Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer.

BACKGROUND: Magnetic resonance imaging (MRI) enables a more sensitive detection of brain metastasis and stereotactic irradiation (SRI) efficiently controls brain metastasis. In limited-stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) in patients with good responses to initial treatment is recommended based on the survival benefit shown in previous clinical trials. However, none of these trials evaluated PCI effects using the management of brain metastasis with MRI or SRI. This study aimed to determine the effects of MRI and SRI on the benefits of PCI in patients with LS-SCLC. METHODS: The clinical records of pathologically proven SCLC from January 2006 to June 2013 in facilities equipped with or had access to SRI in Japan were retrospectively reviewed. Patients with LS-SCLC and complete or good partial responses after initial treatment were included in the study and analyzed by the Kaplan-Meier method. RESULTS: Of 418 patients with SCLC, 124 met criteria and were divided into patients receiving PCI (PCI group; n = 29) and those without PCI (non-PCI groups; n = 95). At baseline, ratios of patients with stage III were significantly advantageous for the non-PCI group, although younger age and high ratios of complete response and MRI confirmed absence of brain metastasis were advantageous for the PCI group. Neither median survival times (25 vs. 34 months; p = 0.256) nor cumulative incidence of brain metastasis during 2 years (45.5 vs. 30.8%; p = 0.313) significantly differed between the two groups. Moreover, these factors did not significantly differ among patients with stage III disease (25 vs. 26 months; p = 0.680, 42.3 vs. 52.3%; p = 0.458, respectively). CONCLUSION: PCI may be less beneficial in patients with LS-SCLC if the management with MRI and SRI is available.

Efficacy of short-term prednisolone treatment in patients with chronic eosinophilic pneumonia.

In patients with chronic eosinophilic pneumonia (CEP), dramatic improvements are seen in response to corticosteroid therapy; however, relapse is common after treatment has ceased. The optimal duration of corticosteroid therapy remains unclear. In a randomised, open-label, parallel group study, eligible patients with CEP received oral prednisolone for either 3 months (3-month group) or 6 months (6-month group), followed by 2 years observation. All patients were treated with an initial dose of prednisolone of 0.5 mg·kg(-1)·day(-1), which was then tapered and discontinued at either 3 or 6 months. The primary end-point was relapse during the follow-up period. In the final analysis, there were 23 patients in the 3-month group and 21 patients in the 6-month group. All patients showed a good response to prednisolone treatment. There were 12 (52.1%) relapses in the 3-month group and 13 (61.9%) relapses in the 6-month group. No significant difference was found in the cumulative rate of relapse (p=0.56). All relapse cases showed improvement upon resumption of prednisolone treatment. No difference was observed in the rate of relapse between the 3- and 6-month prednisolone treatment groups for patients with CEP.

NSD3-NUT-expressing midline carcinoma of the lung: first characterization of primary cancer tissue.

BACKGROUND: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare, aggressive malignancy. Only two pediatric and three adult cases of pulmonary NMCs have been documented. In more than two-thirds of NMC cases, a gene fusion between NUT and BRD4 or BRD3 has been documented; other fusions are rare. CASE PRESENTATION: A 36-year-old woman was admitted because of a rapidly progressing tumor of the lung with metastases to the breast and bone. A biopsy from the lung tumor revealed an undifferentiated neoplasm exhibiting round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated focal EMA, cytokeratin AE1/AE3, cytokeratin CAM 5.2, p63, CD138, and vimentin positivity. Finally, the nuclear staining pattern for NUT confirmed a histopathological diagnosis of NMC. A 5'- rapid amplification of the cDNA end (RACE) procedure successfully identified the partner of the NUT translocation as NSD3, a recently discovered partner. Fluorescence in situ hybridization confirmed the NSD3-NUT gene rearrangement, whereas a BRD3/4-NUT fusion gene was not detected. CONCLUSION: We herein describe the first case of an NSD3-NUT-expressing NMC of the lung. The further accumulation of variant NMCs should provide clues to the establishment of new individualized therapy for NMCs.

[Case of organizing pneumonia associated with sweet's syndrome].

