Publications by authors named "Chang Young Lee"

168 Publications

Smart contact lens and transparent heat patch for remote monitoring and therapy of chronic ocular surface inflammation using mobiles.

Sci Adv 2021 Mar 31;7(14). Epub 2021 Mar 31.

Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Wearable electronic devices that can monitor physiological signals of the human body to provide biomedical information have been drawing extensive interests for sustainable personal health management. Here, we report a human pilot trial of a soft, smart contact lens and a skin-attachable therapeutic device for wireless monitoring and therapy of chronic ocular surface inflammation (OSI). As a diagnostic device, this smart contact lens enables real-time measurement of the concentration of matrix metalloproteinase-9, a biomarker for OSI, in tears using a graphene field-effect transistor. As a therapeutic device, we also fabricated a stretchable and transparent heat patch attachable on the human eyelid conformably. Both diagnostic and therapeutic devices can be incorporated using a smartphone for their wireless communications, thereby achieving instantaneous diagnosis of OSI and automated hyperthermia treatments. Furthermore, in vivo tests using live animals and human subjects confirm their good biocompatibility and reliability as a noninvasive, mobile health care solution.
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http://dx.doi.org/10.1126/sciadv.abf7194DOI Listing
March 2021

Experimental test of Babinet's principle in matter-wave diffraction.

Phys Chem Chem Phys 2021 Apr 15;23(13):8030-8036. Epub 2021 Feb 15.

Department of Physics, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.

We report on an experimental test of Babinet's principle in quantum reflection of an atom beam from diffraction gratings. The He beam is reflected and diffracted from a square-wave grating at near grazing-incidence conditions. According to Babinet's principle the diffraction peak intensities (except for the specular-reflected beam) are expected to be identical for any pair of gratings of complementary geometry. We observe conditions where Babinet's principle holds and also where it fails. Our data indicate breakdown conditions when either the incident or a diffracted beam propagates close to the grating surface. At these conditions, the incident or the diffracted He beam is strongly affected by the dispersive interaction between the atoms and the grating surface. Babinet's principle is also found to break down, when the complementary grating pair shows a large asymmetry in the strip widths. For very small strip widths, edge diffraction from half planes becomes dominant, whereas for the complementary wide strips the atom-surface interactions leads to a strong reduction of all non-specular diffraction peak intensities.
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http://dx.doi.org/10.1039/d0cp05694dDOI Listing
April 2021

Alkalide-Assisted Direct Electron Injection for the Noninvasive n-Type Doping of Graphene.

ACS Appl Mater Interfaces 2021 Jan 24;13(1):1270-1276. Epub 2020 Dec 24.

Department of Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

Although the doping of graphene grown by chemical vapor deposition is crucial in graphene-based electronics, noninvasive methods of n-type doping have not been widely investigated in comparison with p-type doping methods. We developed a convenient and robust method for the noninvasive n-type doping of graphene, wherein electrons are directly injected from sodium anions into the graphene. This method involves immersing the graphene in solutions of [K(15-crown-5)]Na prepared by dissolving a sodium-potassium (NaK) alloy in a 15-crown-5 solution. The n-type doping of the graphene was confirmed by downshifted G and 2D bands in Raman spectra and by the Dirac point shifting to a negative voltage. The electron-injected graphene showed no sign of structural damage, exhibited higher carrier mobilities than that of pristine graphene, and remained n-doped for over a month of storage in air. In addition, we demonstrated that electron injection enhances noncovalent interactions between graphene and metallomacrocycle molecules without requiring a linker, as used in previous studies, suggesting several potential applications of the method in modifying graphene with various functionalities.
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http://dx.doi.org/10.1021/acsami.0c19153DOI Listing
January 2021

The role of postoperative radiotherapy in stage II and III thymoma: a Korean multicenter database study.

J Thorac Dis 2020 Nov;12(11):6680-6689

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Complete resection is a standard treatment for patients with Masaoka-Koga stages II and III thymoma, however the role of postoperative radiotherapy (PORT) is controversial. We analyzed data collected from 4 Korean hospitals to determine the effectiveness of PORT in stage II and III thymoma patients.

Methods: Between January 2000 and December 2013, 1,663 patients underwent surgery for thymic tumors at the 4 hospitals. Among them, 668 patients (527 with stage II and 141 with stage III) were investigated, among whom, 443 received PORT (335 with stage II and 108 with stage III). Propensity score matching (PSM) was performed, and 404 patients (346 with stage II and 58 with stage III) were selected.

Results: Perioperative characteristics were similar in the PORT and non-PORT groups after PSM. On survival analysis of stage II patients, the PORT and non-PORT groups showed no difference in either 5-year recurrence-free survival (RFS) (96.3% 96.6%, P=0.622) or 5-year overall survival (OS) (94.6% 93.8%, P=0.839). However, among stage III patients, the PORT group showed significantly better 5-year RFS (75.7% 50.1%, P=0.040) and 5-year OS (86.5% 54.7%, P=0.001). On multivariate Cox regression analysis, PORT was a significant positive prognostic factor in terms of both RFS (P=0.005) and OS (P=0.004) in patients with stage III thymomas, but not in those with stage II disease (P=0.987 and 0.968, respectively).

Conclusions: PORT improved the RFS and OS in stage III thymoma patients, but showed no survival benefit in stage II patients.
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http://dx.doi.org/10.21037/jtd-20-1713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711424PMC
November 2020

Cervical spinal extradural arteriovenous fistula successfully treated using transarterial balloon-assisted coil embolization.

J Cerebrovasc Endovasc Neurosurg 2020 Sep 21;22(3):182-189. Epub 2020 Sep 21.

Department of Neurosurgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.

