Kezhong Chen

Learning curves and long-term outcome of simulation-based thoracentesis training for medical students

BackgroundSimulation-based medical education has been widely used in medical skills training; however, the effectiveness and long-term outcome of simulation-based training in thoracentesis requires further investigation. The purpose of this study was to assess the learning curve of simulation-based thoracentesis training, study skills retention and transfer of knowledge to a clinical setting following simulation-based education intervention in thoracentesis procedures.MethodsFifty-two medical students were enrolled in this study. Each participant performed five supervised trials on the simulator. Participants performance was assessed by performance score (PS), procedure time (PT), and participants confidence (PC). Learning curves for each variable were generated. Long-term outcome of the training was measured by the retesting and clinical performance evaluation 6 months and 1 year, respectively, after initial training on the simulator.ResultsSignificant improvements in PS, PT, and PC were noted among the first 3 to 4 test trials (p < 0.05). A plateau for PS, PT, and PC in the learning curves occurred in trial 4. Retesting 6 months after training yielded similar scores to trial 5 (p > 0.05). Clinical competency in thoracentesis was improved in participants who received simulation training relative to that of first year medical residents without such experience (p < 0.05).ConclusionsThis study demonstrates that simulation-based thoracentesis training can significantly improve an individuals performance. The saturation of learning from the simulator can be achieved after four practice sessions. Simulation-based training can assist in long-term retention of skills and can be partially transferred to clinical practice.

Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC.

Development and Validation of a Clinical Prediction Model for N2 Lymph Node Metastasis in Non-Small Cell Lung Cancer

BACKGROUND The true incidence of occult N2 lymph node metastasis in patients with clinical N0 non-small cell lung cancer (NSCLC) remains controversial. Estimation of the probability of N2 lymph node metastasis can assist physicians when making diagnosis and treatment decisions. METHODS We reviewed the medical records of 605 patients (group A) and 211 patients (group B) with computed tomography-defined N0 NSCLC that had an exact tumor-node-metastasis stage after surgery. Logistic regression analysis of group As clinical characteristics was used to estimate the independent predictors of N2 lymph node metastasis. A prediction model was then built and internally validated by using cross validation and externally validated in group B. The model was also compared with 2 previously described models. RESULTS We identified 4 independent predictors of N2 disease: a younger age; larger tumor size; central tumor location; and adenocarcinoma or adenosquamous carcinoma pathology. The model showed good calibration (Hosmer-Lemeshow test: p = 0.96) with an area under the receiver operating characteristic curve (AUC) of 0.756 (95% confidence interval, 0.699 to 0.813). The AUC of our model was better than those of the other models when validated with independent data. CONCLUSIONS Our prediction model estimated the pretest probability of N2 disease in computed tomography-defined N0 NSCLC and was more accurate than the existing models. Use of our model can be of assistance when making clinical decisions about invasive or expensive mediastinal staging procedures.

Risk factors of recurrence for resected T1aN0M0 invasive lung adenocarcinoma: a clinicopathologic study of 177 patients

BackgroundThis study aimed at identifying risk factors of recurrence for completely resected pathologic T1aN0M0 lung adenocarcinomas.MethodsWe reviewed the records of 177 T1aN0M0 invasive adenocarcinoma patients, and re-classified achieved surgical specimens according to the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. Impact on recurrence-free survival (RFS) for age, gender, smoking history, lymphovascular invasion (LVI) and new classification was analyzed by log-rank test and Cox regression. Two existing prognostic grouping schemes of new classification were compared, and subsequently, the correlation of high-grade group in the better prognostic grouping model with clinical data was investigated statistically.ResultsThe 5-year recurrence-free rate was 83.7%. The LVI and new adenocarcinoma classification were significantly associated with 5-year RFS (P = 0.012; P = 0.022, respectively). The designation of papillary predominant subtype in the low-grade group, along with lepidic- and acinar predominant subtype had more prognostic significance than the model of combining papillary-, solid- and micropapillary predominant subtypes as the high-grade group (P = 0.005 versus P = 0.181). This high-grade group has increased risk of recurrence in a multivariate Cox regression (adjusted HR 2.815, 95% CI: 1.239 to 6.397, P = 0.013), and is associated significantly more with male gender (adjusted OR 2.214, 95% CI: 1.050 to 4.668, P = 0.037), and, with borderline significance, the presence of LVI (adjusted OR 2.091, 95% CI: 0.938 to 4.662, P = 0.071).ConclusionsOur results showed that the solid- and micropapillary predominant subtype of IASLC/ATS/ERS classification remains the only risk factor for post-operative recurrence of T1aN0M0 adenocarcinomas, suggesting that they can be indicators of aggressive tumor behaviors.

