Minimally invasive mediastinal staging of non-small cell lung cancer

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure widely used for the diagnosis and staging of primary lung cancer. This review focuses on the role of EBUS-TBNA in minimally invasive mediastinal staging, restaging after induction therapy, and procedure-related issues. To better understand the role of EBUS-TBNA, one must consider issues of sedation and rapid onsite examination, sonographic features during the procedure, the number of aspirations per lymph node, and the thoroughness of the procedure. A literature review indicated that EBUS-TBNA showed equivalent or even superior performance to mediastinoscopy in the mediastinal staging of non-small cell lung cancer (NSCLC). Combining endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or the transesophageal approach using an EBUS bronchoscope (EUS-B-FNA) with EBUS-TBNA can provide additional diagnostic benefits. A recent guideline recommended endosonography over mediastinoscopy as the initial procedure for mediastinal nodal staging in patients with NSCLC with abnormal mediastinal and/or hilar lymph nodes on chest computed tomography (CT) or positron emission tomography/CT. The diagnostic sensitivity of EBUS-TBNA for restaging after induction therapy in patients with stage IIIA-N2 NSCLC was lower than that of initial staging. It appears reasonable to perform EBUS-TBNA first for initial mediastinal staging and reserve mediastinoscopy for restaging after induction therapy

Immune Regulatory Function of Cancer-Associated Fibroblasts in Non-small Cell Lung Cancer

Background Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors

The Prevalence and Evolution of Anemia Associated with Tuberculosis

Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (≤65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8±113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment

Molecular Evolution Patterns in Metastatic Lymph Nodes Reflect the Differential Treatment Response of Advanced Primary Lung Cancer

Tumor heterogeneity influences the clinical outcome of patients with cancer, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six patients with lung cancer using whole-exome sequencing and RNA sequencing. Although somatic single-nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomic location of the tumors. Four of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer. Cancer Res; 76(22); 6568-76. ©2016 AACR

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength

First results from the HAYSTAC axion search

The axion is a well-motivated cold dark matter (CDM) candidate first postulated to explain the absence of $CP$ violation in the strong interactions. CDM axions may be detected via their resonant conversion into photons in a "haloscope" detector: a tunable high-$Q$ microwave cavity maintained at cryogenic temperature, immersed a strong magnetic field, and coupled to a low-noise receiver. This dissertation reports on the design, commissioning, and first operation of the Haloscope at Yale Sensitive to Axion CDM (HAYSTAC), a new detector designed to search for CDM axions with masses above $20$ $\mu\mathrm{eV}$. I also describe the analysis procedure developed to derive limits on axion CDM from the first HAYSTAC data run, which excluded axion models with two-photon coupling $g_{a\gamma\gamma} \gtrsim 2\times10^{-14}$ $\mathrm{GeV}^{-1}$, a factor of 2.3 above the benchmark KSVZ model, over the mass range $23.55 < m_a < 24.0$ $\mu\mathrm{eV}$. This result represents two important achievements. First, it demonstrates cosmologically relevant sensitivity an order of magnitude higher in mass than any existing direct limits. Second, by incorporating a dilution refrigerator and Josephson parametric amplifier, HAYSTAC has demonstrated total noise approaching the standard quantum limit for the first time in a haloscope axion search.Comment: Ph.D. thesis. 346 pages, 58 figures. A few typos corrected relative to the version submitted to ProQues

Prognostic Factors for Endotracheal Silicone Stenting in the Management of Inoperable Post-Intubation Tracheal Stenosis

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Sequential Bilateral Lung Resection in a Patient with Mycobacterium Abscessus Lung Disease Refractory to Medical Treatment

Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of M. abscessus lung disease can be problematic. Surgical resection has been tried for patients with localized M. abscessus lung disease refractory to medical treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease who had been diagnosed and treated three times for pulmonary tuberculosis. She was initially diagnosed as having M. intracellulare lung disease; however, M. abscessus was isolated after several months of medication. She had multiple bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly isolated from her sputa despite prolonged treatment with clarithromycin, ethambutol, moxifloxacin, and amikacin. She improved only after sequential bilateral lung resection. Based on the experience with this patient, we suggest that, if medical treatment fails, surgical resection of a diseased lung should be considered even in patients with bilateral lesions

Acquired Omental Cystic Lymphangioma after Subtotal Gastrectomy: A Case Report

We herein describe a case of cystic lymphangioma in the greater omentum of the remnant stomach, which is thought it to be related with subtotal gastrectomy 10 yr ago for early gastric cancer. A 76-yr-old man was admitted to our department with postprandial abdominal discomfort and bowel habit change. Intraabdominal multilocular cystic mass was detected by ultrasonography and computed tomography. We performed a complete En-bloc tumor resection including spleen and distal pancreas, and histological examination confirmed cystic lymphangioma originated from the greater omentum of the remnant stomach. Although the etiology of omental lymphangioma remains largely unclear, these findings suggested strongly that obstruction of the lymphatic vessels after gastric resection for gastric carcinoma might be the most plausible cause. The surgical extirpation with resection of organs involved appears to be a treatment of choice for such unusual case