We present the case of a patient who developed compressive radiculopathy that was found to be associated with a spinal extradural arteriovenous fistula. The fistula was successfully obliterated with transarteiral balloon-assisted coiling, after which the patient was symptom-free. Although spinal extradural arteriovenous fistula is rare, this pathology should be considered in the differential diagnosis of spinal radiculopathy or myelopathy. Endovascular treatment appears to have been successful in resolving the symptoms associated with this pathology.
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http://dx.doi.org/10.7461/jcen.2020.22.3.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522392PMC
September 2020

Minipterional craniotomy for surgical clipping of anterior circulation aneurysms: compatibility between the feasibility, safety and efficiency.

J Cerebrovasc Endovasc Neurosurg 2020 Jun 30;22(2):65-77. Epub 2020 Jun 30.

Department of Neurosurgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.

Objective: The aim of this study was to assess the feasibility, safety and efficiency of minipterional craniotomy (MPT) for surgical clipping of anterior circulation aneurysms.

Methods: A retrospective study was conducted to compare the MPT from Jan 2015 to Dec 2018 and conventional pterional craniotomy (CPT) from Jan 2012 to Dec 2013 in unruptured intracranial aneurysms (UIA) and ruptured intracranial aneurysms (RIA). The feasibility and safety of MPT and CPT were assessed by analyzing medical records, radiologic imaging, and clinical outcomes. The efficiency of MPT and CPT were based on a survey research of temporomandibular dysfunction, facial nerve paralysis, and facial asymmetry.

Results: Total 628 patients who underwent 458 MPT (UIA:313, RIA:145) and 170 CPT (UIA: 106, RIA: 64) with anterior circulation aneurysms were included in this study. The baseline characteristics between MPT and CPT had no difference (>0.05). There was no difference in the incidence of postoperative hemorrhage or ischemic lesions between MPT and CPT (>0.05). The incidence of surgical wound infection was lower in MPT (0.4%) than CPT (3.5%) (=0.002). More than 90% of postoperative pain disappeared faster in MPT (14.25±4.83 days) than CPT (27.59±10.35 days), and the feeling of facial asymmetry in surgical side was also lower for MPT (1.7%) than CPT (7.6%) (<0.001). In the MPT, no patients presented with progress to chronic pain, masticatory disability, discomfort of maximal mouth opening or permanent facial palsy.

Conclusions: We suggest that MPT and CPT had similar clinical outcomes, and MPT showed better functional and cosmetic outcomes than CPT in terms of temporomandibular dysfunction, facial nerve paralysis, and facial asymmetry. Therefore, MPT for surgical clipping of anterior circulation aneurysms can be a compatible technique that satisfies the feasibility, safety and efficiency.
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http://dx.doi.org/10.7461/jcen.2020.22.2.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329563PMC
June 2020

Corrigendum to "Stepwise flowchart for decision making on sublobar resection through the estimation of spread through air space in early stage lung cancer" [Lung Cancer 142 (2020) 28-33].

Lung Cancer 2020 Aug 8;146:391. Epub 2020 Jul 8.

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Republic of Korea.

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http://dx.doi.org/10.1016/j.lungcan.2020.06.011DOI Listing
August 2020

Compartmentalized Arrays of Matrix Droplets for Quantitative Mass Spectrometry Imaging of Adsorbed Peptides.

Anal Chem 2020 07 2;92(13):8715-8721. Epub 2020 Jun 2.

Department of Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.

Mass spectrometry imaging (MSI) based on matrix-assisted laser desorption/ionization (MALDI) provides information on the identification and spatial distribution of biomolecules. Quantitative analysis, however, has been challenging largely due to heterogeneity in both the size of the matrix crystals and the extraction area. In this work, we present a compartmentalized elastomeric stamp for quantitative MALDI-MSI of adsorbed peptides. Filling the compartments with matrix solution and stamping onto a planar substrate extract and concentrate analytes adsorbed in each compartment into a single analyte-matrix cocrystal over the entire stamped area. Walls between compartments help preserve spatial information on the adsorbates. The mass intensity of the cocrystals directly correlates with the surface coverage of analytes, which enables not only quantitative analysis but estimation of an equilibrium constant for the adsorption. We demonstrate via MALDI-MSI relative quantitation of peptides adsorbed along a microchannel with varying surface coverages.
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http://dx.doi.org/10.1021/acs.analchem.9b05316DOI Listing
July 2020

Photoacoustic imaging to localize indeterminate pulmonary nodules: A preclinical study.

PLoS One 2020 21;15(4):e0231488. Epub 2020 Apr 21.

Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

Purpose: Diagnosis and resection of indeterminate pulmonary nodules (IPNs) is a growing challenge with increased utilization of chest computed tomography. Photoacoustic (PA) -guided surgical resection with local injection of indocyanine green (ICG) may have utility for IPNs that are suspicious for lung cancer. This preclinical study explores the potential of PA imaging (PAI) to detect ICG-labeled tumors.

Materials And Methods: ICG uptake by H460 lung cancer cells was evaluated in vitro. A phantom study was performed to analyze PA signal intensity according to ICG concentration and tissue thickness/depth using chicken breast. PA signals were measured up to 48 hours after injection of ICG (mixed with 5% agar) into healthy subcutaneous tissue, subcutaneous H460 tumors and right healthy lung in nude mice.

Results: Intracellular ICG fluorescence was detected in H460 cells co-incubated with ICG in vitro. The concentration dependence of the PA signal was logarithmic, and PA signal decline was exponential with increasing tissue depth. The PA signal of 2 mg/mL ICG was still detectable at a depth of 22 mm in chicken breast. The PA signal from ICG mixed with agar was detectable 48 hours post injection into subcutaneous tissue and subcutaneous H460 tumors in nude mice. Similar features of PA signals from ICG-agar in mice lung were obtained.