A Primary Pulmonary Glomus Tumor Complicated With Hyperpyrexia and Anemia

Pulmonary glomus tumors are extremely rare, with only 19 cases having been reported worldwide. The glomus body is considered to be related to the regulation of body temperature, but the reported cases were not associated with hyperpyrexia. Here, we describe a 28-year-old man with hyperpyrexia and anemia complicated with a coin lesion of the right lung. After resection of the upper lobe of the right lung by video-assisted thoracoscopic surgery, all of the patients symptoms disappeared. The pathologic analysis reported a rare pulmonary glomus tumor. The disease had not recurred by 1 year after operation.

Propensity-matched comparison of video-assisted thoracoscopic with thoracotomy lobectomy for locally advanced non–small cell lung cancer

Objective: We evaluated whether video‐assisted thoracoscopic lobectomy for locally advanced non–small cell lung cancer could be performed safely and with acceptable long‐term outcomes by our improved technique and compared with standard thoracotomy lobectomy in a well‐balanced population. Methods: Patients with clinical stage II and III A non–small cell lung cancers who received lobectomy were reviewed. Video‐assisted thoracoscopic lobectomies were all performed with Wangs technique by the surgeons who had overcome the learning curve and achieved proficiency. By using propensity‐matched analysis, perioperative outcomes and long‐term survival were compared. Results: Matching based on propensity scores produced 120 patients in each group. Conversion rate to thoracotomy was 11.7%. After thoracoscopic lobectomy, hospital length of stay was shorter compared with thoracotomy (9.2 vs 12 days; P = .014) despite similar rates of postoperative complications (30/125 [25%] vs 34/125 [28.3%]; P = .56). Disease‐free survival (49.1% vs 42.2%; P = .40) and overall survival (55.0% vs 57.1%; P = .73) at 5 years were similar between groups. Although advanced pathologic stage (hazard ratio [HR], 2.018; 95% confidence interval [CI], 1.330–3.062) and no postoperative chemotherapy (HR, 1.880; 95% CI, 1.236–2.858) were independently associated with increased hazard of death in multivariable Cox regression at each time point in follow‐up, thoracoscopic lobectomy was not (HR, 1.075; 95% CI, 0.714–1.620; P = .73). Conclusions: With continued experience and optimized technique, video‐assisted thoracoscopic lobectomy can be performed in the majority of cases without compromising perioperative outcomes and oncologic efficacy.

Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers

Objective Multiple primary lung cancers are detected with increasing frequency, but the ideal strategy for diagnosis and treatment remains disputable. This study evaluated both clinical characteristics and genetic alterations to investigate the appropriate strategy for patients with multiple primary lung cancer. Methods A total of 96 patients in our practice were diagnosed with multiple primary lung cancer over 7 years by clinical‐pathologic criteria. According to consolidation/tumor ratio, they were classified into 3 groups: group A (multiple ground‐glass opacity–dominant nodules, consolidation/tumor ratio ≤0.5), group B (1 solid‐dominant nodule, consolidation/tumor ratio >0.5 with other ground‐glass opacity–dominant nodules), and group C (2 solid‐dominant nodules). A series of somatic genetic mutations and fusions were analyzed in a portion of the patients. Results There were 24, 35, and 37 patients in groups A, B, and C, respectively. During follow‐up, 23 patients had recurrence. The 5‐year recurrence‐free survival was 100% in patients with multiple ground‐glass opacity, 68% in those with 1 solid lesion, and 51.4% in those with 2 solid tumors (P = .001). Eighteen patients died of lung cancer. The 5‐year overall survival was 100% in group A, 80.5% in group B, and 59.9% in group C (P = .002). A total of 77 driver mutations were detected in 61 of the 82 lesions. A high rate of discordance of genetic alterations (89.7%) was found between cancers within individual patients. Two patients in group C had concordant driver mutations between the 2 lesions, and both of them harbored tumor recurrence. Conclusions A high discordance of driver mutations between tumors in individual patients and a favorable prognosis were identified in patients with multiple primary lung cancers diagnosed by clinical‐pathologic criteria, which support different strategies from those with metastatic disease.

