Surgical treatment of severe benign tracheal stenosis.

OBJECTIVE: To present clinical experiences regarding surgical treatment of patients with severe cicatricial tracheal stenosis. PATIENTS AND METHODS: From January 2008 to March 2020, 14 patients underwent tracheal resection and reconstruction under general anesthesia. Nine cases had cervical tracheal stenosis and five cases had thoracic tracheal stenosis. The mean diameter and length of strictured trachea was 0 - 8 mm with a mean of 4.5 ± 2.4 mm and 1 - 3 cm with a mean of 1.67 ± 0.63 cm, respectively. General anesthesia and mechanical ventilation were performed in ten cases and four patients underwent femoral arteriovenous bypass surgery due to severe stenosis. End-to-end anastomosis of trachea was performed in 13 cases and the anastomosis between trachea and cricothyroid membrane was performed in one case. Absorbable and unabsorbable sutures were used for the anterior and posterior anastomoses, respectively. Postoperative neck anteflexion was maintained by a suture between the chin and superior chest wall. The relevant data of the 14 patients were retrospectively reviewed, and the operation time, blood loss, postoperative hospital stay, postoperative complications and follow-up were retrieved. RESULTS: There was no intraoperative death. The length of resected trachea ranged from 1.5 to 4.5 cm with a mean of 1.67 ± 0.63 cm. Operation time ranged from 50 - 450 min with a mean of 142.8 ± 96.6 min and intraoperative hemorrhage ranged from 10 - 300 ml with a mean of 87.8 ± 83.6 ml. Follow-up period ranged from 5 to 43 months with a mean of 17.9 ± 10.6 months. None of the patients had recurrent laryngeal nerve paralysis during postoperative follow-up. Ten cases were discharged uneventfully. Anastomosis stenosis occurred in three cases who received interventional therapies. Bronchopleurocutaneous fistula occurred in one patient after 6 days postoperatively and further treatment was declined. CONCLUSION: The strategies of anesthesia, mechanical ventilation, identification of stenosis lesion, the "hybrid" sutures and postoperative anteflexion are critical to be optimized for successful postoperative recovery.

Multi-center experience in an optimized right upper lobectomy surgical procedure in China.

BACKGROUND: This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe. METHODS: This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively. RESULTS: Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival. CONCLUSIONS: The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.

Robot-assisted thymectomy in large anterior mediastinal tumors: A comparative study with video-assisted thymectomy and open surgery.

BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of robot-assisted thymectomy (RAT) in large anterior mediastinal tumors (AMTs) (size ≥6 cm) compared with video-assisted thymectomy (VAT) and open surgery. METHODS: A total of 132 patients with large AMTs who underwent surgical resection from January 2016 to June 2022 were included in this study. A total of 61 patients underwent RAT, 36 patients underwent VAT and 35 patients underwent open surgery. Perioperative outcomes were compared. RESULTS: There were no significant differences in tumor size (p = 0.141), or pathological types (p = 0.903). Compared with the open group, the RAT and VAT groups were associated with a shorter operation time (115.00 vs. 160.00, p = 0.012; 122.50 vs. 160.00, p = 0.071), and less blood loss (50.00 vs. 200.00, p < 0.001; 50.00 vs. 200.00, p < 0.001), respectively. The rate of conversion in the RAT group was similar to that in the VAT group (6.56% vs. 13.89%, p = 0.229). Concomitant resection was less frequently performed in the VAT group than in the RAT and open groups (5.56% vs. 31.15%, p = 0.040; 5.56% vs. 31.43%, p = 0.006). VAT patients had a lower drainage volume (365.00 vs. 700.00 and 910.00 mL, p < 0.001), shorter duration of chest tube (2.00 vs. 3.00 and 4.00, p < 0.001), and shorter hospital stay (5.00 vs. 6.00 and 7.00, p < 0.001) than the RAT and open groups. There was no 30-day mortality in any group. No difference was seen in R0 resection rates (p = 0.846). The postoperative complication rates were similar among the three groups (p = 0.309). Total in-hospital costs (66493.90 vs. 33581.05 and 42876.40, p < 0.001) were significantly higher in the RAT group. CONCLUSIONS: RAT is safe and effective for the resection of large AMTs compared to VAT and open surgery. Vascular resection in RAT is technically feasible. A long-term follow-up is required.