Conclusion: The results from this preclinical study suggests that PAI of injected ICG-agar may be beneficial for identifying deeply located tumors. These features may be valuable for IPNs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231488PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173852PMC
July 2020

Factors Affecting the Number of Stapler Cartridges in Complete Video-Assisted Thoracoscopic Surgery Lobectomy for Non-small Cell Lung Cancer.

Korean J Thorac Cardiovasc Surg 2020 Apr;53(2):53-57

Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Video-assisted thoracoscopic surgery (VATS) lobectomy has become the major surgical option for the treatment of non-small cell lung cancer (NSCLC). Endoscopic instruments such as stapler cartridges are essential for VATS procedures. In this study, we investigated the factors that affect the number of stapler cartridges used in VATS lobectomy.

Methods: A retrospective analysis was conducted of patients who underwent complete VATS lobectomy for NSCLC from January 2013 to December 2015.

Results: In total, 596 patients underwent complete VATS lobectomy. The average number of stapler cartridges used for VATS lobectomy was 5.3±1.9. The number of stapler cartridges used for VATS lobectomy was higher in men (5.5±1.9 vs. 5.0±18, p=0.006), those aged older than 70 years (5.5±2.1 vs. 5.1±1.7, p=0.038), those who underwent upper or middle lobectomy procedures (5.7±1.9 vs. 4.1±1.2, p<0.001), those with a higher fissure sum average (p<0.001), and those in whom surgery was performed by a surgeon with a preference for staplers (5.6±2.0 vs. 4.9±1.6, p<0.001).

Conclusion: The number of stapler cartridges required to perform VATS lobectomy in NSCLC patients appears to be influenced by sex, age, the location of the tumor, the degree of fissure development, and the surgeon's preference.
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http://dx.doi.org/10.5090/kjtcs.2020.53.2.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155176PMC
April 2020

Stepwise flowchart for decision making on sublobar resection through the estimation of spread through air space in early stage lung cancer.

Lung Cancer 2020 04 4;142:28-33. Epub 2020 Feb 4.

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Republic of Korea. Electronic address:

Objectives: The sensitivity for tumor spread through air space (STAS), an independent risk factor for locoregional recurrence after sublobar resection for lung cancer, has been relatively low in frozen sections. We aimed to determine predictors with high negative predictive value for the presence of STAS and to provide the flowchart in combination with these predictors for the decision-making for sublobar resection.

Materials And Methods: Between July 2015 and December 2017, 387 patients who underwent surgery for non-small cell lung cancer (NSCLC) with pathologic findings of the total masses measuring ≤ 2 cm were enrolled. The lesions were divided into two groups according to presence of STAS. We compared the preoperative characteristics, operative data, and developed a flowchart for STAS prediction using receiver operator characteristic curve analysis and multivariable logistic regression.

Results: The STAS-positive group (N = 111) had a significantly higher preoperative tumor size (1.70 [1.5] vs 1.50 [0.69], p < 0.001) and standardized uptake value tumor-to-liver (SUV T/L) ratio (1.40 [1.60] vs 0.60 [1.10], p < 0.001) and a significantly lower two-dimensional ground-glass opacity (GGO) percentage (35.86 [61.00] vs 78.14 [39.00], p < 0.001). Meanwhile, the STAS-negative group (N = 286) had higher lepidic predominance (41.6% vs. 1.8%, p < 0.001). We developed a flowchart for predicting STAS in combination with two-dimensional GGO percentage on computed tomography (CT), SUV T/L ratio on positron-emission CT, and lepidic predominant pattern. The sensitivity, specificity, and negative predictive value for STAS positivity were 79.3%, 68.5%, and 89.5%, respectively.

Conclusions: The stepwise flowchart using two-dimensional GGO percentage on CT, maximum SUV, and lepidic predominance might be helpful in selecting patients with early NSCLC for sublobar resection.
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http://dx.doi.org/10.1016/j.lungcan.2020.02.001DOI Listing
April 2020

Effects of Multidrug-resistant Bacteria in Donor Lower Respiratory Tract on Early Posttransplant Pneumonia in Lung Transplant Recipients Without Pretransplant Infection.

Transplantation 2020 04;104(4):e98-e106

Chest Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Multidrug-resistant (MDR) bacteria in the lower respiratory tracts of allografts may be risk factors for early posttransplant pneumonia (PTP) that causes detrimental outcomes in lung transplant recipients (LTRs). We evaluated the effects of immediate changes in MDR bacteria in allografts on early PTP and mortality rates in LTRs.

Methods: We reviewed 90 adult bilateral LTRs without pretransplant infections who underwent lung transplantation between October 2012 and May 2018. Quantitative cultures were performed with the bronchoalveolar lavage fluids of the allografts preanastomosis and within 3 days posttransplant. The International Society for Heart and Lung Transplantation consensus defines early PTP as pneumonia acquired within 30 days posttransplant and not associated with acute rejection.

Results: MDR Acinetobacter baumannii (11/34, 32.4%) and Staphylococcus aureus (9/34, 26.5%) were identified in 24.4% (22/90) of the preanastomosis allografts. Four LTRs had the same MDR bacteria in allografts preanastomosis and posttransplant. Allograft MDR bacteria disappeared in 50% of the LTRs within 3 days posttransplant. Early PTP and all-cause in-hospital mortality rates were not different between LTRs with and without preanastomosis MDR bacteria (P = 0.75 and 0.93, respectively). MDR bacteria ≥10 CFU/mL in the lungs within 3 days posttransplant was associated with early PTP (odds ratio, 5.8; 95% confidence interval, 1.3-27.0; P = 0.03).

Conclusions: High levels of preexisting MDR bacteria in allografts did not increase early PTP and mortality rates in LTRs. Despite the small and highly selective study population, lung allografts with MDR bacteria may be safely transplanted with appropriate posttransplant antibiotic therapy.
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http://dx.doi.org/10.1097/TP.0000000000003102DOI Listing
April 2020

Rabbit VX2 lung tumor models can form early nodal metastases.