A 76-year-old male was admitted to our hospital because of fever and erythema on the face and extremity. Skin biopsy of the erythematous lesions showed dense neutrophilic infiltrations and diagnosis of Sweet's syndrome was made. Chest computed tomography on admission revealed ground glass opacities in the right upper and lower lung fields. Bronchoalveolar lavage (BAL) showed increased lymphocytes and neutrophils. A search for bacteria, mycobacteia and fungi in BAL fluid was negative. Trans-bronchial lung biopsy revealed intraluminal organization and fibrinous exudates. Neutrophilic infiltrations were scant. These pathological findings were compatible with organizing pneumonia. Bone marrow aspiration was performed because of slight anemia and thrombocytopenia, and a diagnosis of myelodysplastic syndrome was made. Oral prednisone (PSL) of 30 mg/day induced rapid resolution of radiologic and cutaneous lesions and was tapered to 10 mg/day, then radiologic lesions worsened. Steroid pulse therapy followed by PSL 45 mg and immunosuppressive agent resulted in a resolution of his conditions. This case was rare in that organizing pneumonia was associated with Sweet's syndrome.

Prognostic factors for myositis-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM); however, little is known about the factors influencing the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the present study is to assess prognostic factors for PM/DM/CADM-ILD. METHODS: The clinical features and survival of 114 consecutive patients diagnosed with PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed retrospectively. RESULTS: The study group included 30 PM-associated ILD, 41 DM-associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55 patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever. High-resolution computed tomography frequently revealed ground-glass opacities, traction bronchiectasis, and consolidation. Most of the patients were treated with corticosteroids or corticosteroids in combination with immunosuppressive agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in univariate Cox proportional hazards models. Multivariate Cox proportional hazards analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM) as significant predictors of overall mortality. Patients with acute/subacute ILD had a much lower survival rate than those with the chronic form (p<0.001). Patients with CADM-ILD had a lower survival rate than those with PM-ILD (p = 0.034). CONCLUSIONS: Acute/subacute form, older age, lower level of FVC and diagnosis of CADM predict poor outcome in PM/DM/CADM-ILD.

Serial QuantiFERON TB-2G testing over a four-year period in healthcare workers at a city hospital.

OBJECTIVE: To evaluate the performance and practicality of QuantiFERON TB-2G (QFT-2G) testing for screening healthcare workers (HCWs) at a city hospital in Japan without a tuberculosis (TB)-specific ward. METHODS: We performed a chart review of 951 HCWs (251 men and 700 women) who underwent QFT-2G testing as a part of their pre-employment or annual employee screening between April 2007 and March 2010. RESULTS: The initial QFT-2G test was interpreted as positive in 28 (2.9%) HCWs, negative in 884 HCWs (92.9%) and indeterminate in 39 HCWs (4.1%). During the four-year study period, 37 HCWs were diagnosed as being positive at least once. Nine (0.98%) of the 923 HCWs with indeterminate or negative results on the initial testing converted to a positive status, including 6/479 (1.25%) nurses, 2/100 (2.0%) office staff members and 1/147 (0.68%) physicians. No HCWs with a positive result had a history of tuberculosis (TB) or any apparent contact with active TB patients and did not opt for treatment of latent TB. Seven (25%) of the 28 HCWs who were determined to be positive on the initial testing reverted to an indeterminate or negative status. CONCLUSION: In a series of annual serial QFT-2G tests, some HCWs exhibited conversion and/or reversion. Therefore, caution is required when interpreting mild fluctuations in interferon-γ responses.

Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy.

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy. METHODS: Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT(3) receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy. RESULTS: A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2-88.1%) and 67.2% (95% CI, 55.3-77.2%; odds ratio (OR), 0.50; 95% CI, 0.22-1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08-0.70; p < 0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07-0.65; p < 0.01). CONCLUSION: Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT(3) receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.

Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study.