Analysis of the unplanned reoperation following surgical treatment of pulmonary tumor.

BACKGROUND: In this study, we aimed to summarize the extremely important lesson and experience in the whole process of surgical treatments of lung tumors for the benefit of steps taken to prevent against unplanned reoperation. METHODS: Demographical and clinical information of 7732 patients were retrospectively retrieved and reviewed, who were diagnosed with pulmonary tumor and underwent surgical treatments from January 2016 to March 2021. Those patients who underwent unplanned reoperation for the treatment of severe complications were focused carefully and analyzed meticulously. RESULTS: A total of forty-one patients (41/7732) received 44 unplanned reoperations. Among them, eight and thirty-three patients were diagnosed with benign and malignant tumor, respectively. The incidence of unplanned reoperations seemed to be similar on both sides (Left vs. Right: 12/3231 vs. 29/4501, p = 0.103). Lobectomy plus segmentectomy is prone to reoperation (2/16, 12.5%) as compared to the other types of surgery. The complications leading to reoperation was hemothorax, including active hemorrhage (23/44, 52.3%) and clotted hemothorax (6/44, 13.6%), chylothorax (8/44, 18.2%), and the others (7/44, 15.9%) including bronchopleural fistula, torsion, or injury of right middle bronchus and pulmonary bulla rupture. The morbidity and mortality after unplanned reoperation were 17.1% (7/41) and 12.2% (5/41), respectively. CONCLUSIONS: Bronchi or vessel stumps, the surgical edges of the lung parenchyma, and pleural adhesions should be checked to avoid postoperative bleeding. Prophylactic ligation of the thoracic duct should be recommended in case of the suspected oily-like exudation in the lymph node bed. Smooth expansion of the middle lobe is important to avoid narrowing and torsion before transection of the bronchus.

The miR-23a/27a/24-2 cluster promotes postoperative progression of early-stage non-small cell lung cancer.

Even with optimal surgery, many early-stage non-small cell lung cancer (NSCLC) patients die of recurrence. Unfortunately, there are no precise predictors for postoperative recurrence in early-stage NSCLC, and the recurrence mechanism is still unclear. In this study, we found that simultaneous overexpression of all miRNAs in the miR-23a/27a/24-2 cluster was closely associated with postoperative recurrence, ß-catenin upregulation and promoter methylation of p16 and CDH13 in early-stage NSCLC patients. In addition, in vitro and in vivo experiments show that overexpression or inhibition of all miRNAs in the miR-23a/27a/24-2 cluster significantly stimulated or inhibited NSCLC cell stemness, tumorigenicity and metastasis. Furthermore, we demonstrated that the miR-23a/27a/24-2 cluster miRNAs activated Wnt/ß-catenin signaling by targeting their suppressors and stimulated promoter methylation-induced silencing of p16 and CDH13 by affecting DNA methylation-related genes expression. Our findings suggest that simultaneous high expression of all miRNAs in the miR-23a/27a/24-2 cluster represents a new biomarker for predicting postoperative recurrence in early-stage NSCLC. The miR-23a/27a/24-2 cluster miRNAs stimulate early-stage NSCLC progression through simultaneously stimulating Wnt/ß-catenin signaling, and promoter methylation-induced tumor suppressor genes silencing. In addition, simultaneous inhibition of all miRNAs in the miR-23a/27a/24-2 cluster may be a useful strategy for treatment of early-stage NSCLC recurrence.

Comparative short-term outcomes of robotic-assisted surgery for older patients with non-small cell lung cancer: a propensity matched study.

