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1.
Front Oncol ; 14: 1305262, 2024.
Article in English | MEDLINE | ID: mdl-38571504

ABSTRACT

Background: The preoperative inflammatory condition significantly influences the prognosis of malignancies. We aimed to investigate the potential significance of preoperative inflammatory biomarkers in forecasting the long-term results of lung carcinoma after microwave ablation (MWA). Method: This study included patients who received MWA treatment for lung carcinoma from Jan. 2012 to Dec. 2020. We collected demographic, clinical, laboratory, and outcome information. To assess the predictive capacity of inflammatory biomarkers, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of inflammatory biomarkers in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. Results: A total of 354 individuals underwent MWA treatment, of which 265 cases were included in this study, whose average age was 69.1 ± 9.7 years. The AUC values for the Systemic Inflammatory Response Index (SIRI) to overall survival (OS) and disease-free survival (DFS) were 0.796 and 0.716, respectively. The Cox proportional hazards model demonstrated a significant independent association between a high SIRI and a decreased overall survival (hazard ratio [HR]=2.583, P<0.001). Furthermore, a high SIRI independently correlated with a lower DFS (HR=2.391, P<0.001). We developed nomograms utilizing various independent factors to forecast the extended prognosis of patients. These nomograms exhibited AUC of 0.900, 0.849, and 0.862 for predicting 1-year, 3-year, and 5-year OS, respectively. Additionally, the AUC values for predicting 1-year, 3-year, and 5-year DFS were 0.851, 0.873, and 0.883, respectively. Conclusion: SIRI has shown promise as a valuable long-term prognostic indicator for forecasting the outcomes of lung carcinoma patients following MWA.

2.
Thorac Cancer ; 15(15): 1218-1227, 2024 May.
Article in English | MEDLINE | ID: mdl-38606839

ABSTRACT

BACKGROUND: The surgical outcomes for younger patients with non-small cell lung cancer (NSCLC) remain uncertain. The aim of this study was to investigate the clinical features long-term survival outcomes in younger individuals with NSCLC following surgery. METHODS: We queried the Surveillance, Epidemiology, and End Results database from 2010 to 2017, selecting all pathologically confirmed NSCLC cases that underwent cancer-directed surgery. Younger patients were defined as those aged 18-50 years, while older patients were 51-80 years. Propensity score matching (PSM) was implemented to mitigate selection bias. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method. RESULTS: Among the 33 586 treated surgically patients, 2223 (6.6%) were young. Compared to the older group, younger patients had a higher frequency of female gender, non-white ethnicity, carcinoid tumors, stage IV disease, pneumonectomy, and postoperative adjuvant therapies. The 5-year OS rates were significantly higher for younger patients (79.3% vs. 62.0%; p < 0.001), as were the 5-year LCSS rates (82.4% vs. 71.8%; p < 0.001). Post-PSM, younger patients consistently demonstrated significantly better OS and LCSS. Further stage-specific analysis revealed significantly improved 5-year OS rates at each stage and superior 5-year LCSS for stages I-II among younger patients. However, there was no statistically significant difference in LCSS for stages III-IV. CONCLUSIONS: Overall, younger patients with NSCLC treated surgically exhibit superior OS and LCSS compared to their older counterparts, although no statistically significant difference in LCSS for stages III-IV was observed between the two age groups.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Female , Male , Middle Aged , Adult , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Aged , Young Adult , Adolescent , Aged, 80 and over , SEER Program , Treatment Outcome , Age Factors , Pneumonectomy/methods , Survival Rate
3.
Eur J Cardiothorac Surg ; 65(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38479816

ABSTRACT

OBJECTIVES: To evaluate the safety and feasibility of removing drainage tubes at larger size of air leak in patients with prolonged air leak after pulmonary surgery. METHODS: Ninety-five patients who underwent pulmonary surgery with prolonged air leak in our centre were enrolled in this randomized controlled, single-centre, non-inferiority study. The drainage tube was clamped with a stable size of air leak observed over the last 6 h, which was quantified by gas flow rate using the digital drainage system. The control group (n = 48) and the study group (n = 46) had their drainage tube clamped at 0-20 ml/min and 60-80 ml/min, respectively. We continuously monitored clinical symptoms, conducted imaging and laboratory examinations, and decided whether to reopen the drainage tube. RESULTS: The reopening rate in the study group was not lower than that in the control group (2.08% vs 6.52%, P > 0.05). The absolute difference in reopening rate was 4.44% (95% confidence interval -0.038 to 0.126), with an upper limit of 12.6% below the non-inferiority margin (15%). There were significant differences in the length of stay [16.5 (13-24.75) vs 13.5 (12-19.25), P = 0.017] and the duration of drainage [12 (9.25-18.50) vs 10 (8-12.25), P = 0.007] between the control and study groups. No notable differences were observed in chest X-ray results 14 days after discharge or in the readmission rate. CONCLUSIONS: For patients with prolonged air leak, removing drainage tubes at larger size of air leak demonstrated similar safety compared to smaller size of air leak, and can shorten both length of stay and drainage duration. CLINICAL TRIAL REGISTRATION NUMBER: Name of registry: Gas flow threshold for safe removal of chest drainage in patients with alveolar-pleural fistula prolonged air leak after pulmonary surgery. Registration number: ChiCTR2200067120. URL: https://www.chictr.org.cn/.