RATIONALE: Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin, ethambutol, and rifampicin. However, rifampicin is known to reduce the serum levels of clarithromycin. It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen. OBJECTIVES: To compare a three-drug regimen (clarithromycin, ethambutol, and rifampicin) to a two-drug regimen (clarithromycin and ethambutol) for the treatment of Mycobacterium avium lung disease. METHODS: In a preliminary open-label study, we randomly assigned newly diagnosed, but as-yet untreated, patients with disease caused by Mycobacterium avium complex without HIV infection to either the three-drug or the two-drug regimen for 12 months. The primary endpoint was the conversion of sputum cultures to negative after 12 months of treatment. Patient data were analyzed using the intention-to-treat method. MEASUREMENTS AND MAIN RESULTS: Of 119 eligible patients, 59 were assigned to the three-drug regimen and 60 to the two-drug regimen. The rate of sputum culture conversion was 40.6% with the three-drug regimen and 55.0% with the two-drug regimen (difference, -14.4% [95% confidence interval, -32.1 to 3.4]). The incidence of adverse events leading to the discontinuation of treatment was 37.2 and 26.6% for the three-drug and the two-drug regimens, respectively. CONCLUSIONS: This preliminary study suggests that treatment with clarithromycin and ethambutol is not inferior to treatment with clarithromycin, ethambutol, and rifampicin for Mycobacterium avium complex lung disease. Our findings justify a larger clinical trial to compare long-term clinical outcomes for the two treatment regimens. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000002819).

Maintenance therapy with pemetrexed versus docetaxel after induction therapy with carboplatin and pemetrexed in chemotherapy-naïve patients with advanced non-squamous non-small-cell lung cancer: a randomized, phase II study.

PURPOSE: The optimal strategy for maintenance chemotherapy is controversial. We evaluated the efficacy and safety of continuation maintenance with pemetrexed and switch maintenance with docetaxel in advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Chemotherapy-naïve patients with non-squamous NSCLC were enrolled in this randomized phase II study. Patients who achieved disease control after four cycles of induction therapy with carboplatin (AUC 6) and pemetrexed (500 mg/m(2)) were randomized to maintenance therapy with pemetrexed (500 mg/m(2)) or docetaxel (60 mg/m(2)). The primary endpoint was survival without toxicity, defined as the time from the initiation of maintenance therapy to the first date of any grade 3/4 toxicity or death due to any cause. RESULTS: A total of eighty-five patients were enrolled in the induction phase, and 26 patients were assigned to the pemetrexed maintenance therapy and 25 patients were assigned to the docetaxel maintenance therapy. Survival without toxicity was significantly longer in the pemetrexed group (median 20.8 months, 95 % confidence interval (CI) 0.7-not estimable) than in the docetaxel group (median 0.5 months, 95 % CI 0.2-2.0, hazard ratio 0.36, 95 % CI 0.17-0.74). CONCLUSIONS: Continuation maintenance with pemetrexed may be a feasible treatment option for patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin and pemetrexed. Switch maintenance with docetaxel may also be efficacious but frequently causes severe hematologic toxicity.

Multidetector-row computed tomography assessment of adding budesonide/formoterol to tiotropium in patients with chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), multidetector-row computed tomography (MDCT) showed that tiotropium dilated the inner diameters in airways from the third to the sixth generation of the bronchi. Here we aimed to evaluate the morphological effect by adding a budesonide/formoterol combination to tiotropium in COPD patients using three-dimensional MDCT. METHODS: Pulmonary function tests, St. George's Respiratory Questionnaire (SGRQ) and MDCT imaging studies were performed at the beginning and after budesonide/formoterol combination treatment for 12 weeks in 14 patients with COPD. RESULTS: The median age was 73.5 years and the mean forced expiratory volume in 1 s (FEV1) as a percentage of the predicted value was 57.2 ± 18.3%. The luminal area in the fifth generation bronchi and the emphysema volume/CT-derived total lung volume were significantly correlated with FEV1 at baseline (r = 0.682, p < 0.02 and r = -0.868, p < 0.001, respectively). The average luminal area and wall area percentage in the third, fourth and fifth generations were correlated with the SGRQ total score. Budesonide/formoterol induced insignificant pulmonary function changes and significant symptoms improvement. CT images showed an increased inner luminal area and decreased wall area after budesonide/formoterol treatment. Average luminal area was significantly increased from 24.3 ± 9.7 to 26.0 ± 9.9 mm(2) in the third generation, 13.0 ± 6.5 to 14.7 ± 7.3 mm(2) in the fourth generation, 8.0 ± 4.8 to 9.4 ± 4.9 mm(2) in the fifth generation and 5.6 ± 2.7 to 6.7 ± 3.6 mm(2) in the sixth generation (p < 0.01). The average increase of the third generation luminal area was correlated with the FEV1 increase (r = 0.632, p < 0.03). The wall area percentage significantly decreased from 51.5 ± 9.2 to 49.1 ± 9.7 in the third generation, 56.1 ± 9.7 to 53.0 ± 11.1 in the fourth generation, and 62.3 ± 9.9 to 57.6 ± 9.8 in the fifth generation (p < 0.05). Emphysema volume/CT-derived total lung volume was unchanged with treatment. CONCLUSION: MDCT demonstrated budesonide/formoterol induced bronchodilation in the non-small airway. CT imaging can evaluate drug therapeutic effect and may provide additional insights into pharmacotherapy for COPD.

