Experimental demonstration of flexible information rate PON beyond 100 Gb/s with rate-compatible LDPC codes.

The applications of rate-compatible low-density parity-check (RC-LDPC) codes are investigated for a 16 quadrature amplitude modulation (16QAM) signal and coherent detection system. With rate-compatible signals, we can provide the flexible net data rate between 135.5 Gb/s and 169.7 Gb/s in a passive optical network (PON) link. Based on the LDPC codes defined in the IEEE 802.3ca standard, we construct two sets of RC-LDPC codes with a fixed and variable information bit length. Since the puncturing operation may degrade the performance of LDPC codes, we apply the protograph-based extrinsic information transfer (PEXIT) technique to optimize the puncturing positions to mitigate the degradation. Additionally, we explore four low-complexity LDPC decoding algorithms (min sum, offset min sum, variable weight min sum, and relaxed min sum with 2nd min emulation) to investigate the relationship between the computational complexity and decoding performance. Simulation results indicate that the constructed codewords exhibit good performance in the waterfall region across a range of code rates. Finally, we conduct an experimental setup in a dual-polarization 25 GBaud 16QAM coherent PON to verify the effectiveness of the constructed LDPC codes with four decoding algorithms. The experimental results show maximal 4.8 dB receiver sensitivity differences, which demonstrate the feasibility of the method for constructing RC-LDPC codes in future high-speed flexible coherent PON.

Identification of the intersegmental plane via electromagnetic navigation for anatomical segmentectomy.

Accurate identification of the physiological intersegmental plane is crucial for successful anatomical segmentectomy. Current techniques, such as the inflation-deflation method, may result in uncertain cutting lines, leading to unsuitable resection extents. Here, we demonstrated the successful use of electromagnetic navigation with methylene blue dye-marking to preoperatively and precisely identify the physiological intersegmental plane in two patients with small-sized peripheral non-small cell lung cancer (NSCLC). This novel technique offers the potential for precise cutting lines that align closely with the physiological intersegmental plane, thus improving the accuracy and efficacy of anatomical segmentectomy for these selected NSCLC patients.

A combined diagnostic model based on circulating tumor cell in patients with solitary pulmonary nodules.

BACKGROUND: Although many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor-positive circulating tumor cells (FR+ CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model. METHODS: A total of 898 patients with a solitary pulmonary nodule who received FR+ CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model. RESULTS: The positive rate of FR+ CTC between patients with non-small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+ CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+ CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07-1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01-1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01-1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+ CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587-0.713) in the training set and 0.700 (95% CI, 0.603-0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659-0.791) in the training set and 0.828 (95% CI, 0.754-0.902) in the validation set, respectively. CONCLUSIONS: We confirmed the value of FR+ CTC in diagnosing SPNs and developed a prediction model based on FR+ CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.

Age-dependent genomic characteristics and their impact on immunotherapy in lung adenocarcinoma.

BACKGROUND: The incidence of lung cancer tends to be younger, and adenocarcinoma is the main histological type. Even patients with the same tumor type may have significant differences in clinical features, tumor microenvironment and genomic background at different ages. Immune checkpoint inhibitors (ICIs) have been shown to improve clinical outcomes in patients with lung adenocarcinoma (LUAD). However, differences in ICI efficacy between older and younger patients are unknown. Our study aimed to explore the relationship between age and immunotherapy in LUAD. METHODS: In our study, 1313 resected LUAD patients in our hospital were divided into young (age ≤ 50) and old groups (age > 50), and the clinical characteristic differences between them were analyzed. Of these, next-generation sequencing (NGS) was performed on the 311 cases. In addition, immune-related signatures of 508 LUAD patients were analyzed by TCGA RNA expression data. Then, we validated genomic and clinical information of 270 LUAD samples in the MSKCC cohort. RESULTS: ERBB2 and EGFR gene mutations were significantly different between the two groups, and the gene mutation number in the old group was significantly higher than that in the young group. In addition, immune-related signatures of LUAD patients were analyzed by TCGA RNA expression data, which indicated that the patients in the old group might have a better immune microenvironment. Then, we validated the MSKCC cohort and found that the TMB of the old group was significantly higher than that of the young group, and the OS of immunotherapy was longer in the old group. CONCLUSION: Our study was the first to analyze the differences in the genomic landscape and immune-related biomarkers between the young and old groups of LUAD patients and found that the old group had a better efficacy of immunotherapy, providing a reference for the study design and treatment of patients with LUAD.

