Publications by authors named "Jiayuan Sun"

67 Publications

Next-generation sequencing of tissue and circulating tumor DNA: Resistance mechanisms to EGFR targeted therapy in a cohort of patients with advanced non-small cell lung cancer.

Cancer Med 2021 Jul 25;10(14):4697-4709. Epub 2021 Jun 25.

Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has been considered as an effective treatment in epidermal growth factor receptor-mutant (EGFR-mutant) advanced non-small cell lung cancer (NSCLC). However, most patients develop acquired resistance eventually. Here, we compared and analyzed the genetic alterations between tissue assay and circulating tumor DNA (ctDNA) and further explored the resistance mechanisms after EGFR-TKI treatment.

Methods And Materials: Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), Cobas ARMS-PCR and next-generation sequencing (NGS) were performed on tissue samples after pathological diagnosis. Digital droplet PCR (ddPCR) and NGS were performed on plasma samples. The association between genetic alterations and clinical outcomes was analyzed retrospectively.

Results: Thirty-seven patients were included. The success rate of re-biopsy was 91.89% (34/37). The total detection rate of EGFR T790M was 62.16% (23/37) and the consistency between tissue and ctDNA was 78.26% (18/23). Thirty-four patients were analyzed retrospectively. For tissue re-biopsy, 24 patients harbored concomitant mutations. Moreover, tissue re-biopsy at resistance showed 21 patients (21/34, 61.76%) had the concomitant somatic mutation. The three most frequent concomitant mutations were TP53 (18/34, 52.94%), MET (4/34, 11.76%), and PIK3CA (4/34, 11.76%). Meanwhile, 21 patients (21/34, 61.76%) with EGFR T790M mutation. Progression-free survival (PFS) and overall survival (OS) were better in patients with T790M mutation (p = 0.010 and p = 0.017) or third-generation EGFR-TKI treatment (p < 0.0001 and p = 0.073). Interestingly, concomitant genetic alterations were significantly associated with a worse prognosis for patients with EGFR T790M mutation receiving third-generation EGFR-TKIs (p = 0.037).

Conclusions: Multi-platforms are feasible and highly consistent for re-biopsy after EGFR-TKI resistance. Concomitant genetic alterations may be associated with a poor prognosis for patients with EGFR T790M mutation after third-generation EGFR-TKIs.
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http://dx.doi.org/10.1002/cam4.3948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290257PMC
July 2021

Automatic Image Selection Model Based on Machine Learning for Endobronchial Ultrasound Strain Elastography Videos.

Front Oncol 2021 31;11:673775. Epub 2021 May 31.

School of Electronic Information & Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Background: Endoscopic ultrasound (EBUS) strain elastography can diagnose intrathoracic benign and malignant lymph nodes (LNs) by reflecting the relative stiffness of tissues. Due to strong subjectivity, it is difficult to give full play to the diagnostic efficiency of strain elastography. This study aims to use machine learning to automatically select high-quality and stable representative images from EBUS strain elastography videos.

Methods: LNs with qualified strain elastography videos from June 2019 to November 2019 were enrolled in the training and validation sets randomly at a quantity ratio of 3:1 to train an automatic image selection model using machine learning algorithm. The strain elastography videos in December 2019 were used as the test set, from which three representative images were selected for each LN by the model. Meanwhile, three experts and three trainees selected one representative image severally for each LN on the test set. Qualitative grading score and four quantitative methods were used to evaluate images above to assess the performance of the automatic image selection model.

Results: A total of 415 LNs were included in the training and validation sets and 91 LNs in the test set. Result of the qualitative grading score showed that there was no statistical difference between the three images selected by the machine learning model. Coefficient of variation (CV) values of the four quantitative methods in the machine learning group were all lower than the corresponding CV values in the expert and trainee groups, which demonstrated great stability of the machine learning model. Diagnostic performance analysis on the four quantitative methods showed that the diagnostic accuracies were range from 70.33% to 73.63% in the trainee group, 78.02% to 83.52% in the machine learning group, and 80.22% to 82.42% in the expert group. Moreover, there were no statistical differences in corresponding mean values of the four quantitative methods between the machine learning and expert groups (p >0.05).

Conclusion: The automatic image selection model established in this study can help select stable and high-quality representative images from EBUS strain elastography videos, which has great potential in the diagnosis of intrathoracic LNs.
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http://dx.doi.org/10.3389/fonc.2021.673775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201408PMC
May 2021

Endobronchial Ultrasound Multimodal Imaging for the Diagnosis of Intrathoracic Lymph Nodes.

Respiration 2021 Jun 2:1-11. Epub 2021 Jun 2.

Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Endobronchial ultrasound (EBUS) imaging is valuable in diagnosing intrathoracic lymph nodes (LNs), but there has been little analysis of multimodal imaging. This study aimed to comprehensively compare the diagnostic performance of single and multimodal combinations of EBUS imaging in differentiating benign and malignant intrathoracic LNs.

Methods: Subjects from July 2018 to June 2019 were consecutively enrolled in the model group and July 2019 to August 2019 in the validation group. Sonographic features of three EBUS modes were analysed in the model group for the identification of malignant LNs from benign LNs. The validation group was used to verify the diagnostic efficiency of single and multimodal diagnostic methods built in the model group.

Results: 373 LNs (215 malignant and 158 benign) from 335 subjects and 138 LNs (79 malignant and 59 benign) from 116 subjects were analysed in the model and validation groups, respectively. For single mode, elastography had the best diagnostic value, followed by grayscale and Doppler. The corresponding accuracies in the validation group were 83.3%, 76.8%, and 71.0%, respectively. Grayscale with elastography had the best diagnostic efficiency of multimodal methods. When at least two of the three features (absence of central hilar structure, heterogeneity, and qualitative elastography score 4-5) were positive, the sensitivity, specificity, and accuracy in the validation group were 88.6%, 78.0%, and 84.1%, respectively.

Conclusions: In both model and validation groups, elastography performed the best in single EBUS modes, as well as grayscale combined with elastography in multimodal imaging. Elastography alone or combined with grayscale are feasible to help predict intrathoracic benign and malignant LNs.
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http://dx.doi.org/10.1159/000515664DOI Listing
June 2021

Chinese expert consensus on technical specifications of electromagnetic navigation bronchoscopy in diagnosing peripheral pulmonary lesions.

