Cryobiopsy with endobronchial ultrasonography using a guide sheath for peripheral pulmonary lesions and DNA analysis by next generation sequencing and rapid on-site evaluation.

BACKGROUND: The purpose of this study was to evaluate the diagnostic accuracy of Cryo with endobronchial ultrasonography using a guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPLs) to assess the volume of specimen, determine DNA sequencing analysis, and evaluate the utility of rapid on-site evaluation (ROSE). METHODS: Out of 30 patients assessed for eligibility, 23 were enrolled in this prospective study. The histological diagnostic yield of Cryo was evaluated and the volume was compared to that of trans-bronchial biopsy (TBB). DNA analysis of Cryo was performed using next generation sequencing (NGS). ROSE was compared with the final diagnosis. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy rate was 85%, 100%, 100%, 50%, 87% for Cryo and 80%, 100%, 100%, 42.9%, 82.6% for TBB, respectively. The mean volume was 0.078 cm3 for Cryo and 0.003 cm3 for TBB (p < 0.0001). All Cryo specimens provided sufficient quantity and quality of DNA for analysis by NGS. ROSE had a high sensitivity (70%), specificity (100%), PPV (100%), and diagnostic accuracy (73.9%). There were no clinically serious adverse events except mild bleeding in 4 cases. CONCLUSIONS: Cryo with EBUS-GS for PPLs is a safe and potentially useful diagnostic strategy. It has a high diagnostic yield, and provides significantly larger specimens than TBB. It also provides high quantity and quality of DNA for NGS and high concordance rate between ROSE and the final diagnosis.

The efficacy of transbronchial needle aspiration with endobronchial ultrasonography using a guide sheath for peripheral pulmonary lesions suspected to be lung cancer.

BACKGROUND: The efficacy of transbronchial needle aspiration (TBNA) with endobronchial ultrasonography using a guide sheath (EBUS-GS) for cases of peripheral pulmonary lesions (PPLs) has not been well established. The purpose of this study was to evaluate the efficacy of TBNA with EBUS-GS for PPLs. METHODS: We evaluated 130 patients suspected to have lung cancer who underwent transbronchial brushing (brushing), transbronchial biopsy (TBB), and TBNA with EBUS-GS. The pathological diagnostic yields of TBNA were compared to that of TBB and brushing. The histological diagnosis of TBNA was compared to that of surgical specimens. The results of epidermal growth factor receptor (EGFR) gene mutation in TBNA samples were compared to that in TBB or surgical specimens. RESULTS: The diagnostic yields of this study were 62.9% for brushing, 80.0% for TBB, and 77.1% for TBNA. Histological diagnosis was 84.8% for TBB and/or TBNA and pathological diagnosis was 86.7% for all the procedures. TBB and TBNA had significance higher than brushing (p < 0.05). TBB and TBNA had a tendency of higher diagnostic yields than brushing if EBUS probe was adjacent to PPLs (p = 0.058). Histological evaluations were obtained from TBNA specimens from 50 of 105 patients (47.6%) and these were identical to those of surgical specimens from 29 of 32 patients (90.6%). The results of EGFR gene mutation in TBNA specimens were identical to the same tissue obtained by surgery or TBB. CONCLUSIONS: TBNA with EBUS-GS for PPLs was a useful tool for accurate diagnosis and EGFR gene mutation analysis. This method may improve diagnostic accuracy and be useful for molecular testing. This study was approved by the institutional review board (Date of approval: May 27, 2013, approval number: 2816) of Tokyo Women's Medical University Hospital.

Intravenous Immunoglobulin Monotherapy for Granulomatous Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.

Effectiveness of Combined Therapy with Pirfenidone and Erythromycin for Unclassifiable Interstitial Pneumonia Induced by HTLV-1-associated Bronchioloalveolar Disorder (HABA).

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus involved in the pathogenesis of adult T-cell leukemia (ATL) and HTVL-1-associated bronchioloalveolar disorder (HABA). The clinical and pathological findings of HABA have been characterized as either a diffuse panbronchiolitis (DPB) pattern or idiopathic interstitial pneumonia (IIP) pattern. Treatments for HABA include corticosteroids for the IIP pattern and erythromycin for the DPB pattern. We herein report a case of HABA-associated unclassifiable interstitial pneumonia that improved with combined therapy with pirfenidone and erythromycin. This is the first report on the effectiveness of combined therapy with pirfenidone and erythromycin for HABA.

FISH analysis of intrapulmonary malignant mesothelioma without a clinically detectable primary pleural lesion: an autopsy case.

Patients with malignant mesothelioma typically present with a pleural effusion or pleural thickening and masses. A rare autopsy case of mesothelioma presenting with multiple bilateral lung nodules without clinically detectable pleural lesions is presented. A definitive diagnosis of the video-assisted thoracic surgery specimen could not be made, though a pattern of fibrosis mimicking organizing pneumonia was identified. Despite corticosteroid therapy, follow-up chest computed tomography showed enlargement of multiple nodules accompanied by the appearance of pleural thickening and effusions. The patient died of respiratory failure 11 months after initial presentation. Autopsy and retrospective analysis of the video-assisted thoracic surgery specimen using a p16 fluorescence in situ hybridization assay showed p16 homozygous deletion. The final diagnosis was sarcomatoid mesothelioma, and the lung nodules were intrapulmonary metastases from a clinically undetectable pleural sarcomatoid mesothelioma. It is important both to consider the possibility of mesothelioma with unusual clinical, radiological and pathological presentations and to remember that p16 fluorescence in situ hybridization analysis can play an important role in the diagnosis of mesothelioma.

STA-MCA bypass for the treatment of ischemic stroke.

It is considered controversial whether superficial temporal artery (STA)-middle cerebral artery (MCA) bypass affects the outcome of patients with ischemic stroke. This prospective study was undertaken to demonstrate the effect of STA-MCA bypass on the cerebral blood flow and neurological status of the patients with ischemic stroke. Seventy-five patients underwent unilateral or bilateral STA-MCA bypass surgery. The selection of the patients closely adhered to the criteria of the Japan EC-IC Bypass Trial (JET). Cerebral blood flow (CBF) before and after Diamox administration was measured by single photon emission computed tomography (SPECT) using iodine-123-N-isopropyl-p-iodoamphetamine (IMP). MRI, contrast-enhanced 3D CT scans, and angiography were performed on each patient pre- and postoperatively. Bypass surgery was successfully done in all patients. CBF was significantly increased after STA-MCA bypass (P < 0.05). In addition, reservation of CBF was significantly improved after STA-MCA bypass (P < 0.05). Patients with transient ischemic attack (TIA) did not experience recurrence of such episodes after STA-MCA bypass. The neurological deficit was unchanged in patients with complete stroke after bypass surgery. However, the NIH stroke scale was significantly improved after bypass surgery (P < 0.01). In addition, the satisfaction rate of treatment as assessed by the patients themselves was very high after STA-MCA bypass (>90%) compared to the conservative treatment group (<50%). STA-MCA bypass still plays a limited role in the treatment of ischemic stroke, but may become a bright hope in depressed patients after cerebral ischemia.