Subject(s)
Chest Tubes , Device Removal , Humans , Drainage/methods , Length of Stay , Pleural Diseases , Pneumonectomy/methods , Pneumothorax/etiology , Pneumothorax/diagnosis , Device Removal/adverse effects
4.
BMC Anesthesiol ; 23(1): 357, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37919658

ABSTRACT

BACKGROUND: Tracheobronchomegaly (TBM) is a rare disorder mainly characterized by dilatation and malacia of the trachea and major bronchi with diverticularization. This will be a great challenge for airway management, especially in thoracic surgery requiring one-lung ventilation. Using a laryngeal mask airway and a modified double-lumen Foley catheter (DFC) as a "blocker" may achieve one-lung ventilation. This is the first report introducing this method in a patient with TBM. CASE PRESENTATION: We present a 64-year-old man with TBM receiving left lower lobectomy. Preoperative chest computed tomography demonstrated a prominent tracheobronchial dilation and deformation with multiple diverticularization. The most commonly used double-lumen tube or bronchial blocker could not match the distorted airways. After general anesthesia induction, a 4# laryngeal mask was inserted, through which the modified DFC was positioned in the left main bronchus with the guidance of a fiberoptic bronchoscope. The DFC balloon was inflated with 10 ml air and lung isolation was achieved without any significant air leak during one-lung or two-lung ventilation. However, the collapse of the non-dependent lung was delayed and finally achieved by low-pressure artificial pneumothorax. The surgery was successful and the patient was extubated soon after the surgery. CONCLUSIONS: Using a laryngeal mask airway with a modified double-lumen Foley catheter acted as a bronchial blocker could be an alternative method to achieve lung isolation.


Subject(s)
One-Lung Ventilation , Tracheobronchomegaly , Male , Humans , Middle Aged , Intubation, Intratracheal/methods , Airway Management , Trachea , One-Lung Ventilation/methods
5.
Thorac Cancer ; 14(22): 2093-2104, 2023 08.
Article in English | MEDLINE | ID: mdl-37349884

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading cause of death among cancer diseases. The tumorigenic functions of AHNAK2 in LUAD have attracted more attention in recent years, while there are few studies which have reported its high molecular weight. METHODS: The mRNA-seq data of AHNAK2 and corresponding clinical data from UCSC Xena and GEO was analyzed. LUAD cell lines were transfected with sh-NC and sh-AHNAK2, and cell proliferation, migration and invasion were then detected by in vitro experiments. We performed RNA sequencing and mass spectrometry analysis to explore the downstream mechanism and interacting proteins of AHNAK2. Finally, western blot, cell cycle analysis and CO-IP were used to confirm our assumptions regarding previous experiments. RESULTS: Our study revealed that AHNAK2 expression was significantly higher in tumors than in normal lung tissues and higher AHNAK2 expression led to a poor prognosis, especially in patients with advanced tumors. AHNAK2 suppression via shRNA reduced the LUAD cell lines proliferation, migration and invasion and induced significant changes in DNA replication, NF-kappa B signaling pathway and cell cycle. AHNAK2 knockdown also caused G1/S phase cell cycle arrest, which could be attributed to the interaction of AHNAK2 and RUVBL1. In addition, the results from gene set enrichment analysis (GSEA) and RNA sequencing suggested that AHNAK2 probably plays a part in the mitotic cell cycle. CONCLUSION: AHNAK2 promotes proliferation, migration and invasion in LUAD and regulates the cell cycle via the interaction with RUVBL1. More studies of AHNAK2 are still needed to reveal its upstream mechanism.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Adenocarcinoma of Lung/pathology , ATPases Associated with Diverse Cellular Activities/genetics , ATPases Associated with Diverse Cellular Activities/metabolism , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , DNA Helicases/genetics , Down-Regulation , Lung Neoplasms/pathology
6.
Thorac Cancer ; 14(12): 1071-1076, 2023 04.
Article in English | MEDLINE | ID: mdl-36915945

ABSTRACT

BACKGROUND: To investigate the effect of continuous oral aspirin in perioperative period on bleeding in pneumonectomy. METHODS: A total of 170 patients who underwent pneumonectomy in our hospital from March 2021 to March 2022 were selected as the study objects. All patients took oral aspirin before surgery and did not take other antiplatelet agent or anticoagulants at the same time. The continuation group included 85 cases and continued to take aspirin 100 mg/day during the perioperative period, and the interruption group included 85 cases who stopped aspirin for 7 days before surgery and 3 days after surgery, without bridging therapy. The intraoperative blood loss, operation time, conversion to thoracotomy rate, postoperative bleeding rate, blood transfusion rate, thrombotic events, postoperative drainage volume, length of hospital stay, and total hospital cost of the two groups were compared. RESULTS: There were no statistically significant differences in intraoperative blood loss, operative time, rate of conversion to open, postoperative drainage, hospital stay, and cost between the two groups (p > 0.05), and there were no reoperations due to bleeding between the two groups. CONCLUSIONS: Aspirin should be continued throughout the perioperative period in all high-risk patients requiring pneumonectomy after balancing ischemic-bleeding risks.


