Yoshihito Kogure

Prospective study of endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes versus transbronchial lung biopsy of lung tissue for diagnosis of sarcoidosis

OBJECTIVE Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been reported to be an accurate and safe method to confirm a pathologic diagnosis of sarcoidosis. However, only a few retrospective or small prospective studies have been published on EBUS-TBNA versus transbronchial lung biopsy (TBLB), which has been the standard method for making a pathologic diagnosis of sarcoidosis so far. The aim of this study was to compare the diagnostic yield of EBUS-TBNA and TBLB through a flexible bronchoscope in patients with stage I and II sarcoidosis. METHODS A total of 62 patients with suspected stage I and II sarcoidosis were included in this prospective study. EBUS-TBNA was performed (2 lymph nodes, 2 needle passes for each lymph node), followed by TBLB (5 biopsy specimens from multiple lung segments) in the same setting. The final diagnosis of sarcoidosis was based on clinicoradiologic compatibility and pathologic findings. RESULTS Of the 62 patients enrolled, 54 were given a final diagnosis of sarcoidosis. The diagnostic yield of EBUS-TBNA and TBLB for sarcoidois by showing noncaseating epithelioid cell granuloma was 94% (stage I, 97%; stage II, 88%) and 37% (stage I, 31%; stage II, 50%), respectively. The difference was statistically significant (P < .001). One case of pneumothorax and 3 cases of moderate bleeding (7%) resulted from TBLB, and 1 case of severe cough (2%) from EBUS-TBNA. CONCLUSIONS The diagnostic yield of EBUS-TBNA for stage I and II sarcoidosis is higher than for TBLB.

Rapid on-site cytologic evaluation during endobronchial ultrasound-guided transbronchial needle aspiration for diagnosing lung cancer: a randomized study.

Background: Although rapid on-site cytologic evaluation (ROSE) is widely used during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), its role remains unclear. Objectives: The purpose of the present study was to evaluate the efficacy of ROSE during EBUS-TBNA in the diagnosis of lung cancer. Methods: One hundred and twenty patients highly suspected of having lung cancer who had hilar/mediastinal lymphadenopathy or a tumor adjacent to the central airway were enrolled in this study and randomized to undergo EBUS-TBNA with or without ROSE. Results: Twelve patients with visible endobronchial lesions were excluded in the analysis. Thus, a total of 108 patients (55 in the ROSE group, 53 in the non-ROSE group) were analyzed. Additional procedures including EBUS-TBNA for lesions other than the main target lesion and/or transbronchial biopsy in the same setting were performed in 11% of patients in the ROSE group and 57% in the non-ROSE group (p < 0.001). Mean puncture number was significantly lower in the ROSE group (2.2 vs. 3.1 punctures, p < 0.001), and mean bronchoscopy time was similar between both groups (22.3 vs. 22.1 min, p = 0.95). The sensitivity and accuracy for diagnosing lung cancer were 88 and 89% in the ROSE group, and 86 and 89% in the non-ROSE group, respectively. No complications were associated with the procedures. Conclusions: ROSE during EBUS-TBNA is associated with a significantly lower need for additional bronchoscopic procedures and puncture number.

Randomized Study of 21-gauge Versus 22-gauge Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Needles for Sampling Histology Specimens.

Background:Histologic specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) often provide valuable information for diagnosis or management decisions; however, little has been reported about the sampling yield. Besides the conventional 22-gauge needle, a 21-gauge needle is now available for this procedure. The purpose of this study was to elucidate and compare the respective histologic specimen retrieval yields of EBUS-TBNA using 21-gauge and 22-gauge needles. Methods:Sixty patients with hilar/mediastinal lymphadenopathy or a tumor adjacent to the central airway were enrolled and randomized to undergo EBUS-TBNA using a 21-gauge or a 22-gauge needle. Each histologic specimen obtained by EBUS-TBNA on the initial 2 punctures of each patient (total 120 punctures) was blindly categorized by a pathologist as follows: I, diagnostic; II, nondiagnostic but adequate (eg, lymphoid tissue); III, nondiagnostic and inadequate (eg, clot); and IV, no specimens. Results:The specimens obtained by the 21-gauge needle were interpreted as I in 35, II in 8, III in 15, and IV in 2. The specimens obtained by the 22-gauge needle were judged to be I in 34, II in 13, III in 7, and IV in 6. The sampling yield of adequate histologic specimens (I and II) obtained by the 21-gauge and 22-gauge needles was 72% and 78% (P=0.40), respectively. No complications were associated with the procedures. Conclusions:Histologic specimens can be obtained with a high sampling yield using either of the needles. Our study found no difference in the sampling yield between the 2 needles.

Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan

To the Editors: Pulmonary alveolar proteinosis (PAP) is a rare syndrome that predominantly affects the lungs, and is characterised by the accumulation of surfactant lipids and proteins in the alveoli and terminal airways 1. In 1999, we published findings that high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralising autoantibodies were detected specifically in patients with idiopathic PAP 2. Recently, as a result of the excellent sensitivity and specificity of GM-CSF autoantibody assays in identifying this form of PAP 3, it has been proposed that the nomenclature for this condition should be changed to “autoimmune PAP” rather than “idiopathic PAP” 4. Secondary or hereditary PAP is not associated with GM-CSF autoantibodies but develops as a consequence of a separate underlying disorder or genetic background 5. Recently, we demonstrated that the characteristic high-resolution computed tomography (HRCT) findings in secondary PAP are distinct from those in autoimmune PAP 6. However, physicians may not suspect secondary PAP, even when encountering unexplained pulmonary opacities on chest radiograph or computed tomography in patients with pre-existing haematological or infectious diseases, since there is little information available on the clinical features. Here, we outline the clinical features of adult-onset secondary PAP based on our database of 40 pre-mortem cases in which serum GM-CSF autoantibodies were negative, and compare them with other cases in the literature. A total of 404 patients with pre-mortem cytologically or pathologically proven PAP were registered in our study group between 1999 and 2009. We obtained consent from all treating physicians for each identified case according to the guidelines for epidemiological studies from the Ministry of Health, Labour and Welfare 7, and all clinical data were de-identified. 360 (89%) cases were positive for serum GM-CSF autoantibody. The clinical features of 223 of the cases were previously published as …

Endoscopic ultrasound-guided fine needle aspiration and endobronchial ultrasound-guided transbronchial needle aspiration: Are two better than one in mediastinal staging of non–small cell lung cancer?

OBJECTIVE The role of combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with a single bronchoscope is poorly understood. The purpose of the present study was to elucidate the roles of EBUS-TBNA and EUS-FNA with a single bronchoscope in the preoperative hilar and mediastinal staging of non-small cell lung cancer (NSCLC). METHODS A total of 150 patients with potentially resectable known or suspected NSCLC were enrolled in our prospective study. EBUS-TBNA was performed, followed by EUS-FNA, with an EBUS bronchoscope for N2 and N3 nodes≥5 mm in the shortest diameter on ultrasound images, in a single session. RESULTS EBUS-TBNA was performed for 257 lymph nodes and EUS-FNA for 176 lymph nodes. Of the 150 patients, 146 had a final diagnosis of NSCLC. Of these 146 patients, 33 (23%) had N2 and/or N3 nodal metastases. The sensitivity of EBUS-TBNA, EUS-FNA, and the combined approach per patient was 52%, 45%, and 73%, respectively (EBUS-TBNA vs the combined approach, P=.016, McNemars test). The corresponding negative predictive value was 88%, 86%, and 93%. Two patients (1%) developed severe cough from EBUS-TBNA. CONCLUSIONS The combined endoscopic approach with EBUS-TBNA and EUS-FNA is a safe and accurate method for preoperative hilar and mediastinal staging of NSCLC, with better results than with each technique by itself.

Ultrathin Bronchoscopy with Multimodal Devices for Peripheral Pulmonary Lesions. A Randomized Trial

RATIONALE The combination of an ultrathin bronchoscope, navigational technology, and endobronchial ultrasound (EBUS) seems to combine the best of mutual abilities for evaluating peripheral pulmonary lesions, but ultrathin bronchoscopes that allow the use of EBUS have not been developed so far. OBJECTIVES To compare the diagnostic yield of transbronchial biopsy under EBUS, fluoroscopy, and virtual bronchoscopic navigation guidance using a novel ultrathin bronchoscope with that using a thin bronchoscope with a guide sheath for peripheral pulmonary lesions. METHODS In four centers, patients with suspected peripheral pulmonary lesions less than or equal to 30 mm in the longest diameter were included and randomized to undergo transbronchial biopsy with EBUS, fluoroscopy, and virtual bronchoscopic navigation guidance using a 3.0-mm ultrathin bronchoscope (UTB group) or a 4.0-mm thin bronchoscope with a guide sheath (TB-GS group). MEASUREMENTS AND MAIN RESULTS A total of 310 patients were enrolled and randomized, among whom 305 patients (150, UTB group; 155, TB-GS group) were analyzed. The ultrathin bronchoscope could reach more distal bronchi than the thin bronchoscope (median fifth- vs. fourth-generation bronchi; P < 0.001). Diagnostic histologic specimens were obtained in 74% (42% for benign and 81% for malignant lesions) of the UTB group and 59% (36% for benign and 70% for malignant lesions) of the TB-GS group (P = 0.044, Mantel-Haenszel test). Complications including pneumothorax, bleeding, chest pain, and pneumonia occurred in 3% and 5% in the respective groups. CONCLUSIONS The diagnostic yield of the UTB method is higher than that of the TB-GS method. Clinical trial registered with www.umin.ac.jp/ctr/ (UMIN 000003177).

