TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.

BACKGROUND: Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells. RESULTS: A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells. CONCLUSIONS: These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells.

Cullin7 induces docetaxel resistance by regulating the protein level of the antiapoptotic protein Survivin in lung adenocarcinoma cells.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC). Chemotherapy resistance is the main cause of chemotherapy failure. Cullin7 (Cul7) is highly expressed in LUAD and is associated with poor prognosis. Moreover, Cul7 is abnormally overexpressed in docetaxel-resistant LUAD cells. Therefore, further exploration of the role and molecular mechanism of Cul7 in LUAD docetaxel resistance is necessary. Methods: We established docetaxel-resistant cell lines (A549DTX and H358DTX cell lines) by exposing cells to gradually increasing concentrations of docetaxel. Cell (A549, A549DTX, H358, and H358DTX cell lines) sensitivity to docetaxel was determined via a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. And then quantitative polymerase chain reaction (qPCR) and Western blotting were performed to measure the expression of Cul7 and Survivin in A549, A549DTX, H358, and H358DTX cell lines. Subsequently, we knocked down Cul7 in docetaxel-resistant cells and overexpressed Cul7 in parental cells via lentiviral transduction to further validate the correlation between Cul7 and docetaxel resistance, while exploring the molecular mechanism of docetaxel resistance it caused. Immunofluorescence and immunohistochemical (IHC) staining were also used to evaluate the expression and cellular localization of Cul7. To confirm the effect of Cul7 expression on cell apoptosis, we used flow cytometry to detect the apoptosis rate of A549 and A549DTX cells with the same drug concentration. Results: Cul7 was highly expressed in A549DTX and H358DTX cells. However, when Cul7 expression was knocked down in A549DTX and H358DTX cells, cell sensitivity to docetaxel was significantly increased. In addition, we found that Cul7 was coexpressed with Survivin. Silencing Survivin reversed the docetaxel insensitivity caused by Cul7 overexpression. High expression of Cul7 and Survivin in docetaxel-resistant LUAD cells inhibited the intrinsic apoptosis pathway and promoted cell proliferation. Therefore, the Cul7/Survivin axis may play a role in inducing LUAD docetaxel chemoresistance. Conclusions: Cul7 and Survivin were both highly expressed in docetaxel-resistant LUAD cells. Our results suggest that Cul7 may inhibit apoptosis and promote the proliferation of LUAD cells by increasing the Survivin protein level, which in turn contributes to docetaxel chemoresistance in LUAD.

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

CT-based three-dimensional invasiveness analysis of adenocarcinoma presenting as pure ground-glass nodules.

Background: We invest computed tomography (CT) image differences between non-invasive adenocarcinomas (NIAs) and invasive adenocarcinomas (IAs) presenting as pure ground glass nodules (GGNs). Methods: From 2013 to 2019, 48 pure GGNs were surgically resected in 45 patients. Of these, 40 were pathologically diagnosed as non-small cell lung cancers (NSCLCs). We assessed them using the Synapse Vincent (Fujifilm Co., Ltd., Tokyo, Japan) three-dimensional (3D) analysis system; we drew histograms of the CT densities. We calculated the maximum, minimum, means, and standard deviations of the densities. The proportions of GGNs of high CT density were compared between the two groups. The diagnostic performance was investigated via receiver operating curve (ROC) analysis. Results: Of the 40 pure GGNs, 20 were NIAs (4 adenocarcinomas in situ and 16 minimally IAs) and 20 IAs. Significant correlations were evident between histological invasiveness and the maximum and mean CT densities and the standard deviation. Neither the nodule volume nor the minimum CT density significantly predicted invasiveness. A CT volume density proportion >-300 Hounsfield units optimally predicted the invasiveness of pure GGNs; the cutoff was 5.41% with a sensitivity of 85% and a specificity of 95%. Conclusions: CT density reflected the invasiveness of pure GGNs. A CT volume proportion density >-300 Hounsfield units may significantly predict histological invasiveness.