Subject(s)
Aspirin , Blood Loss, Surgical , Humans , Pneumonectomy , Retrospective Studies , Platelet Aggregation Inhibitors
7.
Front Nutr ; 10: 1000046, 2023.
Article in English | MEDLINE | ID: mdl-36742422

ABSTRACT

Background: The Controlled Nutritional Status (CONUT) score is a valid scoring system for assessing nutritional status and has been shown to correlate with clinical outcomes in many surgical procedures; however, no studies have reported a correlation between postoperative complications of bronchiectasis and the preoperative CONUT score. This study aimed to evaluate the value of the CONUT score in predicting postoperative complications in patients with bronchiectasis. Methods: We retrospectively analyzed patients with localized bronchiectasis who underwent lung resection at our hospital between April 2012 and November 2021. The optimal nutritional scoring system was determined by receiver operating characteristic (ROC) curves and incorporated into multivariate logistic regression. Finally, independent risk factors for postoperative complications were determined by univariate and multivariate logistic regression analyses. Results: A total of 240 patients with bronchiectasis were included, including 101 males and 139 females, with an average age of 49.83 ± 13.23 years. Postoperative complications occurred in 59 patients (24.6%). The incidence of complications, postoperative hospital stay and drainage tube indwelling time were significantly higher in the high CONUT group than in the low CONUT group. After adjusting for sex, BMI, smoking history, lung function, extent of resection, intraoperative blood loss, surgical approach and operation time, multivariate analysis showed that the CONUT score remained an independent risk factor for postoperative complications after bronchiectasis. Conclusions: The preoperative CONUT score is an independent predictor of postoperative complications in patients with localized bronchiectasis.

8.
Cancer Med ; 12(2): 1217-1227, 2023 01.
Article in English | MEDLINE | ID: mdl-35758614

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication in patients with lung cancer that seriously affects prognosis and quality of life. At present, the detection rate of patients with early-stage lung cancer is increasing, but there are few studies on the risk factors for postoperative venous thromboembolism (VTE) in patients with stage IA non-small cell lung cancer (NSCLC). This study aimed to establish a nomogram for predicting the probability of postoperative VTE risk in patients with stage IA NSCLC. METHODS: The clinical data of 452 patients with stage IA NSCLC from January 2017 to January 2022 in our center were retrospectively analyzed and randomly divided into a training set and a validation set at a ratio of 7:3. Independent risk factors were identified by univariate and multivariate logistic regression analyses, and a nomogram was established based on the results and internally validated. The predictive power of the nomogram was evaluated by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: The nomogram prediction model included three risk factors: age, preoperative D-dimer, and intermuscular vein dilatation. The areas under the ROC curve of this predictive model were 0.832 (95% CI: 0.732-0.924) and 0.791 (95% CI: 0.668-0.930) in the training and validation sets, respectively, showing good discriminative power. In addition, the probability of postoperative VTE occurrence predicted by the nomogram was consistent with the actual occurrence probability. In the decision curve, the nomogram model had a better net clinical benefit at a threshold probability of 5%-90%. CONCLUSION: This study is the first to develop a nomogram for predicting the risk of postoperative VTE in patients with stage IA NSCLC; this nomogram can accurately and intuitively evaluate the probability of VTE in these patients and help clinicians make decisions on prevention and treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Venous Thromboembolism , Humans , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/complications , Lung Neoplasms/surgery , Lung Neoplasms/complications , Nomograms , Quality of Life , Retrospective Studies , Risk Factors , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
9.
Front Oncol ; 12: 976988, 2022.
Article in English | MEDLINE | ID: mdl-36119540

