Benign Lung Disease Research Articles

A Preliminary Study on Microbiota Characteristics of Bronchoalveolar Lavage Fluid in Patients with Pulmonary Nodules Based on Metagenomic Next-Generation Sequencing

The characteristics and roles of microbes in the occurrence and development of pulmonary nodules are still unclear. We retrospectively analyzed the microbial mNGS results of BALF from 229 patients with pulmonary nodules before surgery, and performed a comparative analysis of lung flora between lung cancer and benign nodules according to postoperative pathology. The analysis also focused on investigating the characteristics of lung microbiota in lung adenocarcinomas with varying histopathology. There were differences in lung microbiota between lung cancer and benign lung nodules. Bacterial diversity was lower in lung cancer than in benign lung nodules. Four species (Porphyromonas somerae, Corynebacterium accolens, Burkholderia cenocepacia and Streptococcus mitis) were enriched in lung cancer compared with the benign lung nodules. The areas under the ROC curves of these four species were all greater than 0.6, and the AUC of Streptococcus mitis was 0.702, which had the highest diagnostic value for differentiating lung cancer from benign lung diseases. The significantly enriched microbiota varied with the different pathological subtypes of lung adenocarcinoma. Streptococcus mitis, Burkholderia oklahomensis and Burkholderia latens displayed a trend of increasing from the benign lung disease group to the AIS group, MIA group and IAC group, whereas Lactobacillus plantarum showed a downward trend. Changes in the abundance of lung microbiota are closely related to the development of infiltrating adenocarcinoma. Our findings provide new insights into the relationship between the changes in lung microbiota and the development of lung cancer.

Remote Adipose Tissue-Derived Stromal Cells of Patients with Lung Adenocarcinoma Generate a Similar Malignant Microenvironment of the Lung Stromal Counterpart.

Cancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumors may alter distant niches of stromal cells is still unclear, especially at early stages. In this short report, we attempt to better understand the biology of this cross-talk. In our "autologous stromal experimental setting," we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases such as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC for up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similar to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analyzed by arrays, a small pool of 5 upregulated molecules including IL1-β, IL-3, MCP-1, TNF-α, and EGF, was commonly shared by both malignant-like autologous A- and L-MSC derived microenvironments vs those benign. The bioinformatics analysis revealed that these proteins were strictly and functionally interconnected to lung fibrosis and proinflammation and that miR-126, 101, 486, and let-7-g were their main targets. Accordingly, we found that in lung cancer tissues and blood samples from the same set of patients here employed, miR-126 and miR-486 displayed the highest expression levels in tissue and blood, respectively. When the miR-126-3p was silenced in A549 treated with AMSC-derived conditioned media from patients with lung adenocarcinoma, cell proliferation decreased compared to control media.

Value of dual-source CT dual-energy parameters combined with serum detection of VEGF and CEA in the diagnosis of early lung cancer

ABSTRACT To discuss the value of dual-source CT dual-energy parameters combined with serum detection of vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) in the diagnosis of early lung cancer (LC). In total, 100 patients with lung lesions in our hospital from January 2020 to January 2022 were selected for retrospective study, and were divided into the lung cancer group (group A) and benign lung disease group (group B) according to the final results of pathological diagnosis, using dual-source CT dual-energy scanning combined with serum detection of VEGF and CEA to analyze the diagnostic values of single detection and combined detection. Among the 100 patients with lung lesions, there were 58 patients with LC and 42 patients with benign lung diseases after pathological examination, with no statistical difference in normalized iodine concentration (NIC) and the increased value of iodine at arterial phase between the two groups (P > 0.05). The NIC value of group A was higher than group B at venous phase (P < 0.05). The serum levels of VEGF and CEA in group A were higher than group B (P < 0.05). The area under the curve, specificity, sensitivity, Youden index and 95% CI of combined diagnosis were higher than single detection of NIC, VEGF and CEA at venous phase. The combined application of dual-source CT dual-energy parameters and serum detection of VEGF and CEA has higher diagnostic value in patients with early LC, which can provide effective reference for clinical diagnosis and treatment, with higher application value in clinic.

Profiling of amines in biological samples using polythioester-functionalized magnetic nanoprobe.