To investigate comparative short-term outcomes of robotic-assisted surgery (RAS) versus video-assisted thoracoscopic surgery (VATS) for older non-small cell lung cancer (NSCLC) patients. Patients ≥ 65 years old with stage I-III NSCLC operated with RAS or VATS from 2016 to 2018 were consecutively included. Propensity score-matched (PSM) method was implemented to balance inter-group biases. Totally 376 participants (224 with VATS and 152 with RAS) were included. After PSM, a cohort (144 with VATS and 107 with RAS) was generated with balanced baseline characteristics. RAS was significantly superior over VATS in the majority of perioperative outcomes, such as operating time (120.8 vs. 165.1 min), conversion rate (0.0% vs. 19.4%), and length of stay (8.6 vs. 10.8 days). RAS versus VATS was significantly associated with comparable rates of postoperative complications (OR 0.642, 95% CI 0.311-1.327), except the rate of pneumonia (OR 0.161, 95% CI 0.048-0.544). RAS leads to analogous postoperative complications and seemingly accelerates the recovery time of older NSCLC patients compared with VATS.

BCAR1 plays critical roles in the formation and immunoevasion of invasive circulating tumor cells in lung adenocarcinoma.

Background: We investigated the roles of breast cancer anti-estrogen resistance 1 (BCAR1/p130Cas) in the formation and immunoevasion of invasive circulating tumor cells (CTCs) in lung adenocarcinoma (LUAD). Methods: Biomarkers of CTCs including BCAR1 and CD274, were evaluated by the CanPatrol method. Proteomics analysis of LUAD cells and exosomes after BCAR1 overexpression (BCAR1-OE) was performed by mass spectrometry. Cell functions and relevant signaling pathways were investigated after BCAR1 knockdown (BCAR1-KO) or BCAR1-OE in LUAD cells. Lastly, in vitro and in vivo experiments were performed to confirm the roles of BCAR1 in the formation and immunoevasion of CTCs. Results: High expression of BCAR1 by CTCs correlated with CD274 expression and epithelial-to-mesenchymal transition (EMT). RAC1, together with BCAR1, was found to play an important role in the carcinogenesis of LUAD. RAC1 functioned with BCAR1 to induce EMT and to enhance cell proliferation, colony formation, cell invasion and migration, and anoikis resistance in LUAD cells. BCAR1 up-regulated CD274 expression probably by shuttling the short isoform of BRD4 (BRD4-S) into the nucleus. CTCs, as well as tumor formation, were prohibited in nude mice xenografted with BCAR1-KO cells. The co-expression of BCAR1/RAC1 and BCAR1/CD274 was confirmed in LUAD. BCAR1 expression in LUAD is an indicator of poor prognosis, and it associates with immunoevasion. Conclusion: BCAR1, as a new target for the treatment of LUAD, plays roles in the formation and immunoevasion of invasive CTCs. The mechanism includes triggering EMT via RAC1 signaling and up-regulating CD274 expression by shuttling BRD4-S into the nucleus.

Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer.

BACKGROUND: Circulating tumor cells (CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition (EMT) markers: CTCs with epithelial markers (E-CTCs), CTCs with mesenchymal markers (M-CTCs), and CTCs with both markers (E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer (LC). AIM: To clarify the diagnostic value of CTCs categorized by EMT markers in LC. METHODS: The study included 106 patients with lung adenocarcinoma, including 42 ground-glass opacities (GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrolTM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic (ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques. RESULTS: Of the 106 LC cases, 94 (89.6%) had at least one CTC. CTCs were detectable in 35 (83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of M-CTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients (80.95% for GGO patients) and the specificity was 78.57%. The Kappa value was 0.415, indicating relative consistency between CanPatrolTM and CytoploRare. CONCLUSION: CTC detection is valuable for distinguishing LC from controls, and particularly E&M-CTC detection warrants further study.

GRP75-mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c-JUN signaling.