ABSTRACT

Background: Recently, the new World Health Organization (WHO) tumor classification removed adenocarcinoma in situ (AIS) from the diagnosis of lung cancer. However, it remains unclear whether the "malignancy" item should be assessed when the modified Caprini Risk Assessment Model (RAM) is used to assess venous thromboembolism (VTE) risk in AIS. The purpose of our study is to assess differences between AIS and stage IA adenocarcinoma (AD) from a VTE perspective. Methods: A retrospective study was performed on AIS and IA adenocarcinoma in our hospital from January 2018 to December 2021, and divided into AIS group and AD group. Propensity score matching (PSM) was used to compare the incidence of VTE and coagulation function, and to analyze whether the RAM is more effective when the "malignancy" item is not evaluated in AIS. Results: 491 patients were included after screening, including 104 patients in the AIS group and 387 patients in the AD group. After PSM, 83 patients were matched. The incidence of VTE and D-dimer in the AIS group was significantly lower than that in the AD group (P<0.05).When using the RAM to score AIS, compared with retaining the "malignancy" item, the incidence of VTE in the intermediate-high-risk group was significantly higher after removing the item (7.9% vs. 36.4%, P=0.018), which significantly improved the stratification effect of the model. Conclusions: The incidence of postoperative VTE in AIS was significantly lower than that in stage IA adenocarcinoma. The stratification effect was more favorable when the "malignancy" item was not evaluated in AIS using the RAM.

10.
Thromb J ; 20(1): 43, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35915486

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication in general thoracic surgery, but the incidence of patients undergoing surgery for bronchiectasis was not known. The purpose of our study was to investigate the incidence of VTE in bronchiectasis patients undergoing lung resection and to evaluate the risk stratification effect of the modified caprini risk assessment model (RAM). METHODS: We prospectively enrolled patients with bronchiectasis who underwent lung resection surgery between July 2016 and July 2020.The postoperative duplex lower-extremity ultrasonography or(and) computed tomographic pulmonary angiography (CTPA) was performed to detect VTE. The clinical characteristics and caprini scores of VTE patients and non-VTE patients would be compared and analyzed. Univariate logistic regression was performed to evaluate whether higher Caprini scores were associated with postoperative VTE risk.In addition, We explored the optimal cutoff for caprini score in patients with bronchiectasis by using the receiver operating characteristic (ROC) curve. RESULTS: One hundred and seventeen patients were eligible based on the prospective study criteria. The postoperative VTE incidence was 8.5% (10/117). By comparing the clinical characteristics and Caprini scores of VTE and non-VTE patients, the median preoperative hospitalization (7 vs 5 days, P = 0.028) and Caprini score (6.5 vs 3,P < 0.001) were significantly higher in VTE patients. In univariate logistic regression, a higher Caprini score was associated with higher odds ratio (OR) for VTE of 1.7, 95% confidence interval (CI) was from 1.2 to 2.5 (P = 0.001), C-statistics was 0.815 in the modified caprini RAM for predicting VTE. In a multivariable analysis adjusting for preoperative hospitalization, a higher Caprini score was associated with higher odds OR for VTE of 1.8 (95%CI: 1.2-2.6, P = 0.002), C-statistics was 0.893 in the caprini RAM for predicting VTE. When taking the Caprini score as 5 points as the diagnostic threshold, the Youden index is the largest. CONCLUSIONS: The postoperative VTE incidence in patients undergoing lung resection for bronchiectasis was 8.5%.The modified caprini RAM effectively stratified bronchiectasis surgery patients for risk of VTE and showed excellent predictive power for VTE. The patients with postoperative caprini scores = 5, should be recommended to take positive measures to prevent postoperative VTE. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR-EOC-17010577.

11.
Thorac Cancer ; 13(9): 1258-1266, 2022 05.
Article in English | MEDLINE | ID: mdl-35315227

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication of lung cancer, but the incidence and risk stratification of postoperative VTE in stage IA non-small-cell lung cancer (NSCLC) patients remains unclear, therefore we conducted a single-center prospective study. METHODS: A total of 314 consecutive patients hospitalized for lung cancer surgery and diagnosed with stage IA NSCLC from January 2017 to July 2021 were included. The patients were divided into the VTE group and the non-VTE group according to whether VTE occurred after the operation. The patient's age, operation time, D-dimer (D-D) value, tumor pathology, and Caprini score were recorded. The different items were compared and included in logistic regression analysis to obtain independent risk factors, and the area under the receiver operating characteristics curve (AUC) was calculated. RESULTS: The incidence of VTE was 7.3%. Significant differences in age, operation time, preoperative and postoperative day 1 D-D value, neuron-specific enolase value, forced expiratory volume in 1 second, maximum ventilation, carbon monoxide diffusion capacity, and pathological diameter were noted between the two groups. Age (95% confidence interval [CI] 1.056-1.216) and postoperative day 1 D-D value (95% CI 1.125-1.767) were independent risk factors. The incidence of VTE in the low-, medium-, and high-risk groups with Caprini scores was 0%, 7.3%, and 11.5%, respectively. The AUC of the Caprini score was 0.704 (p < 0.05). CONCLUSIONS: The incidence of postoperative VTE in patients with stage IA NSCLC was 7.3%. Age and postoperative day 1 D-D value were independent risk factors for VTE. The Caprini score has a certain value in the diagnosis of postoperative VTE of stage IA NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Venous Thromboembolism , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung Neoplasms/complications , Lung Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Retrospective Studies , Risk Factors , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
12.
Thorac Cancer ; 12(3): 297-303, 2021 02.
Article in English | MEDLINE | ID: mdl-33141499

