Tumor blood vessel in 3D reconstruction CT imaging as an risk indicator for growth of pulmonary nodule with ground-glass opacity.

OBJECTIVE: Despite the vital role of blood perfusion in tumor progression, in patients with persistent pulmonary nodule with ground-glass opacity (GGO) is still unclear. This study aims to investigate the relationship between tumor blood vessel and the growth of persistent malignant pulmonary nodules with ground-glass opacity (GGO). METHODS: We collected 116 cases with persistent malignant pulmonary nodules, including 62 patients as stable versus 54 patients in the growth group, from 2017 to 2021. Three statistical methods of logistic regression model, Kaplan-Meier analysis regression analysis were used to explore the potential risk factors for growth of malignant pulmonary nodules with GGO. RESULTS: Multivariate variables logistic regression analysis and Kaplan-Meier analysis identified that tumor blood vessel diameter (p = 0.013) was an significant risk factor in the growth of nodules and Cut-off value of tumor blood vessel diameter was 0.9 mm with its specificity 82.3% and sensitivity 66.7%.While in subgroup analysis, for the GGO CTR < 0.5[C(the maximum diameter of consolidation in tumor)/T(the maximum diameter of the whole tumor including GGO) ratio], tumor blood vessel diameter (p = 0.027) was important during the growing processes of nodules. CONCLUSIONS: The tumor blood vessel diameter of GGO lesion was closely associated with the growth of malignant pulmonary nodules. The results of this study would provide evidence for effective follow-up strategies for pulmonary nodule screening.

Predicting pleural invasion of invasive lung adenocarcinoma in the adjacent pleura by imaging histology.

The aim of the present study was to develop a non-invasive method based on histological imaging and clinical features for predicting the preoperative status of visceral pleural invasion (VPI) in patients with lung adenocarcinoma (LUAD) located near the pleura. VPI is associated with a worse prognosis of LUAD; therefore, early and accurate detection is critical for effective treatment planning. A total of 112 patients with preoperative computed tomography presentation of adjacent pleura and postoperative pathological findings confirmed as invasive LUAD were retrospectively enrolled. Clinical and histological imaging features were combined to develop a preoperative VPI prediction model and validate the model's efficacy. Finally, a nomogram for predicting LUAD was established and validated using a logistic regression algorithm. Both the clinical signature and radiomics signature (Rad signature) exhibited a perfect fit in the training cohort. The clinical signature was overfitted in the testing cohort, whereas the Rad signature showed a good fit. To combine clinical and radiomics signatures for optimal performance, a nomogram was created using the logistic regression algorithm. The results indicated that this approach had the highest predictive performance, with an area under the curve of 0.957 for the clinical signature and 0.900 for the Rad signature. In conclusion, histological imaging and clinical features can be combined in columnar maps to predict the preoperative VPI status of patients with adjacent pleural infiltrative lung carcinoma.

Lung hamartoma resembling lung cancer: a report of three cases.

Pulmonary hamartoma is a benign lung tumor. However, it is difficult to distinguish this lesion from other diseases via imaging. Three patients with pathologically confirmed pulmonary hamartoma in our department were analyzed. We believe it is necessary to combine imaging, pathology, clinical testing, and individual patient assessments to enable an earlier and more definitive diagnosis of pulmonary hamartoma. Therefore, it is necessary to analyze and summarize the clinical manifestations and imaging features of patients with pulmonary hamartoma to improve the early recognition of the disease by clinicians.

Correlation and significance of COX-2, Ki67, VEGF and other immune indexes with the growth of malignant pulmonary nodules.