Introduction: The metabolic balance of amines is closely related to human health. It remains a great challenge to analyze amines with high-throughput and high-coverage. Methods: Polythioester-functionalized magnetic nanoprobes (PMPs) have been prepared under mild conditions and applied in chemoselective capture of amides. With the introduction of polythioester, PMPs demonstrate remarkably increased capture efficiency, leading to the dramatically improved sensitivity of mass spectrometry detection. Results: The analysis method with PMPs treatment has been applied in rapid detection of more than 100 amines in lung adenocarcinoma cell lines, mouse organ tissues, and 103 human serum samples with high-throughput and high-coverage. Statistical analysis shows that arginine biosynthesis differed between lung adenocarcinoma cell lines. Discussion: Phenylalanine, tyrosine and tryptophan biosynthesis differed between tissues. The combination indicators demonstrate a great diagnostic accuracy for distinguishing between health and lung disease subjects as well as differentiating the patients with benign lung disease and lung cancer. With powerful capture ability, low-cost preparation, and convenient separation, the PMPs demonstrate promising application in the intensive study of metabolic pathways and early diagnosis of disease.high-throughput and high-coverage. Here, polythioester-functionalized magnetic nanoprobes (PMPs) have been prepared under mild conditions and applied in chemoselective capture of amides. With the introduction of polythioester, PMPs demonstrate remarkably increased capture efficiency, leading to the dramatically improved sensitivity of mass spectrometry detection. The analysis method with PMPs treatment has been applied in rapid detection of more than 100 amines in lung adenocarcinoma cell lines, mouse organ tissues, and 103 human serum samples with high-throughput and high-coverage. Statistical analysis shows that arginine biosynthesis differed between lung adenocarcinoma cell lines. Phenylalanine, tyrosine and tryptophan biosynthesis differed between tissues. The combination indicators demonstrate a great diagnostic accuracy for distinguishing between health and lung disease subjects as well as differentiating the patients with benign lung disease and lung cancer. With powerful capture ability, low-cost preparation, and convenient separation, the PMPs demonstrate promising application in the intensive study of metabolic pathways and early diagnosis of disease.

Multi-Biomarkers Panel in Identifying Benign and Malignant Lung Diseases and Pathological Types of Lung Cancer.

With the discovery of many tumor markers, there are new strategies for the early diagnosis and treatment of lung cancer and the prediction of prognosis. We examined the multi-protein markers panel (4MP, consisting of Pro-SFTPB, CA125, Cyfra21-1, and CEA) diagnosis performance in differentiating benign and malignant lung diseases and identifying pathological types of lung cancer. Meantime, the complementary performance of three conventional tumor markers (NSE, SCC, and Pro-GRP) for 4MP was assessed. A total of 294 patients with lung cancer or benign lung disease are contained in this study. The AUCs of 4MP and 7MP (NSE, SCC, Pro-GRP, and 4MP) in distinguishing benign lung disease and lung cancer were 0.808 and 0.832, respectively. In distinguishing SQCLC and SCLC, the AUCs were 0.716 and 0.985, respectively. In distinguishing LADC and SCLC, the AUCs were 0.849 and 0.998, respectively. This study demonstrated that 4MP can distinguish lung cancer from benign disease. Traditional biomarkers NSE, SCC, and Pro-GRP can significantly improve the performance of 4MP in the differentiation of LADC, SQCLC, and SCLC, which is expected to contribute to the accurate diagnosis and personalized treatment of patients.

Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases.

The development of a minimally invasive technique for early-stage lung cancer detection is crucial to reducing mortality. Phenotyping of tumor-associated extracellular vesicles (EVs) has the potential for early-stage lung cancer detection, yet remains challenging due to the lack of sensitive, integrated techniques that can accurately detect rare tumor-associated EV populations in blood. Here, we integrated gold core-silver shell nanoparticles and nanoscopic mixing in a microfluidic assay for sensitive phenotypic analysis of EVs directly in plasma without EV pre-isolation. The assay enabled multiplex detection of lung cancer-associated markers PTX3 and THBS1 and canonical EV marker CD63 by surface-enhanced Raman spectroscopy, providing a squared correlation coefficient of 0.97 in the range of 103-107 EVs mL-1 and a limit of detection of 19 EVs mL-1. Significantly, our machine learning-based nanostrategy provided 92.3% sensitivity and 100% specificity in differentiating early-stage lung cancer from benign lung diseases, superior to the CT scan-based lung cancer diagnosis (92.3% sensitivity and 71.4% specificity). Overall, our integrated nanostrategy achieved an AUC value of 0.978 in differentiating between early-stage lung cancer patients (n = 28) and controls consisting of patients with benign lung diseases (n = 23) and healthy controls (n = 26), which showed remarkable diagnostic performance and great clinical potential for detecting the early occurrence of lung cancer.

