Characterizing soluble immune checkpoint molecules and TGF-ß1,2,3 in pleural effusion of malignant pleural mesothelioma.

The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-ß isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the levels of six molecules, clinicopathological characteristics, and efficacy of immune checkpoint inhibitors. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-ß1, TGF-ß2, and TGF-ß3 were variably produced in PE of FP (n = 34) and MPM (n = 79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-ß2 level in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-ß1 and TGF-ß3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.

Phase angle as an indicator of physical activity in patients with stable chronic obstructive pulmonary disease.

OBJECTIVES: Phase angle (PhA) reflects cell membrane integrity and vitality and is an indicator of sarcopenia. PhA is associated with physical function in patients with stable chronic obstructive pulmonary disease (COPD). To our knowledge, the association between PhA and physical activity (PA) has not been investigated. Therefore, the aim of this study was to investigate whether PhA reflects PA in patients with COPD. METHODS: This single-center, cross-sectional, observational study included 103 patients with stable COPD (87 men; mean age, 74.7 ± 8.1 y; mean forced expiratory volume in 1s %predicted value, 58.9 ± 20.4%). PhA was measured by bioelectrical impedance analysis. Patients were stratified into low (n = 54) and high (n = 49) PhA groups based on median values (4.3° ± 0.6° and 5.4° ± 0.5°, respectively). PA was calculated as the average daily duration of high-intensity light PA (HLPA; 2.0-2.9 metabolic equivalents [METs] of PA) and moderate- to vigorous-intensity PA (MVPA; >3 METs). Correlation and multivariate analyses using multiple regression analysis were performed to confirm the association between PhA and PA. RESULTS: The high-PhA group demonstrated greater HLPA (104.4 [16.5-332.5] versus 131.3 [61.1-328.7] min, P = 0.005) and MVPA (19.5 [4.7-96.0] versus 46.6 [8.9-139.3] min, P < 0.001) than the low-PhA group. PhA was positively correlated with HLPA (r = 0.32, P < 0.001) and MVPA (r = 0.49, P < 0.001). MVPA (ß = 0.178, P = 0.029) and HLPA (ß = 0.158, P = 0.026) were associated with PhA independent of age, sex, body mass index, respiratory function, muscle strength, skeletal muscle mass index, and 6-min walking distance. CONCLUSION: In patients with COPD, PhA may reflect PA as well as muscle function.

Assessing the efficacy of saline flush in frequency-domain optical coherence tomography for intracoronary imaging.

BACKGROUND: The increased amount of contrast media in frequency-domain optical coherence tomography (FD-OCT) imaging during percutaneous coronary intervention (PCI) has raised potential concerns regarding impairment of renal function. OBJECTIVES: This study aimed to evaluate the effectiveness of heparinized saline flush in FD-OCT-guided PCI and identify clinical factors contributing to optimal image quality. METHODS: We retrospectively collected 100 lesions from 90 consecutive patients, and a total of 200 pullbacks were analyzed for the initial and final evaluation in which saline was used as the flushing medium. RESULTS: The study population had a mean age of 73, with 52% having chronic kidney disease (CKD). The median amount of contrast used was 28 ml, and no complications were observed associated with saline flush OCT. Imaging quality was then categorized as excellent, good, or unacceptable. Among the total runs, 87% demonstrated clinically acceptable image quality, with 66.5% classified as excellent images and 20.5% classified as good images. Independent predictors of excellent images included lumen area stenosis ≥ 70% (adjusted odds ratio [OR] 2.37, 95% confidence interval [CI] 1.02-5.47, P = 0.044), and the use of intensive flushing (adjusted OR 2.06, 95% CI 1.11-3.86, P = 0.023) defined as a deep engagement of guiding catheter (GC) or a selective insertion of guide extension catheter (GE). Intensive flushing was performed in 60% of the total pullbacks, and it was particularly effective in improving image quality in the left coronary artery (LCA). CONCLUSION: The use of saline flush during FD-OCT imaging was safe and feasible, which had a benefit in renal protection with adequate imaging quality.

Cold atmospheric nitrogen plasma induces metal-initiated cell death by cell membrane rupture and mitochondrial perturbation.