ABSTRACT

BACKGROUND: Cervical mediastinoscopy is useful for diagnosing lung and mediastinal disease. Ultrasound is a safe real-time diagnostic tool widely employed in many surgical fields. Ultrasound was used in cervical mediastinoscopy in our cohort with satisfactory results. This study investigated the safety, feasibility, and availability of video-assisted mediastinoscopy (VAM) combined with ultrasound for mediastinal lymph node biopsy. METHODS: A total of 87 cases involving cervical mediastinal lymph node biopsy performed from November 2015 to May 2020, with complete clinical and pathological information, were retrospectively analyzed in the Department of Thoracic Surgery at Beijing Chaoyang Hospital. The cohort was divided into two groups: ultrasound-guided biopsy under video-assisted mediastinoscopy (UVAM) (44 cases) and routine VAM (43 cases). Operation time, biopsy number and nodal stations, postoperative complications, pathological conditions, and surgical difficulty were compared between the two nodal stations. RESULTS: UVAM was significantly shorter and more lymph node specimens were obtained than with VAM. There was one case of fatal bleeding and two cases of right recurrent laryngeal nerve injury in the VAM group, and no postoperative complications in the UVAM group. CONCLUSIONS: When used with cervical VAM, ultrasound guidance assists physicians assess the space between lymph nodes, surrounding tissues, and large vessels systematically, making biopsy safer and easier, improving lymph node sampling, and decreasing postoperative complications. Furthermore, surgeons can easily learn and master this method. KEY POINTS: Significant findings of the study: Ultrasound was used in combination with cervical mediastinoscopy and the results showed that ultrasound guidance makes biopsy in patients safer and easier, improves lymph node sampling, and decreases postoperative complications. WHAT THIS STUDY ADDS: Surgeons can easily learn and master this method.


Subject(s)
Image-Guided Biopsy/methods , Lymph Nodes/pathology , Mediastinum/pathology , Adult , Aged , Female , Humans , Lymph Node Excision/methods , Male , Mediastinoscopy/methods , Middle Aged
13.
J Thorac Dis ; 12(9): 4805-4816, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33145053

ABSTRACT

BACKGROUND: There is a high incidence of venous thromboembolism (VTE) after lung resection, so it is necessary to identify the risk factors for VTE in these patients. It is also important to evaluate whether the modified Caprini score can accurately assess the risk of VTE in patients after lung resection. METHODS: This retrospective study included 437 patients undergoing lung resection between July 2016 and December 2017. All patients underwent lower extremities ultrasound before and after operation to determine the presence of the newly diagnosed VTE. RESULTS: Forty-seven (10.8%) of the 437 patients were diagnosed with VTE after lung surgery. Multivariate logistic regression analysis showed that age (OR, 2.04; 95% CI, 1.40-2.99), duration of operation (OR, 1.51; 95% CI, 1.08-2.12), lymphocyte count (OR, 0.28; 95% CI, 0.11-0.69), and D-dimer concentration (OR, 1.55; 95% CI, 1.22-1.97) were significantly associated with VTE in lung resection patients. The cut-off values for lymphocyte count and D-dimer concentration determined using receiver operating characteristic (ROC) curve were 1.15×109/L and 1.37 µg/mL respectively. The modified Caprini score divided the patients into three groups: low risk (0-4 points), moderate risk (5-8 points) and high risk (≥9 points), and the incidence of VTE was 12.3% (37/300), 7.5% (10/133) and 0% (0/4), respectively (P>0.05). CONCLUSIONS: In this study, we identified four independent factors for VTE after lung resection patients: age, duration of operation, lymphocyte count, and D-dimer. According to the modified Caprini score, there were fewer patients in the high-risk group, and the incidence of VTE not increased with the increase of risk. Better evaluation of operation time and D-dimer may help the modified Caprini score to better assess VTE risk in these patients.