Peripheral Blood-Derived CircVPS35L as a Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer.

Circular RNAs (circRNAs) are dysregulated in cancers and are stably expressed in body fluids such as blood. We therefore identified and evaluated the clinical value of a newly found circRNA VPS35L (circVPS35L) as a biomarker for the diagnosis of non-small cell lung cancer (NSCLC). Reverse-transcription quantitative PCR (RT-qPCR) was used to determine the expression levels of circVPS35L in tissues, whole blood, and cell lines. The actinomycin D assay and RNase R treatment were utilized to determine the stability of circVPS35L. Receiver operating characteristic (ROC) curve analysis was conducted to predict the diagnostic value of blood-derived circVPS35L in NSCLC. CircVPS35L was found to be downregulated in NSCLC tissues and cell lines. Interestingly, circVPS35L expression was significantly correlated with tumor size (p = 0.0269), histology type (p &lt; 0.0001), and TNM stage (p = 0.0437). Importantly, circVPS35L was poorly expressed in peripheral blood of NSCLC patients when compared with healthy controls and patients with benign lung disease. ROC analysis revealed a higher diagnostic value of circVPS35L than the three conventional tumor markers (CYFR21-1, NSE, and CEA) in patients with NSCLC. Moreover, circVPS35L was highly stable in peripheral blood when exposed to undesirable conditions. These findings demonstrate that circVPS35L has great potential as a novel biomarker for the diagnosis of NSCLC and can be used to distinguish NSCLC from benign lung disease.

Computed tomography aspects of thoracic metastases from osteosarcoma: pictorial essay.

Osteosarcoma is the most common primary bone tumor, with a higher incidence in the second decade of life, and it often leads to pulmonary metastases. The most common pattern seen on computed tomography is one of multiple well-defined nodules in the lung parenchyma, often with calcifications. Because of the variety of presentations of pulmonary metastases in osteosarcoma, including atypical forms, knowledge of the computed tomography aspects of these lesions is important for characterizing and evaluating the extent of the disease, as well as for distinguishing metastatic disease from other benign or malignant lung diseases. This essay discusses the main tomographic findings of pulmonary metastases from osteosarcoma.

Diagnostic Value of Seven Autoantibodies Combined with CEA and CA199 in Non-Small Cell Lung Cancer.

This study aimed to analyze the diagnostic value of seven autoantibodies (7-AABs) combined with carcinoembryonic antigen (CEA) and carbohydrate antigen-199 (CA199) in non-small cell lung cancer (NSCLC) and provide a new method for early screening of NSCLC. The serum levels of 7-AABs, CEA, and CA199 were determined in the NSCLC group (n = 615), benign lung disease group (n = 183), healthy control group (n = 236), and the other tumor group (n = 226). The receiver operating characteristic area under the curve (AUC) analyses were conducted to evaluate the diagnostic efficiency of 7-AABs combined with CEA and CA199 in NSCLC. The positive rate of 7-AABs detection was higher than that of a single antibody detection. The positive rate of the combination of 7-AABs in NSCLC group (27.8%) was significantly higher than that of the benign lung disease group (15.8%) and healthy control group (11.4%). The positive rate of MAGE A1 was higher in patients with squamous cell carcinoma than adenocarcinoma. The levels of CEA and CA199 in the NSCLC group were significantly higher than those of the healthy control group, but had no statistical differences compared with those of benign lung disease group. The sensitivity, specificity, and AUC of the 7-AABs were 27.8%, 86.6%, and 0.665, respectively. The combination of 7-AABs with CEA and CA199 increased the sensitivity to 34.8% and AUC to 0.689. The diagnostic efficiency was enhanced by a combination of 7-AABs, CEA, and CA199 in NSCLC, which was helpful in the screening of NSCLC.