J Thorac Dis 2021 Apr;13(4):2087-2098

Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.21037/jtd-21-369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107541PMC
April 2021

Safety and Performance of Transbronchial Cryobiopsy for Parenchymal Lung Lesions.

Chest 2021 May 7. Epub 2021 May 7.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD. Electronic address:

Background: Despite advances in technology, the bronchoscopic diagnosis of parenchymal pulmonary lesions (PPLs) remains difficult to achieve. Transbronchial lung cryobiopsy (TLCB) offers the potential for larger samples with improved diagnostic yield; however, a paucity of data exists describing its safety and usefulness for the diagnosis of PPL.

Research Question: What is the safety profile of TLCB for PPL?

Study Design And Methods: An observational, retrospective, multicenter cohort study enrolled patients without endobronchial disease undergoing TLCB of PPL from 2015 through 2019. All procedures were performed using both rigid and flexible bronchoscopy with a flexible cryoprobe. Complication rates, including bleeding and pneumothorax rates, were collected. Bleeding was graded on a scale from 0 (trace) to 4 (requiring surgical intervention) with a grade of ≥ 3 considered clinically significant. Pneumothorax, tube thoracostomy placement, diagnostic yield, and need for subsequent interventions were recorded.

Results: One thousand twenty-four patients underwent TLCB. One hundred eighty-eight patients (18%) experienced bleeding; in 36 patients (3.5%), the bleeding was clinically significant. Sixty-eight patients (6.6%) demonstrated a pneumothorax and 64 patients (6.3%) required drainage with tube thoracostomy. All chest drains were removed within 4 days, and no cases of prolonged air leak occurred. A definitive diagnosis was achieved in 932 patients (91%). Adenocarcinoma (46%) and metastatic disease (21%) were the most common diagnoses.

Interpretation: TLCB showed an acceptable safety profile and diagnostic yield for the evaluation of PPL in this large retrospective cohort. Prospective clinical trials are underway to validate these findings further.
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http://dx.doi.org/10.1016/j.chest.2021.04.063DOI Listing
May 2021

Alleviating Class-wise Gradient Imbalance for Pulmonary Airway Segmentation.

IEEE Trans Med Imaging 2021 May 10;PP. Epub 2021 May 10.

Automated airway segmentation is a prerequisite for pre-operative diagnosis and intra-operative navigation for pulmonary intervention. Due to the small size and scattered spatial distribution of peripheral bronchi, this is hampered by a severe class imbalance between foreground and background regions, which makes it challenging for CNN-based methods to parse distal small airways. In this paper, we demonstrate that this problem is arisen by gradient erosion and dilation of the neighborhood voxels. During back-propagation, if the ratio of the foreground gradient to background gradient is small while the class imbalance is local, the foreground gradients can be eroded by their neighborhoods. This process cumulatively increases the noise information included in the gradient flow from top layers to the bottom ones, limiting the learning of small structures in CNNs. To alleviate this problem, we use group supervision and the corresponding WingsNet to provide complementary gradient flows to enhance the training of shallow layers. To further address the intra-class imbalance between large and small airways, we design a General Union loss function that obviates the impact of airway size by distance-based weights and adaptively tunes the gradient ratio based on the learning process. Extensive experiments on public datasets demonstrate that the proposed method can predict the airway structures with higher accuracy and better morphological completeness than the baselines.
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http://dx.doi.org/10.1109/TMI.2021.3078828DOI Listing
May 2021

Dual-source dual-energy thin-section CT combined with small field of view technique for small lymph node in thyroid cancer: a retrospective diagnostic study.

Gland Surg 2021 Apr;10(4):1347-1358

Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: To evaluate the diagnostic performance of quantitative spectral parameters derived from dual-source dual-energy CT at small field of view (FOV) for small lymph node metastasis in thyroid cancer.

Methods: This was a retrospective diagnostic study. From 2016 to 2019, 280 patients with thyroid disease underwent thin-section dual-source dual-energy thyroid CT and thyroid surgery. The data of patients with lymph nodes having a short diameter of 2-6 mm was analyzed. The quantitative dual-energy CT parameters of targeted lymph nodes were measured, and all parameters between metastatic and non-metastatic lymph nodes were compared. These parameters were then fitted to univariable and multivariable binary logistic regression models. The diagnostic role of spectral parameters was analyzed by receiver operating characteristic (ROC) curves and compared with the McNemar test. Small FOV CT images and a mathematical model were used to judge the status of lymph nodes respectively, and then compared with the golden criterion-pathological diagnosis. The cut-off value of the model was 0.4419, with a sensitivity of 90.2% and a specificity of 92.7%.

Results: Of the 216 lymph nodes investigated in this study, 52.3% and 23.6% had a short diameter of 2-3 and 4 mm, respectively. Multiple quantitative CT parameters were significantly different between benign and malignant lymph nodes, and binary regression analysis was performed. The mathematical model was: p=ey/(1+ ey), y=-23.119+0.033× precontrast electron cloud density +0.076× arterial phase normalized iodine concentration +2.156× arterial phase normalized effective atomic number -0.540× venous phase slope of the spectral Hounsfield unit curve +1.676× venous phase iodine concentration. This parameter model had an AUC of 92%, with good discrimination and consistency, and the diagnostic accuracy was 90.3%. The diagnostic accuracy of the CT image model was 43.1%, and for lymph nodes with a short-diameter of 2-3 mm, the diagnostic accuracy was 22.1%.

Conclusions: The parameter model showed higher diagnostic accuracy than the CT image model for diagnosing small lymph node metastasis in thyroid cancer, and quantitative dual-energy CT parameters were very useful for small lymph nodes that were difficult to be diagnosed only on conventional CT images.

Trial Registration: This study is retrospectively registered, and we have registered a prospective study (Registration number: ChiCTR2000035195; http://www.chictr.org.cn).
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http://dx.doi.org/10.21037/gs-20-822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102239PMC
April 2021

Ultrathin bronchoscope combined with virtual bronchoscopic navigation and endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions with or without fluoroscopy: A randomized trial.

Thorac Cancer 2021 06 6;12(12):1864-1872. Epub 2021 May 6.

Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Transbronchial lung biopsy (TBLB) is usually performed to obtain a definitive diagnosis for peripheral pulmonary lesions (PPLs). Ultrathin bronchoscopy combined with virtual bronchoscopic navigation (VBN) and radial endobronchial ultrasound (R-EBUS) are generally considered appropriate diagnostic methods for PPLs; however, they have not yet been explored in combination with fluoroscopy. Therefore, the present prospective randomized controlled trial determined the role of fluoroscopy in ultrathin bronchoscopy combined with VBN and R-EBUS for the diagnosis of PPLs.

Methods: Patients with potentially malignant PPLs were enrolled in the study and randomized into fluoroscopy or nonfluoroscopy groups. In both groups, a 3.0-mm outer and 1.7-mm internal diameter ultrathin bronchoscope was used for transbronchial lung biopsy combined with R-EBUS and VBN. In addition, the fluoroscopy group (FG) underwent fluoroscopy, while the nonfluoroscopy group (NFG) did not.

Results: A total of 126 patients were enrolled and randomized in the study. Among them, 120 patients (60 in the NFG and 60 in the FG) were analyzed. The mean lesion sizes were 26.3 ± 11.4 mm and 29.0 ± 11.3 mm in the NFG and FG, respectively. The diagnostic yield was 73.3% (44/60) in the NFG and 81.7% (49/60) in the FG without statistically significant difference (p = 0.38). No obvious complications occurred in either group.

Conclusions: Ultrathin bronchoscope combined with VBN and R-EBUS without fluoroscopy is a feasible and safe diagnostic method for PPLs.
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http://dx.doi.org/10.1111/1759-7714.13995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201532PMC
June 2021

Endogenous glutamate determines ferroptosis sensitivity via ADCY10-dependent YAP suppression in lung adenocarcinoma.

Theranostics 2021 24;11(12):5650-5674. Epub 2021 Mar 24.

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.

Ferroptosis, a newly identified form of regulated cell death, can be induced following the inhibition of cystine-glutamate antiporter system X because of the impaired uptake of cystine. However, the outcome following the accumulation of endogenous glutamate in lung adenocarcinoma (LUAD) has not yet been determined. Yes-associated protein (YAP) is sustained by the hexosamine biosynthesis pathway (HBP)-dependent O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation), and glutamine-fructose-6-phosphate transaminase (GFPT1), the rate-limiting enzyme of the HBP, can be phosphorylated and inhibited by adenylyl cyclase (ADCY)-mediated activation of protein kinase A (PKA). However, whether accumulated endogenous glutamate determines ferroptosis sensitivity by influencing the ADCY/PKA/HBP/YAP axis in LUAD cells is not understood. Cell viability, cell death and the generation of lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were measured to evaluate the responses to the induction of ferroptosis following the inhibition of system X . Tandem mass tags (TMTs) were employed to explore potential factors critical for the ferroptosis sensitivity of LUAD cells. Immunoblotting (IB) and quantitative RT-PCR (qPCR) were used to analyze protein and mRNA expression. Co-immunoprecipitation (co-IP) assays were performed to identify protein-protein interactions and posttranslational modifications. Metabolite levels were measured using the appropriate kits. Transcriptional regulation was evaluated using a luciferase reporter assay, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). Drug administration and limiting dilution cell transplantation were performed with cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. The associations among clinical outcome, drug efficacy and ADCY10 expression were determined based on data from patients who underwent curative surgery and evaluated with patient-derived primary LUAD cells and tissues. The accumulation of endogenous glutamate following system X inhibition has been shown to determine ferroptosis sensitivity by suppressing YAP in LUAD cells. YAP O-GlcNAcylation and expression cannot be sustained in LUAD cells upon impairment of GFPT1. Thus, Hippo pathway-like phosphorylation and ubiquitination of YAP are enhanced. ADCY10 acts as a key downstream target and diversifies the effects of glutamate on the PKA-dependent suppression of GFPT1. We also discovered that the protumorigenic and proferroptotic effects of ADCY10 are mediated separately. Advanced-stage LUADs with high ADCY10 expression are sensitive to ferroptosis. Moreover, LUAD cells with acquired therapy resistance are also prone to higher ADCY10 expression and are more likely to respond to ferroptosis. Finally, a varying degree of secondary labile iron increase is caused by the failure to sustain YAP-stimulated transcriptional compensation for ferritin at later stages further explains why ferroptosis sensitivity varies among LUAD cells. Endogenous glutamate is critical for ferroptosis sensitivity following the inhibition of system X in LUAD cells, and ferroptosis-based treatment is a good choice for LUAD patients with later-stage and/or therapy-resistant tumors.
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http://dx.doi.org/10.7150/thno.55482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058707PMC
March 2021

Circulating Genetically Abnormal Cells Add Non-Invasive Diagnosis Value to Discriminate Lung Cancer in Patients With Pulmonary Nodules ≤10 mm.

Front Oncol 2021 11;11:638223. Epub 2021 Mar 11.

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Lung cancer screening using low-dose computed tomography (LDCT) often leads to unnecessary biopsy because of the low specificity among patients with pulmonary nodules ≤10 mm. Circulating genetically abnormal cells (CACs) can be used to discriminate lung cancer from benign lung disease. To examine the diagnostic value of CACs in detecting lung cancer for patients with malignant pulmonary nodules ≤10 mm.

Methods: In this prospective study, patients with pulmonary nodules ≤10 mm who were detected at four hospitals in China from January 2019 to January 2020 were included. CACs were detected using fluorescence hybridization. All patients were confirmed as lung cancer or benign disease by further histopathological examination. Multivariable logistic regression models were established to detect the presence of lung cancer using CACs and other associated characteristics. Receiver operating characteristic analysis was used to evaluate the performance of CACs for lung cancer diagnosis.

Results: Overall, 125 patients were included and analyzed. When the cutoff value of CACs was >2, the sensitivity and specificity for lung cancer were 70.5 and 86.4%. Male (OR = 0.330, P = 0.005), maximum solid nodule (OR = 2.362, P = 0.089), maximum nodule located in upper lobe (OR = 3.867, P = 0.001), and CACs >2 (OR = 18.525, P < 0.001) met the P < 0.10 criterion for inclusion in the multivariable models. The multivariable logistic regression model that included the dichotomized CACs (>2 ≤2) and other clinical factors (AUC = 0.907, 95% CI = 0.842-0.951) was superior to the models that only considered dichotomized CACs or other clinical factors and similar to the model with numerical CACs and other clinical factors (AUC = 0.913, 95% CI = 0.850-0.956).

