Preoperative evaluation of visceral pleural invasion in peripheral lung cancer utilizing deep learning technology.

PURPOSE: This study aimed to assess the efficiency of artificial intelligence (AI) in the detection of visceral pleural invasion (VPI) of lung cancer using high-resolution computed tomography (HRCT) images, which is challenging for experts because of its significance in T-classification and lymph node metastasis prediction. METHODS: This retrospective analysis was conducted on preoperative HRCT images of 472 patients with stage I non-small cell lung cancer (NSCLC), focusing on lesions adjacent to the pleura to predict VPI. YOLOv4.0 was utilized for tumor localization, and EfficientNetv2 was applied for VPI prediction with HRCT images meticulously annotated for AI model training and validation. RESULTS: Of the 472 lung cancer cases (500 CT images) studied, the AI algorithm successfully identified tumors, with YOLOv4.0 accurately localizing tumors in 98% of the test images. In the EfficientNet v2-M analysis, the receiver operating characteristic curve exhibited an area under the curve of 0.78. It demonstrated powerful diagnostic performance with a sensitivity, specificity, and precision of 76.4% in VPI prediction. CONCLUSION: AI is a promising tool for improving the diagnostic accuracy of VPI for NSCLC. Furthermore, incorporating AI into the diagnostic workflow is advocated because of its potential to improve the accuracy of preoperative diagnosis and patient outcomes in NSCLC.

Preoperative predictors for recurrence sites associated with poor post-recurrence survival after surgery of non-small cell lung cancer: a multicenter study.

BACKGROUND: The recurrence site that influences post-recurrence survival (PRS) in patients with non-small cell lung cancer (NSCLC) undergoing surgery and the preoperative predictors of recurrence remain unclear. METHODS: Cohorts 1 and 2 had 4520 (who underwent complete resection for p-stage 0-IIIA NSCLC) and 727 (who experienced recurrence after surgery) patients, respectively. The initial sites of recurrence were the lungs (309 cases), thoracic lymph nodes (225 cases), pleura (112 cases), bone (110 cases), central nervous system (86 cases), adrenal gland (25 cases), abdomen (60 cases), cervical and axillary lymph nodes (38 cases), chest wall (13 cases), skin (5 cases), and eye and tongue (3 cases). For cohort 2 analysis, the initial recurrence site that resulted in poor PRS was analyzed by multivariable analysis using a Cox proportional hazard model. For cohort 1 analysis, the preoperative predictors of recurrence patterns with poor PRS were analyzed by multivariable analysis using a logistic regression model. RESULTS: In cohort 2 analysis, recurrence in the central nervous system (hazard ratio [HR], 1.70; p < 0.001), bone (HR, 1.75; p < 0.001), abdomen (HR, 2.39; p < 0.001), and pleura (HR, 1.69; p < 0.001) were independent poor prognostic recurrent sites for PRS and they were high-risk sites (HRS). Intrathoracic lymph nodes, cervical and axillary lymph nodes, lungs, chest wall, adrenal gland, eye and tongue, and skin were low-risk sites (LRS) that did not affect PRS. Patients with multiple LRS without HRS recurrence had a worse prognosis than those with a single LRS without HRS recurrence (5-year PRS 20.2% vs. 37.7%, p < 0.001) and were comparable to those with HRS recurrence (p = 1.000). In cohort 1 analysis, preoperative predictors for HRS and multiple LRS recurrences were positron emission tomography (PET) maximum standardized uptake value (maxSUV) ≥ 3.2 (HR, 5.09; p < 0.001), clinical nodal metastasis (HR, 2.00; p < 0.001), tumor size ≥ 2.4 cm (HR, 1.96; p < 0.001) and carcinoembryonic antigen (CEA) ≥ 5 ng/ml (HR, 1.41; p = 0.004). The cumulative incidence rates of HRS and multiple LRS recurrences within 5 years were 55.9%, 40.9%, 26.3%, 11.1%, and 3.5% (p < 0.001) in patients with 4, 3, 2, 1 and 0 of the above risks, respectively. CONCLUSIONS: HRS and multiple LRS were vital recurrences associated with poor PRS. Preoperative PET maxSUV, clinical nodal metastasis, tumor size, and CEA level predicted the incidence of vital recurrence.

[Digital Innovation for Lung Segmentectomy for Early-stage Small Lung Cancer].