14.
J Cell Physiol ; 235(2): 1197-1208, 2020 02.
Article in English | MEDLINE | ID: mdl-31270811

ABSTRACT

Chemotherapy is the first-line treatment option for patients with lung cancer. However, therapeutic resistance occurs through an incompletely understood mechanism. Our research wants to investigate the influence of Caveolin-1 (Cav-1) on the therapeutic sensitivity of lung cancer in vitro. Results in this study demonstrated that Cav-1 levels were markedly inhibited in A549 lung cancer cells after exposure to cisplatin. Knockdown of caveolin further enhanced cisplatin-triggered cancer death in A549 cells. The functional investigation demonstrated that Cav-1 inhibition amplified the mitochondrial stress signaling induced by cisplatin, as evidenced by the mitochondrial reactive oxygen species burst, cellular metabolic disruption, mitochondrial membrane potential reduction, and mitochondrial caspase-9-related apoptosis activation. At the molecular level, cav-1 augmented cisplatin-mediated mitochondrial damage by inhibiting Parkin-related mitochondrial autophagy. Mitophagy activation effectively attenuated the promotive impact of Cav-1 knockdown on mitochondrial damage and cell death. Furthermore, our data indicated that Cav-1 affected Parkin-related mitophagy by activating the Rho-associated coiled-coil kinase 1 (ROCK1) pathway; inhibition of the ROCK1 axis prevented cav-1 knockdown-mediated cell death and mitochondrial damage. Taken together, our results provide ample data illuminate the necessary action exerted by Cav-1 on affecting cisplatin-related therapeutic resistance. Silencing of Cav-1 inhibited Parkin-related mitophagy, thus amplifying cisplatin-mediated mitochondrial apoptotic signaling. This finding identifies the Cav-1/ROCK1/Parkin/mitophagy axis as a potential target to overcome cisplatin-related resistance in lung cancer cells.


Subject(s)
Caveolin 1/metabolism , Cisplatin/pharmacology , Gene Expression Regulation/drug effects , Lung Neoplasms/drug therapy , Ubiquitin-Protein Ligases/metabolism , rho-Associated Kinases/metabolism , A549 Cells , Amides/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Caveolin 1/genetics , Humans , Lung Neoplasms/metabolism , Mitophagy/drug effects , Mitophagy/physiology , Pyridines/pharmacology , RNA, Small Interfering , Reactive Oxygen Species , Ubiquitin-Protein Ligases/genetics , rho-Associated Kinases/genetics
15.
J Cell Mol Med ; 24(1): 1087-1098, 2020 01.
Article in English | MEDLINE | ID: mdl-31755214

ABSTRACT

Cyclin-dependent kinase 7 (CDK7) is a protein kinase that plays a major role in transcription initiation. Yes-associated protein (YAP) is a main effector of the Hippo/YAP signalling pathway. Here, we investigated the role of CDK7 on YAP regulation in human malignant pleural mesothelioma (MPM). We found that in microarray samples of human MPM tissue, immunohistochemistry staining showed correlation between the expression level of CDK7 and YAP (n = 70, r = .513). In MPM cells, CDK7 expression level was significantly correlated with GTIIC reporter activity (r = .886, P = .019). Inhibition of CDK7 by siRNA decreased the YAP protein level and the GTIIC reporter activity in the MPM cell lines 211H, H290 and H2052. Degradation of the YAP protein was accelerated after CDK7 knockdown in 211H, H290 and H2052 cells. Inhibition of CDK7 reduced tumour cell migration and invasion, as well as tumorsphere formation ability. Restoration of the CDK7 gene rescued the YAP protein level and GTIIC reporter activity after siRNA knockdown in 211H and H2052 cells. Finally, we performed a co-immunoprecipitation analysis using an anti-YAP antibody and captured the CDK7 protein in 211H cells. Our results suggest that CDK7 inhibition reduces the YAP protein level by promoting its degradation and suppresses the migration and invasion of MPM cells. Cyclin-dependent kinase 7 may be a promising therapeutic target for MPM.


Subject(s)
Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Biomarkers, Tumor/metabolism , Cyclin-Dependent Kinases/antagonists & inhibitors , Gene Expression Regulation, Neoplastic , Mesothelioma/pathology , Pleural Neoplasms/pathology , Transcription Factors/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis , Biomarkers, Tumor/genetics , Case-Control Studies , Cell Proliferation , Cyclin-Dependent Kinases/genetics , Cyclin-Dependent Kinases/metabolism , Down-Regulation , Humans , Mesothelioma/genetics , Mesothelioma/metabolism , Pleural Neoplasms/genetics , Pleural Neoplasms/metabolism , Prognosis , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolism , Tumor Cells, Cultured , YAP-Signaling Proteins , Cyclin-Dependent Kinase-Activating Kinase
16.
Zhongguo Fei Ai Za Zhi ; 22(12): 761-766, 2019 Dec 20.
Article in Chinese | MEDLINE | ID: mdl-31874671

ABSTRACT

The risk of perioperative venous thromboembolism (VTE) is pretty high in thoracic cancer patients. Perioperative VTE influences the recovery of patients after operation and quality of life in the future, even seriously leading to death. To strengthen the knowledge and attention of thoracic surgeons on perioperative VTE in thoracic cancer patients, China National Research Collaborative Group on VTE in Thoracic Surgery released the edition of VTE prophalaxis in thoracic cancer patients: Chinese experts consensus in 2018. This article is to interpret the diagnostic value and risk prediction value of D-dimer in VTE in detail, and briefly introduce the role of other biomarkers in VTE of tumor patients. The consensus interpretation aims to deepen the understanding of thoracic surgeons on the clinical significance of D-dimer in VTE.


