Risk Factors of Infectious Complications After Endobronchial Ultrasound-Guided Transbronchial Biopsy.

BACKGROUND: Infectious complications after endobronchial ultrasound-guided transbronchial biopsy with a guide sheath (EBUS-GS-TBB) are serious in that they may delay or change scheduled subsequent therapy. The aim of this study was to identify risk factors for infection after EBUS-GS-TBB. RESEARCH QUESTION: What are the risk factors for infection after EBUS-GS-TBB? STUDY DESIGN AND METHODS: We retrospectively reviewed the medical records of 1,045 consecutive patients who had undergone EBUS-GS-TBB for peripheral lung lesions between January 2013 and December 2017 at Fujita Health University Hospital. We evaluated the following risk factors for infectious complications after EBUS-GS-TBB: relevant patient characteristics (age and comorbidities), lesion size, CT scan features of target lesion (intratumoral low-density areas [LDAs] and cavitation), stenosis of responsible bronchus observed by bronchoscopy, and laboratory data before EBUS-GS-TBB (WBC count and C-reactive protein concentration). RESULTS: Forty-seven of the study patients developed infectious complications (24 with pneumonia, 14 with intratumoral infection, three with lung abscess, three with pleuritis, and three with empyema), among whom the complication caused a delay in cancer treatment in 13 patients, cancellation of cancer treatment in seven patients, and death in three patients. Multivariate analysis showed that cavitation (P = .007), intratumoral LDAs (P < .001), and stenosis of responsible bronchus observed by bronchoscopy (P < .001) were significantly associated with infectious complications after EBUS-GS-TBB. Prophylactic antibiotics had been administered to 13 patients in the infection group. Propensity matched analysis could not show significant benefit of prophylactic antibiotics in preventing post-EBUS-GS-TBB infections. INTERPRETATION: Cavitation, LDAs for CT scan features of target lesions, and stenosis of responsible bronchus observed by bronchoscopy are risk factors of post-EBUS-GS-TBB infection. In the cohort, prophylactic antibiotics failed to prevent infectious complications.

Diagnostic contribution of cytological examination to endobronchial ultrasound-guided transbronchial biopsy for lung malignancies.

Although endobronchial ultrasound guided transbronchial biopsy (TBB) with a guide sheath (EBUS-GS) is widely used for diagnosis of peripheral pulmonary lesions, the diagnostic contribution of cytology (bronchial brushing, bronchial washing and biopsy forceps rinse) has not been established. To determine the diagnostic contribution of cytological examination to EBUS-GS-TBB, we reviewed medical records of patients with lung malignancies who had undergone TBB with EBUS-GS (EBUS-GS group, n=187) or TBB without EBUS-GS (conventional TBB [CTBB] group, n=197) at Nagoya University Hospital. Although the mean size of target lesions was significantly larger in the CTBB group than the EBUS-GS group, the total diagnostic rate was equivalent between two groups (EBUS-GS: 73.3%, CTBB: 66.0%). In the EBUS-GS group, cytological procedures increased the diagnostic rate by 9.1% (17/137), compared with only 4.1% (8/130) in the CTBB group. Sensitivity of cytology among biopsy-negative patients was significantly higher in EBUS-GS group than CTBB group (P=0.022). Furthermore, in the EBUS-GS group, among 17 patients whose malignant diagnoses could only be established cytologically, bronchial brushing contributed to the malignant diagnosis in 64.7% (11/17). These data may suggest that cytological examination, especially bronchial brushing, may be an important diagnostic contributor in EBUS-GS-TBB.

Prognosis of pulmonary fibrosis presenting with a usual interstitial pneumonia pattern on computed tomography in patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis: a retrospective single-center study.

BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data. RESULTS: The numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups. CONCLUSIONS: MPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.

Flow cytometric analysis of lymphocyte profiles in mediastinal lymphadenopathy of sarcoidosis.