Genomic and clinicopathological features of lung adenocarcinomas with micropapillary component.

Background: Lung adenocarcinoma (LA) with a micropapillary component (LAMPC) is a histological subtype of lung cancer that has received increasing attention due to its correlation with poor prognosis, and its tendency to recur and metastasize. At present, comprehensive genomic profiles and clinicopathological features for LAMPC remain unclear and require further investigation. Methods: From September 2009 to October 2020, a total of 465 LAMPC patients were recruited and divided into four groups according to MPC proportions, and the correlations between varying proportions of MPCs and clinicopathological characteristics were analyzed. Twenty-nine (29) LAMPC patients and 89 LA patients without MPC (non-MPC) that had undergone NGS testing were selected for further study The comprehensively analyze genomic variations and the difference between LAMPC and MPC were determined. In addition, Gene alterations of LAMPC between Chinese and Western populations were also compared using cBioPortal data. Results: A higher proportion of MPCs, associated with higher tumor stage, pleural invasion, and vascular tumor thrombus formation, was determined in LA patients. Compared to non-MPC patients, LAMPC patients were determined to have a lower frequency of single nucleotide variants and a higher frequency of insertion-deletion mutations. Mutations in TP53, CTNNB1, and SMAD4, and ALK rearrangements/fusions were significantly more frequent in LAMPC patients. ERBB2 mutations were only detected in non-MPC patients. Gene mutations in the Wnt pathway were significantly more common in LAMPC patients as compared to non-MPC patients. ALK fusions were more prevalent in younger patients. Patients with KRAS or LBP1B mutations had significantly larger tumor diameters than patients with wild-type KRAS or LBP1B. Patients with KRAS mutations were more likely to develop vascular tumor thrombus. Using the cBioPortal public database, we determined that mutations in EGFR were significantly higher in Chinese patients than in a Memorial Sloan Kettering Cancer Center (MSKCC) Western cohort. ALK fusions were exclusively detected in the Chinese cohort, while mutations in KEAP1 and NOTCH4 were only detected in the MSKCC cohort. Our analysis of signaling pathways revealed that Wnt pathway gene mutations were significantly higher in the Chinese cohort. Conclusion: LA patients with higher proportions of MPCs were determined to have a higher tumor stage, pleural invasion, and vascular tumor thrombosis formation. We comprehensively analyzed the genomic mutation characteristics of LAMPC patients and identified multiple, novel MPC-related gene alterations and pathway changes. Our data provide further understanding of the nature of the LAMPC and potential drug-targeted gene alterations, which may lead to new therapeutic strategies.

Effects of Camrelizumab Combined with First-Line Chemotherapy on Serum SCC, VEGF Levels, and Adverse Reactions in Patients with Advanced Squamous Cell Carcinoma of the Lung.

Objective: To study the effects of camrelizumab accompanied by first-line chemotherapy on serum SCC, VEGF levels, and adverse reactions in people undergoing advanced lung squamous cell carcinoma. Methods: Data sources of the study subjects were 60 people suffering from advanced squamous cell carcinoma of the lung hospitalized from January 2018 to October 2019. They were assigned to two groups, including the control group and the observation group in a random manner, and each consisted of 30 patients. Those in the observation group received camrelizumab (SHR-1210), and gemcitabine plus cisplatin (GP) chemotherapy were treated in the control group. Finally, according to the results, we compare the data of patients in both groups so as to find out the similarities and differences. Results: Among them, the effective efficiency of clinical treatment in the control group reached 36.67%, and that in the observation group reached 56.67%. Intuitively, it can be concluded that the control group showed lower results than the observed group. The observed group turned out to have higher periodic survival and progression free survival (PFS) of patients than the other group. During and after the cycle treatment, the data of SCC and VEGF were reduced to some extent, but the control group appeared to have a more evident reduction rate than the other group. Conclusion: SHR-1210 combined with chemotherapy has a considerable effect in practical application and has excellent clinical performance.