World J Surg Oncol 2019 Dec 29;17(1):231. Epub 2019 Dec 29.

Division of Thoracic Surgery, Toronto General Hospital, University Health Network, 200 Elizabeth St, 9N-957, Toronto, ON, M5G2C4, Canada.

Background: The rabbit squamous cell cancer line, VX2, has been used to generate various tumor models in rabbits. It is notable for its ability to generate nodal metastases. However, the timing and extent of nodal metastases vary by primary inoculation site and methodology. The development of metastases specifically in lung cancer models has not been well-described. We sought to characterize the generation of nodal metastases in rabbit transbronchial VX2 lung tumor models.

Methods: Rabbit VX2 lung tumor models were created in the right lung via transbronchial injection and serially imaged by computed tomography. Rabbits (n = 15) were sacrificed from between 5 and 24 days post-inoculation for collection of the ipsilateral and contralateral paratracheal lymph nodes. These underwent histopathological evaluation for metastases using hematoxylin and eosin as well as cytokeratin AE1/AE3 immunohistochemical staining.

Results: Nodal metastases were detectable as early as 1 week after inoculation but were more prevalent with longer inoculation; all rabbits at > 2 weeks post-inoculation had nodal metastases. Contralateral metastases were in general seen later than ipsilateral metastases. Lymph node volume did not predict the likelihood of nodal metastases (p = 0.4 and p = 0.07 for ipsilateral and contralateral nodal metastases, respectively), but primary tumor volume was significantly associated with the likelihood of nodal metastases (p = 0.001 and p = 0.005 for ipsilateral and contralateral nodal metastases, respectively). Ipsilateral metastases were detectable at a tumor diameter of 1 cm; contralateral metastases were more variable but in general required a tumor diameter of 2 cm.

Conclusions: Rabbit transbronchial VX2 lung tumor models generate nodal metastases relatively early after inoculation. These results suggest such models may be valuable tools in the investigation of novel therapeutic modalities relevant for the treatment of both early-stage and locally advanced lung cancer.
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http://dx.doi.org/10.1186/s12957-019-1774-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936139PMC
December 2019

Predictors of post-thymectomy long-term neurological remission in thymomatous myasthenia gravis: an analysis from a multi-institutional database.

Eur J Cardiothorac Surg 2020 05;57(5):867-873

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: Thymectomy is the treatment of choice for thymomatous myasthenia gravis (MG) for both oncological and neurological aspects. However, only a few studies comprising small numbers of patients have investigated post-thymectomy neurological outcomes. We examined post-thymectomy long-term neurological outcomes and predictors of thymomatous MG using a multi-institutional database.

Methods: In total, 193 patients (47.3 ± 12.0 years; male:female = 90:103) with surgically resected thymomatous MG between 2000 and 2013 were included. Complete stable remission (CSR) and composite neurological remission (CNR), defined as the achievement of CSR and pharmacological remission after thymectomy, were evaluated. Predictors for CSR and CNR were examined by Cox regression analysis.

Results: The median duration between MG and thymectomy was 3.1 months. In addition, 161 patients (83.4%) had symptoms less than Myasthenia Gravis Foundation of America clinical classification III. All patients underwent an extended thymectomy; there were no perioperative deaths. The 10-year cumulative probability of CSR and CNR was 36.9% and 69.1%, respectively. Mild preoperative symptoms were a significant predictor for CSR (P = 0.040), and a large tumour was a predictor for CNR (P < 0.001). Patients with a large tumour were associated with early MG onset and no steroid treatment. Surgical methods, thymoma stage and histological subtypes were not associated with long-term neurological remission.

Conclusions: Large tumour size and preoperative mild symptoms were predictors for long-term neurological outcome in thymomatous MG. Considering that patients with early onset of MG and no immunosuppressive treatment tend to have large tumours, early surgical intervention for patients with thymomatous MG having mild symptoms might be beneficial for controlling neurological outcomes.
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http://dx.doi.org/10.1093/ejcts/ezz334DOI Listing
May 2020

Hygroscopic Micro/Nanolenses along Carbon Nanotube Ion Channels.

Nano Lett 2020 02 5;20(2):812-819. Epub 2019 Nov 5.

Department of Materials Science and Engineering , Gachon University , Seongnam 13120 , Republic of Korea.

Nanolenses of alkali metal halides can be a unique optical element due to their hygroscopicity, optical transparency, and high mobility of constituent ions. It has been challenging, however, to form and place such lenses in a controlled manner. Here, we report micro/nanolenses of various alkali metal halides arranged as a one-dimensional (1D) array, using the exterior of single-walled carbon nanotubes (SWNTs) as a template for forming the lenses. Applying an electrical bias to an aqueous solution of alkali metal halides placed at the end of an SWNT array causes ionic transport along the exterior of SWNTs and the subsequent formation of salt micro/nanocrystals. The crystals serve as micro/nanolenses that optically visualize individual SWNTs and amplify their Raman scattering by orders of magnitude. Molecules dissolved in the ionic solution can be electrokinetically transported along the nanotubes, captured within the lenses, and analyzed by Raman spectroscopy, which we demonstrate by detecting ∼12 attomoles of glucose and 2 femtomoles of urea. The hygroscopic salt nanolenses are robust under various ambient conditions indefinitely, by transitioning to liquid droplets above their deliquescence relative humidity, yet can be removed nondestructively by water. Our approach could have broad implications in the optical visualization of 1D nanostructures, molecular transport or chemical reactions in 1D space, and molecular spectroscopy in salty environments.
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http://dx.doi.org/10.1021/acs.nanolett.9b01767DOI Listing
February 2020

Safety of perioperative low dose aspirin therapy in major lung resection.