Conclusion: CACs presented a significant diagnostic value in detecting lung cancer for patients with pulmonary nodules ≤10 mm.
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http://dx.doi.org/10.3389/fonc.2021.638223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991838PMC
March 2021

Deletions in the gene are associated with fiber traits in cashmere-producing goats.

Anim Biotechnol 2021 Feb 13:1-7. Epub 2021 Feb 13.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.

Keratin-associated proteins (KAPs) are important structural components of fibers that predominantly present in the ortho-cortex. These proteins form a cross-linked network with keratin intermediate filaments (KIFs), thus producing a strong hair shaft. The keratin-associated protein 6-1 gene () is a member of the KAPs family that has a potential correlation with fiber traits. In this study, we investigated the influence of sequence polymorphisms on the fiber characteristics of a Chinese cashmere-producing goat breed ( = 844). Two main variants were found, including a three base pair (bp) deletion (namely B) and a 36-bp deletion (namely C), while the reference genotype of was named A. Among them, the B variant was first reported on cashmere goats. This study then correlated these genotypes with the collected fiber data to investigate the potential association of these variants. The results showed that variant A is associated with decreased fiber diameter ( < 0.01), while variant C is associated with deceased fiber length ( < 0.01). These two related variants of the gene have potential applications as gene-makers to improve the fiber diameter and length in cashmere-producing goats.
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http://dx.doi.org/10.1080/10495398.2021.1881529DOI Listing
February 2021

Deep learning with convex probe endobronchial ultrasound multimodal imaging: A validated tool for automated intrathoracic lymph nodes diagnosis.

Endosc Ultrasound 2021 Feb 9. Epub 2021 Feb 9.

School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Background And Objectives: Along with the rapid improvement of imaging technology, convex probe endobronchial ultrasound (CP-EBUS) sonographic features play an increasingly important role in the diagnosis of intrathoracic lymph nodes (LNs). Conventional qualitative and quantitative methods for EBUS multimodal imaging are time-consuming and rely heavily on the experience of endoscopists. With the development of deep-learning (DL) models, there is great promise in the diagnostic field of medical imaging.

Materials And Methods: We developed DL models to retrospectively analyze CP-EBUS images of 294 LNs from 267 patients collected between July 2018 and May 2019. The DL models were trained on 245 LNs to differentiate benign and malignant LNs using both unimodal and multimodal CP-EBUS images and independently evaluated on the remaining 49 LNs to validate their diagnostic efficiency. The human comparator group consisting of three experts and three trainees reviewed the same test set as the DL models.

Results: The multimodal DL framework achieves an accuracy of 88.57% (95% confidence interval [CI] [86.91%-90.24%]) and area under the curve (AUC) of 0.9547 (95% CI [0.9451-0.9643]) using the three modes of CP-EBUS imaging in comparison to the accuracy of 80.82% (95% CI [77.42%-84.21%]) and AUC of 0.8696 (95% CI [0.8369-0.9023]) by experts. Statistical comparison of their average receiver operating curves shows a statistically significant difference (P < 0.001). Moreover, the multimodal DL framework is more consistent than experts (kappa values 0.7605 vs. 0.5800).

Conclusions: The DL models based on CP-EBUS imaging demonstrated an accurate automated tool for diagnosis of the intrathoracic LNs with higher diagnostic efficiency and consistency compared with experts.
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http://dx.doi.org/10.4103/EUS-D-20-00207DOI Listing
February 2021

Bronchoscopic submucosal dissection with Hybrid Knife: a new technique treating tracheal leiomyoma.

Eur J Cardiothorac Surg 2021 Feb 7. Epub 2021 Feb 7.

Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.

Primary tracheal leiomyoma is exceedingly rare and recommended management has not been defined yet. Surgical management has been considered to be the standard treatment historically. Bronchoscopic intervention may be an ideal alternative for patients who refuse or are not fit for surgery. We report the first bronchoscopic submucosal dissection using an innovative water-jet Hybrid Knife performed on a patient with recurrent primary tracheal leiomyoma.
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http://dx.doi.org/10.1093/ejcts/ezab040DOI Listing
February 2021

The feasibility of navigation bronchoscopy-guided pulmonary microcoil localization of small pulmonary nodules prior to thoracoscopic surgery.

Transl Lung Cancer Res 2020 Dec;9(6):2380-2390

Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Accurate preoperative localization of small pulmonary nodules facilitates the rapid and precise video-assisted thoracoscopic surgery (VATS). This study aims to evaluate the feasibility, safety, and efficacy of navigation bronchoscopy-guided pulmonary microcoil placement for preoperative pulmonary nodule localization.

Methods: Twelve lung lesions were simulated by mixing lipiodol in three porcine models. After 1 week, two microcoils per lesion were deployed under bronchoscopic guidance. Computed tomography scans were then performed 1 day, 1 week, 2 weeks, and 4 weeks after the deployment to assess the position of the microcoils relative to the lesions. Surgical resection of the simulated lesions was performed under fluoroscopy 5 weeks after the deployment and the accuracy, stability, and associated complications of the microcoil localization were evaluated. Following this, an exploratory clinical study was conducted on three patients with pure ground-glass pulmonary nodules.

Results: The mean diameter of the twelve simulated lung lesions was 9.55±2.36 mm, and the mean distance from the pleura to the lesions was 8.29±2.99 mm. Twenty-four pulmonary microcoils were implanted in the bronchi surrounding the lesions. Four weeks later, the mean distance between the microcoils and the center of the lesions was 16.12±8.97 mm and the average migration of the microcoils relative to the baseline position (1 day after implantation) was 3.48±4.56 mm. All microcoils and target lesions were successfully resected in both the animal experiment and clinical study and no complications, such as pneumothorax, were observed during marker implantation or postoperative follow-up.

Conclusions: The preoperative localization of pulmonary nodules by navigation bronchoscopy-guided microcoil placement is a safe, stable, and effective technique with minimal complication risk. This procedure can assist subsequent thoracoscopic resection.
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http://dx.doi.org/10.21037/tlcr-20-1206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815366PMC
December 2020

Diagnostic value of radial endobronchial ultrasonographic features in predominant solid peripheral pulmonary lesions.

