECTIVES: To facilitate marking and to reduce its complications, we performed barium marking using an ultrathin bronchoscope with virtual bronchoscopic (VB) navigation before thoracoscopic surgery for small pulmonary peripheral lesions. We then evaluated the feasibility, safety, and efficacy of this technique. DESIGN: A pilot study. SETTING: A tertiary teaching hospital. PATIENTS: The subjects were consecutive patients with small pulmonary peripheral lesions (ie,

[Early image of squamous cell carcinoma in the peripheral lung field on high-resolution CT scan].

A 65-year-old man presented with the shadow of an abnormal nodule in the left lower lung field in a chest radiograph. We diagnosed this as an old inflammatory change because prior chest radiographs had shown the same nodule in the same lung field. However, a high-resolution CT scan showed a hazy ground-glass opacity (GGO) near the nodule. Two years later, this GGO changed into a small nodule. After a CT-guided transbronchial lung biopsy performed by ultra-thin fiberoptic bronchoscopy, we diagnosed this nodule as squamous cell carcinoma. We speculated that the hazy GGO detected in the peripheral lung field on high-resolution CT two years before diagnosis may have been an early image of squamous cell carcinoma.