Subject(s)
Fibrin Fibrinogen Degradation Products/analysis , Thoracic Neoplasms/diagnosis , Venous Thromboembolism/diagnosis , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Perioperative Period , Risk Factors , Thoracic Neoplasms/metabolism , Venous Thromboembolism/metabolism
17.
Chin Med J (Engl) ; 132(20): 2402-2407, 2019 Oct 20.
Article in English | MEDLINE | ID: mdl-31567476

ABSTRACT

BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé (BHD) syndrome, which is an autosomal dominant disorder caused by mutation of the folliculin (FLCN) gene. This study was established to investigate the mutation of the FLCN gene and the phenotype in a family with PSP. METHODS: We investigated the clinical and genetic characteristics of a large Chinese family with recurrent spontaneous pneumothorax. Genetic testing was performed by Sanger sequencing of the coding exons (4-14 exons) of the FLCN gene. RESULTS: Among ten affected members in a multi-generational PSP kindred, with a total of 18 episodes of spontaneous pneumothorax, the median age for the initial onset of pneumothorax was 42.5 years (interquartile range: 28.8-57.2 years). Chest computed tomography scan of the proband showed pulmonary cysts and pneumothorax. A novel nonsense mutation (c.1273C>T) in exon 11 of FLCN gene that leads to a pre-mature stop codon (p.Gln425*) was identified in the family. The genetic analysis confirmed the diagnosis of BHD syndrome in this family in the absence of skin lesions or renal tumors. CONCLUSIONS: A novel nonsense mutation of FLCN gene was found in a large family with PSP in China. Our results expand the mutational spectrum of FLCN gene in patients with BHD syndrome.


Subject(s)
Birt-Hogg-Dube Syndrome/genetics , Codon, Nonsense , Pneumothorax/genetics , Proto-Oncogene Proteins/genetics , Tumor Suppressor Proteins/genetics , Adult , Female , Genetic Testing , Humans , Male , Middle Aged , Recurrence
18.
Thorac Cancer ; 10(7): 1597-1604, 2019 07.
Article in English | MEDLINE | ID: mdl-31206253

ABSTRACT

BACKGROUND: The rationality of selective mediastinal lymph node dissection based on lobe-specific metastasis is still controversial. The correlation of lymph node metastasis in lobe-specific lymphatic drainage regions (LSDRs) and non-LSDRs has not been widely reported. The purpose of this study was to investigate the variables affecting nodal metastasis in non-LSDRs and to further evaluate the rationality of selective lymphadenectomy in clinical stage IA non-small cell lung cancer (NSCLC) patients. METHODS: The clinicopathological information of 316 patients with clinical stage IA NSCLC who underwent lobectomy with systematic lymph node dissection between June 2014 and June 2018 was retrospectively collected for analysis. RESULTS: The overall lymph node metastasis rate was 19.3%. For 35 patients with positive LSDR lymph nodes, the non-LSDR lymph node metastasis rate was 31.4%. Only one patient (0.4%) among 281 patients with negative LSDR lymph nodes had nodal spread in non-LSDRs. Univariate analysis identified that solid consistency, worse differentiation, and positive status in LSDRs were unfavorable predictive variables of lymph node metastasis in non-LSDRs. Multivariate analysis showed that nodal metastasis in LSDRs was the only independent predictor of nodal involvement in non-LSDRs (P < 0.001). CONCLUSION: For patients with clinical stage IA NSCLC, non-LSDR lymph node metastasis mainly depends on the involvement of the LSDR lymph node. Our observations may indicate the potential implications for the reasonable management of lymphadenectomy in stage IA NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lymphatic Metastasis/pathology , Adult , Aged , Female , Humans , Lymph Node Excision , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Pneumonectomy , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
19.
Eur J Cardiothorac Surg ; 55(3): 455-460, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30289479