Cold atmospheric plasma (CAP) is a novel biomedical tool used for cancer therapy. A device using nitrogen gas (N2 CAP) produced CAP that induced cell death through the production of reactive nitrogen species and an increase in intracellular calcium. In this study, we investigated the effect of N2 CAP-irradiation on cell membrane and mitochondrial function in human embryonic kidney cell line 293T. We investigated whether iron is involved in N2 CAP-induced cell death, as deferoxamine methanesulfonate (an iron chelator) inhibits this process. We found that N2 CAP induced cell membrane disturbance and loss of mitochondrial membrane potential in an irradiation time-dependent manner. BAPTA-AM, a cell-permeable calcium chelator, inhibited N2 CAP-induced loss of mitochondrial membrane potential. These results suggest that disruption of intracellular metal homeostasis was involved in N2 CAP-induced cell membrane rupture and mitochondrial dysfunction. Moreover, N2 CAP irradiation generated a time-dependent production of peroxynitrite. However, lipid-derived radicals are unrelated to N2 CAP-induced cell death. Generally, N2 CAP-induced cell death is driven by the complex interaction between metal movement and reactive oxygen and nitrogen species produced by N2 CAP.

A quantitative analysis of long-term follow-up computed tomography of idiopathic pulmonary fibrosis: the correlation with the progression and prognosis.

BACKGROUND: Quantitative analyses of computed tomography (CT) images using computer-aided detection (CAD) are correlated with visual assessments and pulmonary function test findings and might be useful for predicting the prognosis of patients with idiopathic pulmonary fibrosis (IPF). PURPOSE: To evaluate the association between the quantitative analysis of long-term follow-up CT of IPF and the progression and prognosis. MATERIAL AND METHODS: A total of 48 patients with IPF who received over one year of follow-up CT were included in this study. The results of quantitative analyses (emphysema, ground-glass attenuation [GGA], consolidation, reticulation, and honeycombing) using a CAD software program of initial and follow-up CT findings were evaluated, and the association with the progression of the total lesion of IPF and prognosis using Spearman's rank correlation and Cox regression analyses was considered. RESULTS: Results of quantitative analyses of consolidation, reticulation, honeycombing, and the total lesion on initial CT were correlated with progressive changes in the total lesion of IPF per year (r = 0.4375, 0.4128, 0.4649, and 0.4095, respectively). The results of quantitative analyses of honeycombing (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03-1.89, P = 0.0314) and GGA (HR = 0.85, 95% CI = 0.72-0.99, P = 0.0384) at initial CT were prognostic factors according to a multivariate Cox regression analysis. CONCLUSION: The quantitative analysis of honeycombing using a CAD software program of CT findings may be useful for predicting the progression and prognosis of patients with IPF.

Preoperative neutrophil-to-lymphocyte ratio correlates with PD-L1 expression in immune cells of patients with malignant pleural mesothelioma and predicts prognosis.

We assessed the prognostic value of five complex inflammatory and nutritional parameters, namely neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), C-reactive protein-to-NLR ratio (C/NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) using data from patients with malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP). Moreover, the correlation between these five parameters and programmed cell death protein 1 ligand-1 (PD-L1) expression in the tumor microenvironment was evaluated. This study included consecutive MPM patients who underwent EPP. The histological subtype of the eligible patients (n = 61) correlated with all five parameters. Moreover, the PD-L1 expression scores for immune cells correlated with NLR and PLR, and the PD-L1 expression scores for both tumor cells and immune cells were inversely correlated with both PNI and LMR. Univariate analysis elucidated that NLR, PNI, and C/NLR were predictors of 5-year overall survival (OS), and multivariate analysis revealed that NLR was an independent predictor of 5-year OS, suggesting that NLR is a preoperative, prognostic factor for patients with MPM who are scheduled for EPP. To the best of our knowledge, this is the first study to evaluate the prognostic potentials of NLR, PNI, C/NLR, PLR, and LMR simultaneously in patients with MPM who underwent EPP.

Epstein-Barr virus detection in endoscopic submucosal dissection-proven early gastric cancer with mixed-type histology.