Comparison between costotransverse foramen block and thoracic paravertebral block for VATS pulmonary resection: A randomized noninferiority trial.

STUDY OBJECTIVE: The present study assessed whether costotransverse foramen block (CTFB) is noninferior to thoracic paravertebral block (TPVB) for postoperative analgesia in video-assisted thoracoscopic surgery (VATS) pulmonary resection. DESIGN: Single-center, double-blinded, randomized, non-inferiority trial. SETTING: Operating room and intensive care unit or ward in a tertiary hospital. PATIENTS: Patients aged 20 to 80 years with American Society of Anesthesiology physical status 1 to 3 scheduled for elective VATS pulmonary resection. INTERVENTIONS: Sixty patients were randomly allocated 1:1 to receive CTFB or TPVB using 15 mL aliquots of 0.5% ropivacaine at the T4-5 and T6-7 intercostal levels immediately after the induction of general anesthesia. MEASUREMENTS: The primary outcome was the area under the curve (AUC) of numeric rating scale (NRS, 0 to 10) during 24 h postoperatively (noninferiority limit was 24; NRS 1 per hour). The secondary outcomes included postoperative opioid consumption, rescue analgesic use, postoperative nausea and vomiting, pulmonary function, dermatomal spread of the blockade, and quality of recovery. MAIN RESULTS: Forty-seven patients were included for final analysis. The difference between the mean 24-h AUCs of NRS in the CTFB (34.25 ± 16.30, n = 24) and TPVB (39.52 ± 17.13, n = 23) groups was -5.27 (95% confidence interval [CI], -15.09 to 4.55), with the upper limit of 95% CI being far below the predefined noninferiority margin of 24. There was no significant difference in the dermatomal spread of the blockades between the groups, as both reached the upper and lower most levels of T3 and T7 (median). Additionally, there were no significant differences in other secondary outcomes between the two groups. CONCLUSIONS: The analgesic effect of CTFB was noninferior to that of TPVB during 24 h postoperatively in VATS pulmonary resection. Moreover, CTFB may offer potential safety benefits by keeping the tip of the needle far from the pleura and vascular structure.

Improving the efficiency of identifying malignant pulmonary nodules before surgery via a combination of artificial intelligence CT image recognition and serum autoantibodies.

OBJECTIVE: To construct a new pulmonary nodule diagnostic model with high diagnostic efficiency, non-invasive and simple to measure. METHODS: This study included 424 patients with radioactive pulmonary nodules who underwent preoperative 7-autoantibody (7-AAB) panel testing, CT-based AI diagnosis, and pathological diagnosis by surgical resection. The patients were randomly divided into a training set (n = 212) and a validation set (n = 212). The nomogram was developed through forward stepwise logistic regression based on the predictive factors identified by univariate and multivariate analyses in the training set and was verified internally in the verification set. RESULTS: A diagnostic nomogram was constructed based on the statistically significant variables of age as well as CT-based AI diagnostic, 7-AAB panel, and CEA test results. In the validation set, the sensitivity, specificity, positive predictive value, and AUC were 82.29%, 90.48%, 97.24%, and 0.899 (95%[CI], 0.851-0.936), respectively. The nomogram showed significantly higher sensitivity than the 7-AAB panel test result (82.29% vs. 35.88%, p < 0.001) and CEA (82.29% vs. 18.82%, p < 0.001); it also had a significantly higher specificity than AI diagnosis (90.48% vs. 69.04%, p = 0.022). For lesions with a diameter of ≤ 2 cm, the specificity of the Nomogram was higher than that of the AI diagnostic system (90.00% vs. 67.50%, p = 0.022). CONCLUSIONS: Based on the combination of a 7-AAB panel, an AI diagnostic system, and other clinical features, our Nomogram demonstrated good diagnostic performance in distinguishing lung nodules, especially those with ≤ 2 cm diameters. KEY POINTS: • A novel diagnostic model of lung nodules was constructed by combining high-specific tumor markers with a high-sensitivity artificial intelligence diagnostic system. • The diagnostic model has good diagnostic performance in distinguishing malignant and benign pulmonary nodules, especially for nodules smaller than 2 cm. • The diagnostic model can assist the clinical decision-making of pulmonary nodules, with the advantages of high diagnostic efficiency, noninvasive, and simple measurement.