In recent years, the number of cases of small-size lung cancer(<2 cm) has increased with the widespread of computed tomography (CT) in medical checkup and comprehensive medical checkup. Although lobectomy has been the standard surgical treatment for early-stage small-size lung cancer, it has become possible to evaluate the CT findings of small tumors in terms of ground-glass areas and solid areas, and it has become clear that the former has a low histological malignancy while the latter has a high malignancy. Lung cancers with high ground-glass opacity have low malignant potential and are therefore being aggressively treated by limited resection. The number of lung segmentectomies is expected to increase in the future, and accurate identification of pulmonary intersegmental planes is important in this operation. Especially in thoracoscopic surgery, where the field of view and surgical operation are limited, tumor localization and intersegmental planes identification are particularly important and require preoperative and intraoperative planning. In order to perform safe and reliable lung segmentectomy, we create a three-dimensional (3D) lung model by Synapse Vincent for preoperative simulation of pulmonary vascular, tumor location, and intersegmental plane. In addition, preoperative simulations are performed using wearable goggles to freely move the 3D lung model in a virtual reality (VR) space. Intraoperatively, in addition to indocyanine green (ICG)-based intersegmental identification, digital assistance is used for tumor and intersegmental identification using mixed reality( MR) goggles. We describe the current status and future prospects of segmentectomy in our institution.

Clinical Impact of Sarcopenia 1 Year After Surgery for Patients with Early-Stage Non-small Cell Lung Cancer.

BACKGROUND: Sarcopenia is associated with prognostic outcomes for patients with various solid tumors, whereas the clinical significance of sarcopenia 1 year after surgery (post-sarcopenia) for non-small cell lung cancer (NSCLC) has not been investigated. This study aimed to clarify the clinical impact of post-sarcopenia and factors associated with post-sarcopenia in NSCLC patients without preoperative sarcopenia. METHODS: This study enrolled 443 patients with clinical stage 1 or 2 NSCLC (234 patients without preoperative sarcopenia [NS group] and 209 patients with preoperative sarcopenia [S group]) who underwent computed tomography (CT) at two time points (before surgery and a year afterward) or more. The study assessed CT images at the L3 level to calculate the psoas muscle area index (PAI). The PAI cutoff value for sarcopenia was defined as 6.36 cm2/m2 for the men and 3.92 cm2/m2 for the women. RESULTS: In the NS group, the diagnosis for 40.1% of the women and 52.6% of the men was post-sarcopenia (NS-S group). The overall survival (OS) for the S and NS-S cohorts was worse than for the non-sarcopenic patients before and after surgery (p < 0.001 and p = 0.017, respectively). In the multivariable analysis, sarcopenia, either before or after surgery (hazard ratio, 3.272; p = 0.002), in the NS group was independently associated with OS, whereas the factors associated with post-sarcopenia were male sex (p = 0.002), aging (p < 0.001), and low body mass index (p < 0.001). CONCLUSIONS: Sarcopenia, either before or after surgery, is prognostic in early-stage NSCLC. Male sex, aging, and low body mass index (BMI) are associated with post-sarcopenia.

Radiomics with Artificial Intelligence for the Prediction of Early Recurrence in Patients with Clinical Stage IA Lung Cancer.

BACKGROUND: We seek to explore the ability of computed tomography (CT)-based radiomics coupled with artificial intelligence (AI) to predict early recurrence (< 2 years after surgery) in patients with clinical stage 0-IA non-small cell lung cancer (c-stage 0-IA NSCLC). PATIENTS AND METHODS: Data of 642 patients were collected for early recurrence and assigned to the derivation and validation cohorts at a ratio of 2:1. Using the AI software Beta Version (Fujifilm Corporation, Japan), 39 AI imaging factors, including 17 factors from the AI ground-glass nodule analysis and 22 radiomic features from nodule characterization analysis, were extracted. RESULTS: Multivariate analysis showed that male sex (p = 0.016), solid part size (p < 0.001), CT value standard deviation (p = 0.038), solid part volume ratio (p = 0.016), and bronchus translucency (p = 0.007) were associated with recurrence-free survival (RFS). Receiver operating characteristics analysis showed that the area under the curve and optimal cutoff values relevant to recurrence were 0.707 and 1.49 cm for solid part size, and 0.710 and 22.9% for solid part volume ratio, respectively. The 5-year RFS rates for patients in the validation set with solid part size ≤ 1.49 cm and > 1.49 cm were 92.2% and 70.4% (p < 0.001), whereas those for patients with solid part volume ratios ≤ 22.9% and > 22.9% were 97.8% and 71.7% (p < 0.001), respectively. CONCLUSIONS: CT-based radiomics coupled with AI contributes to the noninvasive prediction of early recurrence in patients with c-stage 0-IA NSCLC.