BACKGROUNDS: Early gastric cancer (EGC) with mixed-type histology is a significant risk factor for additional surgery after endoscopic submucosal dissection (ESD). On the other hand, Epstein-Barr virus-associated gastric cancer (EBVaGC) with mixed-type histology is a favorable risk factor with regard to lymph node metastasis. METHODS: We performed EBV detection in 13 ESD-proven lesions in 13 cases of early gastric cancer with mixed-type histology using EBV-encoded small RNA1 in situ hybridization (EBER1 ISH). RESULTS: EBVaGC was diagnosed in only one (7.7%) of the tested lesions. That EBVaGC patient underwent surgery and there was no residual lesion and no lymph metastasis. EBVaGC is not frequent in EGC with mixed-type histology. CONCLUSIONS: EBV testing of gastric biopsy specimens seems not to be useful to predict the mixed-type histology results of ESD. However, EBV testing for ESD specimens of EGC with mixed-type histology is expected to be useful for avoiding excessive additional surgery.

Effects of tumor-infiltrating CD8+ T cells, PD1/PD-L1 axis, and expression patterns of HLA class I on the prognosis of patients with malignant pleural mesothelioma who underwent extra-pleural pneumonectomy.

Programmed cell death protein-1 (PD1), PD1 ligand 1 (PD-L1), and human leukocyte antigen (HLA) class I molecule play pivotal roles in T cell-induced anti-tumor immunity; however, the clinical impact of these parameters in resected malignant pleural mesothelioma (MPM) cases is unknown. We immunohistochemically evaluated the tumor infiltrated lymphocytes (TILs), PD1/PD-L1 axis, and expression of HLA class I in resected specimens from 58 patients with MPM who underwent extra-pleural pneumonectomy (EPP). Higher infiltration of CD3-TIL, CD8-TIL, and PD1-TIL, loss of HLA class I, and overexpression of PD-L1 by tumor cells (PD-L1 TC) or immune cells (PD-L1 IC) were observed in 34 (58.6%), 27 (46.6%), 41 (70.7%), 45 (77.6%), 29 (50.0%), and 33 (56.4%) of 58 cases, respectively. Interestingly, the CD3-TIL score positively correlated with PD-L1 TC and PD1-TIL scores. HLA class I expression level was inversely correlated with the expression levels of PD-L1 TC and PD-L1 IC. Multivariate analysis showed that age, histology, and node metastasis were independent prognostic factors for 5-year overall survival (OS) and loss of HLA class I coincided with a positive prognosis (p = 0.011). The concomitant lack of infiltrating CD8+ T cells with no loss of HLA class I predicted worse 5-year OS (p = 0.007). Moreover, cluster classifications among multiple immunoparameters showed that categories among CD3/PD-L1 TC/HLA class I (p = 0.043), CD8/PD1/HLA class I (p = 0.032), CD8/PD-L1 TC/HLA class I (p = 0.011), and PD1/PD-L1 TC/HLA class I (p = 0.032) predicted 5-year OS in EPP cases for MPM. These immunoparameters could guide surgical indications for patients with MPM.

Prognostic values of preoperative C-reactive protein, albumin, and neutrophil ratios in patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy.

INTRODUCTION: A preoperative validation system for predicting the clinical outcome of extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) is required, as EPP for MPM is one of the most invasive operation types. Recently, several inflammatory and nutritional parameters, such as C-reactive protein (CRP) and albumin, have been re-focused on as useful prognostic factors for several types of cancer; however, few of these reports involved MPM. METHODS: As a retrospective study, clinicopathological characteristics and preoperative inflammatory and nutritional parameters were calculated in consecutive patients with MPM who underwent EPP. The prognostic value of the variables was examined using Cox regression, and the candidate preoperative parameters were entered into a multivariate model to determine their independent effects. RESULTS: Of the 61 eligible cases, the CRP/albumin ratio (CAR) was associated with histology, and the CRP index multiplied by the neutrophil ratio (C-NR index) was associated with histology and pathological stage. Patients with CAR >0.125 had a significantly poor survival outcome, and patients with a C-NR index >0.58 also had a significantly poor prognosis. Multivariate analysis showed that age, histology, CRP, albumin, CAR, and C-NR index were independent predictors of 5-year overall survival. CONCLUSION: Our results demonstrated that the CAR and C-NR indices are promising preoperative predictive parameters for the clinical outcomes of EPP in patients with MPM.