NIR fluorescence imaging and treatment for cancer immunotherapy.

Cancer immunotherapy has emerged as one of the most powerful anticancer therapies. However, the details on the interaction between tumors and the immune system are complicated and still poorly understood. Optical fluorescence imaging is a technique that allows for the visualization of fluorescence-labeled immune cells and monitoring of the immune response during immunotherapy. To this end, near-infrared (NIR) light has been adapted for optical fluorescence imaging because it is relatively safe and simple without hazardous ionizing radiation and has relatively deeper tissue penetration into living organisms than visible fluorescence light. In this review, we discuss state-of-the-art NIR optical imaging techniques in cancer immunotherapy to observe the dynamics, efficacy, and responses of the immune components in living organisms. The use of bioimaging labeling techniques will give us an understanding of how the immune system is primed and ultimately developed.

Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores.

The residual tumor after surgery is the most significant prognostic factor of patients with epithelial ovarian cancer. Near-infrared (NIR) fluorescence-guided surgery is actively utilized for tumor localization and complete resection during surgery. However, currently available contrast-enhancing agents display low on-target binding, unfavorable pharmacokinetics, and toxicity, thus not ideal for clinical use. Here we report ultrabright and stable squaraine fluorophores with optimal pharmacokinetics by introducing an asymmetric molecular conformation and surface charges for rapid transporter-mediated cellular uptake. Among the tested, OCTL14 shows low serum binding and rapid distribution into cancer tissue via organic cation transporters (OCTs). Additionally, the charged squaraine fluorophores are retained in lysosomes, providing durable intraoperative imaging in a preclinical murine model of ovarian cancer up to 24 h post-injection. OCTL14 represents a significant departure from the current bioconjugation approach of using a non-targeted fluorophore and would provide surgeons with an indispensable tool to achieve optimal resection.

Circulating Tumor Cell Detection in Lung Cancer Animal Model.

BACKGROUND: Metastasis and recurrence of primary cancer are the main causes of cancer mortality. Disseminated tumor cells refer to cancer cells that cause metastasis from primary cancer to other organs. Several recent studies have suggested that circulating tumor cells (CTCs) are associated with the clinical stage, cancer recurrence, cancer metastasis, and prognosis. There are several methods of isolating CTCs from whole blood; in particular, using a membrane filtration system is advantageous due to its cost-effectiveness and availability in clinical settings. In this study, an animal model of lung cancer was established in nude mice using the human large cell lung cancer cell line H460. METHODS: Six-week-old nude mice were used. The H460 lung cancer cell line was injected subcutaneously into the nude mice. Blood samples were obtained from the orbital area before cell line injection, 2 weeks after injection, and 2 weeks after tumor excision. Blood samples were filtered using a polycarbonate 12-well Transwell membrane (Corning Inc., Corning, NY, USA). An indirect immunofluorescence assay was performed with the epithelial cell adhesion molecule antibody. The number of stained cells was counted using fluorescence microscopy. RESULTS: The average size of the tumor masses was 35.83 mm. The stained cells were counted before inoculation, 2 weeks after inoculation, and 2 weeks after tumor excision. Cancer cells generally increased after inoculation and decreased after tumor resection. CONCLUSION: The CTC detection method using the commercial polycarbonate 12-well Transwell (Corning Inc.) membrane is advantageous in terms of cost-effectiveness and convenience.

LncRNA LINC00240 suppresses invasion and migration in non-small cell lung cancer by sponging miR-7-5p.