J Thorac Dis 2019 Sep;11(Suppl 15):S1897-S1899

Department of Thoracic and Cardiovascular Surgery, College of Medicine, Yonsei University, Seoul, Republic of Korea.

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http://dx.doi.org/10.21037/jtd.2019.08.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783751PMC
September 2019

Clinical implications of uncertain resection in scenarios of metastasis of the highest or most distant mediastinal lymph node station following surgical treatment of non-small-cell lung cancer.

Lung Cancer 2019 12 25;138:1-5. Epub 2019 Sep 25.

Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: The positive highest nodal station after operation is one of the definitions of "uncertain resection" proposed by the International Association for the Study of Lung Cancer. This study was performed to determine the prognostic value of positive highest or the most distant nodal station in patients with N2 non-small-cell lung cancer (NSCLC).

Materials And Methods: Three hundred thirty-nine patients who underwent complete anatomical resection and mediastinal lymph node (LN) dissection for N2 NSCLC between 2000 and 2015 were reviewed. Cases of operative mortality, extracapsular invasion of LN and incomplete resection were excluded from analysis.

Results: The mean age was 61.58 ± 9.43 years, and 235(69.3%) patients were male. The numbers of total dissected LNs and positive LNs were 29.90 ± 11.92 and 5.49 ± 5.90, respectively. The subcategory of N stage was divided as follows: N2a1, 91(26.8%); N2a2, 132(38.9%); and N2b, 116(34.2%). One hundred forty-two (41.9%) patients showed highest LN metastasis, and 162(47.8%) patients showed most distant LN metastasis. Kaplan-Meier analysis revealed no differences between distant LN negative and positive patients regarding 5-year overall survival (43.1% vs. 39.2%; p = 0.428) and between highest LN negative and positive patients regarding 5-year overall survival (42.1% vs. 40.0%; p = 0.539). On multivariable analysis, metastasis to the most distant mediastinal LN (hazard ratio (HR): 1.050; p = 0.755) and metastasis to the highest mediastinal LN (HR: 1.015; p = 0.924) were not related to overall survival.

Conclusion: The current definition of uncertain resection based on metastasis of the highest or most distant LNs did not show survival differences in completely resected N2 NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2019.09.018DOI Listing
December 2019

Dynamic changes in PD-L1 expression and CD8 T cell infiltration in non-small cell lung cancer following chemoradiation therapy.

Lung Cancer 2019 10 1;136:30-36. Epub 2019 Aug 1.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8 tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CD8 TIL counts following CCRT and their relationship to treatment outcome.

Materials And Methods: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8 TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method.

Results: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8 TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8 TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017).

Conclusions: CCRT dynamically alters PD-L1 expression and CD8 TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2019.07.027DOI Listing
October 2019

Indoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma.

Lung Cancer 2019 05 3;131:139-146. Epub 2019 Apr 3.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: Radon, a natural radiation, is the leading environmental cause of lung cancer in never-smokers. However, the radon exposure impact on the mutational landscape and tumor mutation burden (TMB) of lung cancer in never-smokers has not been explored. The aim of this study was to investigate the mutational landscape of lung adenocarcinoma in never-smokers who were exposed to various degrees of residential radon.

Materials And Methods: To investigate the effect of indoor radon exposure, we estimated the cumulative exposure to indoor radon in each house of patients with lung cancer with a never-smoking history. Patients with at least 2 year-duration of residence before the diagnosis of lung adenocarcinoma were included. Patients were subgrouped based on the median radon exposure level (48 Bq/m): radon-high vs. radon-low and targeted sequencing of tumor and matched blood were performed in all patients.

Results: Among 41 patients with lung adenocarcinoma, the TMB was significantly higher in the radon-high group than it was in the radon-low group (mean 4.94 vs. 2.6 mutations/Mb, P = 0.01). The recurrence rates between radon-high and radon-low group did not differ significantly. Mutational signatures of radon-high tumors showed features associated with inactivity of the base excision repair and DNA replication machineries. The analysis of tumor evolutionary trajectories also suggested a series of mutagenesis induced by radon exposure. In addition, radon-high tumors revealed a significant protein-protein interaction of genes involved in DNA damage and repair (P <  0.001).

Conclusions: Indoor radon exposure increased the TMB in never-smoker patients with lung adenocarcinoma and their mutational signature was associated with defective DNA mismatch repair.
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http://dx.doi.org/10.1016/j.lungcan.2019.04.002DOI Listing
May 2019

Three-Dimensional, High-Resolution Printing of Carbon Nanotube/Liquid Metal Composites with Mechanical and Electrical Reinforcement.

Nano Lett 2019 Aug 17;19(8):4866-4872. Epub 2019 Apr 17.

Nano Science Technology Institute, Department of Materials Science and Engineering , Yonsei University , Seoul 03722 , Republic of Korea.

The formation of three-dimensional (3D) interconnections is essential in integrated circuit packaging technology. However, conventional interconnection methods, including the wire-bonding process, were developed for rigid structures of electronic devices, and they are not applicable to the integration of soft and stretchable electronic devices. Hence, there is a strong demand for 3D interconnection technology that is applicable to soft, stretchable electronic devices. Herein, we introduce the material and the processing required for stretchable 3D interconnections on the soft forms of devices and substrates with high resolutions. Liquid-metal-based composites for use as stretchable interconnection materials were developed by uniformly dispersing Pt-decorated carbon nanotubes in a liquid metal matrix. The inclusion of carbon nanotubes in the liquid metal improves the mechanical strength of the composite, thereby overcoming the limitation of the liquid metal that has a low mechanical strength. The composites can be 3D printed with various dimensions: the minimum diameters are about 5 μm and have a breakdown current density comparable to that of metal wires.
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http://dx.doi.org/10.1021/acs.nanolett.9b00150DOI Listing
August 2019

Feasibility and surgical outcomes of video-assisted thoracoscopic pulmonary resection in patients with advanced-stage lung cancer after neoadjuvant chemoradiotherapy.