Ubiquitin C-terminal hydrolase-L1 has prognostic relevance and is a therapeutic target for high-grade neuroendocrine lung cancers.

High-grade neuroendocrine lung cancer (HGNEC), which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is a rapidly proliferating, aggressive form of lung cancer. The initial standard chemotherapeutic regimens of platinum doublets are recommended for SCLC and have been frequently used for LCNEC. However, there are currently no molecularly targeted agents with proven clinical benefit for this disease. The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCHL1) is a neuroendocrine cell-specific product that is known as a potential oncogene in several types of cancer, but little is known about the biological function of UCHL1 and its therapeutic potential in HGNEC. In this study, we found that preclinical efficacy evoked by targeting UCHL1 was relevant to prognosis in HGNEC. UCHL1 was found to be expressed in HGNEC, particularly in cell lines and patient samples of SCLC, and the combined use of platinum doublets with selective UCHL1 inhibitors improved its therapeutic response in vitro. Immunohistochemical expression of UCHL1 was significantly associated with postoperative survival in patients with HGNEC and contributed towards distinguishing SCLC from LCNEC. Circulating extracellular vesicles (EV), including exosomes isolated from lung cancer cell lines and serum from early-stage HGNEC, were verified by electron microscopy and nanoparticle tracking analysis. Higher levels of UCHL1 mRNA in EV were found in the samples of patients with early-stage HGNEC than those with early-stage NSCLC and healthy donors' EV. Taken together, UCHL1 may be a potential prognostic marker and a promising druggable target for HGNEC.

A combination therapy of photodynamic therapy (PDT) and airway stent placement using a transparent silicone stent.

The aim of this study was to evaluate the feasibility of a combination therapy of photodynamic therapy (PDT) and airway stent placement using a transparent silicone stent (gold studded stent [GSS]). Laser irradiation (664 nm, continuous wave) was performed through the GSS using a straight and cylindrical fiber 1.0 cm away from a power meter. There are two types of GSS: the TD type for the trachea and the BD type for the bronchus. Laser outputs were set to 150 mW, 180 mW, 210 mW, 240 mW, 270 mW, and 300 mW. The laser powers passing through the both types of GSS were measured three times for each outputs and the averages were calculated. Based on the results, animal experiment was performed using two female pigs. Under general anesthesia, a GSS (BD type) was inserted into trachea of pigs, and PDT using NPe6 as a photosensitizer was performed by 100 J/cm2 laser irradiation on parts of the trachea with and without a GSS. Immediately after and 1 week after PDT, pig tracheas were harvested and histological analysis was performed. Histological analysis of areas with or without the stent showed edematous changes between the cartilage and submucosal layer immediately after PDT, and necrotic changes 1 week later. The effectiveness of NPe6-PDT for pigs' trachea covered by the stent was same as trachea without the stent. The use of a GSS may enable PDT to be effective even in the area covered by the stent.

Correlation between whole tumor size and solid component size on high-resolution computed tomography in the prediction of the degree of pathologic malignancy and the prognostic outcome in primary lung adenocarcinoma.

BACKGROUND: The presence of ground glass opacity (GGO) on high-resolution computed tomography (HRCT) is well known to be pathologically closely associated with adenocarcinoma in situ. PURPOSE: To determine whether it is more useful to evaluate the whole tumor size or only the solid component size to predict the pathologic high-grade malignancy and the prognostic outcome in lung adenocarcinoma. MATERIAL AND METHODS: Using HRCT data of 232 patients with adenocarcinoma who underwent curative resection, we retrospectively measured the whole tumor and solid component sizes with lung window setting (WTLW and SCLW) and whole tumor sizes with a mediastinal window setting (WTMW). RESULTS: There was significant correlation between the WTLW and the measurements of pathological whole tumor (pWT) (r = 0.792, P < 0.0001). The SCLW and WTLW values significantly correlated with the area of pathological invasive component (pIVS) (r = 0.762, P < 0.0001 and r = 0.771, P < 0.0001, respectively). The receiver operating characteristics area under the curve for WTLW, SCLW, and WTMW used to identify lymph node metastasis or lymphatic or vascular invasion were 0.693, 0.817, and 0.824, respectively. Kaplan-Meier curves of disease-free survival (DFS) and overall survival (OS) were better divided according to SCLW and WTMW, compared with WTLW. Multivariate analysis of DFS and OS revealed that WTMW was an independent prognostic factor (HR = 0.72, 95% confidence interval [CI] = 0.58-0.90, P = 0.004 and HR = 0.74, 95% CI = 0.57-0.96, P = 0.022, respectively). CONCLUSION: The predictive values of the solid tumor size visualized on HRCT especially in the mediastinal window for pathologic high-grade malignancy and prognosis in lung adenocarcinoma were greater than those of whole tumor size.