J Thorac Dis 2020 Dec;12(12):7656-7665

Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Transbronchial lung biopsy (TBLB) of peripheral pulmonary lesions (PPLs) is usually performed for a definite diagnosis. Radial probe endobronchial ultrasonography is often acknowledged as a good guidance method for TBLB as it can help physicians confirm the lesions' position. It is also a non-invasive imaging diagnostic method. This clinical study was designed to evaluate the ability of radial endobronchial ultrasonography (R-EBUS) to differentiate benign from malignant predominant solid PPLs based on imaging features.

Methods: Patients with predominant solid PPLs were enrolled in this study retrospectively. TBLB was performed using R-EBUS with or without other guidance techniques. One typical sonographic image and one video of each lesion were recorded for analysis. Six radial probe endobronchial ultrasonographic image features (size, shape, echogenicity, margin, blood vessel, and linear-discrete air bronchogram) were studied by ultrasonography specialists and physicians who were blinded to the final diagnosis. The sum score model of the combined predictive factors indicated the best diagnostic accuracies for predicting malignant PPLs. The model group results were used to establish the diagnostic standard for a verification group.

Results: A total of 303 patients were enrolled in the model group from July 2018 to July 2019 at the Shanghai Chest Hospital (214 with malignant and 89 with benign lesions). The mean lesion long axis on computed tomographic images was 34.39±13.79 mm. There were significant statistical differences between benign and malignant lesions in the long axis, short axis, shape, margin, blood vessel, and linear-discrete air bronchogram assessed by radial endobronchial ultrasound. Long axis, lobulation, distinct but not sharp margin, absence of blood vessel, and absence of linear-discrete air bronchogram were good predictive factors of malignant lesions. A sum score model value of 79.54% of these combined factors indicated the best diagnostic accuracy for predicting malignant lesions. Eighty-seven patients were enrolled in the verification group from August to October 2019. The sum score model showed a diagnostic accuracy of 82.76%.

Conclusions: Radial endobronchial ultrasonographic features can differentiate malignant from benign lesions and thus have potential diagnosis value in predominant solid PPLs.
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http://dx.doi.org/10.21037/jtd-2020-abpd-004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797840PMC
December 2020

Scoring model of convex probe endobronchial ultrasound multimodal imaging in differentiating benign and malignant lung lesions.

J Thorac Dis 2020 Dec;12(12):7645-7655

Department of Respiratory Endoscopy, Shanghai Jiao Tong University, Shanghai, China.

Background: Convex probe endobronchial ultrasound images can reflect the morphology, blood flow status and stiffness of the lesions. Endobronchial ultrasound multimodal imaging has great value for the diagnosis of intrathoracic lymph nodes. This study aimed to analyze the application of endobronchial ultrasound multimodal imaging on lung lesions.

Methods: Patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration in Shanghai Chest Hospital from July 2018 to December 2019 were retrospectively enrolled. Nine grayscale features (long and short axes, margin, shape, lobulation sign, echogenicity, necrosis, liquefaction, calcification, and air-bronchogram), blood flow volume and elastography five-score method were analyzed to explore the best diagnostic method. The gold standard for diagnosing lesions depends on the histological and cytopathological findings of endobronchial ultrasound-guided transbronchial needle aspiration, transthoracic biopsy, resected sample of lesions, microbiological examination or clinical follow-up of at least 6 months.

Results: Endobronchial ultrasound multimodal imaging of 97 malignant lung lesions and 19 benign lung lesions from 116 patients were analyzed. There were statistically significant differences in distinct margin, presence of lobulation sign, presence of necrosis, and elastography grading score 4-5 between malignant and benign lung lesions, among which presence of lobulation sign and elastography grading score 4-5 were independent predictors. A diagnostic scoring model was then constructed based on the above four features, and when two or more features were present, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for malignant lung lesions prediction were 92.78%, 57.89%, 91.84%, 61.11% and 87.07%, respectively.

Conclusions: The combination of endobronchial ultrasound grayscale and elastography has potential value for malignant and benign lung lesions differentiation. The diagnostic scoring model established in this study needs further validation to guide the malignant and benign diagnosis of lung lesions.
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http://dx.doi.org/10.21037/jtd-2020-abpd-005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797845PMC
December 2020

Introduction to new column of advance in bronchoscopy for peripheral pulmonary diseases.

Authors:
Jiayuan Sun

J Thorac Dis 2020 Dec;12(12):7642-7644

Chief Physician, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

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http://dx.doi.org/10.21037/jtd-2020-abpd-007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797842PMC
December 2020

A pilot study of the ultrathin cryoprobe in the diagnosis of peripheral pulmonary ground-glass opacity lesions.

Transl Lung Cancer Res 2020 Oct;9(5):1963-1973

Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: It is very difficult to obtain samples of peripheral pulmonary ground-glass opacity lesions (GGOs) by traditional transbronchial biopsy. This study was conducted to evaluate the diagnostic efficacy and safety of transbronchial cryobiopsy (TBCB) of GGOs using a newly developed ultrathin cryoprobe with an outer diameter of 1.1 mm.

Methods: We retrospectively analyzed 20 patients with 23 GGOs who underwent TBCB using the ultrathin cryoprobe from October 2018 to November 2019 in the Shanghai Chest Hospital. The TBCB procedure was performed under the guidance of virtual bronchoscopic navigation (VBN), electromagnetic navigation bronchoscopy (ENB), endobronchial ultrasound, and fluoroscopy. We collected the baseline information of participants, reported diagnostic yield and complications, and analyzed factors may have affected the diagnostic yield.

Results: A total of 23 GGOs (12 pure GGOs, 11 mixed GGOs), with an average diameter of 21.58±11.88 mm, underwent TBCB, and the diagnostic yield was 82.61% (19/23). Of the 19 GGOs diagnosed by TBCB, 12 were adenocarcinomas, 5 were inflammation, 1 was occupational interstitial lung disease, and 1 was a pulmonary meningothelial-like nodule. The remaining 4 undiagnosed lesions were confirmed to be adenocarcinomas by further analysis. The diagnostic yield was unchanged by factors including size (GGOs ≥20 mm, GGOs <20 mm), navigation (VBN, ENB), fluoroscopic visibility (visible, invisible), GGO-component (pure GGOs, mixed GGOs), and guide sheath (K-201, K203). There was no presentation of pneumothorax or severe hemorrhage.