OBJECTIVE: This study intends to explore the factors affecting the growth of pulmonary nodules in the natural process by immunohistochemical method. METHODS: 40 cases of pulmonary nodules followed up for more than 3 years were divided into growth group (n = 20) and stable group (n = 20). The expressions of cyclooxygenase-2 (COX-2), Ki67, vascular endothelial growth factor (VEGF), CD44V6, epidermal growth factor receptor (EGFR), double microsome 2 (MDM2) and transforming growth factor (TGF)-ß1 in pulmonary nodules were detected by immunohistochemical method so as to explore the relationship between it and the growth of pulmonary nodules. RESULTS: Compared with stable pulmonary nodules, the positive rates of COX-2, Ki67 and VEGF in the growth group were 85%, 80% and 55%, respectively. There was significant difference between the stable group and the growth group (P < 0.05). The correlation between other indexes and the growth of pulmonary nodules was not statistically significant (Pcd44v6 = 0.104;PEGFR = 0.337; PMDM2 = 0.49; PTGF-ß1 = 0.141). In the subgroup of patients with non-invasive lung cancer, there was a correlation between VEGF and the growth of pulmonary nodules (P < 0.05). CONCLUSION: The high expression of COX-2, Ki67 and VEGF proteins may be significantly related to the growth of pulmonary nodules, and VEGF may be an important factor affecting the growth of malignant pulmonary nodules. This study intends to provide a research direction for further searching for the essential causes of the growth of pulmonary nodules.

Prognostic significance of TG/HDL-C and non-HDL-C/HDL-C ratios in patients with non-small cell lung cancer: a retrospective study.

OBJECTIVE: Lung cancer is a malignancy with high a mortality rate that threatens human health. This study is aimed to explore the correlation among the triglyceride/high-density lipoprotein ratio (TG/HDL-C), non-high-density lipoprotein/high-density lipoprotein ratio (non-HDL-C/HDL-C) and survival of patients with non-small cell lung cancer (NSCLC) undergoing video-associated thoracic surgery (VATS). METHODS: This retrospective study analyzed 284 patients with NSCLC who underwent VATS at Hebei General Hospital, Shijiazhuang, China. The time-dependent receiver operating characteristic curve was used to determine the optimal cutoff value and evaluate the area under the curve. Kaplan-Meier and Cox regression analyses were performed to determine the prognostic effect. RESULTS: The median overall survival (OS) was 46 months. Patients with low TG/HDL-C and low non-HDL-C/HDL-C had a longer OS. The low non-HDL-C/HDL-C group showed a longer mean survival time (59.00 vs. 52.35 months). Multivariate analysis revealed that TG/HDL-C and non-HDL-C/HDL-C were significantly correlated with OS. CONCLUSIONS: TG/HDL-C and non-HDL-C/HDL-C are associated with the prognosis of patients with NSCLC who received VATS. Preoperative serum TG/HDL-C and non-HDL-C/HDL-C may be effective independent prognostic factors for predicting the outcomes of patients with NSCLC.

Pulmonary cryptococcosis mimicking lung cancer: 3 case report.

INTRODUCTION AND IMPORTANCE: Pulmonary cryptococcosis is an opportunistic pathogen. However, it is difficult to differentiate it from other diseases by imaging. Therefore, the clinical presentation and imaging features of patients with pulmonary cryptococcosis are analyzed and summarized to improve clinicians' early recognition of the disease. CASE PRESENTATION: We present a case where preoperative imaging was difficult to differentiate between pulmonary cryptococcosis and non-small cell lung cancer. A pathological biopsy was taken by surgical treatment to clarify the diagnosis. CLINICAL DISCUSSION: Three cases of Cryptococcus pulmonary patients diagnosed by pathology in our department were analyzed. We believe that the diagnosis should be confirmed as soon as possible through surgery, relevant laboratory tests, and pathological examinations, and antifungal treatment should be carried out in time. CONCLUSION: We believe that an earlier and clearer diagnosis of pulmonary cryptococcosis requires an earlier interplay of imaging, pathology, testing, and individual patient differences.

Development and Validation of a Preoperative CT-Based Nomogram to Differentiate Invasive from Non-Invasive Pulmonary Adenocarcinoma in Solitary Pulmonary Nodules.