Chylothorax in POEMS syndrome.

Chylothorax results from various causes, such as malignancy, trauma, or infection. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a multisystemic syndrome that is associated with plasma cell disorder. Pleural effusion is a common manifestation of POEMS syndrome, but the association of POEMS syndrome with chylothorax has not been reported. We report on a 61-year-old female patient who initially presented with dyspnea and bilateral leg edema. Importantly, the patient had normal renal function. Her chest X-ray and computed tomographic imaging showed bilateral pleural effusion, and her chest drainage revealed chylothorax. Detailed examination failed to reveal the definitive cause of the chylothorax. She received several treatments for chylothorax, namely, a low-fat diet or fasting, total parenteral nutrition, a somatostatin analog (octreotide), thoracic duct ligation by video-assisted thoracic surgery, and pleurodesis. However, further examination revealed endocrinopathy, monoclonal plasma cell disorder, peripheral neuropathy, and elevation of the serum level of vascular endothelial growth factor. The patient's condition was consequently diagnosed as POEMS syndrome. Eventually, her chylothorax was controlled by pleurodesis, and she was transferred to another hospital for stem cell transplantation. Herein, we report on the apparent first case of POEMS syndrome with chylothorax. In some cases of idiopathic chylothorax, the underlying primary disease may be latent, such as in the present patient. POEMS syndrome is rare, but this syndrome should be included in the differential diagnosis of chylothorax with unexplained etiology.

Omitting Lymph Node Dissection for Small Ground-Glass Opacity-Dominant Tumors.

BACKGROUND: The purpose of this study was to determine the optimal extent of lymph node dissection required in patients with small (≤3 cm) radiologically ground-glass opacity-dominant, peripheral, non-small cell lung cancer tumors. METHODS: The study analyzed the clinicopathologic findings and surgical outcomes of 988 patients with radiologic, ground-glass opacity-dominant non-small cell lung cancer without lymph node involvement who underwent complete resection of the primary tumor between 2010 and 2020. Patients were followed up for 54.5 months (median). Kaplan-Meier curves and the log-rank test were used in statistical analyses of the prognosis. RESULTS: Median age, whole tumor size, solid tumor size, and maximum standardized uptake values were 68 years, 1.7 cm, 0.4 cm, and 0.9, respectively. Sixty percent of the cohort was female (n = 590). Wedge resection, segmentectomy, and lobectomy were performed in 206, 372, and 410 patients, respectively. A total of 982 of 988 (99%) tumors were adenocarcinomas. One patient had hilar lymph node involvement; however, no mediastinal lymph node metastasis or hilar or mediastinal lymph node recurrence was detected. The 5-year overall survival rate was 96.5% (95% CI, 94.8%-97.7%). Excellent survival outcomes were achieved regardless of procedure (wedge resection, 94.7% [95% CI, 89.1%-97.5%]; segmentectomy, 96.9% [95% CI, 93.7%-98.5%]; and lobectomy, 97.1% [95% CI, 94.4%-98.5%]). CONCLUSIONS: Omitting lymph node dissection may be acceptable with curative intent for small tumors with radiologic ground-glass opacity dominance. Appropriate surgical procedures such as wedge resection, segmentectomy, or lobectomy can provide satisfactory outcomes in patients with indolent tumors if surgical margins are secured.

Feasibility and Comparative Prognosis of Segmentectomy vs. Lobectomy in Centrally Located Small and Solid Dominant cN0 Non-Small Cell Lung Cancer.