Necroptosis-Related Prognostic Signature and Nomogram Model for Predicting the Overall Survival of Patients with Lung Cancer.

Background: Necroptosis is a type of programmed cell death mode and it serves an important role in the tumorigenesis and tumor metastasis. The purpose of this study is to develop a prognostic model based on necroptosis-related genes and nomogram for predicting the overall survival of patients with lung cancer. Method: Differentially expressed necroptosis-related genes (NRDs) between lung cancer and normal samples were identified. Univariate and LASSO regression analyses were performed to establish a risk score (RS) model, followed by validation within TCGA and GSE37745. The correlation between RS model and tumor microenvironment, mutation status, or drug susceptibility was analyzed. By combining clinical factors, nomogram was developed to predict 1-, 3-, and 5-year survival probability of an individual. The biological function involved by different risk groups was conducted by GSEA. Results: A RS model containing six NRDs (FLNC, PLK1, ID1, MYO1C, SERTAD1, and LEF1) was constructed, and patients were divieded into low-risk (LR) and high-risk (HR) groups. Patients in HR group were associated with shorter survival time than those in the LR group; this model had better prognostic performance. Nomogram based on necroptosis score, T stage, and stage had been confirmed to predict survival of patients. The number of resting NK cells and M0 macrophages was higher in HR group. In addition, higher tumor mutational burden and drug sensitivity were observed in the HR group. Patients in HR group were involved in p53 signaling pathway and cell cycle. Conclusion: This study constructed a robust six-NRDs signature and established a prognostic nomogram for survival prediction of lung cancer.

The long-term oncologic outcomes of robot-assisted bronchial single sleeve lobectomy for 104 consecutive patients with centrally located non-small cell lung cancer.

Background: Up to now, no study has described the long-term survival and its prognostic factors of robot-assisted sleeve lobectomy. Here, the present cohort study reported the long-term oncologic outcomes of robot-assisted sleeve lobectomy to evaluate the oncological feasibility of sleeve lobectomy via a robotic surgical system in patients with centrally located non-small cell lung cancer (NSCLC). Methods: A total of 104 consecutive patients with centrally located NSCLC who underwent robot-assisted bronchial single sleeve lobectomy between October 2014 and May 2021 were retrospectively reviewed. Bronchial single sleeve lobectomy only refers to the resection and end-to-end anastomosis reconstruction of the bronchus, without the resection of the pulmonary vessels or carina. The recurrence status during follow-up, 5-year overall survival (OS) and disease-free survival (DFS) were assessed. Results: In the total cohort, 47 (45.2%) patients had pathological stage I disease, 28 (26.9%) patients had pathological stage II disease, and 29 (27.9%) patients had pathological stage III disease. Recurrence occurred in 26 (25.0%) patients, including locoregional recurrence in 10 (9.6%) patients and distant recurrence in 16 (15.4%) patients. No endobronchial nor perianastomotic recurrence was detected. The Kaplan-Meier curves indicated that the 5-year DFS and OS rates in the cohort were 67.9% and 73.0%, respectively. In terms of pathological stages, the 5-year DFS and OS rates were 82.9% and 82.2% for stage I patients, 57.8% and 69.7% for stage II patients, and 54.5% and 63.7% for stage III patients, respectively. Multivariable analyses demonstrated that higher pathological stage or N2 stage were independent risk factors for poorer DFS and OS. Conclusions: Robot-assisted bronchial single sleeve lobectomy could be an oncologically adequate procedure for patients with centrally located NSCLC, due to the long-term survival was similar to that reported for video-assisted thoracoscopic surgery (VATS) or open technique. Further studies of comparative studies or high-quality randomized controlled trials are required.

Single utility port approach in robot-assisted sleeve segmentectomy for bronchial carcinoid tumor.

Bronchial carcinoid tumors are low-grade malignant and lung-sparing surgery is preferred for the removal of these tumors. We describe a surgical technique of robot-assisted sleeve segmentectomy via single utility port approach with three robotic arms. This operation was performed in an aged patient with decreased pulmonary function, whose carcinoid tumor was located at the origin of the right superior segmental bronchus. A 1.5-cm incision was performed in the eighth intercostal space of the midaxillary line and another 4-cm incision was made in the fifth intercostal space of the anterior axillary line. Postoperative recovery of the patient was smooth without postoperative complications.