BACKGROUND: lncRNAs have important roles in regulating cancer biology. Accumulating evidence has established a link between the dysregulation of lncRNAs and microRNA in cancer progression. In previous studies, miR-7-5p has been found to be significantly down-regulated in mesenchymal-like lung cancer cell lines and directly regulated EGFR. In this work, we investigated the lncRNA partner of miR-7-5p in the progression of lung cancer. METHODS: We investigated the expression of miR-7-5p and the lncRNA after transfection with an miR-7-5p mimics using a microarray. The microarray results were validated using quantitative real time-polymerase Chain Reaction (qRT-PCR). The regulatory effects of lncRNA on miR-7-5p and its target were evaluated by changes in the expression of miR-7-5p after transfection with siRNAs for lncRNA and the synthesis of full-length lncRNA. The effect of miR-7-5p on lncRNA and the miRNA target was evaluated after transfection with miRNA mimic and inhibitor. The role of lncRNA in cancer progression was determined using invasion and migration assays. The level of lncRNA and EGFR in lung cancer and normal lung tissue was analyzed using TCGA data. RESULTS: We found that LINC00240 was downregulated in lung cancer cell line after miR-7-5p transfection with an miR-7-5p mimic. Further investigations revealed that the knockdown of LINC00240 induced the overexpression of miR-7-5p. The overexpression of miR-7-5p diminished cancer invasion and migration. The EGFR expression was down regulated after siRNA treatment for LINC00240. Silencing LINC00240 suppressed the invasion and migration of lung cancer cells, whereas LINC00240 overexpression exerted the opposite effect. The lower expression of LINC00240 in squamous lung cancer was analyzed using TCGA data. CONCLUSIONS: Taken together, LINC00240 acted as a sponge for miR-7-5p and induced the overexpression of EGFR. LINC00240 may represent a potential target for the treatment of lung cancer.

Type A aortic dissection after 'zone 0' thoracic endovascular aortic repair for type 1 hybrid aortic arch replacement of arch aneurysm.

The recent rise in minimally invasive cardiovascular procedures is being accompanied by an increase in related complications. We report on an acute type A aortic dissection performed in an 82-year-old man 1 week after staged 'zone 0' hybrid thoracic endovascular aortic repair (TEVAR). Previously, the patient had undergone type I hybrid arch debranching and staged 'zone 0' TEVAR for an aortic arch aneurysm. 'Zone 0' TEVAR after type I hybrid debranching might increase the risk for aortic injury on the residual native aorta and should, therefore, be closely followed up to enable the early diagnosis of complications.

Feasibility of electromagnetic navigation bronchoscopy-guided lung resection for pulmonary ground-glass opacity nodules.

BACKGROUND: Recent advances in imaging modalities and recommended low-dose computed tomography screening programs have made it easier to diagnose early lung cancer. However, the diagnosis of small ground-glass nodules (GGNs) has been problematic due to inappropriate specimen procurement and failure of conventional percutaneous core needle biopsy. Thus, we aimed to evaluate the usefulness of electromagnetic navigation bronchoscopy (ENB)-guided video-assisted lung resection for not only the diagnosis but also treatment of GGNs. METHODS: From 2017 to 2019, 110 patients with suspicious lung cancer lesions that were not diagnosed by conventional procedure underwent ENB-guided lung resection. Among 35 cases of GGNs, 33 cases of localization were included in this study (two cup biopsy cases were excluded). We used SuperDimension™ for the ENB procedure. After general anesthesia, indigo carmine (0.3-0.5 mL) was injected, and GGNs were resected through video-assisted thoracoscopic surgery. RESULTS: Of the 33 GGNs, 16 were pure (2 adenocarcinomas in situ, 5 minimally invasive adenocarcinomas (MIAs), 3 adenocarcinomas, and 6 benign lesions) and 17 were mixed (1 MIA, 11 adenocarcinomas, and 5 benign lesions). The mean size of all lesions was 11.2±7.78 mm, mean distance to the pleura was 11.2±14.2 mm, and mean ENB procedure time was 18.8±8.88 minutes. Dye localization and surgical resection of GGN were successful in all cases. There was no procedure-related complication. CONCLUSIONS: ENB is a feasible and highly accurate localization method for minimally invasive lung resection of small GGNs.

