Bronchus sign on thin-section computed tomography is a powerful predictive factor for successful transbronchial biopsy using endobronchial ultrasound with a guide sheath for small peripheral lung lesions: a retrospective observational study.

BACKGROUND: Recent advances in bronchoscopy, such as transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS), have improved the diagnostic yield of small-sized peripheral lung lesions. In some cases, however, it is difficult to obtain adequate biopsy samples for pathological diagnosis. Adequate prediction of the diagnostic accuracy of TBB with EBUS-GS is important before deciding whether bronchoscopy should be performed. METHODS: We retrospectively reviewed 149 consecutive patients who underwent TBB with EBUS-GS for small-sized peripheral lung lesions (≤30 mm in diameter) from April 2012 to March 2013. We conducted an exploratory analysis to identify clinical factors that can predict an accurate diagnosis by TBB with EBUS-GS. All patients underwent thin-section chest computed tomography (CT) scans (0.5-mm slices), and the CT bronchus sign was evaluated before bronchoscopy in a group discussion. The final diagnoses were pathologically or clinically confirmed in all studied patients (malignant lesions, 110 patients; benign lesions, 39 patients). RESULTS: The total diagnostic yield in this study was 72.5% (95% confidence interval: 64.8-79.0%). Lesion size, lesion visibility on chest X-ray, and classification of the CT bronchus sign were factors significantly associated with the definitive biopsy result in the univariate analysis. In the multivariate analysis, only the CT bronchus sign remained as a significant predictive factor for successful bronchoscopic diagnosis. The CT bronchus sign was also significantly associated with the EBUS findings of the lesions. CONCLUSION: Our results suggest that the CT bronchus sign is a powerful predictive factor for successful TBB with EBUS-GS.

Pharmacokinetics of gefitinib in a patient with non-small cell lung cancer undergoing continuous ambulatory peritoneal dialysis.

A 72-year-old man undergoing continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure and who had undergone right upper lobectomy for lung adenocarcinoma (pT2aN0M0) 2 years ago was admitted for recurrence of lung cancer presenting as multiple brain metastases. An epidermal growth factor receptor mutation analysis of his lung cancer revealed a deletion of 15 nucleotides (E746-A750) in exon 19. After whole-brain radiotherapy, we started daily administration of 250 mg gefitinib under the continuation of CAPD and performed a pharmacokinetic analysis. We speculated that the plasma concentration of gefitinib reached the steady state at least by day 16 after the start of gefitinib (626.6 ng/ml at trough level). On day 46, the plasma concentration was 538.4 ng/ml at trough level and the concentration in the peritoneal dialysis fluid was 34.6 ng/ml, suggesting that CAPD appeared to have little effect on the pharmacokinetics of gefitinib. During gefitinib therapy, there were no significant adverse events except for grade 2 diarrhea. Gefitinib could be safely administered to a patient undergoing CAPD.

[Efficacy and safety of cisplatin plus pemetrexed as a first-line treatment for Japanese patients with advanced non-squamous non-small-cell lung cancer -- a retrospective analysis].

BACKGROUND: Cisplatin plus pemetrexed is considered the standard of care for the first-line treatment of patients with advanced non-squamous non-small-cell lung cancer (NSCLC). However, little is known about the efficacy and safety of this regimen in Japanese patients in a daily clinical setting. METHODS: We retrospectively analyzed 40 patients who received cisplatin (75 mg/m/(2)) and pemetrexed (500 mg/m(2)) as a first-line treatment for advanced non-squamous NSCLC. RESULTS: Recorded Grade 3 or 4 hematological toxicities included neutropenia in 7 cases (17.5%), leukopenia in 5 cases (12.5%), anemia in 1 case (2.5%), thrombocytopenia in 1 case (2.5%), and febrile neutropenia in 1 case (2.5%). Grade 3 or 4 nonhematological toxicities included anorexia in 3 cases (7.5%), infection in 1 case (2.5%), rash in 1 case (2.5%), and increased transaminase expression in 1 case (2.5%). Therefore, the adverse events were mostly mild. There were no treatment related deaths. The overall response rate was 37.5%, median progression free survival was 5.6 months, and median overall survival (OS) was 18.8 months. In an epidermal growth factor receptor (EGFR) mutation status subgroup analysis, the median OS of patients with wild-type EGFR or unknown status (n=28)was 16.8 months. CONCLUSION: Cisplatin plus pemetrexed was well tolerated as a first-line treatment and effective in Japanese patients with advanced non-squamous NSCLC.

Upregulation of CD11b on eosinophils in aspirin induced asthma.