Risk of Acute Lung Injury after Esophagectomy.

To develop a new approach for identifying acute lung injury (ALI) in surgical ward setting and to assess incidence rate, clinical outcomes, and risk factors for ALI cases after esophagectomy. We also compare the degree of lung injury between operative and non-operative sides. Consecutive esophageal cancer patients (n=1022) who underwent esophagectomy from Dec 2012 to Nov 2018 in our hospital were studied. An approach for identifying ALI was proposed that integrated radiographic assessment of lung edema (RALE) score to quantify degree of lung edema. Stepwise logistic regression identified risk factors for postoperative ALI incidence. The degree of bilateral lung injury was compared using the RALE score. The approach for identifying ALI in surgical ward setting was defined as acute onset, PaO2/FiO2≤300 mmHg, bilateral opacities on bedside chest radiograph with a RALE score≥16, and exclusion of cardiogenic pulmonary edema. Incidence rate of ALI was estimated to be 9.7%. ALI diagnosis was associated with multiple clinical complications, prolonged hospital stay, higher medical bills, and higher perioperative mortality. Nine risk factors including BMI, ASA class, DLCO%, duration of surgery, neutrophil percentage, high-density lipoprotein, and electrolyte disorders were identified. The RALE score of the lung lobes of the operative side was higher than the non-operative side. A new approach for identifying ALI in esophageal cancer patients receiving esophagectomy was proposed and several risk factors were identified. ALI is common and has severe outcomes. The lung lobes on the operative side are more likely to be affected than the non-operative side.

Systems biomarker characteristics of circulating alkaline phosphatase activities for 48 types of human diseases.

BACKGROUND: Most human diseases are accompanied by systems changes. Systems biomarkers should reflect such changes. The phosphorylation and dephosphorylation of biomolecules maintain human homeostasis. However, the systems biomarker characteristics of circulating alkaline phosphatase, a routine blood test conducted for many human diseases, have never been investigated. METHOD: This study retrieved the circulating alkaline phosphatase (ALP) activities from patients with 48 clinically confirmed diseases and healthy individuals from the database of our hospital during the past five years. A detailed analysis of the statistical characteristics of ALP was conducted, including quantiles, receiving operator curve (ROC), and principal component analysis. RESULTS: Among the 48 diseases, 45 had increased, and three had decreased median levels of ALP activities compared to the healthy control. Preeclampsia, hepatic encephalopathy, pancreatic cancer, and liver cancer had the highest median values, whereas nephrotic syndrome, lupus erythematosus, and nephritis had decreased median values compared to the healthy control. Further, area under curve (AUC) values were ranged between 0.61 and 0.87 for 19 diseases, and the ALP activities were the best systems biomarker for preeclampsia (AUC 0.87), hepatic encephalopathy (AUC 0.87), liver cancer (AUC 0.81), and pancreatic cancer (AUC 0.81). CONCLUSIONS: Alkaline phosphatase was a decent systems biomarker for 19 different types of human diseases. Understanding the molecular mechanisms of over-up-and-down-regulation of ALP activities might be the key to understanding the whole-body systems' reactions during specific disease progression.

Electromagnetic navigational bronchoscopy-guided dye marking to identify the subsegmental bronchus in thoracoscopic anatomic subsegmentectomy.

Video-assisted thoracoscopic surgery (VATS) subsegmentectomy has been widely used to resect small-sized lung lesions in clinical practice. Precise identification of the subsegmental bronchus is one of the essential steps in performing thoracoscopic anatomic subsegmentectomy. Here, we report a thoracoscopic right S2 a segmentectomy with preoperative electromagnetic navigational bronchoscopy (ENB)-guided injection of methylene blue to identify the subsegmental bronchus in a 51-year-old male. We successfully performed complicated surgery using this method. This ENB-guided dye marking method may accurately distinguish the subsegmental bronchus to effectively guide surgery.