Biweekly combination therapy with gemcitabine and carboplatin compared with gemcitabine monotherapy in elderly patients with advanced non-small-cell lung cancer: a randomized, phase-II study.

INTRODUCTION: The strategy of chemotherapy in the elderly is controversial. We wanted to evaluate the efficacy and safety of biweekly gemcitabine and low-dose carboplatin combination therapy in elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: In this phase-II trial, chemotherapy-naive elderly patients (aged ≥76 years) with NSCLC were randomly treated with biweekly combination therapy with gemcitabine and carboplatin (1000 mg/m(2) gemcitabine and carboplatin at an area under the curve (AUC) of 3 on days 1 and 15, every 4 weeks) or gemcitabine monotherapy (1000 mg/m(2) on days 1, 8 and 15, every 4 weeks). The primary endpoint was overall response rate and analysis was based on intention-to-treat. RESULTS: Thirty-one patients were randomly assigned combination therapy and 30 were assigned monotherapy. The median age was 79.0 years. Response rate was 22.6% (95% confidence interval (CI): 11.4-39.8%) for biweekly combination therapy and 10.0% (95% CI: 3.5-25.6%) for monotherapy. Median progression-free survival in combination chemotherapy was 3.9 months (95% CI: 0.5-8.5 months), which was significantly longer that that in monotherapy (2.4 months, 95% CI: 0.5-6.7 months). The prevalence of hematological and non-hematological adverse events reaching grade 3/4 was not significantly different between combination therapy and monotherapy. CONCLUSIONS: Biweekly gemcitabine and low-dose carboplatin combination chemotherapy showed acceptable efficacy, toxicity, and tolerability in those aged ≥76 years with NSCLC. Further investigations with a large population are required to confirm our results.

Rheumatoid lung disease: prognostic analysis of 54 biopsy-proven cases.

OBJECTIVE: To investigate the prognostic significance of histopathological characteristics in patients with biopsy-proven rheumatoid lung disease (RLD). MATERIALS AND METHODS: Retrospective analysis was conducted on samples from 54 RLD patients who underwent surgical lung biopsies (SLBs) at Hamamatsu University Hospital and affiliated hospitals between 1980 and 2009. The overall survival rate, the spectrum of histopathological diagnosis and their associated prognostic significance were investigated. RESULTS: The study group consisted of 30 men and 24 women with a median age of 60.3 years. Histopathological analysis revealed the following: usual interstitial pneumonia (UIP), 15 cases; nonspecific interstitial pneumonia/fibrosis, 16 cases; organizing pneumonia, 4 cases; unclassifiable, 2 cases; desquamative interstitial pneumonia, 1 case; and bronchiolar disease, 16 cases. In survival outcome, 10 yr survival rate was 76.6%. Patients with UIP had significantly worse prognosis than those with non-UIP (RLD cases except those with UIP) (p = 0.0452). CONCLUSION: RLD includes several histopathological groups. Patients with UIP have worse survival than those with other types of RLD. Histopathological diagnosis may have a major impact on prognostication in patients with RLD.

Effect of switching from salmeterol/fluticasone to formoterol/ budesonide combinations in patients with uncontrolled asthma.

BACKGROUND: Combination therapy with an inhaled corticosteroid (ICS) and a long-acting ß(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen. METHODS: This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250µg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160µg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period. RESULTS: Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC. CONCLUSIONS: Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.

Nonspecific interstitial pneumonia: prognostic significance of high-resolution computed tomography in 59 patients.