OBJECTIVES: This study aimed to determine the feasibility of segmentectomy in patients with central, whole tumor size ≤2 cm and radiologically solid-dominant cN0 non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 1240 patients who underwent lobectomy or segmentectomy for small and radiologically solid-dominant cN0 NSCLC between January 2010 and December 2022. The inclusion criteria encompassed centrally located tumors defined as tumors located in the inner two-thirds of the pulmonary parenchyma. Propensity score matching was applied to balance the baseline characteristics. RESULTS: Among the 299 eligible patients, no significant differences in recurrence-free survival (RFS) and overall survival (OS) were observed between the segmentectomy (n = 121) and lobectomy (n = 178) groups (P = .794 and .577, respectively). After propensity score matching, no significant differences in hilar and mediastinal lymph node upstaging were found among the 93 matched patients (P = 1.00) and locoregional recurrence was comparable between those who underwent segmentectomy (n = 4) and lobectomy (n = 4). RFS and OS did not significantly differ between the two groups (P = .700 and .870, respectively). Propensity score-adjusted multivariable Cox analysis for RFS and OS indicated that segmentectomy was not an independent prognostic factor (RFS: hazard ratio, 0.89; 95% confidence interval, 0.43-1.85; P = .755; OS: hazard ratio, 1.09; 95% confidence interval, 0.38-3.14; P = .860). CONCLUSIONS: Segmentectomy may be a viable treatment option with local control and prognosis comparable to that of lobectomy in appropriately selected patients with central, small (≤2 cm), and radiologically solid-dominant NSCLC.

Association between pathological infiltrative tumor growth pattern and prognosis in patients with resected lung squamous cell carcinoma.

INTRODUCTION: Lung squamous cell carcinoma (LUSC) usually shows expansive growth with large tumor nests; few reports on invasive growth patterns (INF) in LUSC have been associated with poor prognosis in gastrointestinal and urothelial cancers. In this study, we examine the association between INF and the prognosis of LUSC. MATERIALS AND METHODS: We analyzed INF as a potential prognostic factor in 254 consecutive patients with LUSC who underwent complete surgical resection at our hospital between 2008 and 2017. INF was classified into 3 categories based on the structure of the tumor other than the large round solid nest of tumor cells. RESULTS: INF was categorized as INFa in 59 patients (23 %) with only well-demarcated large solid tumor cell nests, INFb in 89 patients (35 %) with medium to small, alongside large solid nests, and INFc in 98 patients (39 %) with cord-like/small nests or isolated cells plus large or medium solid nests. No significant lymph node metastasis differences were observed between INFc and INFa/b tumors. However, in patients with p-stage I, INFc had a poorer prognosis with regard to recurrence-free survival (RFS), with a 5-year RFS rate of 53.3 %, compared to 74.9 % for INFa/b (p = 0.010). CONCLUSION: Our study highlights a novel pathological concept of INF in LUSC, and contributed to the proposal that it is a factor indicating an unfavorable prognosis in patients with early-stage LUSC. A prospective multicenter study is warranted for INFc patients, as careful follow-up and adjuvant chemotherapy might lead to the early detection and prevention of recurrence.

AI-driven Characterization of Solid Pulmonary Nodules on CT Imaging for Enhanced Malignancy Prediction in Small-sized Lung Adenocarcinoma.

OBJECTIVES: Distinguishing solid nodules from nodules with ground-glass lesions in lung cancer is a critical diagnostic challenge, especially for tumors ≤2 cm. Human assessment of these nodules is associated with high inter-observer variability, which is why an objective and reliable diagnostic tool is necessary. This study focuses on artificial intelligence (AI) to automatically analyze such tumors and to develop prospective AI systems that can independently differentiate highly malignant nodules. MATERIALS AND METHODS: Our retrospective study analyzed 246 patients who were diagnosed with negative clinical lymph node metastases (cN0) using positron emission tomography-computed tomography (PET/CT) imaging and underwent surgical resection for lung adenocarcinoma. AI detected tumor sizes ≤2 cm in these patients. By utilizing AI to classify these nodules as solid (AI_solid) or non-solid (non-AI_solid) based on confidence scores, we aim to correlate AI determinations with pathological findings, thereby advancing the precision of preoperative assessments. RESULTS: Solid nodules identified by AI with a confidence score ≥0.87 showed significantly higher solid component volumes and proportions in patients with AI_solid than in those with non-AI_solid, with no differences in overall diameter or total volume of the tumors. Among patients with AI_solid, 16% demonstrated lymph node metastasis, and a significant 94% harbored invasive adenocarcinoma. Additionally, 44% were upstaging postoperatively. These AI_solid nodules represented high-grade malignancies. CONCLUSION: In small-sized lung cancer diagnosed as cN0, AI automatically identifies tumors as solid nodules ≤2 cm and evaluates their malignancy preoperatively. The AI classification can inform lymph node assessment necessity in sublobar resections, reflecting metastatic potential.