Perioperative safety and feasibility outcomes of stage IIIA-N2 non-small cell lung cancer following neoadjuvant immunotherapy or neoadjuvant chemotherapy: a retrospective study.

BACKGROUND: We sought to determine the perioperative safety and feasibility outcomes of stage IIIA (N2) non-small cell lung cancer (NSCLC) following neoadjuvant immunotherapy or neoadjuvant chemotherapy. METHODS: The clinical details of patients who attended the Affiliated Hospital of Qingdao University between January 2019 and December 2020 were retrospectively evaluated. Eligible patients had pathologically proven stage IIIA (N2) NSCLC and were randomly prescribed neoadjuvant therapy. Those in the neoadjuvant immunotherapy group received two cycles of nivolumab (3 mg/kg) and those in the control group received neoadjuvant chemotherapy (1,000 mg/m2 gemcitabine and 80 mg/m2 cisplatin). All patients were scheduled to undergo surgery. The primary endpoint was the risk of major complications within 30 days of surgery and the secondary endpoints were interval to surgery and 30-day mortality. RESULTS: A total of 107 eligible patients were evaluated of whom 25 were allocated to the neoadjuvant immunotherapy group and 82 to the neoadjuvant chemotherapy group. The median interval to surgery was similar in the two groups at 29.2 days [95% confidence interval (CI), 27.1 to 31.4 days] in the immunotherapy group and 28.7 days (95% CI, 27.6 to 29.8 days) in the chemotherapy group (P=0.656). While treatment-related adverse events were reported in most patients, all 25 patients completed two cycles of neoadjuvant immunotherapy and 80 of 82 patients completed two cycles of neoadjuvant chemotherapy, although one patient in the latter group died within 30 days of surgery. There was no statistically significant difference between the groups in the probability of grade 3 or higher postoperative complications within 30 days after surgery (P=0.757). CONCLUSIONS: Most patients achieved the primary and secondary endpoints of the study. However, the major pathological response (MPR) showed statistically significant differences between the neoadjuvant immunotherapy and neoadjuvant chemotherapy groups.

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p.

BACKGROUND: As a type of non-coding RNA, circular RNAs (circRNAs) are considered to be functional molecules associated with human cancers. An increasing number of circRNAs have been verified in malignant progression in a number of cancers. The circRNA, circFBXW7, has been proven to play an important role in tumor proliferation and metastasis. However, whether circFBXW7 influences progression in lung adenocarcinoma (LUAD) remains unclear. METHODS: Quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify circFBXW7 in LUAD cell lines and LUAD tissues. Kaplan-Meier analysis was then used to compare the disease-free survival (DFS) and overall survival (OS) of these LUAD patients. The biological function of circFBXW7 was examined by overexpression and knockdown of circFBXW7 using MTT assay, EdU assay, wound-healing assay, and Transwell in vitro assays. To explore the mechanism of the circFBXW7, RNA pull-down assay, dual luciferase reporter assay, and RNA immunoprecipitation (RIP) assay were employed to examine the interaction between circFBXW7 and miR-942-5p. Western blot was used to study the fundamental proteins associated with the epithelial-mesenchymal transition (EMT) pathway. In vivo studies with BALB/c nude mice subcutaneously injected with cells stably overexpressing circFBXW7 were performed to further validate the in vitro results. RESULTS: circFBXW7 was downregulated in LUAD cell lines and tissues, and LUAD patients with lower levels had shorter DFS and OS. The in vitro study showed that circFBXW7 overexpression inhibited proliferation and migration of A549 and HCC2279 cell lines. These results were confirmed by circFBXW7 knockdown, which showed the reverse effect. The in vivo model showed that the circRNA levels influenced the tumor growth. Finally, we determined that circFBXW7 target miRNA-942-5p which regulates the EMT gene BARX2. The modulation of circFBXW7 levels produced significant changes in EMT genes in vitro and in vivo. CONCLUSIONS: Our findings showed that circFBXW7 inhibits proliferation and migration by controlling the miR-942-5p/BARX2 axis in LUAD cell lines and its levels correlates with patient survival suggesting that regulating circFBXW7 could have therapeutic value in treating LUAD patients.

Different efficacy in the non-small cell lung cancer patient with bilateral synchronous lesions treated with neoadjuvant gefitinib therapy: a case report.