Plasma Progastrin-Releasing Peptide and Chromogranin A Assays for Diagnosing and Monitoring Lung Well-Differentiated Neuroendocrine Tumors: A Brief Report

IntroductionThe use of chromogranin A (CGA) as a circulating biomarker in lung carcinoids (LCs) is limited by low specificity and sensitivity. This study aimed to evaluate plasma progastrin-releasing peptide (ProGRPp) as an alternative to plasma CGA (CGAp), for the diagnosis and follow-up of LC. MethodsProGRPp and CGAp concentrations were measured in 107 patients with LC and 105 patients with benign lung disease (BLD). ResultsProGRPp distinguished patients with LC with active disease in the pretreatment (n = 43) and post-treatment (n = 43) groups from those with BLD: area under the curve for both 0.864 (p < 0.0001); sensitivity 67.4% and 58.1%, respectively; specificity 96.2%; at 64 pg/mL cutoff. CGAp failed to differentiate both LC groups from those with BLD: area under the curve 0.579 and 0.526 (for both p > 0.1); sensitivity 34.9% and 25.6%, respectively; specificity 73.3%; at 104 ng/mL cutoff. Only ProGRPp correlated with the Ki67 proliferation index (r = 0.40, p < 0.001) and was associated with mitotic count (p = 0.025), stage (p = 0.018), grade (p = 0.019), and the expression of thyroid transcription factor-1 (p = 0.005). ProGRPp had a high sensitivity (92.3%) in LC with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Abnormal postoperative ProGRPp level was associated with residual disease (p = 0.029). The changes in ProGRPp level during treatment, a decrease greater than 30% and an increase greater than 8%, were associated with image-based outcomes, partial response and disease progression, respectively (p < 0.0001). CGAp did not reflect the disease course. ConclusionsProGRPp was superior to CGAp in diagnosing LC with correlations concerning proliferation, grading, staging, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia co-occurrence, and response to treatment. ProGRPp is an optimal emerging biomarker to be further evaluated.

Screening of potential microbial markers for lung cancer using metagenomic sequencing.

Lung cancer is the most prevalent cancer with high mortality in China, and it is associated with the dysbiosis of the lung microbiome. This study attempted to screen for specific microorganisms as potential biomarkers for distinguishing benign lung disease from lung cancer. Bronchoalveolar lavage fluid (BALF) sample was selected in the study instead of saliva to avoid contamination with oral microorganisms, and microbial taxonomic and functional differences in BALF samples from patients with lung cancer and those with those from patients with benign lung diseases were performed based on metagenomic next-generation sequencing, for the first time, so that microorganisms other than bacteria could be included. The results showed that the intrasample diversity of malignant samples was different from benign samples, and the microbial differences among malignant samples were smaller, with lower microbial diversity, significantly changed microbial abundance and metabolic functions. Metabolic function analysis revealed amino acid-related metabolism was more prevalent in benign samples, whereas carbohydrate-related metabolism was more prevalent in malignant samples. By LEfSe, Metastat and Random Forest analysis, we identified a series of important differential microorganisms. Importantly, the model combining five key genera plus one tumor marker (neuron-specific enolase) as indicators presented the optimal disease typing performance. Thus results suggest the value of these differential microorganisms enriched in tumors in mechanism research and may be potential new targets for lung cancer therapy. More importantly, the biomarkers identified in this study can be conducive to improve the clinical diagnosis of lung cancer and have good application prospects.

MiR-375 Combined with SHOX2 Methylation has Higher Diagnostic Efficacy for Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is a high-risk type of lung cancer. This study aims to improve the diagnostic efficacy of NSCLC through the combined detection of miR-375 and short-stature homeobox 2 (SHOX2) methylation. Patients with NSCLC (n = 121) and benign lung disease (BLD) (n = 121) were included. miR-375 and SHOX2 methylation levels were detected. The correlations between miR-375, SHOX2 methylation, and clinical characteristics of NSCLC were analyzed. The diagnostic efficacy of miR-375, SHOX2 methylation, and their combined detection was analyzed. The risk factors of NSCLC were analyzed. The results showed that levels of miR-375 and SHOX2 methylation in NSCLC patients were higher than those in BLD. High expression of miR-375 and positive SHOX2 methylation indicated worse pathological features of NSCLC patients. miR-375 combined with SHOX2 methylation had higher diagnostic efficacy than the single diagnosis. miR-375, SHOX2 methylation, smoking history, neuron-specific enolase (NSE), and CYFRA21-1 levels were risk factors for NSCLC; the risk of NSCLC increased 25.763 times for each unit increase in plasma miR-375 level (OR = 25.763, CI: 1.726-384.529), and the risk of NSCLC increased 4.096 times for each unit increase in SHOX2 methylation (OR = 4.096, CI: 1.195-14.036). miR-375 targeted SHOX2. Overall, miR-375 and SHOX2 methylation and their combined detection were expected to be biomarkers for the diagnosis of NSCLC.