Artificial intelligence-based radiomics for the prediction of nodal metastasis in early-stage lung cancer.

We aimed to investigate the value of computed tomography (CT)-based radiomics with artificial intelligence (AI) in predicting pathological lymph node metastasis (pN) in patients with clinical stage 0-IA non-small cell lung cancer (c-stage 0-IA NSCLC). This study enrolled 720 patients who underwent complete surgical resection for c-stage 0-IA NSCLC, and were assigned to the derivation and validation cohorts. Using the AI software Beta Version (Fujifilm Corporation, Japan), 39 AI imaging factors, including 17 factors from the AI ground-glass nodule analysis and 22 radiomics features from nodule characterization analysis, were extracted to identify factors associated with pN. Multivariate analysis showed that clinical stage IA3 (p = 0.028), solid-part size (p < 0.001), and average solid CT value (p = 0.033) were independently associated with pN. The receiver operating characteristic analysis showed that the area under the curve and optimal cut-off values of the average solid CT value relevant to pN were 0.761 and -103 Hounsfield units, and the threshold provided sensitivity, specificity, and negative predictive values of 69%, 65%, and 94% in the entire cohort, respectively. Measuring the average solid-CT value of tumors for pN may have broad applications such as guiding individualized surgical approaches and postoperative treatment.

Clinical utility of psoas muscle volume in assessment of sarcopenia in patients with early-stage non-small cell lung cancer.

PURPOSE: Sarcopenia influences postoperative outcomes of patients with non-small cell lung cancer (NSCLC). Imaging tools for evaluating and diagnosing sarcopenia have developed, and a novel method of psoas volume index (PVI) obtained by measuring bilateral psoas major muscle volume has been reported. However, the relationship between sarcopenia based on PVI and clinical outcomes has not been fully investigated for patients with early-stage NSCLC. This study aimed to clarify the utility of PVI values in assessing the relationshipe between sarcopenia and clinical outcomes. METHODS: This study included 645 patients with stage I-II NSCLC who underwent curative lung resection between 2012 and 2017. Bilateral psoas major muscle volumes were calculated semi-automatically using a three-dimensional workstation. The cutoff value of PVI for defining sarcopenia was < 60.5 cm3/m3 for men and < 43.6 cm3/m3 for women. RESULTS: The avrage time to obtaine PVI was only 25 s with the 3D system, and interobserver agreements for evauating sarcopenia on PVI was 1. A total of 159 patients (24.7%) were preoperatively diagnosed with sarcopenia. On multivariate analysis, sarcopenia was an independent prognostic factor for overall survival (OS, p < 0.001), recurrence-free survival (RFS, p < 0.001), and lung cancer-specific survival (LCS, p < 0.001). The 5-year OS, RFS, and LCS were significantly worse in sarcopenic patients than non-sarcopenic patients (88.8 vs. 72.4%, p < 0.001; 80.1 vs. 65.0%, p < 0.001; 92.4 vs. 78.9%, p < 0.001, respectively). CONCLUSION: Sarcopenia diagnosed using PVI is an independent prognostic predictor of OS, RFS, and LCS in early-stage NSCLC.

Extracellular vesicle-associated microRNA signatures related to lymphovascular invasion in early-stage lung adenocarcinoma.

Lymphovascular invasion (LVI) is a fundamental step toward the spread of cancer. Extracellular vesicles (EVs) promote cellular communication by shuttling cargo, such as microRNAs (miRNAs). However, whether EV-associated miRNAs serve as biomarkers for LVI remains unclear. This study aimed to identify EV-associated miRNAs related to LVI and validate the miRNA levels from patients with early-stage lung adenocarcinoma (LADC). Blood samples were collected from patients undergoing pulmonary resection for stage I LADC before surgery. The patients were classified into three groups according to the presence of LVI and postoperative recurrence. Serum-derived EVs in the derivation cohort were used for small RNA sequencing, while the selected LVI miRNA candidates were validated via real-time quantitative polymerase chain reaction using 44 patient and 16 healthy donor samples as the validation cohorts. Five miRNAs (miR-99b-3p, miR-26a-5p, miR-93-5p, miR-30d-5p, and miR-365b-3p) were assessed, and miR-30d-5p (p = 0.036) levels were significantly downregulated in the LVI-positive group. miR-30d-5p levels in healthy donors were lower than those in LADC patients. Patients with high miR-30d-5p levels had favorable survival compared to those with low miR-30d-5p levels. miR-30d-5p level in EVs may serve as a promising biomarker for detecting LVI in patients with early-stage LADC.