Gefitinib, the first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has become the standard of care for the first-line of therapy for advanced non-small cell lung cancer (NSCLC) with common EGFR mutation. However, the efficacy of preoperative gefitinib therapy in patients with common EGFR mutations remains poorly defined. We describe a NSCLC patient with bilateral synchronous lesions who had a significantly positive response to gefitinib before radical surgical resection. At the time of initial diagnosis, we were unable to confirm whether the two lesions were metastatic or synchronous primary lesions. Accordingly, we performed CT-guided percutaneous left lung biopsy resulting in a diagnosis of lung adenocarcinoma with exon 21 L858R point mutation of EGFR, This diagnosis was followed by preoperative gefitinib therapy for 8 weeks leading to a significant reduction in the lesion in the left lower lobe. Then the left lower lobectomy and mediastinal lymphadenectomy were performed. In addition, 3 months following resection of the left lower lobe tumor the patient underwent a right lower lobe wedge resection. This report indicates that NSCLC patient harboring common EGFR mutation accepting the first-generation EGFR-TKI gefitinib as a neoadjuvant targeted therapy option is safe, feasible, and well-tolerated.

Robotic sleeve lobectomy for centrally located non-small cell lung cancer: A propensity score-weighted comparison with thoracoscopic and open surgery.

OBJECTIVE: To evaluate the surgical and oncologic outcomes of robotic sleeve lobectomy in comparison with video-assisted thoracoscopic surgery (VATS) and open surgery. METHODS: Surgical outcomes in patients with non-small cell lung cancer who underwent sleeve lobectomy via robotic, VATS, and thoracotomy were assessed using the χ2 test, Fisher exact test, and the Kruskal-Wallis rank sum test. Log-rank test and Cox proportional hazards model were used in survival analyses. Propensity score-weighted matching was used to achieve the balance of baseline among the 3 groups. RESULTS: Between 2012 and 2017, 188 patients were included and divided into robotic (n = 49), VATS (n = 73), and open (n = 66) groups. After weighted matching that retained all patients, no statistical difference in 90-day mortality or morbidity among the 3 groups was shown. Patients in the robotic group had less bleeding loss (P < .001), operative time (P < .001), and tube drainage time (P < .001) than the other 2 groups. No positive bronchial margin or conversion presented in the robotic group. In multivariable analyses, surgical technique was independently associated with neither overall survival nor disease-free survival (P > .050). CONCLUSIONS: Robotic sleeve lobectomy is a safe, feasible, and effective procedure. Compared with VATS and open techniques, robotic sleeve lobectomy has a similar oncologic prognosis for patients with centrally located non-small cell lung cancer. Further studies with a larger sample size and long-term follow-up are needed.

Relevance and prognostic ability of Twist, Slug and tumor spread through air spaces in lung adenocarcinoma.

BACKGROUND: Tumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial-mesenchymal transition (EMT) and STAS. MATERIALS AND METHODS: Our study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin-eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist. RESULTS: In this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence-free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis. CONCLUSIONS: STAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS.

[Clinical Application of Vectorial Localization of Peripheral Pulmonary Nodules Guided by Electromagnetic Navigation Bronchoscopy in Thoracic Surgery].