Use of Gadoxetic Acid-enhanced Liver MRI and Mortality in More than 30 000 Patients with Hepatocellular Carcinoma: A Nationwide Analysis.

Background The impact on survival of gadoxetic acid-enhanced MRI in addition to multiphase contrast material-enhanced CT for initial staging in patients with hepatocellular carcinoma (HCC) is unknown. Purpose To compare all-cause mortality in patients with HCC who underwent CT only, CT plus non-gadoxetic acid-enhanced MRI, or CT plus gadoxetic acid-enhanced MRI as part of their initial diagnostic work-up. Materials and Methods The authors performed a nationwide retrospective cohort study of patients diagnosed with HCC in South Korea between January 2008 and December 2010. Follow-up extended through December 2014. The primary outcome was all-cause mortality. Cox proportional hazards regression model with adjustment of confounding factors was used to estimate hazard ratios (HRs) for all-cause mortality. Results Among 30 023 patients with HCC (mean age ± standard deviation, 58.5 years ± 10.7, 23 978 men), the proportions of patients in whom HCC was diagnosed using CT only, CT plus non-gadoxetic acid-enhanced MRI, and CT plus gadoxetic acid-enhanced MRI were 56.1%, 12.9%, and 31.0%, respectively. In adjusted analysis using CT only as the reference category, the HR for mortality for CT plus gadoxetic acid-enhanced MRI was 0.64 (95% confidence interval [CI]: 0.62, 0.67; P < .001), and the HR for CT plus non-gadoxetic acid-enhanced MRI was 0.71 (95% CI: 0.68, 0.75; P < .001). Use of CT plus gadoxetic acid-enhanced MRI was associated with lower mortality compared with CT plus non-gadoxetic acid-enhanced MRI (adjusted HR, 0.90; 95% CI: 0.85, 0.95; P < .001), but this survival advantage was restricted to patients with localized disease. Conclusion In patients with hepatocellular carcinoma, additional use of contrast-enhanced MRI was associated with lower mortality. Furthermore, CT plus gadoxetic acid-enhanced MRI was associated with better survival than CT plus non-gadoxetic acid-enhanced MRI but only in patients with localized disease. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kim in this issue.

Different macrophage polarization between drug-susceptible and multidrug-resistant pulmonary tuberculosis.

BACKGROUND: Macrophages play a key role in the infection process, and alternatively activated macrophages (M2 polarization) play important roles in persistent infection via the immune escape of pathogens. This suggests that immune escape of pathogens from host immunity is an important factor to consider in treatment failure and multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB). In this study, we investigated the association between macrophage polarization and MDR-TB/XDR-TB and the association between macrophage polarization and the anti-TB drugs used. METHODS: iNOS and arginase-1, a surface marker of polarized macrophages, were quantified by immunohistochemical staining and imaging analysis of lung tissues of patients who underwent surgical treatment for pulmonary TB. Drug susceptibility/resistance and the type and timing of anti-tuberculosis drugs used were investigated. RESULTS: The M2-like polarization rate and the ratio of the M2-like polarization rate to the M1-like polarization rate were significantly higher in the MDR-TB/XDR-TB group than in the DS-TB group. The association between a high M2-like polarization rate and MDR-TB/XDR-TB was more pronounced in patients with a low M1-like polarization rate. Younger age and a higher M2-like polarization rate were independent associated factors for MDR-TB/XDR-TB. The M2-like polarization rate was significantly higher in patients who received anti-TB drugs containing pyrazinamide continuously for 4 or 6 weeks than in those who received anti-TB drugs not containing pyrazinamide. CONCLUSIONS: The M2-like polarization of macrophages is associated with MDR-TB/XDR-TB and anti-TB drug regimens including pyrazinamide or a combination of pyrazinamide, prothionamide and cycloserine.