A Novel Class of HIV-1 Inhibitors Targeting the Vpr-Induced G2-Arrest in Macrophages by New Yeast- and Cell-Based High-Throughput Screening.

The human immunodeficiency virus type 1 (HIV-1) accessory protein, Vpr, arrests the cell cycle of the G2 phase, and this Vpr-mediated G2 arrest is implicated in an efficient HIV-1 spread in monocyte-derived macrophages. Here, we screened new candidates for Vpr-targeting HIV-1 inhibitors by using fission yeast- and mammalian cell-based high-throughput screening. First, fission yeast strains expressing the HIV-1 Vpr protein were generated and then treated for 48 h with 20 µM of a synthetic library, including 140,000 chemical compounds. We identified 268 compounds that recovered the growth of Vpr-overexpressing yeast. The selected compounds were then tested in mammalian cells, and those displaying high cytotoxicity were excluded from further cell cycle analysis and imaging-based screening. A flow cytometry analysis confirmed that seven compounds recovered from the Vpr-induced G2 arrest. The cell toxicity and inhibitory effect of HIV-1 replication in human monocyte-derived macrophages (MDM) were examined, and three independent structural compounds, VTD227, VTD232, and VTD263, were able to inhibit HIV-1 replication in MDM. Furthermore, we showed that VTD227, but not VTD232 and VTD263, can directly bind to Vpr. Our results indicate that three new compounds and their derivatives represent new drugs targeting HIV-1 replication and can be potentially used in clinics to improve the current antiretroviral therapy.

Clinicopathological feature of a resected large mixed squamous cell and glandular papilloma: A case report.

INTRODUCTION AND IMPORTANCE: Solitary endotracheal papilloma is a rare benign lung tumor. It is classified into the following three histological subtypes: squamous cell papilloma (SP), glandular papilloma (GP), and mixed squamous cell and glandular papilloma (MSGP). MSGP is the rarest among them. Herein, we describe a case of a large MSGP. CASE PRESENTATION: A 59-year-old woman underwent computed tomography for the examination of cough, and an 8.2-cm-sized lung mass was noted in the left lingual segment. Bronchoscopy revealed that the left B5 lumen was completely occluded by a tumor. Transbronchial lung biopsy suggested GP; thereafter, a left upper lobectomy was performed. Macroscopic findings showed that the dilated B5 lumen was filled with cauliflower-like tumors. Histopathological findings showed that the majority of the tumors had pseudostratified columnar epithelium, while some had stratified squamous epithelium. The patient was diagnosed with MSGP. Although koilocytosis-like changes, such as perinuclear halo and nuclear deformation, were observed in some portions of the squamous epithelium, immunohistochemical staining was negative for human papillomavirus (HPV). CLINICAL DISCUSSION: HPV infection is reportedly associated with SP but not with GP and MSGP. Therefore, MSGP is considered to be caused by squamous metaplasia of a part of GP; this hypothesis is consistent with the present case. However, only one case of MSGP with HPV infection was recently reported, and the etiology and histological features of MSGP remain unclear. CONCLUSION: There are few reported cases of MSGP, and further case reports are needed to clarify its pathogenesis.

Rapid development and rupture of a pneumatocele caused by pulmonary dissection in the early postoperative period of lung resection: a case report.

Air leakage after lung resection is a common complication usually caused by direct injury to the lung parenchyma. Herein we illustrate a case of pneumatocele that developed rapidly in the right middle lobe and ruptured 16 days after right upper lobectomy. A 73-year-old man with chronic obstructive pulmonary disease underwent thoracoscopic right upper lobectomy and partial thymectomy for primary lung cancer and thymic nodules, respectively. Although a small amount of air leakage was observed after the operation, air leakage completely improved on postoperative day (POD) 2, and the chest drain tube was removed on POD 3. The patient's condition was complicated with eosinophilic pneumonia. Steroid therapy was started on POD 13. Dyspnea suddenly developed immediately after defecation on POD 16. Computed tomography (CT) scan showed a large pneumatocele in the right middle lobe, which was not found by CT scan on POD 11. He underwent reoperation on POD 20, and a large thick-walled pneumatocele in the right middle lobe was directly sewn. Histopathologically, the wall of bulla consisted of thickened visceral pleura and thin lung parenchyma, suggesting that this pneumatocele was induced by dissection of subpleural lung parenchyma.