Lymphocyte profiles in mediastinal lymph nodes may reflect the immune status of patients with sarcoidosis. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is useful for the diagnosis of diseases with mediastinal lymphadenopathy including sarcoidosis. The purpose of this study was to determine lymphocyte profiles of lymph nodes in sarcoidosis by analyzing EBUS-TBNA samples. We prepared single cell suspensions from EBUS-TBNA samples of mediastinal lymph nodes from patients with sarcoidosis or lung cancer and analyzed surface markers (CD3, CD4, CD8, CD19, CD25) and FoxP3 expression in the resultant lymphocytes using flow cytometry. We studied 26 patients with sarcoidosis and 16 with lung cancer with mediastinal lymph node metastases. In sarcoidosis, the CD4/CD8 ratio was significantly more elevated in lymph nodes than in bronchoalveolar lavage fluid (P<0.001), although both were strongly correlated. The CD4/CD8 ratio was significantly higher in stage I than in stage II both in the BAL fluid and lymph nodes. When compared with lung cancer lymph node metastasis, the CD4/CD8 ratio was significantly higher in sarcoidosis, whereas the CD3/CD19 ratio was significantly higher in lung cancer. The proportion of regulatory T cells (CD4+, CD25+, FoxP3 high) did not differ between sarcoidosis and lung cancer samples. Lymphocyte profiles in mediastinal lymphadenopathy can be analyzed by flow cytometry of EBUS-TBNA samples. These findings might help elucidate the immunopathology of sarcoidosis.

Feasibility of tissue re-biopsy in non-small cell lung cancers resistant to previous epidermal growth factor receptor tyrosine kinase inhibitor therapies.

BACKGROUND: When epidermal growth factor receptor (EGFR) gene mutation-positive non-small cell lung cancer (NSCLC) acquires resistance to the initial tyrosine kinase inhibitor (TKI) treatment, reassessing the tumor DNA by re-biopsy is essential for further treatment selection. However, the process of TKI-sensitive tumor re-progression and whether re-biopsy is possible in all cases of acquired resistance to EGFR-TKI remain unclear. METHODS: We retrospectively analyzed data from 69 consecutive patients with EGFR gene mutation-positive advanced NSCLC who had been treated with EGFR-TKI and exhibited disease relapse after initial disease remission. The relapsing lesions were identified at the time of RECIST-progressive disease (PD) and clinical-PD (when the attending physician judged the patient as clinically relapsing and stopped EGFR-TKI therapy). We determined the potential re-biopsy methods for each relapsing lesion and evaluated their feasibility according to difficulty and invasiveness criteria as follows: category A, accessible by conventional biopsy techniques; category B, difficult (but possible) to biopsy and accessible with invasive methods; and category C, extremely difficult to biopsy or inaccessible without using highly invasive methods, including surgical biopsy. RESULTS: The total feasibility rate of re-biopsy (category A or B) was 68% at RECIST-PD and 84% at clinical-PD, and the most common accessible relapsing lesions were primary tumors at RECIST-PD and pleural effusion at clinical-PD. All relapsing lesions at primary sites (categories A and B) were assessed as having the potential for re-biopsy. However, re-biopsy for metastasis was assessed as difficult in a substantial proportion of the study population (42 and 20% category C at RECIST-PD and clinical-PD, respectively). CONCLUSIONS: Re-biopsy of relapsing disease is feasible in many cases, although it may present difficulties in cases with, e.g., metastatic relapsing lesions. To facilitate treatment strategies in NSCLC patients with relapse after EGFR-TKI therapy, re-biopsy should be standardized with the use of simpler and more reliable methods.

A simple method of bronchial occlusion with silicone spigots (Endobronchial Watanabe Spigot; EWS®) using a curette.

BACKGROUND: Bronchial occlusion with an Endobronchial Watanabe Spigot (EWS) has been shown to be useful in managing prolonged bronchopleural fistulas and intractable hemoptysis. EWS bronchial occlusion using a curette is less technically demanding. This retrospective study evaluated the clinical utility and simplicity of this method. METHODS: A total of 18 consecutive patients (15 men, 3 women, aged 47-85 years) who underwent bronchial occlusion using an EWS from April 2012 to August 2014 were evaluated. The method involves sticking the tip of a curette into an EWS to the first joint, allowing it to be turned in any direction or at any angle. The time required to occlude the target bronchus was measured on routinely recorded digital videos. Other parameters evaluated included success rates, complications, and clinical outcomes. RESULTS: Of the 18 patients, 11 underwent bronchial occlusion for intractable pneumothorax, 5 for postoperative bronchopleural fistula, two for intractable empyema, and one for hemoptysis. Each patient required 1-7 EWSs (median 4). Target bronchi included the right upper (n = 8), left upper (n = 5), right lower (n = 2), left lower (n = 2), and right middle (n = 1) bronchi. The success rate of EWS insertion into the target bronchus was 100%. Time per EWS occlusion ranged from 65-528 sec (median 158.5 sec). Of the 62 insertions, 36 (58.1%) were completed within 3 min, and 58 (93.5%) within 5 min. Successful outcomes were observed in 15 (83.3%) of the 18 patients. CONCLUSIONS: EWS bronchial occlusion using a curette is a simple method for managing intractable bronchopleural fistulas in daily clinical settings.

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.

[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.