Conclusions: The ultrathin cryoprobe is feasible, safe, and has a high diagnostic yield in the diagnosis of pulmonary GGOs. There is vast potential for the ultrathin cryoprobe as a tool for the diagnosis of GGOs, especially for cases suspicious of early-stage lung cancer.

Trial Registration: ClinicalTrials.gov. No: NCT03716284. Registered: 20 October, 2018. URL: ClinicalTrials.gov.
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http://dx.doi.org/10.21037/tlcr-20-957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653104PMC
October 2020

Expert panel consensus statement on the applications and precaution strategies of bronchoscopy in patients with COVID-19.

Endosc Ultrasound 2020 Jul-Aug;9(4):211-219

Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus with higher transmissibility compared with SARS coronavirus (SARS-CoV) and Middle East respiratory distress syndrome coronavirus. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an unprecedented global crisis that has not been experienced, which is still disrupting health systems, economies, and societies around the world by the rapid spread. Bronchoscopy plays an important role in diagnosis and therapy of pulmonary diseases, especially in patients with severe pulmonary infection, however, application of bronchoscopy in patients suspected or confirmed SARS-CoV-2 infection is extremely limited for the potential airborne transmission from aerosol generated during the procedure. This consensus statement was completed by expert panel of Interventional & Minimally Invasive Respiratory Committee of China Medical Education Association, and the issues were summarized as seven key topics to define the indications of bronchoscopy and matters needing attentions on the bronchoscopy procedures in patients with COVID-19, as well as the protective precaution strategies to avoid nosocomial SARS-CoV-2 infection.
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http://dx.doi.org/10.4103/eus.eus_45_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529002PMC
August 2020

Diagnostic value of endobronchial ultrasound image features: A specialized review.

Endosc Ultrasound 2021 Jan-Feb;10(1):3-18

Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) technology is important in the diagnosis of intrathoracic benign and malignant lymph nodes (LNs). With the development of EBUS imaging technology, its role in noninvasive diagnosis, as a supplement to pathology diagnosis, has been given increasing attention in recent years. Many studies have explored qualitative and quantitative methods for the three EBUS modes, as well as a variety of multimodal analysis methods, to find the optimal method for the noninvasive diagnosis using EBUS for LNs. Here, we review and comment on the research methods and predictive diagnostic value, discuss the existing problems, and look ahead to the future application of EBUS imaging.
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http://dx.doi.org/10.4103/eus.eus_43_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980684PMC
July 2020

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Prevent Acidic pH-Induced Damage in Human Nucleus Pulposus Cells.

Med Sci Monit 2020 May 21;26:e922928. Epub 2020 May 21.

Department of Spine Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).

BACKGROUND The exosomes (Exo) derived from mesenchymal stem cells (MSCs) are capable of attenuating the apoptosis of nucleus pulposus cells (NPCs) elicited by proinflammatory cytokines. However, it remains unknown whether MSC-derived Exo also exert a protective effect on NPCs in the pathological acid environment. MATERIAL AND METHODS NPCs were divided into 3 groups: Group A, pH 7.1-7.3; Group B, pH 6.5-6.7 and Group C, pH 5.9-6.1. The NPCs were cultured in the above-defined acidic medium, and 3 different amounts of Exo were added into the media. Finally, the expression of the caspase-3, aggrecan, collagen II, and MMP-13 was analyzed and compared among the different groups. RESULTS Compared with cells cultured at pH 7.1-7.3 (Group A), proliferation activity of NPCs cultured at pH 5.9-6.7 (Group B and C) decreased significantly. Collagen II and aggrecan expression was also obviously reduced with the decrease of cell proliferation. Conversely, the expression of caspase-3 and MMP-13 significantly increased. Further experiments showed that proliferation activity was significantly attenuated in NPCs cultured at pH 5.9-6.1 without Exo treatment (Group E) compared with those cultured at pH 7.1-7.3 without Exo treatment (Group D). CONCLUSIONS In the pathological acid environment, MSC-derived Exo promotes the expression of chondrocyte extracellular matrix, collagen II, and aggrecan, and reduces matrix degradation by downregulating matrix-degrading enzymes, protecting NPCs from acidic pH-induced apoptosis. This study reveals a promising strategy for treatment of IVD degeneration.
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http://dx.doi.org/10.12659/MSM.922928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257871PMC
May 2020

The value of navigation bronchoscopy in the diagnosis of peripheral pulmonary lesions: A meta-analysis.

Thorac Cancer 2020 05 4;11(5):1191-1201. Epub 2020 Mar 4.

Department of Respiratory Endoscopy, Shanghai Jiao Tong University, Shanghai, China.

Background: To compare the diagnostic yield of peripheral pulmonary lesions (PPLs) with and without navigation system.

Methods: Studies dating from January 1990 to October 2019 were collected from databases. Diagnostic yield of navigation bronchoscopy and non-navigation bronchoscopy was extracted from comparative studies. Subgroup analysis was adopted to test diagnostic yield variation by lesion size, lobe location of the lesion, distance from the hilum, bronchus sign and nature of the lesion.

Results: In total, 2131 patients from 10 studies were enrolled into the study. Diagnostic yield of navigation bronchoscopy was statistically higher than non-navigation bronchoscopy for PPLs (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.32, 2.18, P < 0.001), particularly for PPLs in the peripheral third lung (OR 2.26, 95% CI 1.48, 3.44, P < 0.001) and for bronchus sign positive PPLs (OR 2.26, 95% CI 1.21, 4.26, P = 0.011). Navigation bronchoscopy had better performance than non-navigation bronchoscopy when PPLs were ≤ 20 mm (OR 2.09, 95% CI 1.44, 3.03, P < 0.001). It also elevated diagnostic yield of malignant PPLs (OR 1.67, 95% CI 1.26, 2.22, P < 0.001) and PPLs in the bilateral upper lobes (OR 1.50, 95% CI 1.09, 2.08, P = 0.014).

Conclusions: Navigation bronchoscopy enhanced diagnostic yield when compared to non-navigation bronchoscopy, particularly for PPLs in the peripheral third lung, PPLs being bronchus sign positive, PPLs ≤ 20 mm, malignant PPLs and PPLs in the bilateral upper lobes.