Antineutrophil cytoplasmic antibody-negative granulomatosis with polyangiitis localized to the lungs.

Patients with granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, sometimes exhibit no clinical features. Here, we describe a case of antineutrophil cytoplasmic antibody (ANCA)-negative GPA presenting with only lung granuloma. A 55-year-old woman with a right upper lung mass underwent lobectomy for suspected lung cancer; however, only granuloma was detected, and the etiology was not identified. Serum ANCA results were negative. Four years postoperatively, another pulmonary nodule appeared in the left lung's apex. The kidneys and sinuses were not impaired, but re-examination of the resected specimen revealed necrotizing vasculitis and granulomas around the vessels. Thus, the patient was diagnosed with GPA localized to the lungs. Although this was a non-life-threatening disease, the patient was administered oral prednisolone (PSL) and intravenous cyclophosphamide (IVCY) to prevent fatal complications of GPA as she was non-elderly and had no comorbidities, leading to a decrease in the mass size. Detailed re-examination by expert pulmonary pathologists could aid in GPA diagnosis when clinical features are absent, as in our case. In patients with granulomas of unknown etiology, a careful multidisciplinary approach is pivotal in the diagnosis. If patients tolerate adverse effects, a PSL and IVCY combination may prevent fatal outcomes, even in patients with non-life-threatening disease.

Huntingtin-Interacting Protein 1 Promotes Vpr-Induced G2 Arrest and HIV-1 Infection in Macrophages.

Human immunodeficiency virus type 1 (HIV-1) modulates the host cell cycle. The HIV-1 accessory protein Vpr arrests the cell cycle at the G2 phase in dividing cells, and the ability of Vpr to induce G2 arrest is well conserved among primate lentiviruses. Additionally, Vpr-mediated G2 arrest likely correlates with enhanced HIV-1 infection in monocyte-derived macrophages. Here, we screened small-interfering RNA to reveal candidates that suppress Vpr-induced G2 arrest and identified Huntingtin-interacting protein 1 (HIP1) required for efficient G2 arrest. Interestingly, HIP1 was not essential for Vpr-induced DNA double-strand breaks, which are required for activation of the DNA-damage checkpoint and G2 arrest. Furthermore, HIP1 knockdown suppressed HIV-1 infection in monocyte-derived macrophages. This study identifies HIP1 as a factor promoting Vpr-induced G2 arrest and HIV-1 infection in macrophages.

[A Case of Tumor Embolization to the Internal Iliac Vein Four Years after the Surgery for Rectal Cancer].

60-year-old man was admitted to our hospital with a chief complaint of melena. Lower gastrointestinal endoscopy revealed a type 2 tumor on the anterior wall of the rectum(Rb). He was referred to our department, and he underwent abdominoperineal rectal resection with D3 dissection and right lateral node dissection for Rb, cT2, N0, M0 intestinal cancer. Pathological diagnosis was a tub2, pT2, N0, Ly0, V0, pDM0(30 mm), pPM0(160 mm), pR0, pStage Ⅰ cancer. Therefore, postoperative adjuvant chemotherapy was not performed. Subsequent follow-up examinations were conducted on a regular basis to confirm no recurrence. However, 4 years after the surgery, high levels of tumor markers, such as CEA(59.2 ng/mL) and CA19-9(75.5 U/mL), were detected. CT showed tumor embolism to the internal iliac vein and multiple lung metastases. After IVC filter placement, chemoradiotherapy was performed. Although the tumor embolism disappeared, multiple lung metastases increased. Additionally, brain metastasis appeared 6 years after the operation. After that, according to the policy of BSC, he died 7 years after the surgery.