BACKGROUND: More patients with pulmonary nodules are being referred to thoracic surgeons under the increasing use of computed tomography scans (CT). Impalpable peripheral subpleural solitary pulmonary nodules are difficult to be localized by video assisted thoracic surgery. Although some common techniques including CT-guided puncture positioning and electromagnetic navigation bronchoscopy (ENB)-guided methylene blue staining positioning, can bring good results in positioning, there are still some complications such as pneumothorax, hemorrhage and inaccurate positioning. Vectorial localization guided by electromagnetic navigational bronchoscopy followed by thoracoscopic resection is a novel alternative technique by us firstly for definitive diagnosis, which can avoid the possible injury of pleural or enlargement of the location area, providing some guidance for ENB-guided location technology. The main objective of this study was to evaluate the feasibility and our initial experience of vectorial localization guided by electromagnetic navigation followed by video-assisted thoracoscopic pulmonary solitary nodules resection. METHODS: We retrospectively analyzed 22 cases who undergoing vectorial localization of peripheral pulmonary lesion guided by electromagnetic navigation prior to video assisted lung resection, and characteristics and intraoperative outcomes were explored. RESULTS: Twenty-two nodules of twenty-two patients were all localized by this method successfully with an average location time (17.5±4.2) min. The average nodule size was (11.0±3.6) mm. The distance between the locatable guide probe (LG) and lesion on the electromagnetic navigation bronchoscopy screen was (14.5±10.1) mm. The distance between the lesion and probe mark on the dissected specimen was (15.3±11.0) mm. There was no displacement of any case. No conversion to thoracotomy was found. And there were no adverse events during the localization and operation procedure. Length of hospital stay was (3.8±1.2) d and the operative mortality was 0.0%. Malignant lesions were found in 19 patients and they were all completely resected with negative microscopic margins. CONCLUSIONS: Our initial experience with vectorial localization of peripheral pulmonary lesion guided by electromagnetic navigation and minimally invasive resection proved that this technique was an alternative accurate and safe way for small pulmonary nodules. Thoracic surgeons should further investigate this method and apply it to clinical practice.

Learning curve for robot-assisted lobectomy of lung cancer.

BACKGROUND: Robotic lobectomy is widely used for lung cancer treatment. So far, few studies have been performed to systematically analyze the learning curve. Our purpose is to define the learning curve to provide a training guideline of this technique. METHODS: A total of 208 consecutive patients with primary lung cancer who underwent robotic-assisted lobectomy by our surgical team were enrolled in this study. Baseline information and postoperative outcomes were collected. Learning curves were then analyzed using the cumulative sum (CUSUM) method. Patients were divided into three groups according to the cut-off points of the learning curve. Intraoperative characteristics and short-term outcomes were compared among the three groups. RESULTS: CUSUM plots revealed that the docking time, console time and total surgical time in patients were 20, 34 and 32 cases, respectively. Comparison of the surgical time among the 3 phases revealed that the total surgical time (197.03±27.67, 152.61±21.07, 141.35±29.11 min, P<0.001), console time (150.97±26.13, 103.89±18.04, 97.49±24.80 min, P<0.001) and docking time (13.53±2.08, 11.95±1.10, 11.89±1.49 min, P<0.001) were decreased significantly. Estimated blood loss differed among groups (90.63±45.41, 87.63±59.84, 60.29±28.59 mL, P=0.001) and was associated with shorter operative time. There was no conversion or 30-day mortality. No significant differences were observed among other clinic-pathological characteristics among the groups. CONCLUSIONS: For a surgeon, the learning time of robotic lobectomy was in the 32th operation. For a bedside assistant, at least 20 cases were required to achieve the level of optimal docking.

Robotic Bronchial Sleeve Lobectomy for Central Lung Tumors: Technique and Outcome.

BACKGROUND: The use of the surgical robot for standard lobectomy has widely spread worldwide. However there are relatively few studies of robotic bronchial sleeve lobectomy for central lung tumors. METHODS: We retrospectively evaluated 67 consecutive patients who underwent robotic bronchial sleeve lobectomy, a procedure without pulmonary vessel end-to-end anastomosis, performed by a single surgeon between October 2014 and March 2018. A half-continuous suture technique with two Prolene (Ethicon, Inc, Somerville, NJ) sutures for bronchial anastomosis was applied. The operative techniques and outcomes were analyzed. RESULTS: Complete resection was achieved in all patients undergoing different types of robotic bronchial sleeve lobectomy. There were no conversions to thoracotomy. The mean total surgical duration was 166.5 minutes (range, 78-286), total bronchial anastomosis time was 20.8 minutes (range, 10-44), estimated blood loss was 98.8 mL (range, 20-300), and postoperative hospital stay was 6.8 days (range, 4-13). No patient died within 90 days after surgery. The postoperative morbidity rate was 20.9%. Multivariate analysis showed that preoperative comorbidity, older age, and surgeon's early experience were risk factors for postoperative morbidity. CONCLUSIONS: Robotic bronchial sleeve lobectomy and the novel anastomotic technique are both feasible and safe for carefully selected patients.