BACKGROUND: Although a challenge test using non-steroidal anti-inflammatory drugs (NSAIDs) is crucial for diagnosis of aspirin-induced asthma (AIA), it also has drawbacks in terms of possible side effects. Therefore, alternative in-vitro diagnostic methods for AIA are awaited. METHODS: Nineteen stable non-AIA patients (9 males and 10 females; mean age, 49.4 ± 4.8 years), and 20 AIA patients (9 males and 11 females; mean age, 51.1 ± 4.8 years) were enrolled in this study. CD11b and CD16 expressions on the peripheral-blood granulocytes after administration of aspirin and different concentrations of PGE2 in vitro were examined using flowcytometry. RESULTS: Aspirin induced a significant increase in CD11b expression on eosinophils (CD16 negative granulocytes) in 19 AIA patients and one non-AIA patient. Increase in CD11b expression on eosinophils by aspirin administration was suppressed by PGE2 in a dose-dependent manner. CONCLUSIONS: The measurement of CD11b expression on peripheral-blood eosinophils showed very high sensitivity and specificity of (-95%) in diagnosing AIA. Although this method requires laboratory facilities for flowcytometry, it may be very useful in diagnosis of AIA without side effects. In addition, PGE2 may be involved in regulation of CD11b expression on eosinophils by aspirin administration.

A phase II study of S-1 monotherapy as second-line treatment for advanced non-small cell lung cancer.

PURPOSE: To assess the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative, S-1, for previously treated patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced (clinical stage IIIB-IV) NSCLC who had previously received one platinum-based chemotherapy were enrolled. S-1 was administered orally at the dosage decided by using the nomogram based on patient BSA b.i.d. for 28 consecutive days, repeated every 6 weeks. RESULTS: Between August 2005 and July 2007, 50 patients were entered into this study. Six patients achieved partial response (PR), and the overall response rate of eligible patients was 12.5% (6/48) (95% confidence interval (95%CI), 3.1-21.9%). Disease control rate was 39.6% (19/48) (95%CI, 25.7-53.4%). Median progression-free survival was 2.5 months. Median survival time was 8.2 months, and 1-year survival rate was 29.6%. No grade 4 toxicities were encountered. Grade 3 hematological toxicities comprised neutropenia in one patient (2.1%) and anemia in one patient (2.1%). Grade 3 non-hematological toxicities were observed in only five patients (10.4%). Treatment-related death did not occur. CONCLUSION: S-1 is an active and well-tolerated monotherapy for second-line treatment of advanced NSCLC.

[A case of advanced small cell lung cancer complicated by chronic renal failure treated with amrubicin].

A 64-year old man first visited our clinic approximately 10 years ago because of diabetic nephropathy that had developed into chronic renal failure. He was hospitalized to examine a left S10 tumor shadow. Based on the results of these examinations, a primary left S10 T2N0M1, ED small cell lung cancer, was diagnosed. During his outpatient visits nephropathy was found. Following admission, he began dialysis (HD). During the detailed examinations, chemotherapy with amrubicin (AMR)was performed and the blood concentration of the drug was measured. The results showed no significant variations in blood concentration before and after the dialysis. While PR was achieved in this patient, a reduction in grade 4 eosinophils was observed as an adverse reaction.

[Clinical characterization of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia pattern].

OBJECTIVE AND METHODS: To assess the clinical significance of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia (NSIP) pattern (IP/NSIP groups), we measured the levels of serum (n = 14) and bronchoalveolar lavage fluid (BALF, n = 10) CA19-9 in IP/NSIP groups. RESULT: The serum levels of CA19-9 did not correlate with the serum levels of LDH, of KL-6, or of SP-D or with the intensity of chest Ga-67 scintigraphy. There were no significant differences between the serum CA19-9 levels before therapy and those after therapy in improving patients. The levels of CA19-9 in fibrotic NSIP groups (serum:n = 7, 138.3 + /- 79.6 U/ml BALF: n = 5, 845.8 + /- 334.2 U/ml) were significantly higher than those in cellular NSIP groups (serum: n = 7, 12.8 +/-2.1 U/ml, BALF: n = 5, 40.8 +/- 16.2 U/ml). Immunohistochemical stains of CA19-9 showed the strong positivity in the bronchiolar epitheliums located in severe fibrotic lesions and the mucus within the lumens of microscopic honeycomb. The serum levels of CA19-9 were increased in both worsening patients. CONCLUSION: We speculated that the serum levels of CA19-9 may reflect the progression of lung fibrosis but not the disease activity in IP-NSIP groups.