Key Points: The current study provided systematic evaluation on the diagnostic value of navigation bronchoscopy by comparing it with non-navigation bronchoscopy, and exploring the factors affecting the diagnostic yield.
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http://dx.doi.org/10.1111/1759-7714.13373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180606PMC
May 2020

Design of a prospective, multicenter, and cohort study of an innovative electromagnetic navigation bronchoscopy in diagnosing pulmonary nodules among Chinese population.

J Thorac Dis 2019 Dec;11(12):5592-5600

Department of Respiratory Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

Electromagnetic navigation bronchoscopy (ENB) has been demonstrated to increase the diagnostic yield of peripheral pulmonary lesions. We designed two prospective clinical trials using an innovative ENB system that can combine with both thick and thin bronchoscope, including a randomized controlled clinical study to assess the usefulness of the ENB system and a real-world study to explore the optimal way to use this system. Patients with peripheral pulmonary nodules (PPNs) suspicious of lung cancer with the long diameter more than 8 mm and no more than 30 mm will be enrolled in the study. A total of 400 patients will be enrolled in the randomized controlled clinical study and randomly divided into two groups, endobronchial ultrasound (EBUS) combined with guide sheath (GS) with or without ENB. The real-world study is a single arm and observational study, at least 750 subjects will be enrolled in the study. ENB combined with or without other guided bronchoscopy techniques, fluoroscopy, and rapid on-site cytologic evaluation (ROSE) will be performed according to the judgment of the operator. The primary endpoint of the two studies is the diagnostic yield of ENB in diagnosing PPNs. The secondary endpoint includes the diagnostic yields for malignant and benign diseases, navigation time, time for finding lesions, total operation time, complication rate, etc. Enrollment for the study began in July 2018 and is currently in progress. With up to 1,150 subjects estimated to be enrolled, the study will provide evidence on the usage of the novel ENB system in diagnosing PPNs.
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http://dx.doi.org/10.21037/jtd.2019.11.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988046PMC
December 2019

Determining factors of endobronchial ultrasound-guided transbronchial needle aspiration specimens for lung cancer subtyping and molecular testing.

Endosc Ultrasound 2019 Nov-Dec;8(6):404-411

Department of Respiratory Endoscopy and Pulmonary Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: This study is to explore the determining factors for testing epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) fusion after subtyping by immunohistochemistry (IHC) using samples obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

Materials And Methods: Patients suspected with advanced lung cancer were performed EBUS-TBNA without rapid on-site evaluation(ROSE) from January 2015 to March 2016 in Shanghai Chest Hospital. All samples diagnosed as lung cancer by histopathology underwent IHC to identify subtypes. EGFR mutation and ALK fusion were tested in adenocarcinoma and non-small-cell lung cancer-not otherwise specified (NSCLC-NOS) using remnant tissue samples.

Results: A total of 453 patients were diagnosed with lung cancer, including 44.15% (200/453) with adenocarcinoma and 11.04% (50/453) with NSCLC-NOS. With the average passes of 3.41 ± 0.68, samples obtained from EBUS-TBNA were adequate for performing EGFR mutation and ALK fusion gene analysis in 80.4% (201/250) of specimens after routine IHC. On univariate analysis, successful molecular testing was associated with passes per lesion (P = 3.80E-05), long-axis diameters (P = 6.00E-06) and short-axis diameters (P = 4.77E-04), and pathology subtypes of lesions (P = 3.00E-03). Multivariate logistic regression revealed that passes per lesion (P = 1.00E-03), long-axis diameters (P = 3.50E-02), and pathology subtypes (P = 8.00E-03) were independent risk factors associated with successful molecular testing.

Conclusions: With at least three passes of per lesion, EBUS-TBNA is an efficient method to provide adequate samples for testing of EGFR mutation and ALK gene arrangement following routine histopathology and IHC subtyping. Determining factors associated with successful pathology subtyping and molecular testing using samples obtained by EBUS-TBNA are passes of per lesion, long-axis diameter, and pathology subtypes. During the process of EBUS-TBNA, selecting larger lymph nodes and the puncturing at least 3 passes per lesion may result in higher success rate in lung cancer subtyping and molecular testing.
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http://dx.doi.org/10.4103/eus.eus_8_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927142PMC
November 2019

Initial Experience with Hybrid Argon Plasma Coagulation as a Novel Local Treatment Method for Tracheobronchial Mucoepidermoid Carcinoma.

Respiration 2019;98(5):461-466. Epub 2019 Sep 27.

Department of Respiratory Endoscopy and Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China,

Tracheobronchial mucoepidermoid carcinoma (MEC) is a type of salivary gland tumor. Surgical resection is the main treatment for MEC, but it is associated with risks. Hybrid argon plasma coagulation (HybridAPC®) is an innovative technique combining APC with a water cushion function which can be used for the treatment of MEC. We aimed to evaluate the efficacy and safety of HybridAPC for MEC in 2 patients diagnosed with MEC based on histological examination of biopsies. Full preoperative assessments were done by white-light bronchoscopy, autofluorescence imaging, narrow-band imaging, and radial probe endobronchial ultrasound. HybridAPC was administered after these evaluations. Both patients were followed up for more than 3 months. HybridAPC ablation was completed successfully, with no complications. HybridAPC thus appears to be a safe and efficient treatment for MEC.
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http://dx.doi.org/10.1159/000501239DOI Listing
September 2020

Next-Generation Sequencing for Genotyping of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Samples in Lung Cancer.

Ann Thorac Surg 2019 07 15;108(1):219-226. Epub 2019 Mar 15.

Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China; Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China. Electronic address:

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can obtain a small amount of specimen. This study aims to evaluate the feasibility and robustness of using EBUS-EBNA samples to perform capture-based targeted next-generation sequencing (NGS).

Methods: Tissue samples from patients with advanced non-small cell lung cancer were collected by EBUS-TBNA and were formalin-fixed paraffin-embedded. Three representative genes, EGFR, ALK, and ROS1, were examined by amplification refractory mutation system polymerase chain reaction, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction. The remaining samples were processed with NGS assay with a 56-gene panel. Classic driver mutations detected by NGS were verified by conventional methods.