Purpose: This study aimed to develop and validate a preoperative CT-based nomogram combined with clinical and radiological features for distinguishing invasive from non-invasive pulmonary adenocarcinoma. Patients and Methods: A total of 167 patients with solitary pulmonary nodules and pathologically confirmed adenocarcinoma treated between January 2020 and December 2020 at Hebei General Hospital were retrospectively assessed. To evaluate the probability of invasive pulmonary adenocarcinoma, we developed three models, the multivariate logistic regression model, the stepwise logistic regression model, and the cross-validation model. The Akaike information criterion (AIC) was used to compare the relative strength of different models, and the area under the curve (AUC) was used to quantify the predictive accuracy. The best performing model was presented as a nomogram, calibrated and evaluated for clinical utility. Results: The stepwise logistic regression model revealed highest and mean attenuations of non-enhanced CT images, and lobulation and vacuole presence were predictive factors of invasive pulmonary adenocarcinoma. This model (AIC = 67.528) with the lowest AIC value compared with that of the multivariate logistic regression model (AIC = 69.301) or the cross-validation model (AIC = 81.216) was identified as the best model, and its AUC value (0.9967; 95% CI, 0.9887-1) was higher than those of the other two models. The calibration curve showed optimal agreement in invasive pulmonary adenocarcinoma probability as predicted by the nomogram and the actual value. Conclusion: We developed and validated a nomogram that could estimate the preoperative probability of invasive pulmonary adenocarcinoma in patients with solitary pulmonary nodules, which may be useful in clinical decision-making associated with personalized surgical intervention and therapeutic regimen selection.

The advanced lung cancer inflammation index predicts outcomes of patients with non-small cell lung cancer following video-assisted thoracic surgery.

OBJECTIVE: The advanced lung cancer inflammation index (ALI) predicts overall survival (OS) in patients with advanced lung cancer. However, few studies have tested ALI's prognostic effect in patients with non-small cell lung cancer (NSCLC) following video-assisted thoracic surgery (VATS), especially patients at stage III. This study investigated the relationship between ALI and outcomes of patients with NSCLC following VATS. METHODS: We retrospectively examined 339 patients with NSCLC who underwent VATS at Hebei General Hospital, China. Preoperative clinical and laboratory parameters were collected and analyzed. Optimal cutoff values of potential prognostic factors, including ALI, were determined. Kaplan-Meier and Cox regression analyses were used to determine each factor's prognostic value. RESULTS: The median OS was 31 months. The optimal cutoff value for ALI was 41.20. Patients with high ALI (≥41.20) displayed increased OS (33.87 vs. 30.24 months), higher survival rates, and milder clinical characteristics. Univariate and multivariate analyses showed a significant correlation between ALI and the prognosis of patients with NSCLC, including those at stage IIIA, who underwent VATS. CONCLUSIONS: Low ALI correlated with poor outcomes in patients with NSCLC following VATS. Preoperative ALI might be a potential prognostic biomarker for patients with NSCLC following VATS, including patients at stage IIIA.

Neutrophil-Lymphocyte Ratio as a Predictive Factor of Growing Malignant Pulmonary Ground-glass Opacity.

BACKGROUND: The object of the study was to elucidate the relationship between the neutrophil-lymphocyte ratio (NLR) and the growth of pulmonary ground-glass opacity (GGO) in stage IA lung adenocarcinoma. METHODS: All patients with GGO following surgical procedures were enrolled, with the time of follow-up and the variation tendency of GGO recorded. Meanwhile, laboratory parameters, age, gender, smoking history, histology, tumor size, and stage were recorded. Logistic regression was used to evaluate the value of NLR and the cutoff value was calculated by SPSS 22.0. RESULTS: In the whole cohort, 30 cases of growing GGO and 43 cases of stable GGO undergoing surgical procedures were diagnosed as lung adenocarcinoma. There was significant statistical difference between the two groups. Multivariable analysis showed that NLR could predict the GGOs with growth (odds ratio 5.198, 95% confidence interval (95%CI: 1.583-14.581, P=0.002). Receiver operating characteristics analysis for NLR showed the optimal cutoff value of 2.38, with a sensitivity of 60.0% and specificity of 81.4%. CONCLUSION: Our study demonstrated that the NLR appeared to have value as a promising clinical predictor of GGOs with growth. Further studies are needed to confirm this conclusion.

Comparison of non-intubated and intubated video-assisted thoracoscopic surgeries of major pulmonary resections for lung cancer-a meta-analysis.