Malignant pleural mesothelioma with heterologous elements.

AIMS: Malignant pleural mesothelioma with heterologous elements (such as osseous, cartilaginous or rhabdomyoblastic differentiation) is very rare. We tried to differentiate such mesothelioma cases from extraskeletal pleural osteosarcoma, which is very challenging. METHODS: We compared 10 malignant pleural mesotheliomas (three biphasic and seven sarcomatoid types) with two pleural osteosarcomas using clinicopathological and immunohistochemical methods, and also fluorescence in situ hybridisation (FISH) to examine for homozygous deletion of p16. RESULTS: The median age was 72 years for mesotheliomas, and 69 years for osteosarcoma. For mesothelioma, eight cases were male and two were female. Growth was diffuse in all mesothelioma cases except case 10, where it was localised, as it was for the two osteosarcomas. Among mesothelioma cases, 80% displayed osteosarcomatous and 60% chondromatous elements, while 10% exhibited rhabdomyoblastic ones. Immunohistochemical labelling for calretinin and AE1/AE3 was present in 8/10 and 7/10 mesotheliomas, respectively, but in only one osteosarcoma. Loss of methylthioadenosine phosphorylase was seen in 5/7 mesotheliomas. FISH analysis revealed homozygous deletion of p16 in 5/8 mesothelioma and 2/2 osteosarcoma. Median survival was 6.5 months after biopsy or surgical operation in mesothelioma, and 12 months after operation in osteosarcoma. CONCLUSIONS: Although median survival was longer for osteosarcoma than for malignant mesothelioma, we could not differentiate mesothelioma from pleural osteosarcoma on the combined basis of clinicopathological and immunohistochemical data, and FISH analysis. However, diffuse growth was more frequent in mesothelioma than in osteosarcoma.

Correlation between pleural tags on CT and visceral pleural invasion of peripheral lung cancer that does not appear touching the pleural surface.

OBJECTIVES: To evaluate the association between a sign and visceral pleural invasion (VPI) of peripheral non-small-cell lung cancer (NSCLC) that does not appear touching the pleural surface. METHODS: A total of 221 consecutive patients with NSCLC that did not appear touching the pleural surface, ≤ 3 cm in solid tumor diameter, and was surgically resected between January 2009 and December 2015 were included. We focused on the flat distortion of the tumor caused by an arch-shaped linear tag between the tumor and the pleura on CT and named it a bridge tag sign. We evaluated the associations between the clinicopathological features of the tumor, including the bridge tag sign, and VPI. We also evaluated the associations between histopathological findings and the bridge tag sign. The utility of the bridge tag sign in the diagnosis of VPI was statistically assessed. RESULTS: The bridge tag sign was observed in 48 (20.8%) patients. VPI was positive in 9 (4.1%) patients; among these, the bridge tag sign was positive in 8 patients. In multivariate analysis, a bridge tag sign was significantly associated with VPI. The bridge tag sign was associated with longer contact length of the pleura with the tumor and trapezoid type pleural retraction. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of VPI were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively. CONCLUSIONS: A bridge tag sign on CT might improve the accuracy of the prediction of VPI. KEY POINTS: • We present the bridge tag sign which is defined as a flat distortion of an NSCLC tumor by an arch-shaped linear tag between the tumor and chest wall or interlobar fissure. • The bridge tag sign was an independent predictive factor for visceral pleural invasion. • The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of visceral pleural invasion were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively.

Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps.

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract, and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Therefore, this study was done to assess the relationship of HRSV with A3.01 cells, a human CD4+ T cell line. Using flow cytometry and fluorescent focus assay, we found that A3.01 cells are susceptible but virtually not permissive to HRSV infection. Dequenching experiments revealed that the fusion process of HRSV in A3.01 cells was nearly abolished in comparison to HEp-2 cells, an epithelial cell lineage. Quantification of viral RNA by RT-qPCR showed that the replication of HRSV in A3.01 cells was considerably reduced. Western blot and quantitative flow cytometry analyses demonstrated that the production of HRSV proteins in A3.01 was significantly lower than in HEp-2 cells. Additionally, using fluorescence in situ hybridization, we found that the inclusion body-associated granules (IBAGs) were almost absent in HRSV inclusion bodies in A3.01 cells. We also assessed the intracellular trafficking of HRSV proteins and found that HRSV proteins colocalized partially with the secretory pathway in A3.01 cells, but these HRSV proteins and viral filaments were present only scarcely at the plasma membrane. HRSV infection of A3.01 CD4+ T cells is virtually unproductive as compared to HEp-2 cells, as a result of defects at several steps of the viral cycle: Fusion, genome replication, formation of inclusion bodies, recruitment of cellular proteins, virus assembly, and budding.