Thorac Cancer 2019 05 13;10(5):1241-1247. Epub 2019 Apr 13.

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Video-assisted thoracoscopic surgery (VATS) is regarded as the standard treatment for lung cancer. However, the feasibility and safety of VATS for lung cancer after neoadjuvant chemoradiotherapy (CRT) is unclear. This study evaluated the feasibility and safety of VATS in patients who had received neoadjuvant CRT.

Methods: Between January 2008 and December 2017, 85 patients who were administered neoadjuvant CRT and underwent anatomic lung resection were enrolled. Fifty-nine patients underwent open thoracotomy and 26 patients underwent VATS. The clinical characteristics and perioperative outcomes were reviewed.

Results: In six of the initial 32 patients who underwent VATS, the procedure was converted to thoracotomy. Adjacent structural invasion (33.9% vs. 11.5%; P = 0.037) and combined resection (16.9% vs. 0%; P = 0.025) were higher in the open group than in the VATS group. Surgical duration was higher in the open group than in the VATS group (203.86 ± 65.97 vs. 173.27 ± 59.87 minutes; P = 0.046). With regard to postoperative outcomes, the length of the hospital stay was longer in the open group compared to the VATS group (14.46 ± 16.94 vs. 8.62 ± 4.72 days; P = 0.017). There was no significant difference in the three-year disease-free survival (69.3% vs. 67.9%; P = 0.879) or overall survival rates (76.6% vs. 61.9%; P = 0.516).

Conclusion: In selected patients, VATS pulmonary resection after neoadjuvant CRT showed results comparable to that of thoracotomy in terms of postoperative outcomes, operative morbidities, and survival rate.
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http://dx.doi.org/10.1111/1759-7714.13074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501002PMC
May 2019

Neoadjuvant therapy for thymic neoplasms reduces tumor volume per 3D-reconstructed images but does not improve the complete resection rate.

PLoS One 2019 26;14(3):e0214291. Epub 2019 Mar 26.

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: Complete resection of thymic neoplasms is important for achieving a favorable prognosis; however, the efficacy of neoadjuvant therapy remains controversial. We investigated the effect of induction therapy on complete resection and survival using 3-dimensionally reconstructed images to measure tumor volume.

Methods: Eighty-nine patients who underwent surgical resection for Masaoka-Koga stage III-IV thymic neoplasms between January 2000 and December 2013 were enrolled, including 71 and 18 in the primary surgery and neoadjuvant therapy groups, respectively. Baseline characteristics, postoperative outcomes, and survival rates were analyzed. Moreover, baseline and post-neoadjuvant therapy tumor volumes were compared among patients in the neoadjuvant group.

Results: Adjacent mediastinal structure invasion was significantly rarer in the primary surgery group than in the neoadjuvant group (1.27±1.09 vs. 2.61±1.42, p<0.001). On subgroup analysis of patients who underwent neoadjuvant therapy, tumor volumes decreased significantly from 206.08±132.32 cm3 to 81.25±71.24 cm3 post-therapy (p = 0.001). Interestingly, only the pre-neoadjuvant tumor volume was significantly associated with complete resection, while the post-neoadjuvant volume was not (p = 0.012 and p = 0.458, respectively). Moreover, despite significantly reduced tumor volumes, patients in the neoadjuvant therapy group did not exhibit significantly different R0 resection rates (odds ratio 1.490, p = 0.581) or overall survival (p = 0.285) compared to those in the primary surgery group.

Conclusions: Neoadjuvant therapy does not significantly influence the R0 resection rate or overall survival relative to primary surgery. Nevertheless, it may by useful for patients planning surgical resection because it significantly reduces the presurgical tumor volume and extent of invasion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214291PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435136PMC
December 2019

Comprehensive analysis of the characteristics and treatment outcomes of patients with non-small cell lung cancer treated with anti-PD-1 therapy in real-world practice.

J Cancer Res Clin Oncol 2019 Jun 25;145(6):1613-1623. Epub 2019 Mar 25.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.

Purpose: Immune checkpoint inhibitors (ICI) have shown marked responses in patients with non-small cell lung cancer (NSCLC) in clinical trials. However, because such trials comprise cohorts selected based on specific criteria, it is unclear if their results represent routine clinical practice.

Methods: We examined 155 patients with advanced NSCLC who were administered either nivolumab or pembrolizumab at Yonsei Cancer Center, Korea between March 2014 and January 2019. Patient characteristics, EGFR/ALK mutation status, metastatic locations, response to ICIs, and adverse events were retrospectively analyzed.

Results: The median age was 64 years and 72.9% of patients were male; former or current smokers constituted 67.1% of the subjects. Adenocarcinoma was predominant (67.7%), and 50.3% of the patients underwent ≥ 2 previous treatments. Twenty-three patients (14.8%) were EGFR mutation- or ALK rearrangement-positive. The objective response rate (ORR) was 23.9% [95% confidence interval (CI) 17.4-31.4%]; the median progression-free survival (PFS) and overall survival (OS) were 3.06 (95% CI 1.893-4.21) and 10.25 (95% CI 5.39-15.11) months, respectively. Multivariate analysis identified ECOG performance status, EGFR mutation/ALK rearrangement status, liver metastasis and PD-L1 proportion as independent predictors of OS. Furthermore, 61.9% of the patients had adverse events of any grade; 38.1% had immune-related adverse events that were associated with PFS and OS on multivariate analysis.