OBJECTIVE: The aim of this study was to compare the safety feasibility and safety feasibility of non-intubated (NIVATS) and intubated video-assisted thoracoscopic surgeries (IVATS) during major pulmonary resections. METHODS: A meta-analysis of eight studies was conducted to compare the real effects of two lobectomy or segmentectomy approaches during major pulmonary resections. RESULTS: Results showed that the patients using NIVATS had a greatly shorter hospital stay and chest-tube placement time (weighted mean difference (WMD): - 1.04 days; 95% CI - 1.50 to - 0.58; P < 0.01) WMD - 0.71 days; 95% confidence interval (CI), - 1.08 to - 0.34; P < 0.01, respectively) while compared to those with IVATS. There were no significant differences in postoperative complication rate, surgical duration, and the number of dissected lymph nodes. However, through the analysis of highly selected patients with lung cancer in early stage, the rate of postoperative complication in the NIVATS group was lower than that in the IVATS group [odds ratio (OR) 0.44; 95% CI 0.21-0.92; P = 0.03, I2 = 0%]. CONCLUSIONS: Although the comparable postoperative complication rate was observed for major thoracic surgery in two surgical procedures, the NIVATS method could significantly shorten the hospitalized stay and chest-tube placement time compared with IVATS. Therefore, for highly selected patients, NIVATS is regarded as a safe and technically feasible procedure for major thoracic surgery. The assessment of the safety and feasibility for patients undergoing NIVATS needs further multi-center prospective clinical trials.

Advanced Lung Cancer Inflammation Index is a Prognostic Factor of Patients with Small-Cell Lung Cancer Following Surgical Resection.

PURPOSE: Advanced lung cancer inflammation index (ALI) has been shown to predict overall survival (OS) in advanced non small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC) and operable NSCLC. However, there were no studies of the correlation between ALI and operable SCLC. Therefore, this study is aimed to explore the relationship between ALI and the prognosis of operable SCLC. PATIENTS AND METHODS: A total of 48 patients with SCLC who underwent surgery at Hebei General Hospital and Zigong First People's Hospital were screened between 2016 and 2020. ALI was calculated as follows: body mass index (BMI, kg/m2)×serum albumin (ALB, g/dL)/neutrophil to lymphocyte ratio (NLR). Receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of ALI. Patients were divided into two groups according to the cutoff point of ALI: low ALI group with ALI<48.2 and high ALI group with ALI≥48.2. Kaplan-Meier and Cox regression analysis were performed to assess the potential prognostic factors associated with OS. RESULTS: The optimal cutoff value of ALI was determined as 48.2. The low ALI group displayed more adverse clinical characteristics and poorer survival rates. Multivariate analysis revealed that ALI and Charlson comorbidity index (CCI) were significantly correlated with OS. CONCLUSION: Low ALI was correlated with poor prognosis in patients with SCLC who underwent surgery. Preoperative ALI might serve as a potential prognostic marker for patients with operable SCLC.

Down-Regulation of Hypoxia-Inducible Factor-1α and Downstream Glucose Transporter Protein-1 Gene by ß-elemene Enhancing the Radiosensitivity of Lung Adenocarcinoma Transplanted Tumor.

PURPOSE: To study the effect of ß-elemene on the radiosensitivity of A549 cell xenograft tumor and potential mechanisms by which ß-elemene regulates the expression of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter protein-1 (GLUT-1). METHODS: Using an A549 cell transplantation tumor model with male nude mice, we studied the effect of ß-elemene on the radiosensitivity of non-small cell lung cancer (NSCLC). The expression of HIF-1α and GLUT-1 was detected by real-time PCR, Western blotting and immunohistochemistry. The relationship between the radiosensitivity of ß-elemene and the expression of HIF-1α and GLUT-1 was analyzed. RESULTS: ß-elemene and radiotherapy intervened in the growth of transplanted tumors in varying degrees. The enhancement factor (EF=2.44>1) was calculated; ß-elemene at 45 mg/kg had the most significant enhanced effect on radiosensitivity. When ß-elemene was used in combination with radiation, the expression of HIF-1α and GLUT-1 was significantly decreased, and there was a positive correlation between the two genes. CONCLUSION: ß-elemene exhibits a radiosensitizing effect on A549 cell xenograft tumor. The underlying molecular mechanism is probably associated with the down-regulation of HIF-1α and GLUT-1 expression, suggesting that ß-elemene may directly or indirectly inhibit the expression of HIF-1α and GLUT-1. There is a positive significant correlation between expression of HIF-1α and GLUT-1. HIF-1α and downstream GLUT-1 could be used as a new target for the radiosensitization of NSCLC.