BACKGROUND: Recurrence is a major challenge in early-stage lung adenocarcinoma (LUAD) treatment. Here, we investigated the role and mechanism of high-mobility group AT-hook 1 (HMGA1) and glucose-regulated protein 75-kDa (GRP75) in stage I LUAD and evaluated their potential as biomarkers for predicting the recurrence and prognosis of stage I LUAD. METHODS: The TCGA dataset was used to investigate the clinical significance of HMGA1 and GRP75 in early-stage LUAD. The biological functions of HMGA1 and GRP75 in LUAD were investigated both in vitro and in vivo through overexpression and knockdown experiments. The interaction and regulation between HMGA1 and GRP75 were evaluated with coimmunoprecipitation and ubiquitination assays. The downstream signaling pathway of the GRP75/HMGA1 axis was investigated by mRNA-sequencing analysis. RESULTS: Both HMGA1 expression levels and GRP75 expression levels were associated with recurrence in stage I LUAD patients. In particular, HMGA1 had potential as an independent prognostic factor in stage I LUAD patients. Overexpression of GRP75 or HMGA1 significantly stimulated LUAD cell growth and metastasis, while silencing GRP75 or HMGA1 inhibited LUAD cell growth and metastasis in vitro and in vivo. Importantly, GRP75 inhibited ubiquitination-mediated HMGA1 degradation by directly binding to HMGA1, thereby causes HMGA1 upregulation in LUAD. In addition, the GRP75/HMGA1 axis played its role by activating JNK/c-JUN signaling in LUAD. CONCLUSIONS: The activation of GRP75/HMGA1/JNK/c-JUN signaling is an important mechanism that promotes the progression of stage I LUAD, and a high level of HMGA1 is a novel biomarker for predicting recurrence and a poor prognosis in stage I LUAD patients.

Smoking history and the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Some studies imply a strong correlation between smoking history and the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Hence, a systematic review and meta-analysis was conducted to comprehensively investigate this correlation. METHODS: Three online databases including PubMed, Embase and Cochrane Library were searched. Abstracts and presentations from European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) were also reviewed. The deadline of search was Nov 9, 2019. Randomized clinical trials (RCT) of ICIs that reported hazard ratio (HR) for overall survival (OS) or progressive-free survival (PFS) by the smoking status of NSCLC patients were eligible for our study. We focused on publications issued in English. A random effects model was implemented in the synthesis, and a two-step interaction test was used to investigate the difference of ICIs efficacy among patients with different smoking histories. RESULTS: Twelve RCTs involving 6,497 NACLC patients [5,569 (85.72%) current/former smokers and 928 (114.28%) never smokers] were eligible for our systematic review and meta-analysis. The pooled HRs [95% confidential interval (CI)] of OS and PFS were 0.74 (0.67, 0.81) and 0.72 (0.59, 0.88) respectively for current/former smokers in the experimental group with ICIs versus those in the control group. The pooled HRs (95% CI) of OS and PFS were 0.81 (0.60, 1.08) and 0.92 (0.55, 1.54) respectively for never smokers in the experimental group with ICIs compared with those in the control group. The difference of ICIs efficacy in terms of OS between current/former and never smokers was insignificant [interaction HR (95% CI), 0.77 (0.69, 0.86), I2=25.4%, P_hetero=0.21]. CONCLUSIONS: The efficacy of ICIs in patients with smoking history is seemingly superior over patients without smoking history, but insignificantly. The difference can be explained by several factors such as insufficient sample size of non-smokers, and confounding factors. We suggest that smoking history cannot be recognized as a predictor of immune therapy in advanced NSCLC.

BCAR1 promotes proliferation and cell growth in lung adenocarcinoma via upregulation of POLR2A.