Comparison of plasma to tissue DNA mutations in surgical non-small cell lung cancer patients

Objective: Noninvasive liquid biopsies of circulating tumor DNA (ctDNA) can be used to assess non–small cell lung cancer (NSCLC), but previous work focused on patients with advanced‐stage cancer. Thus, we evaluated the feasibility and their potential clinical application of circulating tumor DNA approached for surgical patients with NSCLC. Method: Consecutive patients with suspected lung cancer who underwent curative‐intent lung resection were enrolled prospectively in this study. Targeted DNA sequencing with a next‐generation sequencing platform was used to identify a series of somatic mutations in matched tumor tissue DNA (tDNA) and plasma ctDNA samples. Plasma was collected before, during, and after surgery. Concordance was defined as matched tDNA and ctDNA with the same identified mutations or with no mutations. Results: In the enrolled 76 patients with lung cancer who were included, 31 had concordant mutations and 21 had no mutation in both ctDNA and tDNA, yielding an overall concordance of 68.4%. ctDNA samples obtained before and during surgery had the same mutations with a low variance in mutation frequency (1.2%) that was reduced to an average of 0.28% after surgery (P < .001). More patients were positive as assayed by ctDNA (48; 63.2%) than with serum tumor protein markers (36; 49.3%). The area under the curve was greater in ctDNA (0.887, 95% confidence interval [CI], 0.788‐0.986) than for the 2 prediction models (0.803, 95% CI, 0.647‐0.959; 0.69, 95% CI, 0.512‐0.869) for estimating malignancy of solitary pulmonary nodules. Conclusion: ctDNA mutation analysis for stage I‐III surgical patients with NSCLC is feasible. More studies are needed to investigate its clinical application.

Comparison of plasma to tissue DNA mutations in surgical patients with non–small cell lung cancer

Objective: Noninvasive liquid biopsies of circulating tumor DNA (ctDNA) can be used to assess non–small cell lung cancer (NSCLC), but previous work focused on patients with advanced‐stage cancer. Thus, we evaluated the feasibility and their potential clinical application of circulating tumor DNA approached for surgical patients with NSCLC. Method: Consecutive patients with suspected lung cancer who underwent curative‐intent lung resection were enrolled prospectively in this study. Targeted DNA sequencing with a next‐generation sequencing platform was used to identify a series of somatic mutations in matched tumor tissue DNA (tDNA) and plasma ctDNA samples. Plasma was collected before, during, and after surgery. Concordance was defined as matched tDNA and ctDNA with the same identified mutations or with no mutations. Results: In the enrolled 76 patients with lung cancer who were included, 31 had concordant mutations and 21 had no mutation in both ctDNA and tDNA, yielding an overall concordance of 68.4%. ctDNA samples obtained before and during surgery had the same mutations with a low variance in mutation frequency (1.2%) that was reduced to an average of 0.28% after surgery (P < .001). More patients were positive as assayed by ctDNA (48; 63.2%) than with serum tumor protein markers (36; 49.3%). The area under the curve was greater in ctDNA (0.887, 95% confidence interval [CI], 0.788‐0.986) than for the 2 prediction models (0.803, 95% CI, 0.647‐0.959; 0.69, 95% CI, 0.512‐0.869) for estimating malignancy of solitary pulmonary nodules. Conclusion: ctDNA mutation analysis for stage I‐III surgical patients with NSCLC is feasible. More studies are needed to investigate its clinical application.

Validation of the Eighth Edition of the TNM Staging System for Lung Cancer in 2043 Surgically Treated Patients With Non–small-cell Lung Cancer

Purpose The International Association for the Study of Lung Cancer has proposed a revision of the Tumor, Node, Metastasis (TNM) classification for lung cancer. The purpose of this study is to evaluate the prognostic value of the eighth edition of the TNM staging system in surgically treated patients with non–small‐cell lung cancer. Methods Data from 2043 consecutive patients with non–small‐cell lung cancer who underwent surgical treatment in our single center between January 2006 and September 2015 were collected and analyzed retrospectively. Cox proportional hazard models were used to assess the prognostic significance of the T and N descriptors. Results The reversed overall survival curves of stage IIA and stage IIB in the seventh edition were corrected in the eighth edition. Better prognostic value in predicting overall survival, including a higher log rank test of trend χ2 statistic (433.6 vs. 414.2), a smaller Akaike Information Criterion value (4759.6 vs. 4768.2), a higher Harrell C‐index (0.776 vs. 0.769), and a lower integrated Brier score (0.092 vs. 0.093), was observed for the eighth edition relative to the seventh edition. Recurrence‐free survival analysis of subsets of patients stratified by T and N descriptors showed a stepwise deterioration. Significant differences were found between patients of subdivided stage IA (IAI vs. IA2; P = .003 and IA2 vs. IA3; P = .004). Conclusion The eighth edition of the TNM staging system for lung cancer has prognostic value superior to that of the seventh edition. It was able to predict recurrence‐free survival well. Micro‐Abstract The eighth TNM staging system for lung cancer requires external validation. The present study evaluated its performance among 2043 surgically treated patients with non–small‐cell lung cancer. The system demonstrated better performance than the seventh edition.