Circulating Tumor Cells as a Screening and Diagnostic Marker for Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: Circulating tumor cells (CTCs) have become potential diagnostic biomarker for several types of cancer, including lung cancer. In this study, we aim to determine whether CTCs detected by CellCollector can be used for early-stage diagnosis of lung cancer. METHODS: In this study, we recruited 64 volunteers, among whom 44 were suspected lung cancer patients requiring surgical treatment and 20 were healthy volunteers. We simultaneously analyzed PD-L1 expression in CTCs isolated using the GILUPI CellCollector and copy number variation by next-generation sequencing (NGS). RESULTS: We enrolled a total of 44 patients with suspected lung cancer who required surgery and 20 healthy volunteers. The patients were classified into 4 groups based on their pathological results: benign disease, in situ cancer, microinvasive, and invasive. The CTCs detection rate for each group was 10.00% (1/10), 45% (5/11), 50% (7/14), and 67% (6/9), respectively. Among the patients with lung cancer, the CTCs detection rate increased with disease progression. The rate of CTCs positivity was 52.94% (18/34) in patients who were diagnosed with lung cancer by pathology and 10% (1/10) in patients with benign disease. CTCs were not detected in the control group. The area under the receiver operating characteristic (ROC) curve, a measure for distinguishing patients with primary lung cancer, was 0.715 (95% CI 0.549-0.880, P=0.041). The sensitivity and specificity of the in vivo CTCs detection strategy for the diagnosis of early-stage lung cancer were 52.94% and 90%, respectively. CTCs were associated with clinical pathology but not with the size and location of the nodules. CONCLUSION: CTCs isolation using the CellCollector in vivo detection method might be effective for distinguishing between benign and malignant nodules and may be used for early-stage diagnosis of lung cancer.

Meta-analysis of segmentectomy versus wedge resection in stage IA non-small-cell lung cancer.

BACKGROUND: Although limited resection was once considered the surgical treatment for patients with Phase IA non-small-cell lung cancer (NSCLC), there has been an ongoing controversial surgical indication for wedge resection and segmentectomy in recent years. The objective of this study was to compare overall survival (OS) and disease-free survival (DFS) of segmentectomy and wedge resection for early stage NSCLC, using a meta-analysis. METHODS: Systematic research was conducted using four online databases to search for studies published before 2017. The DFS and OS for early stage NSCLC after segmentectomy and wedge resection were compared. The studies were selected according to rigorous predefined inclusion criteria, and meta-analyzed using the log (hazard ratio; ln[HR]) and its standard error (SE) calculations. RESULTS: Included in this meta-analysis were nine studies, published from 2006 to 2017, with a total of 7,272 patients. Survival outcome of segmentectomy was comparable to wedge resections for stage IA lung cancer because of OS (similar hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.83-1.05, P=0.26) and DFS (similar HR: 0.81, 95% CI: 0.60-1.09, P=0.17). Nevertheless, for stage IA NSCLC with tumor size ≤2 cm, segmentectomy was superior to wedge resection (combined HR: 0.82, 95% CI: 0.70-0.97, P=0.02). However, there were no significant differences in OS rates, 1.07 (95% CI: 0.78-1.46, P=0.68), between segmentectomy and wedge resection for IA NSCLC with a tumor size of ≤1 cm. CONCLUSION: This study concluded that segmentectomy could achieve better OS than wedge resection for stage IA NSCLC with a tumor size of ≤2 cm. However, surgeons could conduct segmentectomy and wedge resection for NSCLC ≤1 cm according to patient profile and the location of tumor. These results should be confirmed by further randomized clinical trials.