Results: Of the 85 samples from patients with advanced non-small cell lung cancer, 77 were performed successfully with all assays. Forty-one mutations in EGFR, ALK, and ROS1 were detected in both conventional methods and NGS, representing a 100% concordance. In contrast, four EGFR mutations detected by NGS were not covered in the targeted regions of amplification refractory mutation system polymerase chain reaction, leading to a negative call in these patients. Altogether, NGS detected 12 additional variants, including six KRAS mutations, one BRAF mutation, one RET fusion, one MET amplification concurrent with EGFR L858R, one KRAS amplification together with EGFR 19del, and one ERBB2 amplification. The mean number of needle passes per lymph node was 5.2 in samples successfully applied in all assays.

Conclusions: NGS assay can be successfully conducted with limited tissue samples obtained from EBUS-TBNA. Compared with conventional methods, NGS assay provides more comprehensive information on genetic alterations in tumors, which greatly assists therapeutic decision making for advanced lung cancer.
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http://dx.doi.org/10.1016/j.athoracsur.2019.02.010DOI Listing
July 2019

The Cryoablation for Peripheral Pulmonary Lesions Using a Novel Flexible Bronchoscopic Cryoprobe in the ex vivo Pig Lung and Liver.

Respiration 2019;97(5):457-462. Epub 2019 Feb 21.

Department of Endoscopy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China,

Background: Percutaneous cryoablation has been used for the treatment of lung cancer and has been shown to be safe and effective. However, some lung cancer lesions cannot be reached by percutaneous puncture; using bronchoscopy cryoablation is necessary in these cases.

Purposes: To examine the efficiency and security of a flexible cryoprobe, we measured the size and temperature distribution of the frozen area (ice ball) in ex vivo pig lung and liver and the temperature of the bronchoscope.

Methods: We evaluated flexible cryoprobe cryoablation using a bronchoscope in ex vivo pig lung and a flexible cryoprobe alone in ex vivo pig liver. Seven temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.3, 0.6, 0.9, 1.2, 1.5, and 1.8 cm from the cryoprobe. Two temperature sensors were positioned at the surface of the bronchoscope. The ex vivo pig lung and liver were perfused with 37°C saline and the former was inflated using a ventilator to simulate in vivo lung conditions. The whole operation is usually 2-3 freezing cycles.

Results: In ex vivo pig liver, probes made ice balls of 33.2 ± 0.2 mm in diameter. In ex vivo pig lung, probes made ice balls of 35.1 ± 1.7 mm in diameter. The temperature at the surface of the bronchoscope at distances of 1 and 10 cm from the cryoprobe reached 21.1 ± 0.1 and 10.5 ± 0.2°C.

Conclusion: A flexible cryoprobe using a bronchoscope in ex vivo pig lung and liver was a sufficiently safe treatment method.
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http://dx.doi.org/10.1159/000494142DOI Listing
September 2020

Diagnosing a solitary pulmonary nodule using multiple bronchoscopic guided technologies: A prospective randomized study.

Lung Cancer 2019 03 16;129:48-54. Epub 2019 Jan 16.

Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Air Force Medical University, Xi'an, PR China. Electronic address:

Background: The rate of detection of pulmonary nodules on computed radiography (CR) is approximately 0.09-0.2%, so rapid identification of the nature of solitary pulmonary nodules (SPNs) with a likelihood of malignancy is a critical challenge in the early diagnosis of lung cancer.

Objective: We conducted this study to compare the diagnostic yield and safety of endobronchial ultrasonography with a guide sheath (EBUS-GS), and the combination of EBUS-GS and virtual bronchoscopic navigation (VBN).

Methods: This was a prospective, multicenter, multi-arm, randomized controlled trial involving a total of 1010 subjects. All the patients recruited underwent a chest CT scan which found SPNs that needed to be diagnosed. The subjects were randomly divided into one of three groups: a traditional, non-guided, bronchoscopy biopsy group (NGB group), an EBUS-GS guided bronchoscopy biopsy group (EBUS group), and a guided bronchoscopy biopsy group that combined EBUS-GS with VBN (combined group). The primary endpoint was to investigate the differences between the diagnostic yields of the three groups.

Results: There was no significant difference in the diagnostic yield between the EBUS group (72.3%) and the combined group (74.3%), but the diagnostic yield for the NGB group was 41.2%. The time required to reach biopsy position was significantly less in the combined group (7.96 ± 1.18 min in the combined group versus 11.92 ± 5.37 min in the EBUS group, p < 0.05). However, the bronchoscope operation time was the same in the EBUS-GS and combined groups. The diagnostic yield for peripheral pulmonary lesions (PPLs) >20 mm in diameter was significantly higher than for those <20 mm in diameter.

Conclusion: The results of our study suggest that guided bronchoscopy could increase the diagnostic yield in the context of peripheral lesions. There was no significant difference in the diagnostic yield between the EBUS and combined groups, but use of EBUS-GS with VBN could significantly shorten the bronchoscope arrival time.
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http://dx.doi.org/10.1016/j.lungcan.2019.01.006DOI Listing
March 2019

Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy.

Eur Respir J 2019 03 7;53(3). Epub 2019 Mar 7.

Dept of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Anlotinib has been demonstrated in clinical trials to be effective in prolonging the progression-free survival (PFS) and overall survival (OS) of refractory advanced nonsmall cell lung cancer (NSCLC) patients. However, the underlying molecular mechanisms and predictive biomarkers of anlotinib are still unclear.

Methods: A retrospective analysis of anlotinib administered to 294 NSCLC patients was performed to screen for underlying biomarkers of anlotinib-responsive patients. Transcriptome and functional assays were performed to understand the antitumour molecular mechanisms of anlotinib. Changes in serum CCL2 levels were analysed to examine the correlation of the anlotinib response between responders and nonresponders.

Results: Anlotinib therapy was beneficial for prolonging OS in NSCLC patients harbouring positive driver gene mutations, especially patients harbouring the epithelial growth factor receptor (EGFR) mutation. Moreover, anlotinib inhibited angiogenesis in an NCI-H1975-derived xenograft model inhibiting CCL2. Finally, anlotinib-induced serum CCL2 level decreases were associated with the benefits of PFS and OS in refractory advanced NSCLC patients.

Conclusions: Our study reports a novel anti-angiogenesis mechanism of anlotinib inhibiting CCL2 in an NCI-H1975-derived xenograft model and suggests that changes in serum CCL2 levels may be used to monitor and predict clinical outcomes in anlotinib-administered refractory advanced NSCLC patients using third-line therapy or beyond.
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http://dx.doi.org/10.1183/13993003.01562-2018DOI Listing
March 2019
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