Endobronchial Ultrasound-Guided Transbronchial Biopsy Using Novel Thin Bronchoscope for Diagnosis of Peripheral Pulmonary Lesions

Background: The aim of this study was to evaluate the diagnostic utility of endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) using a novel 3.4-mm thin bronchoscope and a 1.4-mm ultrasonic probe for peripheral pulmonary lesions. Methods: A total of 86 patients with suspected peripheral lesions were included in this prospective study. EBUS-TBBs were performed using a prototype 3.4-mm thin bronchoscope and a 1.4-mm radial ultrasonic probe under fluoroscopic guidance. Results: Twelve patients with endobronchial lesions within the segmental bronchi and three patients who did not return to follow-up were excluded from this analysis. Thus, a total of 71 patients with peripheral pulmonary lesions (mean size, 31.2 ± 12.7 mm) were included in the final analysis. The mean bronchus level reached with the thin bronchoscope was 4.6 generations. Diagnostic histologic specimens were obtained in 49 of 71 patients (69%:80% for malignant lesions and 52% for benign lesions). A definitive diagnosis of malignancy for lesions ≥20 mm and lesions <20 mm was made in 82% (31 of 38) and 67% (four of six), respectively. There were no significant complications. Conclusion: The EBUS-TBB using a 3.4-mm thin bronchoscope and a 1.4-mm radial probe is feasible, accurate, and safe for the diagnosis of peripheral pulmonary lesions.

A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L

BACKGROUND Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC. PATIENTS AND METHODS The study treatment consisted of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point was objective response rate (ORR) by independent review. The secondary end points included overall survival (OS), progression-free survival (PFS), and safety. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05. RESULTS Forty patients from 21 centers were enrolled for this study from May 2008 to November 2010. Of the 39 patients evaluable for analysis, 36 were pathologically diagnosed by independent review, and 97% patients were eventually TC. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval 21%-53%; P = 0.031). The median PFS was 7.5 (6.2-12.3) months, while OS did not reach the median value. Major adverse event was grade 3-4 neutropenia in 34 patients (87%). There was no treatment-related death. CONCLUSIONS In this largest trial with TC, CbP showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, which is the current standard treatment of thymic neoplasm. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.

Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan

BackgroundSecondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown. The purpose of this study was to evaluate whether development of sPAP worsens the prognosis of MDS.MethodsThirty-one cases of sPAP and underlying MDS were retrospectively classified into mild and severe cases consisting of very low-/low-risk groups and intermediate-/high-/very high-risk groups at the time of diagnosis of MDS, according to the prognostic scoring system based on the World Health Organization classification. Next, we compared the characteristics, disease duration, cumulative survival, and prognostic factors of the groups.ResultsIn contrast to previous reports on the prognosis of MDS, we found that the cumulative survival probability for mild MDS patients was similar to that in severe MDS patients. This is likely due to the poor prognosis of patients with mild MDS, whose 2-year survival rate was 46.2%. Notably, 75% and 62.5% of patients who died developed fatal infectious diseases and exacerbation of PAP, respectively, suggesting that the progression of PAP per se and/or PAP-associated infection contributed to poor prognosis. The use of corticosteroid therapy and a diffusing capacity of the lung for carbon monoxide of less than 44% were predictive of poor prognosis.ConclusionDevelopment of sPAP during the course of MDS may be an important adverse risk factor in prognosis of patients with mild MDS.

Randomized Study of Endobronchial Ultrasound-Guided Transbronchial Biopsy: Thin Bronchoscopic Method versus Guide Sheath Method

Introduction: In endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB), techniques using a thin bronchoscope or a guide sheath have been proposed for accurate biopsy instrument reinsertion into the bronchial route indicated by a radial ultrasonic probe. The purpose of this study was to compare the diagnostic yields of these techniques for peripheral pulmonary lesions. Methods: Patients with suspected peripheral pulmonary lesions were included in this prospective, randomized, noninferiority study and assigned to undergo EBUS-TBB under fluoroscopic guidance using a prototype 3.4-mm thin bronchoscope or a 4.0-mm bronchoscope with a guide sheath. Results: A total of 205 patients were enrolled and randomized, of whom 203 patients (101 thin bronchoscopic method; 102 guide sheath method) were included in the analysis. Diagnostic histologic specimens were obtained in 65% (41% for benign and 75% for malignant lesions) of the thin bronchoscopy group and 62% (25% for benign and 71% for malignant lesions) of the guide sheath group. Diagnostic performance of the thin bronchoscopic method was confirmed to be noninferior to the guide sheath method (difference in diagnostic yields, 3.6%; 90% confidence interval, −7.5 to 14.7%). Mean procedure time was significantly shorter in the thin bronchoscopy group than the guide sheath group (27 versus 33 minutes; p = 0.002). Complications including pneumothorax, moderate bleeding, and pneumonia occurred in 5% and 2% in the respective groups (p = 0.28). Conclusions: EBUS-TBB using the thin bronchoscope was noninferior to the guide sheath method for the diagnosis of peripheral pulmonary lesions and was associated with shorter procedural time.