OBJECTIVE: To retrospectively analyze the prognostic implications of high-resolution computed tomography (HRCT) findings for patients with biopsy-proven nonspecific interstitial pneumonia (NSIP). METHODS: Fifty-nine patients with NSIP (25 idiopathic NSIP, 34 collagen-vascular disease-associated NSIP) were included. Two chest radiologists independently evaluated the extent, presence, and distribution of various HRCT findings. Cox hazards analysis was used to evaluate the relationship between HRCT findings and prognosis. RESULTS: The 5-year survival rate was 83% and the 10-year survival rate was 66%. Univariate analysis revealed that the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis and that of airs-pace consolidation were associated with favorable outcome, whereas that of intralobular reticular opacities was associated with worse prognosis. Multivariate analysis showed that the extent of air-space consolidation was an independent factor of favorable outcome. CONCLUSION: In NSIP, the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis, air-space consolidation, and intralobular reticular opacities correlate with survival.

Phase II study of erlotinib as third-line monotherapy in patients with advanced non-small-cell lung cancer without epidermal growth factor receptor mutations.

OBJECTIVE: There are few standard therapeutic options beyond second-line treatment. We aimed to evaluate the efficacy and safety of erlotinib monotherapy as third-line chemotherapy in patients with advanced non-small-cell lung cancer without epidermal growth factor receptor mutations. METHODS: In this phase II trial, patients who did not have epidermal growth factor receptor mutations and who had previously received two cytotoxic chemotherapy regimens containing platinum were treated with erlotinib (150 mg, per os) until disease progression or unacceptable toxicity. RESULTS: Twenty patients were eligible for the assessment of efficacy and safety. Three cases showed a partial response, and eight cases showed stable disease with an overall response rate of 15.0% (95% confidence interval: 5.2-36.0%) and a disease control rate of 55.0% (95% confidence interval: 34.2-74.2%). Median progression-free survival and overall survival time were 2.1 and 6.7 months, respectively. Although dose reduction was required in one patient because of skin toxicity, grade 3/4 toxicity or pulmonary disease was not observed. CONCLUSIONS: Erlotinib as third-line therapy showed an acceptable response rate, survival time and toxicity. It could be a potential third-line therapy for patients without epidermal growth factor receptor mutations.

Distinct prognosis of idiopathic nonspecific interstitial pneumonia (NSIP) fulfilling criteria for undifferentiated connective tissue disease (UCTD).

BACKGROUND: Although idiopathic nonspecific interstitial pneumonia (NSIP) was initially identified as a provisional diagnosis, the 2008 American Thoracic Society Project concluded that idiopathic NSIP is a distinct form of idiopathic interstitial pneumonia. However, an association between idiopathic NSIP and autoimmune diseases still attracts interest. In this context, a recent study proposed an intriguing concept that idiopathic NSIP is the pulmonary manifestation of undifferentiated connective tissue disease (UCTD). However, this has not been confirmed in a large number of patients with idiopathic NSIP. The present study was conducted to investigate the proportion and characteristics of patients with idiopathic NSIP who meet the criteria for UCTD. METHODS: We reviewed 47 consecutive patients with idiopathic NSIP and examined whether they met prespecified criteria for UCTD. Furthermore, we compared the clinical characteristics between patients fulfilling the UCTD criteria (UCTD-NSIP) and those not meeting them (Non-UCTD-NSIP). RESULTS: Of 47 patients with idiopathic NSIP, 22 (47%) met the UCTD criteria. Common symptoms associated with connective tissue diseases (CTDs) were skin change (50%) and Raynaud's phenomenon (41%) in UCTD-NSIP. UCTD-NSIP showed a female predominance and significantly higher percentages of lymphocytes with a lower CD4/CD8 ratio in bronchoalveolar lavage than Non-UCTD-NSIP. Interestingly, UCTD-NSIP had a significantly better survival than Non-UCTD-NSIP. CONCLUSIONS: Idiopathic NSIP included subjects who fulfilled the UCTD criteria, and these subjects had different clinical characteristics with significantly better outcome than those who did not meet the criteria. These data suggest that a part, but not all, of patients with idiopathic NSIP show CTD-like features with a distinct prognosis.

Real-time PCR is more specific than conventional PCR for induced sputum diagnosis of Pneumocystis pneumonia in immunocompromised patients without HIV infection.