Conclusions: The real-world ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials despite the patients' different baseline characteristics. Our findings can aid in establishing effective immunotherapeutic management of NSCLC in routine clinical practice.
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http://dx.doi.org/10.1007/s00432-019-02899-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527531PMC
June 2019

Matter-Wave Diffraction from a Periodic Array of Half Planes.

Phys Rev Lett 2019 Feb;122(4):040401

Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.

We report on reflection and diffraction of beams of He and D_{2} from square-wave gratings of a 400-μm period and strip widths ranging from 10 to 200  μm at grazing-incidence conditions. In each case we observe fully resolved matter-wave diffraction patterns including the specular reflection and diffracted beams up to the second diffraction order. With decreasing strip width, the observed diffraction efficiencies exhibit a transformation from the known regime of quantum reflection from the grating strips to the regime of edge diffraction from a half-plane array. The latter is described by a single-parameter model developed previously to describe phenomena as diverse as quantum billiards, scattering of radio waves in urban areas, and reflection of matter waves from microstructures. Our data provide experimental confirmation of the widespread model. Moreover, our results demonstrate that neither classical reflection nor quantum reflection are essential for reflective diffraction of matter waves from a structured solid, but it can result exclusively from half-plane edge diffraction.
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http://dx.doi.org/10.1103/PhysRevLett.122.040401DOI Listing
February 2019

Evaluation of Novel Imaging Devices for Nanoparticle-Mediated Fluorescence-Guided Lung Tumor Therapy.

Ann Thorac Surg 2019 06 8;107(6):1613-1620. Epub 2019 Feb 8.

Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: Nonsurgical and minimally invasive approaches for early-stage peripheral lung cancer are needed to avoid the known morbidity of surgical resection, particularly in high-risk patients. We previously demonstrated the utility of multifunctional porphyrin-phospholipid nanoparticles (porphysomes) for fluorescence imaging and phototherapy after preferential accumulation into tumors. The objective of this study was to demonstrate the feasibility of porphysome-mediated imaging and photothermal therapy using a newly developed fiberscope and thoracoscope.

Methods: To prepare this technology for clinical translation, we developed a porphysome-specific fiberscope (scanning fiber endoscope and porphysome-specific thoracoscope), both capable of detecting porphysome fluorescence, for image-guided transbronchial and transpleural photothermal therapy to treat endobronchial/peribronchial and subpleural tumors, respectively. These were tested in three animal models: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and ex vivo pig lung into which A549 tumor tissue was transplanted.

Results: The scanning fiber endoscope, with a 1.2-mm diameter, is small enough to pass through the working channel of a conventional bronchoscope and could visualize porphysome-laden tumors located inside or close to the peripheral bronchial wall. The porphysome-specific thoracoscope system had high sensitivity for porphysome fluorescence and enabled image-guided thoracoscopic resection of porphysome-accumulating tumors close to the pleura. Porphysomes also enhanced the efficacy of scanning fiber endoscope-guided transbronchial photothermal therapy and porphysome-specific thoracoscope-guided transpleural photothermal therapy, resulting in selective and efficient tumor tissue ablation in the rabbit and pig models.

Conclusions: These results support the potential for clinical translation of this novel platform to affect nonsurgical and minimally invasive treatment options for early-stage peripheral lung cancer.
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http://dx.doi.org/10.1016/j.athoracsur.2019.01.008DOI Listing
June 2019

First Evaluation of the Next-Generation Endobronchial Ultrasound System in Preclinical Models.

Ann Thorac Surg 2019 05 2;107(5):1464-1471. Epub 2019 Jan 2.

Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: The next-generation convex probe endobronchial ultrasound (CP-EBUS) was developed to improve the ease of operation and the acquisition of EBUS skills for new trainees. The aim of this study was to evaluate the changes in the prototype next-generation CP-EBUS compared with the current CP-EBUS.

Methods: The prototype next-generation CP-EBUS, with a decreased forward oblique view, more flexible angulation range, smaller ultrasound probe, and sharper needle angle, was compared with the current CP-EBUS. The operability, which was evaluated by using a 5-level Likert-type scale, and safety were evaluated in 2 live pigs, a cadaveric lung, and 10 ex vivo human lungs by 9 bronchoscopists. The time required to access the upper lobe bronchus and the time required to detect prespecified lymph node stations by 7 novice bronchoscopists with both CP-EBUS were compared with assess the operability difference for new trainees.

Results: In all evaluated models, operability (eg, maneuverability, endoscopic visibility, bronchial trees selectivity, insertability to the upper airway) was scored 5 (significantly improved). All trainee bronchoscopists were able to access the upper lobe bronchi and detect each lymph node except 4R significantly faster than with the current CP-EBUS without any airway damage.

Conclusions: The next-generation CP-EBUS has improved operability, which resulted in better access to each lobar bronchus and more prompt detection of mediastinal or hilar lymph nodes. These improvements may allow more precise lymph node staging and diagnosis, as well as improve EBUS procedural skill acquisition, once introduced to clinical practice.
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http://dx.doi.org/10.1016/j.athoracsur.2018.11.068DOI Listing
May 2019

Prognostic significance of supradiaphragmatic lymph node metastasis detected by F-FDG PET/CT in advanced epithelial ovarian cancer.

BMC Cancer 2018 Nov 26;18(1):1165. Epub 2018 Nov 26.

Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Background: Supradiaphragmatic lymph node metastases (SdLNM) are frequently identified using F-FDG positron emission tomography/computed tomography (PET/CT) in advanced epithelial ovarian cancers (AEOC). This study aimed to determine the prognostic significance of SdLNM detected by PET/CT in patients with AEOC.

Methods: Medical records of patients diagnosed with AEOC were retrospectively registered from January 2009 to July 2015. Patients were categorized according to PET/CT stage: PET/CT stage III, PET/CT stage IV with SdLNM, and PET/CT stage IV with other metastases. Clinicopathologic characteristics, recurrence patterns, survival outcomes were compared according to PET/CT stage. Anatomical distribution of SdLNM and effect of thoracic debulking surgery were estimated.