ABSTRACT

OBJECTIVES: Venous thromboembolism (VTE) is a common postoperative complication. Previous studies have shown that the incidence of VTE after major thoracic surgery ranges from 2.3% to 15%. However, there have been no such data from China so far. To evaluate the incidence of postoperative VTE, we conducted a single-centre, prospective cohort study. METHODS: Patients who underwent lung resections between July 2016 and March 2017 were enrolled in this study. None of the patients received any prophylaxis perioperatively. All patients were screened for deep venous thrombosis (DVT) using non-invasive duplex lower-extremity ultrasonography 30 days before surgery and within 30 days after surgery and before discharge. Chest tomography, pulmonary embolism protocol was carried out if patients had one of the following conditions: (i) typical symptoms of pulmonary embolism, (ii) high Caprini score (≥9 points) and (iii) newly diagnosed postoperative DVT. RESULTS: Two hundred and sixty-two patients undergoing lung surgery were enrolled, including 115 benign and 147 malignant disease cases. The procedures included 84 sublobar lung resections, 161 lobectomies, 5 pneumonectomies and 12 mixed procedures. The overall postoperative incidence of VTE was 11.5% (30 of 262). Twenty-four patients were diagnosed with DVT (80.0%) and 6 with DVT + pulmonary embolism (20.0%). None of the patients diagnosed with VTE had obvious symptoms of VTE. The median time for VTE detection was 5 days postoperatively. The incidence of VTE was 7.0% in patients with benign lung diseases and 15.0% in those with malignant lung diseases (P < 0.05). Using the Caprini risk assessment model, 63 cases were scored as low risk, 179 as moderate risk and 20 as high risk, and each group had an incidence of postoperative VTE of 0%, 12.3% (22 of 179) and 40.0% (8 of 20), respectively (P < 0.05). In patients with lung cancer, 98% were moderate or high risk, and only 3 patients were scored in the low risk category. The incidence of VTE in patients at moderate risk and high risk was 12.0% and 36.8%, respectively, while it was 0 in low-risk patients. CONCLUSIONS: The following conclusions were drawn: (i) the overall incidence of postoperative VTE after lung surgery without VTE prophylaxis is substantial; (ii) lower-extremity ultrasonography was helpful in detecting asymptomatic DVT in symptomatic or high-risk patients; and (iii) VTE prophylaxis should be considered as a mandatory part of perioperative care. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-EOC-17010577.


Subject(s)
Pneumonectomy , Postoperative Complications/epidemiology , Venous Thromboembolism/epidemiology , Adult , Aged , China/epidemiology , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Perioperative Care , Prevalence , Prospective Studies , Venous Thromboembolism/prevention & control
20.
Ann Transl Med ; 7(23): 724, 2019 Dec.
Article in English | MEDLINE | ID: mdl-32042740

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the incidence of venous thromboembolism (VTE) in epidermal growth factor receptor (EGFR) mutations patients with lung adenocarcinoma, to provide clinical basis for the perioperative prevention and treatment of VTE in patients with lung cancer. METHODS: This study included patients with invasive lung adenocarcinoma confirmed by pathology from July 2016 to March 2018 after surgical pulmonectomy in Thoracic Surgery Department of Beijing Chaoyang Hospital. All enrolled patients were tested for relevant gene mutations. All patients were classified as adenocarcinoma subtypes by the 2011 International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). Patients were divided into the VTE group and the control group according to whether VTE occurred postoperatively. Baseline data, gene test results, operative data and tumor pathology data between the two groups were compared. RESULTS: According to the inclusion criteria, a total of 323 patients underwent lung cancer surgery were analyzed in this study, including 148 males and 175 females, aged from 25 to 82 years old. Postoperative VTE occurred in 33 patients, with an incidence of 10.2%. Compared the baseline data, there were significant differences in age and BMI between the two groups, but no significant differences in other indicators. Comparing the results of postoperative genetic tests, the cases of exon 18, 19, 20, 21, 30, 31 mutation, exon 18 and 20 mixed mutation and exon 20 and 21 mixed mutation were 5, 42, 6, 57, 1, 3, 1 and 1. The total EGFR mutation rate in the enrolled patients was 36.2% (117/323). Among them, the proportion of EGFR mutation in the VTE group was significantly higher than that in the non-VTE group (60.6% vs. 33.4%, P=0.002). Exon mutations in specific regions and mixed region of EGFR were not statistically significant between them; there was no statistical difference in the concomitant KRAS and ALK gene mutations between them. Comparing the pathological conditions, the proportion of acinar dominant lung adenocarcinoma in the VTE group was higher than that in the non-VTE group (57.6% vs. 30.7%, P=0.002); other histologic subtypes showed no statistical difference. The D-dimer difference before and 1 day after surgery, preoperative FEV1, surgical method, duration of surgery and blood loss were statistically significant differences between the two groups. The results of univariate analysis showed that there were significant differences between the VTE group and the control group in proportion of EGFR mutant lung adenocarcinoma, age, BMI, D-dimer difference before and 1 day after surgery, preoperative FEV1, surgical method, duration of surgery, blood loss and proportion of acinar dominant lung adenocarcinoma (P<0.05). However, VTE was not significantly correlated with gender, ALK or KRAS gene mutation and other factors. Multi-factor logistics regression analysis shows that Patients with EGFR gene mutation infiltrating lung adenocarcinoma, acinar dominant lung adenocarcinoma, FEV1 and difference of D-dimer (d1-pre) are independent risk factors for postoperative lung cancer complicated with VTE. CONCLUSIONS: The incidence of VTE was 10.2% in patients with invasive lung adenocarcinoma without prophylactic anticoagulant therapy. EGFR gene mutation is an independent risk factor for postoperative VTE in lung cancer, and the incidence of VTE in adenocarcinoma with alveolar predominance is the highest. Other independent risk factors included the difference of D-dimer (d1-pre) and preoperative FEV1.

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