BACKGROUND: This study was designed to investigate the effects of a novel carcinogenetic molecule, p130cas (breast cancer antiestrogen resistance protein 1 or BCAR1) on proliferation and cell growth in lung adenocarcinoma. The study also aimed to identify the possible underlying signal networks of BCAR1. METHODS: First, we evaluated proliferation, cell colony formation, apoptosis, and cell cycle after BCAR1 was knocked out (KO) using CRISPR-Cas9 technology in H1975 and H1299 human lung adenocarcinoma cells. Subsequently, BCAR1 was upregulated in 293T cells and immunoprecipitation-mass spectrometry (IP-MS) was used with bioinformatics analysis to screen for potential networks of BCAR1 interacting proteins. Ultimately, we validated the correlated expressions of BCAR1 and a selected hub gene, RNA polymerase II subunit A (POLR2A), in 54 lung adenocarcinoma tissues, as well as in H1975 and H1299 cells. RESULTS: Cell proliferation of H1975 and H1299 was significantly inhibited following BCAR1-KO. Colony formation of H1975 cells was also significantly decreased following BCAR1-KO. IP-MS demonstrated 419 potential proteins that may interact with BCAR1. Among them, 68 genes were significantly positively correlated to BCAR1 expression, as verified by TCGA. Six hub genes were revealed by PPI String. High expression of POLR2A, MAPK3, MOV10, and XAB2 predicted poor prognosis in lung adenocarcinoma, as verified by the K-M plotter database. POLR2A and MAPK3 are involved in both catalytic activity and transferase activity. POLR2A and BCAR1 were significantly increased in lung cancer tissues as compared with matched normal tissues. High expression of POLR2A was significantly positively correlated to BCAR1 overexpression and predicted poor prognosis in 54 lung cancer cases. POLR2A expression was significantly decreased following BCAR1-KO in H1975 and H1299 cells. CONCLUSIONS: BCAR1 promotes proliferation and cell growth, probably via upregulation of POLR2A and subsequent enhancement of catalytic and transferase activities. However, additional robust studies are required to elucidate the mechanisms involved.

Is the presence of lung injury in COVID-19 an independent risk factor for secondary lung cancer?

The morbidity and mortality of lung cancer are increasing. The Corona Virus Disease 2019 (COVID-19) is caused by novel coronavirus 2019-nCoV-2, leading to subsequent pulmonary interstitial fibrosis with chronic inflammatory changes, e.g., inflammatory factors repeatedly continuously stimulating and attacking the alveolar epithelial cells. Meanwhile, 2019-nCoV-2 can activate PI3K/Akt and ERK signaling pathways, which can play the double roles as both anti-inflammatory and carcinogenic factors. Moreover, hypoxemia may be developed, resulting in the up-regulation of HIF-1 α expression, which can be involved in the occurrence, angiogenesis, invasion and metastasis of lung cancer. Additionally, the immune system in 2019-nCoV-2 infected cases can be suppressed to cause tumor immune evasion. Therefore, we speculate that COVID-19 may be a risk factor of secondary lung cancer.

Erratum: P130cas is required for TGF-ß1-mediated epithelial-mesenchymal transition in lung cancer.

[This corrects the article DOI: 10.3892/ol.2014.2123.].

Circulating tumor cells prior to initial treatment is an important prognostic factor of survival in non-small cell lung cancer: a meta-analysis and system review.

BACKGROUND: Our study aimed to verify the prognostic value of circulating tumor cells (CTCs) prior to initial treatment on survival of non-small cell lung cancer (NSCLC) by using meta-analysis and system review of published studies. MATERIALS AND METHODS: The PubMed, EMBASE and Cochrane Library were searched, respectively, to identify all studies that addressed the issues of CTCs prior to initial treatment and progression-free survival (PFS) and overall survival (OS). Finally, ten citations were included for analysis and assessment of publication bias by using review manager 5.3 statistical software and STATA 15.0. RESULTS: Randomized model analyzing multivariate Cox Proportional Hazards Regression indicated that higher abundance of CTCs significantly predicts poorer prognosis of lung cancer cases basing both on PFS (Z = 2.31, P = 0.02) and OS of advanced cases (Z = 2.44, P = 0.01), and systematic study aslo indicated the similar results. CONCLUSION: High CTCs prior to initial treatment can predict shorter PFS and OS in NSCLC, and further studies are warranted in the future.

Combination of electromagnetic navigation bronchoscopy-guided biopsy with a novel staining for peripheral pulmonary lesions.