BACKGROUND AND OBJECTIVE: The diagnosis of Pneumocystis pneumonia (PCP) is based on microscopic examination of respiratory specimens. PCP patients without AIDS have a lower burden of P. jiroveci than those with AIDS, which leads to difficulty in detecting the organisms. Although conventional PCR (c-PCR) has been used to detect the DNA, it is frequently positive in patients with colonization. Real-time PCR (r-PCR), a method to detect the DNA quantitatively, might be helpful in distinguishing between infection and colonization. We investigated the utility of real-time PCR in the diagnosis of PCP in non-AIDS patients. METHODS: Induced sputum samples obtained from 86 non-HIV immunocompromized patients with clinical symptoms of pulmonary infection were evaluated for the presence of Pneumocystis jiroveci-specific DNA using c-PCR and r-PCR. The diagnosis of PCP was confirmed by typical clinical and radiological findings and response to treatment. RESULTS: Of the 86 patients, 17 were diagnosed as having PCP. Twenty-eight samples were positive for c-PCR, but the false-positive rate was high (46.4%). Sensitivity, specificity and positive predictive values (PPV) of c-PCR were 88.2%, 81.2% and 53.6%, respectively. Concentrations of the DNA detected by r-PCR were significantly higher in PCP patients than in non-PCP patients. Using 30 copies per tube as a cut-off value for the diagnosis of PCP, the sensitivity (82.4%) of r-PCR was almost equal to c-PCR. Notably, its specificity and PPV were higher than c-PCR (98.6% and 93.3%, respectively). CONCLUSIONS: r-PCR on induced sputum is more useful for diagnosing PCP than c-PCR in non-HIV immunocompromized patients, especially in terms of distinguishing between colonization and infection.

Phase II study of combination chemotherapy with S-1 and weekly cisplatin in patients with previously untreated advanced non-small cell lung cancer.

We aimed to evaluate the efficacy and safety of combination chemotherapy with S-1 and low-dose weekly cisplatin in patients with advanced non-small cell lung cancer (NSCLC). In this phase II trial, previously untreated patients with stage IIIB/IV NSCLC were treated with oral administration of S-1 at 80 mg/m(2) for 21 days and three consecutive weekly low doses of cisplatin (25 mg/m(2)) followed by a 2-week rest period. Twenty-six patients were eligible for the assessment of efficacy and safety. Six partial responses were observed with an overall response rate of 23.1% (95% confidence interval: 12.3-31.6%). The median survival time and median progression-free survival were 13.4 months and 5.4 months, respectively. Grade 3/4 hematologic toxicities were observed in 9 patients (34.6%), including one grade 4 neutropenia and thrombocytopenia. As for non-hematologic adverse reactions, although grade 3 events were observed in 4 patients (15.3%), no severe renal toxicity or vomiting was found. S-1 and weekly low-dose cisplatin combination chemotherapy in patients with advanced NSCLC showed an acceptable response rate, overall survival time, and toxicity. Because this regimen can be performed in an outpatient setting, it might be an alternative useful and convenient option. Further investigations with a large population are required to confirm our results.

[Acute respiratory failure due to pneumocystis pneumonia successfully treated with combined use of sivelestat sodium hydrate].

A 22-year-old man was admitted to our hospital with fever, cough and dyspnea. His chest radiograph showed diffuse ground-glass attenuation in both lung fields. Arterial blood gas analysis showed hypoxemia (PaO2 28.7 Torr breathing room air) and he required mechanical ventilation within 6 hours after admission. Gomori methenamine silver (GMS) stain of the bronchoalveolar lavage (BAL) fluid smear showed round and indented organisms, and polymerase chain reaction revealed pneumocystis jirovecii in the BAL fluid. The HIV antibody was positive and peripheral blood CD4-positive lymphocytes decreased to 4.0%. Pneumocystis pneumonia complicated with acquired immunodeficiency syndrome (AIDS) was diagnosed. There was no four-fold rise in screen viral titers. We treated him with antibiotics, trimethoprim-sulfamethoxazole, ganciclovir, fos-fluconazole, steroid pulse therapy and sivelestat sodium hydrate. Respiratory failure was relieved within 5 days following treatment. The percentage of neutrophils in the BAL fluid was elevated (44.6%). Neutrophil elastase on admission was increased and improved to the normal range after treatment. Sivelestat sodium hydrate is an anti-neutrophil elastase inhibitor and may be one of the treatment options for acute respiratory failure due to pneumocystis pneumonia in AIDS patients.