Intraoperative bronchial blood flow evaluation using indocyanine green fluorescence for bronchoplasty: A case report.

INTRODUCTION AND IMPORTANCE: Blood flow evaluation of bronchial arteries using indocyanine green fluorescence (ICG-FL) is rarely reported during pulmonary resection. We present the case of a patient with bronchiectasis and a history of bronchial artery embolization (BAE) for hemoptysis. Bronchial artery blood flow was evaluated using ICG-FL during lobectomy with bronchoplasty. CASE PRESENTATION: A 63-year-old woman presented with right middle lobe bronchiectasis (due to nontuberculous mycobacteriosis) and repeated hemoptysis, which had previously been corrected each time with hemostasis by BAE. Bronchoscopy revealed a swollen blood vessel proximal to the right middle lobe bronchus that was suspected of being the origin of bleeding. Right middle lobectomy with bronchoplasty was performed to prevent hemoptysis. ICG-FL was used to detect the patency of the right bronchial arteries, and the arteries surrounding the right middle lobe bronchus were ligated. The proximal side of the right middle lobe bronchus was cut in a deep wedge shape, and the bronchus was anastomosed. ICG-FL revealed that the blood supply was maintained at the bronchial anastomosis. No bronchial anastomotic leakage was observed after the surgery. CLINICAL DISCUSSION: The key to successful bronchoplasty is the maintenance of blood flow. Bronchial artery blood flow theoretically decreases after BAE. In this case, ICG-FL was able to detect bronchial artery patency before cutting the bronchus as well as the maintenance of blood flow at the bronchial anastomosis after bronchoplasty. CONCLUSION: Intraoperative blood flow evaluation of the bronchus using ICG-FL may reduce the risk of bronchial anastomotic leakage caused by ischemia after bronchoplasty.

Endoscopic and pathologic motifs for the clinical diagnosis of Epstein-Barr virus-associated gastric cancer.

Objectives: Based on the recent therapeutic trends for gastric cancer (GC), the clinical impact of the diagnosis of Epstein-Barr virus (EBV)-associated GC (EBVaGC) appears to be important. We retrospectively analyzed endoscopic and pathologic motifs of GC lesions to narrow the number of candidates for EBV testing. Methods: We performed EBV tests for 32 upper gastrointestinal lesions of 32 patients in the clinical setting. These tests were ordered by endoscopists or by pathologists without an endoscopist's order. EBV-encoded small RNA1 (EBER1) in situ hybridization was used for the EBV tests. The endoscopic motif for the EBV test was the location in the upper part of the stomach or remnant stomach, mainly the depressed type with a submucosal tumor-like protrusion of the lesion. The pathologic motif was carcinoma with lymphoid stroma (CLS) or CLS-like histology of the lesion. We retrospectively analyzed the results of EBV tests for the endoscopic and pathologic motifs. Results: The final pathological diagnoses of the 32 subjects were 26 GCs including CLS, gastric endocrine cell carcinoma, gastric hepatoid carcinoma, gastric T-cell lymphoma, gastritis of the remnant stomach, esophageal adenocarcinoma, and esophageal squamous cell carcinoma. When nontypical lesions were excluded, the EBER1-positive rate was 42.3% (11/26) in GCs. Of the 14 GC lesions ordered examined by endoscopists, three (21.4%) were EBVaGC. Eight of the 12 (66.7%) GCs ordered examined by pathologists were EBVaGC. Conclusions: The pathologic motif is expected to be useful and the endoscopic motif may be helpful for EBVaGC diagnosis.