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPLs) is a challenging task for pulmonologists, especially for small PPLs. Conventional localization of these small PPLs, which are > 1 cm away from the visceral pleura in operation, is quite difficult. Currently used methods inevitably damage the visceral pleura and may cause a series of complications, such as pneumothorax and hemothorax. Hence, the present study aimed to find out an intraoperative localization method with no damage to the visceral pleura. METHODS: We retrospectively reviewed 21 patients with PLLs who underwent electromagnetic navigation bronchoscopy (ENB)-guided biopsy plus a new methylene blue staining with the help of massage (Massage Staining) in our department between August 2017 and December 2018. RESULTS: The median age of these 21 patients was 51.3 ± 2.1 years. The diameter of the PPLs was 8.2 ± 2.3 mm. The rate of successful biopsy was 76.2%, and the rate of excellent or satisfactory of Massage Staining was 81.0%, while all lesions of these 21 cases were included in the range of staining, and the median distance from the edge of the stained site to the edge of the lesion was 29 ± 18 mm. The duration of ENB-guided biopsy plus Massage Staining was 26.7 ± 5.3 min, and the intraoperative blood loss was 3.3 ± 1.5 ml. No pneumothorax, hemorrhage, and tracheal injury occurred intraoperatively. CONCLUSIONS: The ENB-guided biopsy combined with Massage Staining is an innovative one-stop strategy designed to enhance the precision of thoracic surgery. The Massage Staining avoids damage to the visceral pleura, causes the low incidence of complications, but yields precise localization of PPLs.

Restoration of mutant K-Ras repressed miR-199b inhibits K-Ras mutant non-small cell lung cancer progression.

BACKGROUND: miRNAs play crucial role in the progression of K-Ras-mutated nonsmall cell lung cancer (NSCLC). However, most studies have focused on miRNAs that target K-Ras. Here, we investigated miRNAs regulated by mutant K-Ras and their functions. METHODS: miRNAs regulated by mutant K-Ras were screened using miRNA arrays. miR-199b expression levels were measured by qRT-PCR. The protein expression levels were measured using Western blot and immunohistochemistry. The effects of miR-199b on NSCLC were examined both in vitro and in vivo by overexpressing or inhibiting miR-199b. DNA methylation was measured by bisulfite sequencing. RESULTS: An inverse correlation was observed between K-Ras mutation status and miR-199b levels in NSCLC specimens and cell lines. The inhibition of miR-199b stimulated NSCLC growth and metastasis, while restoration of miR-199b suppressed K-Ras mutation-driven lung tumorigenesis as well as K-Ras-mutated NSCLC growth and metastasis. miR-199b inactivated ERK and Akt pathways by targeting K-Ras, KSR2, PIK3R1, Akt1, and Rheb1. Furthermore, we determined that mutant K-Ras inhibits miR-199b expression by increasing miR-199b promoter methylation. CONCLUSION: Our findings suggest that mutant K-Ras plays an oncogenic role through downregulating miR-199b in NSCLC and that overexpression of miR-199b is a novel strategy for the treatment of K-Ras-mutated NSCLC.

Size dependent anti-invasiveness of silver nanoparticles in lung cancer cells.

The molecular mechanism of cancer cell death caused by silver nanoparticles (AgNPs) of different sizes is investigated. Compared with the larger nanoparticles, 13 nm AgNPs significantly inhibit the migration and invasiveness of lung adenocarcinoma A549 cells, induce elevated reactive oxygen species and lead to NF-κB directed cellular apoptosis.

Clinical updates of approaches for biopsy of pulmonary lesions based on systematic review.