Potential Clinical Utility of FDG-PET in Non-malignant Pulmonary Disorders: A Pilot Study

Fluorodeoxyglucose (FDG) positron emission tomography (PET) is emerging as an important non- invasive investigation in benign pulmonary conditions too. The aim of this study was to investigate its utility in the diagnosis and monitoring of various benign pulmonary diseases. In this prospective observational hospital-based study 50 consecutive patients (26 males) with benign lung diseases underwent computed tomography of chest followed by FDG-PET at baseline and after treatment where appropriate. The findings of FDG scan are reported in the context of clinical, histopathological, physiological and radiological findings. All patients showed increased FDG uptake in the lung corresponding to CT findings. Of the 9 patients with sarcoidosis stage 1 (n=1), stage 2 (n=3) and stage 3 (n=5), additional uptake in the myocardium and thyroid was noted in two patients which resulted in a change in the modality of treatment. Repeat FDG scan post-treatment showed decreased uptake in all patients which was consistent with clinico-radiologic, microbiological or spirometry findings. Increased uptake was seen in one patient with pulmonary tuberculosis (TB) and in one patient with TB mediastinal lymphadenopathy at the end of intensive phase discordant with clinical and microbiological response. Of nine cases of idiopathic interstitial pneumonias (IIPs), additional intense FDG uptake was found in two cases which corresponded to the areas of honeycombing. FDG-PET scan can be used as an important adjunct non-invasive investigation in diagnosing and monitoring of various benign lung conditions. It also helps in assessing whole body disease burden which may change therapeutic decisions.

Polyurea-Modified Magnetic Particles with Versatile Probes for Chemoselective Capture of Carbonyl Metabolites and Biomarker Discovery.

Playing a great role in human physiologies and pathologies, carbonyl metabolites are intimately associated with a variety of diseases, though the effective analysis method of them remains a challenge. A hydrazide-terminated polyurea-modified magnetic particle (HPMP) with versatile probes is developed to address this issue. The capture ability of HPMPs for carbonyl metabolite is more than 1200µmol g-1 , which is increased by 4 orders of magnitude via the introduction of polyurea. With a broad linear range of over 4 orders of magnitude, remarkably improved sensitivity, and limit of detection at attomole quantities, HPMPs are applied in relative quantification of more than 1500 carbonyl metabolites in 113 human serum samples with high throughput and high coverage. The combined indicators of these metabolites demonstrates a great diagnostic accuracy for distinguishing between health and disease subjects as well as differentiating the patients with benign lung disease and lung cancer. Combining powerful capture ability, low-cost preparation, and convenient operation, the HPMPs demonstrate extensive application in biomarker discovery and the detailed study of the biochemical landscape.

Autoantibody panel on small extracellular vesicles for the early detection of lung cancer

This study evaluated a different form of autoantibody, which is on small extracellular vesicles (sEVs), as a biomarker for early detection of lung cancer. The sEVs were isolated from plasma by ultracentrifugation and validated with morphology and typical markers. The autoantibody levels were quantified by enzyme-linked immunosorbent assay, and further analysis indicated that the autoantibody panel on sEVs was better than that from serum to distinguish benign lung disease (n = 32) from lung cancer (n = 90). In the prospective study, autoantibody on sEVs performed better in identification of patients with a higher risk of lung cancer. Furthermore, with immunogold labeling transmission electron microscopy, Nanoflow cytometry and binding tests, we illustrated that the autoantibodies could bind to the antigens on sEVs, which may explain the detected autoantibodies on sEVs. Besides, the binding resulted in the attenuation of complement-mediated cytotoxicity, which may contribute to the immune escape of lung cancer.

Association of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP with Clinicopathological Characteristics and Chemotherapeutic Outcomes of Lung Cancer.