Results: A total of 295 patients were identified, including 176 patients who underwent primary debulking surgeries (PDS). Progression-free (P = 0.671) and overall (P = 0.525) survival did not differ significantly between patients with PET/CT IV with SdLNM and PET/CT IV with other metastases; however, patients with PET/CT IV with SdLNM had significantly poorer progression-free (P < 0.001) and overall (P = 0.016) survival than those with PET/CT stage III. Recurrence patterns were similar in all groups; intraperitoneal metastasis was the most common (78.8%) and thoracic recurrence alone accounted for less than 10%. Debulking of SdLNM lesions did not improve progression-free survival (P = 0.425) or overall survival (P = 0.465) of patients with AEOC.

Conclusions: SdLNM detected using preoperative PET/CT are a negative prognostic factor in AEOC. Resection of suspicious SdLNM may not have effect to survival of patients with AEOC.
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http://dx.doi.org/10.1186/s12885-018-5067-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260780PMC
November 2018

Molecular Diagnostic Assays and Clinicopathologic Implications of MET Exon 14 Skipping Mutation in Non-small-cell Lung Cancer.

Clin Lung Cancer 2019 01 11;20(1):e123-e132. Epub 2018 Oct 11.

Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Recent studies revealed MET exon 14 skipping (METex14) as a biomarker that predicts the response to MET inhibitors in non-small-cell lung cancer (NSCLC). However, METex14 genomic alterations exhibit a highly diverse sequence composition, posing a challenge for clinical diagnostic testing. This study aimed to find a reasonable diagnostic assay for METex14 and identify its clinicopathologic implications.

Materials And Methods: We performed a comprehensive analysis of METex14 in 414 EGFR/KRAS/ALK/ROS1-negative (quadruple negative) surgically resected NSCLCs. We used real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Sanger sequencing for the first assay, followed by next-generation sequencing (NGS; hybrid-capture targeted DNA/RNA sequencing). Clinicopathologic implications of the METex14 group were analyzed in a total of 880 NSCLCs.

Results: METex14 was confirmed in 13 (3.1%) patients by DNA- and RNA-NGS. After comparison of assay results, qRT-PCR and NGS demonstrated the highest concordance rate. The mean variant allele frequency was 10.5% and 49% in DNA- and RNA-NGS, respectively. DNA-NGS revealed various lengths of indel and substitutions around and in exon 14. Moreover, METex14 was associated with adenocarcinoma (4.8%; 11/230) or sarcomatoid carcinoma (9.5%; 2/21), old age, never-smokers, and early stage of disease.

Conclusions: METex14 occurs in about 3% of NSCLCs and has characteristic clinicopathologic features. NGS should be the first assay of choice as a multiplex testing. Sanger sequencing can detect METex14, but sensitivity can be hampered by large deletions or low allele frequency. qRT-PCR, an mRNA-based method, is sensitive and specific and can be appropriate for screening METex14 as a single gene testing.
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http://dx.doi.org/10.1016/j.cllc.2018.10.004DOI Listing
January 2019

Petrous Carotid Aneurysm Causing Pulsatile Tinnitus: Case Report and Review of the Literature.

J Cerebrovasc Endovasc Neurosurg 2018 Mar 31;20(1):35-39. Epub 2018 Mar 31.

Department of Neurosurgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.

We present the case of a patient who developed pulsatile tinnitus that was found to be associated with a petrous carotid aneurysm. The aneurysm was successfully obliterated using stent-assisted coiling, after which the patient was symptom-free. Although aneurysms arising from the petrous segment of the internal carotid artery are rare, this pathology must be considered as a causative factor in patients with pulsatile tinnitus. Endovascular treatment appears to have been successful in resolving the symptoms associated with this pathology.
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http://dx.doi.org/10.7461/jcen.2018.20.1.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196136PMC
March 2018

Porphyrin-High-Density Lipoprotein: A Novel Photosensitizing Nanoparticle for Lung Cancer Therapy.

Ann Thorac Surg 2019 02 11;107(2):369-377. Epub 2018 Oct 11.

Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario; Department of Medical Biophysics, University of Toronto, Toronto, Ontario; Guided Therapeutics, Princess Margaret Cancer Centre and TECHNA Institute, University Health Network, Toronto, Ontario; Institute of Biomaterial and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: We have developed ultrasmall porphyrin-high-density lipoprotein (HDL) nanoparticles (<20 nm), called "porphyrinHDL," that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become fluorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted to scavenger receptor class B type I (SR-BI) expressed on lung cancer cells as a first step toward development of a minimally invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer.

Methods: The in vitro uptake of porphyrinHDL and the corresponding PDT efficacy were evaluated in both SR-BI-positive and SR-BI-negative lung cancer cell lines. A clinically relevant orthotopic lung cancer model in mice was used to examine fluorescence activation and quantification of uptake in tumor. In addition, we investigated the effect of porphyrinHDL-mediated PDT.

Results: PorphyrinHDL promoted proper intracellular uptake in the H460 human lung cancer cell line. When irradiated with a 671-nm PDT laser, porphyrinHDL produced significant therapeutic effectiveness in vitro. After systemic administration in mice with orthotopic lung cancer xenografts, porphyrinHDL demonstrated selective accumulation and photoactivation in tumor with significantly enhanced disease-to-normal tissue contrast. Moreover, porphyrinHDL-PDT significantly induced cell apoptosis in lung tumors (73.2%) without toxicity in normal tissues or damage to adjacent critical structures.

Conclusions: SR-BI-targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.
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http://dx.doi.org/10.1016/j.athoracsur.2018.08.053DOI Listing
February 2019