Development and validation of an immune-related gene prognostic index for lung adenocarcinoma.

Background: Lung cancer is the most common malignant tumor in the world, and its prognosis is still not optimistic. The aim of this study was to establish an immune-related gene (IRG) prognostic index (IRGPI) for lung adenocarcinoma (LUAD) based on IRGs, and to explore the prognosis, molecular and immune features, and response to immune checkpoint inhibitor (ICI) therapy in IRGPI-classified different subgroups of LUAD. Methods: Based on the LUAD transcriptome RNA-sequencing data in TCGA database, the differentially expressed genes (DEGs) were selected. Subsequently, DEGs were intersected with IRGs to obtain differentially expressed immune-related genes (DEIRGs). Weighted gene co-expression network analysis (WGCNA) identified hub genes in DEIRGs. Finally, univariate and multivariate Cox regression analyses were used to build an IRGPI model. Subsequently, TCGA patients were divided into high- and low-risk groups, and the survival of patients in different groups was further analyzed. Besides, we validated the molecular and immune characteristics, relationship with immune checkpoints, angiogenesis-related genes, and immune subtypes distribution in different subgroups. Meanwhile, we further validated the response to ICI therapy in different subgroups. Results: The IRGPI was constructed based on 13 DEIRGs. Compared with the low-risk group, overall survival (OS) was lower in the high-risk group, and the high-risk score was independently associated with poorer OS. Besides, the high-risk score was associated with cell cycle pathway, high mutation rate of TP53 and KRAS, high infiltration of M0 macrophages, and immunosuppressive state, and these patients had poorer prognosis but the TIDE score of the high-risk group was lower than that of the other group, which means that the high-risk group could benefit more from ICI treatment. In contrast, the low-risk score was related to low mutation rate of TP53 and KRAS, high infiltration of plasma cells, and immunoactive state, and these patients had better prognosis but the low-risk group less benefit from ICI treatment based on the results of TIDE score. Conclusions: IRGPI is a prospective biomarker based on IRGs that can distinguish high- and low-risk groups to predict patient prognosis, help characterize the tumor immune microenvironment, and evaluate the benefit of ICI therapy in LUAD.

Sublobar resection utilizing near-infrared thoracoscopy with intravenous indocyanine green for intralobar pulmonary sequestration: a case report and literature review.

BACKGROUND: Pulmonary sequestration is a rare pulmonary malformation, with intralobar pulmonary sequestration being the most common subtype. Lobectomy has generally been performed for its treatment, owing to unclear boundaries of the lesion. However, recent reports have introduced lung resection using intravenous indocyanine green (ICG) as a treatment for pulmonary sequestrations. CASE DESCRIPTION: A 34-year-old woman presented with chest pain, and enhanced chest computed tomography (CT) displayed a solid mass of 4.5 × 3.1 cm in the right S10 area. An aberrant artery was found running from the celiac artery through the diaphragm to the thoracic cavity. The patient was diagnosed as having pulmonary sequestration Pryce type III, and surgical resection was performed. Intrathoracic findings demonstrated that the precise area of the pulmonary sequestration could not be clearly identified, and a 5-mm aberrant artery was present in the pulmonary ligament. Following the separation of the aberrant artery, intravenous injection of ICG clearly delineated the border between the normal lung tissue and the pulmonary sequestration. Wedge resection was then performed without any postoperative events, and the pathological diagnosis was also pulmonary sequestration. CONCLUSIONS: We herein reported a case of a patient who underwent sublobar resection for intrapulmonary sequestration using intravenous ICG injection, together with a literature review. Our case suggests that a comprehensive understanding of abnormal vessels and pulmonary vasculature in pulmonary resection for intrapulmonary sequestrations, complemented with the use of ICG, might potentially avoid unnecessary pulmonary resection and enable sublobar surgical resection.