The aim of this study was to investigate the association of serum carcinoembryonic antigen (CEA), nerve-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag), and pro-gastrin-releasing peptide (ProGRP) with the clinicopathological characteristics and chemotherapeutic outcomes of patients with lung cancer. A total of 189 patients with lung cancer (lung cancer group) diagnosed at the Fourth Affiliated Hospital of Anhui Medical University from January 2020 to December 2021 were included. During the same period, 199 patients with benign lung disorders were included as the benign lung disease group and 75 healthy people were selected as the control group. The serum concentrations of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP in all the 3 groups were analyzed and compared in patients with different lung cancer tumor-node-metastasis (TNM) stages and pathological classifications. Atotal of 11 patients with small cell lung cancer (SCLC) and 18 patients with lung adenocarcinoma (LAC) were further evaluated forthe dynamic changes of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP before chemotherapy and during the 6 courses of chemotherapy, and the outcome of chemotherapy was evaluated every 2 courses. The serum concentrations of CEA, NSE, CYFRA21-1, SCC-Ag, and ProGRP in the lung cancer group were significantly higher than those in the control group (P < .05). We found statistically significant differences in serum CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP among patients with different pathological types (LAC, squamous cell carcinoma, or SCLC) and different stages (I-IV). The ProGRP and NSE had the highest expression in SCLC, CEA showed the highest expression in LAC, whereas CYFRA21-1 and SCC-Ag showed the highest expression in lung squamous cell carcinoma (LSCC). The concentrations of all the markers were elevated in the advanced pathological stages. The receiver operating characteristic curve analysis showed that the diagnostic value of the combined detection of CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP for lung cancer was significantly higher than using a single biomarker (P < .05). Our dynamic monitoring results show that ProGRP progressively decreased in remission cases of SCLC and CEA progressively decreased in LAC remission cases. CEA, NSE, CYFRA 21-1, SCC-Ag, and ProGRP have good clinical value in the early diagnosis, differential diagnosis, and progression monitoring of lung cancer. The ProGRP and CEA concentrations are beneficial for evaluating the outcome of chemotherapy in SCLC and LAC. The combined detection of multiple biomarkers shows improved clinical value in the early diagnosis of lung cancer.

Clinical Outcomes of Pulmonary Resections for Benign Lung Diseases in Adults

Benign lung diseases (BLD) are a spectrum of diseases that require medical and surgical attention. Surgical treatment in majority cases provides curative treatment in majority of the cases. Objective: To assess the clinical outcome in patients who undergo pulmonary resection for various indications in BLD. Methods: A prospective study was conducted in The Department of Thoracic surgery at Jinnah Postgraduate Medical Center, Karachi from June 2021 to June 2022. All symptomatic patients above the age of 12 years with radiological evidence of resectable lung disease with good cardiopulmonary reserve were included. Results: Eighty-four patients were included; sixty-six (78.6%) were males. Most common indication for resection was bronchiectasis (n=32; 38.1%) and aspergilloma (n=22; 26.2%). Majority of the patients presented with productive cough (44; 52.3%), chest pain (41; 48.8%) and hemoptysis (28;33%). Eighteen (81.8%) out of 22 patients of aspergilloma were complex in nature. Lobectomy (67; 78.8%) was most commonly performed followed by wedge resection (10; 11.7%). Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) both were significantly improved after lung resection (p˂0.001). The most common complications were post resection fluid (n=12; 14.2%), residual pleural space (n=10;11.9%). Three patients (3.6%) died; two (2.38%) due to respiratory failure and one (1.2%) after myocardial infraction. Conclusions: Despite limitations, lobectomy and lesser pulmonary resections are safe procedures when patients are carefully selected and prepared. Management in a dedicated Thoracic Surgical unit is essential to keep the complication rate under control and patients should be assessed for symptomatic (spirometric) and radiological improvement on follow up visits to document ongoing clinical improvement for an improved quality of life

Folate receptor-positive circulating tumor cells in the preoperative diagnosis of indeterminate pulmonary nodules.

BackgroundThe use of FR + CTC to distinguish lung cancer from benign lung disease has been well studied. However, the effective method to differentiate precursor glandular lesions from benign/malignant pulmonary diseases is rare.Methods380 patients with indeterminate pulmonary nodules were prospectively recruited. Peripheral blood samples were collected from all participants before surgery for analyzing FR + CTC levels. The performance of FR + CTC to identify lung precursor lesions were analyzed by receiver operating characteristic (ROC) curve.ResultsFR + CTC can effectively differentiate precursor from benign pulmonary diseases in all included patients (cutoff: 9.22 FU/3 ml, AUC = 0.807, (p < 0.0001, sensitivity: 69.17%, specificity: 82.46%) and patients with single pulmonary lesion (cutoff: 9.03 FU/3 ml, AUC = 0.842, p = 0.0001, sensitivity: 75.20%, specificity: 83.00%). However, FR + CTC cannot differentiate precursor from benign pulmonary diseases in multiple lesions patients (p = 0.110). FR + CTC neither differentiate precursor from malignant pulmonary lesions in all included patients (p = 0.715), single nor multiple lesions patients (p = 0.867, p = 0.692, respectively). Total number of pulmonary nodules, MTD, location (lower vs upper) were independent risk factors for malignancy (AOR, 95% CI: 3.104 (1.525, 6.316), 3.148 (1.722, 5.754), 2.098 (1.132, 3.888), respectively.ConclusionPreoperative FR + CTC can be identified in precursor glandular lesions and utilized to differentiate from benign pulmonary diseases. Total number of pulmonary nodules, MTD, location (lower vs upper) were independent risk factors for malignancy.