Postoperative change in wideband absorbance after tympanoplasty in chronic suppurative otitis media.

OBJECTIVE: To identify the wideband absorbance (WBA) of reconstructed TM comparing with perforated and normal TM, and to investigate the efficacy of WBA to predict postoperative hearing outcome. METHODS: Ninety-eight adults (128 ears) with normal TM and 40 patients (40 ears) who were diagnosed with chronic suppurative otitis media (CSOM) and underwent tympanoplasty type 1 were enrolled. Pure tone audiometry and WBA were measured before and 6 and 12 months after surgery. Finally, only 29 patients in CSOM group completed all the tests. RESULTS: Significant differences in WBA were observed between normal ears, CSOM, and reconstructed ears at middle to high frequencies. During follow-up, absorbance decreased at low frequencies and increased at middle to high. Significant positive correlation at low to middle frequency was observed between change in air-bone gaps (ABG) and absorbance at corresponding frequencies. CONCLUSION: WBA in patients with CSOM was significantly different from normal TM, and a significant change in WBA was observed after tympanoplasty with improvement of ABG. WBA may be a useful tool for monitoring the postoperative change in absorbance of sound energy in the middle ear.

Evaluation of appearance-related distress after canaloplasty using the DAS-24 questionnaire.

Background: The main purpose of the canaloplasty is hearing improvement. But there are needs for evaluation of the esthetic or psychosocial effects of canaloplasty.Aims/Objectives: This study investigated the esthetic influence of canaloplasty, with regard to the creation of a patent external auditory canal.Materials and methods: We enrolled 34 patients diagnosed with microtia and congenital aural atresia (CAA). All patients underwent canaloplasty and Derriford Appearance Scale (DAS) questionnaire was used to evaluate patients' distress due to their appearance. A general self-consciousness score (GSC) of DAS was evaluated and compared preoperatively, and postoperatively with the audiological outcomes.Results: Preoperatively, the GSC scores were higher in individuals 12 years or older compared to those of patients less than 12 years of age. One year postoperatively, the GSC score significantly decreased from 27.02(±6.0) to 21.76(±6.0). In detailed item analysis, the postoperative GSC score significantly improved in 8 items. The preoperative mean air-bone gap (ABG) of 49.88 dB decreased to a mean of 28.09 dB at 6 months and to 29.02 dB at 1 year postoperatively.Conclusion and significance: Canaloplasty is a procedure that not only improves hearing in patients with CAA, but also effectively reduces patients' distress due to their appearance.

Single-center experience of extracorporeal membrane oxygenation mainly anticoagulated with nafamostat mesilate.

BACKGROUND: Bleeding remains the chief concern during extracorporeal membrane oxygenation (ECMO). Recently, several studies proposed nafamostat mesilate (NM) as an alternative anticoagulant to heparin due to reduced bleeding complications and comparable thromboembolic episodes. The aim of this study was to evaluate the clinical outcomes of ECMO anticoagulated mainly with NM. METHODS: This was a retrospective observational case series of patients who were placed on ECMO between January 2011 and December 2017 at Chungnam National University Hospital. The main outcomes were bleeding and thromboembolic episodes. RESULTS: During the study period, a total of 91 ECMO runs on 87 patients were identified. There were 54 veno-venous runs and 37 veno-arterial runs. Among the 87 patients, 47 (54.0%) patients were successfully weaned and 29 (33.3%) survived to discharge. Most of the runs were anticoagulated with NM (n=68, 74.7%), followed by heparin (n=22, 24.2%) and argatroban (n=1, 1.1%). The mean duration of ECMO support was 11.3±11.1 days. The overall incidence of bleeding was 46.2% (n=42); 26 runs were anticoagulated with NM (26/68, 38.2%) and 16 with heparin (16/22, 72.7%) (P=0.005). The overall incidence of thromboembolic episodes was 12.1% (n=11). In the NM group, the incidence of hyperkalemia requiring any type of intervention was 17.6% (n=12). CONCLUSIONS: In this single center study, NM appears to be associated with fewer bleeding complications during ECMO without increasing the incidence of thromboembolic episodes.