BACKGROUND: Convenient approaches for accurate biopsy are extremely important to the diagnosis of lung cancer. We aimed to systematically review the clinical updates and development trends of approaches for biopsy, i.e., CT-guided PTNB (Percutaneous Transthoracic Needle Biopsy), ENB (Electromagnetic Navigation Bronchoscopy), EBUS-TBNA (Endobroncheal Ultrasonography-Transbronchial Needle Aspiration), mediastinoscopy and CTC (Circulating Tumor Cell). METHODS: Medline and manual searches were performed. We identified the relevant studies, assessed study eligibility, evaluated methodological quality, and summarized diagnostic yields and complications regarding CT-guided PTNB (22 citations), ENB(31 citations), EBUS-TBNA(66 citations), Mediastinoscopy(15 citations) and CTC (19 citations), respectively. RESULTS: The overall sensitivity and specificity of CT-guided PTNB were reported to be 92.52% ± 3.14% and 97.98% ± 3.28%, respectively. The top two complications of CT-guided PTNB was pneumothorax (946/4170:22.69%) and hemorrhage (138/1949:7.08%). The detection rate of lung cancer by ENB increased gradually to 79.79% ± 15.34% with pneumothorax as the top one complication (86/1648:5.2%). Detection rate of EBUS-TBNA was 86.06% ± 9.70% with the top three complications, i.e., hemorrhage (53/8662:0.61%), pneumothorax (46/12432:0.37%) and infection (34/11250:0.30%). The detection rate of mediastinoscopy gradually increased to 92.77% ± 3.99% with .hoarseness as the refractory complication (4/2137:0.19%). Sensitivity and specificity of CTCs detection by using PCR (Polymerase Chain Reaction) were reported to be 78.81% ± 14.72% and 90.88% ± 0.53%, respectively. CONCLUSION: The biopsy approaches should be chosen considering a variety of location and situation of lesions. CT-guided PTNB is effective to reach lung parenchyma, however, diagnostic accuracy and incidence of complications may be impacted by lesion size or needle path length. ENB has an advantage for biopsy of smaller and deeper lesions in lung parenchyma. ENB plus EBUS imaging can further improve the detection rate of lesion in lung parenchyma. EBUS-TBNA is relatively safer and mediastinoscopy provides more tissue acquisition and better diagnostic yield of 4R and 7th lymph node. CTC detection can be considered for adjuvant diagnosis.

Anxiety after Sympathectomy in patients with primary palmar hyperhidrosis may prolong the duration of compensatory hyperhidrosis.

BACKGROUND: Compensatory hyperhidrosis (CH) is a frequent side effect after sympathectomy for the treatment of primary palmar hyperhidrosis. We determined the effects of demographic and clinical factors which may increase the duration of CH (DCH). METHODS: One hundred twenty-two patients who had undergone sympathectomies from 2014 to 2016 were retrospectively reviewed. Anxiety was evaluated using the State and Trait Anxiety Inventory score. Follow-up evaluations continued until CH remitted. A Cox proportional hazards model was used to determine the association between DCH and variables. RESULTS: DCH ranged from 5 to 27 weeks (median, 11.47 weeks). Severe CH (HR = 0.318, 95% CI, 0.136-0.741) and exacerbated anxiety 1 month post-operatively (HR = 0.816, 95% CI, 0.746-0.893) may prolong CH. A positive correlation between post-operative anxiety and DCH was common in patients with moderate or severe CH, and in cases with forearm CH. CONCLUSIONS: Pre- and post-operative anxiety should be evaluated, and anti-anxiety treatment is offered to patients with moderate-to-severe CH to shorten the DCH.

miR-124 Inhibits Lung Tumorigenesis Induced by K-ras Mutation and NNK.

Dysregulated miRNAs play important role in K-ras mutation or smoking caused lung tumorigenesis. Here, we investigate the role and mechanism of miR-124 in K-ras mutation or smoking-caused lung tumorigenesis and evaluate the therapeutic potential of miR-124 agomiR in K-ras mutation or smoking-caused lung cancer treatment. Our data show that smoking suppresses miR-124 expression, and decreased miR-124 expression is inversely correlated with the p-Akt level and predicts poor overall survival in non-small-cell lung cancer (NSCLC) patients. The overexpression of miR-124 suppressed NSCLC growth by inhibiting the Akt pathway by targeting Akt1 and Akt2. In addition, the systemic delivery of miR-124 agomiR dramatically suppressed tumorigenesis in both NNK-induced lung cancer model and K-rasLA1 transgenic mice by increasing apoptosis and inhibiting cell proliferation. Our findings suggest that smoking inhibits the expression of miR-124, and decreased miR-124 contributes to Akt activation, thereby promoting NSCLC progression. Our findings also represent a novel potential therapeutic strategy for lung cancer.