Multi-Fluorescence Real-Time PCR Assay for Detection of RIF and INH Resistance of M. tuberculosis.

BACKGROUND: Failure to early detect multidrug-resistant tuberculosis (MDR-TB) results in treatment failure and poor clinical outcomes, and highlights the need to rapidly detect resistance to rifampicin (RIF) and isoniazid (INH). METHODS: In Multi-Fluorescence quantitative Real-Time PCR (MF-qRT-PCR) assay, 10 probes labeled with four kinds of fluorophores were designed to detect the mutations in regions of rpoB, katG, mabA-inhA, oxyR-ahpC, and rrs. The efficiency of MF-qRT-PCR assay was tested using 261 bacterial isolates and 33 clinical sputum specimens. Among these samples, 227 Mycobacterium tuberculosis isolates were analyzed using drug susceptibility testing (DST), DNA sequencing and MF-qRT-PCR assay. RESULTS: Compared with DST, MF-qRT-PCR sensitivity and specificity for RIF-resistance were 94.6 and 100%, respectively. And the detection sensitivity and specificity for INH-resistance were 85.9 and 95.3%, respectively. Compared with DNA sequencing, the sensitivity and specificity of our assay were 97.2 and 100% for RIF-resistance and 97.9 and 96.4% for INH-resistance. Compared with Phenotypic strain identification, MF-qRT-PCR can distinguish 227 M. tuberculosis complexes (MTC) from 34 Non-tuberculous mycobacteria (NTM) isolates with 100% accuracy rate. CONCLUSIONS: MF-qRT-PCR assay was an efficient, accurate, reliable, and easy-operated method for detection of RIF and INH-resistance, and distinction of MTC and NTM of clinical isolates.

A Color-Reaction-Based Biochip Detection Assay for RIF and INH Resistance of Clinical Mycobacterial Specimens.

The widespread occurrence of drug-resistant Mycobacterium tuberculosis places importance on the detection of TB (tuberculosis) drug susceptibility. Conventional drug susceptibility testing (DST) is a lengthy process. We developed a rapid enzymatic color-reaction-based biochip assay. The process included asymmetric multiplex PCR/templex PCR, biochip hybridization, and an enzymatic color reaction, with specific software for data operating. Templex PCR (tem- PCR) was applied to avoid interference between different primers in conventional multiplex- PCR. We applied this assay to 276 clinical specimens (including 27 sputum, 4 alveolar lavage fluid, 2 pleural effusion, and 243 culture isolate specimens; 40 of the 276 were non-tuberculosis mycobacteria specimens and 236 were M. tuberculosis specimens). The testing process took 4.5 h. A sensitivity of 50 copies per PCR was achieved, while the sensitivity was 500 copies per PCR when tem-PCR was used. Allele sequences could be detected in mixed samples at a proportion of 10%. Detection results showed a concordance rate of 97.46% (230/236) in rifampicin resistance detection (sensitivity 95.40%, specificity 98.66%) and 96.19% (227/236) in isoniazid (sensitivity 93.59%, specificity 97.47%) detection with those of DST assay. Concordance rates of testing results for sputum, alveolar lavage fluid, and pleural effusion specimens were 100%. The assay provides a potential choice for TB diagnosis and treatment.

A molecular modeling study of the interaction between SRP-receptor complex and peptide translocon.

The signal recognition particle (SRP) mediated protein translocation pathway is universal and highly conserved in all kingdoms of life. Significant progresses have been made to understand its molecular mechanism, yet many open questions remain. A structure model, showing how nascent peptide inserts into peptide translocon with the help of SRP protein Ffh and its receptor FtsY, is desired to facilitate our studies. In this work, we presented such a model derived by computational docking of the Ffh-FtsY complex onto the translocon. This model was compatible with most available experiments. It suggested that the Ffh-FtsY complex approached the translocon with its G domains and was locked up by the cytoplasmic loop of SecG and the C5/C6 loops of SecY. Several residues were expected to play important roles in regulating GTP hydrolysis. Additionally, a hypothesis on the yet ambiguous function of FtsY A domain was proposed. These interesting results invite experimental investigations.