Novel Asymmetrical Linear Stapler (NALS) for pathologic evaluation of true resection margin tissue.

BACKGROUND: The use of limited resection for lung cancer has increased with the accumulation of knowledge about early lung cancer. To decrease locoregional recurrence after a limited resection, it is important to confirm R0 resection at the true resection margin. In this study, we report a novel linear stapler that preserves the true resection margin tissue after organ resection. METHODS: We used a Novel Asymmetrical Linear Stapler (NALS) made by Meditulip. On the resected organ side of NALS, there is a single row of titanium fasteners. To verify the utility of NALS and to compare its preservation of the resection margin tissue to a conventional stapler, we performed wedge resection of the lung in a porcine animal model and examined the pathology of the true resection margin. RESULTS: Using NALS, we successfully divided and closed the lung tissues, as with the conventional stapler. There was no bleeding on either side or no air leakage from the remnant stapled tissue. The distance between the cutting edge and the titanium fasteners was 3.10 mm with NALS, which was sufficient to resect the true resection margin tissue for pathology evaluation. There was no squeezing artifact at the true resection margin on microscopic evaluation with NALS. With the conventional stapler, it is difficult to evaluate the pathology at the true resection margin due to the severe squeezing artifact. CONCLUSIONS: NALS preserves the true resection margin tissue and thus should be useful for evaluating the resection margin with a frozen section biopsy in oncology surgery.

Electromagnetic navigation bronchoscopy-Chungnam National University Hospital experience.

BACKGROUND: To find small pulmonary nodules or ground grass nodules (GGNs) with video-assisted thoracoscopic surgery (VATS) is very difficult. There are several conventional methods to localize small nodules or GGNs, which require additional radiation exposure and may cause some complications such as pneumothorax or hemothorax. We aimed to evaluate the effectiveness and feasibility of electromagnetic navigational bronchoscopy-guided pulmonary localization in a minimally invasive thoracic surgery field. METHODS: We retrospectively reviewed the medical records from a prospectively collected database of the patients who underwent ENB procedure for biopsy and/or localization of pulmonary resection at the Chungnam National University Hospital from January 2017 to January 2018. RESULTS: A total of 37 ENB-guided dye-markings or biopsies for 37 lesions in 30 patients were performed. Thirty-two ENB-guided localizations using dye-marking for resection were performed in 25 patients. The median nodule size was 9 mm (IQR: 7-13 mm), and the median distance from the pleura was 6 mm (IQR: 3-10 mm). The failure of an ENB-guided localization was noted in 4 cases (12.5%). There was no major complication noted with the procedure, and just two patients showed mild intrabronchial bleeding stopped spontaneously. The most common lobar location was right lower lobe (11 cases, 34.4%), and all cases of localization failure were right lower lobe. A pathologic diagnosis was obtained from surgically resected specimen (not from ENB biopsy: 32 of 32 localizations, 100%), neoplastic lesions were 23 cases (72%). Of them, a primary lung cancer and metastatic lung cancer were noted in 11 cases, and in 11cases, respectively. All margins of the nodules were negative. CONCLUSIONS: The ENB-guided dye localization by a well-trained thoracic surgeon enables accurate intraoperative identification of GGN or a small pulmonary nodule, with minimal complications and enables minimally invasive surgery including single port surgery.

Validation of Nafamostat Mesilate as an Anticoagulant in Extracorporeal Membrane Oxygenation: A Large-Animal Experiment.

BACKGROUND: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. METHODS: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. RESULTS: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin (IL)-1ß levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. CONCLUSION: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.