Detection of CEA and ProGRP Levels in BALF of Patients with Peripheral Lung Cancer and Their Relationship with CT Signs.

Background Lung cancer is a common clinical thoracic malignant tumor, which had a serious impact on the safety of patients, currently ranking first in all malignant tumors in morbidity and mortality, with generally less than 5% survival rate in 5 years. Objective To investigate the relationship and significance between carcinoembryonic antigen (CEA) and precursor gastrin-releasing peptide (ProGRP) changing levels in bronchoalveolar lavage fluid (BALF) and CT imaging features in patients with peripheral lung cancer. Methods A total of 90 patients diagnosed with peripheral lung cancer as the lung cancer group and 60 patients with benign lung diseases as the control group in our hospital from May 2019 to October 2021 were selected to compare the differences of CEA and ProGRP in BALF by the classification of CT features. Results The levels of CEA and ProGRP in the BALF of the lung cancer group were significantly higher than those of the control group; the proportion of patients with lobulation sign, burr sign, ground glass sign, pleural effusion, and lesion diameter ≥ 3.0 cm in the lung cancer group was higher than that in the control group; the CEA level in BALF of lung cancer patients with spicule sign, pleural effusion, and lesion diameter ≥ 3.0 cm was significantly higher than that without these symptoms, while ProGRP level in the BALF of lung cancer patients with lobulation sign, burr sign, ground glass sign, pleural effusion, and lesion diameter ≥ 3.0 cm was significantly higher than that of lung cancer patients without these symptoms. Conclusion The check of CEA and ProGRP in BALF in combination with CT features has a certain clinical value for the diagnosis of lung cancer. At the same time, the increased levels of CEA and ProGRP in BALF have a certain correlation with the changes of malignant signs of lung cancer in CT examination.

Diagnostic value of tumor associated autoantibody panel in early detection of lung cancer in Chinese population: Protocol for a prospective, observational, and multicenter clinical trial

Lung cancer is the leading cause of cancer deaths. Although targeted therapies and programmed cell death protein 1 (PD-1) blockade have offered great advances, five-year survival rates remained low. Diagnosis of lung cancer at an earlier stage is the most efficient approach to improve survival. Tumor associated autoantibodies (TAAb) have been proven a promising innovative biomarker of lung cancer. We aimed to comprehensively evaluate the sensitivity, specificity, and accuracy of TAAbs in lung cancer detection, especially in early-stage patients, through a multicenter prospective observational clinical trial, and to screen out the novel combination of TAAbs with the best detection value for Chinese population. We aimed to enroll 1,400 participants from three clinical centers and divide into two cohorts. One cohort is participants with newly pathologically confirmed lung cancer as the case cohort, and the other is participants with benign nodules, matched healthy controls and other benign lung diseases as the control cohort. Cases and controls were randomly distributed into training or validation set. The level of 14 autoantibody candidates in their plasma were detected. A Monte-Carlo Simulated Annealing method was implemented to develop a composite panel of autoantibodies to distinguish between matched lung cancer cases and controls in the training set. The newly developed autoantibody panel was tested in the validation set for sensitivity, specificity and accuracy. This is the first and largest clinical trial designed to develop a novel autoantibody panel for lung cancer detection specifically for Chinese people. We performed a multicenter, prospective, observational study to find a novel panel of autoantibody markers that can help the diagnosis of lung cancer and the characterization of pulmonary nodules in Chinese population. The results may help to provide evidence-based recommendations to clinicians for lung cancer early detection and pulmonary nodule management. This study is registered in the ClinicalTrials.gov (NCT04216511).