Salivary metabolomic biomarkers for non-invasive lung cancer detection.

Identifying novel biomarkers for early detection of lung cancer is crucial. Non-invasively available saliva is an ideal biofluid for biomarker exploration; however, the rationale underlying biomarker detection from organs distal to the oral cavity in saliva requires clarification. Therefore, we analyzed metabolomic profiles of cancer tissues compared with those of adjacent non-cancerous tissues, as well as plasma and saliva samples collected from patients with lung cancer (n = 109 pairs). Additionally, we analyzed plasma and saliva samples collected from control participants (n = 83 and 71, respectively). Capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry were performed to comprehensively quantify hydrophilic metabolites. Paired tissues were compared, revealing 53 significantly different metabolites. Plasma and saliva showed 44 and 40 significantly different metabolites, respectively, between patients and controls. Of these, 12 metabolites exhibited significant differences in all three comparisons and primarily belonged to the polyamine and amino acid pathways; N1-acetylspermidine exhibited the highest discrimination ability. A combination of 12 salivary metabolites was evaluated using a machine learning method to differentiate patients with lung cancer from controls. Salivary data were randomly split into training and validation datasets. Areas under the receiver operating characteristic curve were 0.744 for cross-validation using training data and 0.792 for validation data. This model exhibited a higher discrimination ability for N1-acetylspermidine than that for other metabolites. The probability of lung cancer calculated using this model was independent of most patient characteristics. These results suggest that consistently different salivary biomarkers in both plasma and lung tissues might facilitate non-invasive lung cancer screening.

Prognostic Significance of Ground-Glass Opacity Components in 5-Year Survivors With Resected Lung Adenocarcinoma.

BACKGROUND: Reports on the prognosis for 5-year survivors with lung adenocarcinoma after resection are sparse. This study aimed to identify factors associated with overall survival (OS) and cancer-specific survival (CSS) for 5-year survivors with completely resected lung adenocarcinoma, and to determine whether preoperative imaging factors, including the presence of ground-glass opacity (GGO) components, affect late recurrence in long-term survivors. METHODS: Complete resection of lung adenocarcinoma was performed for 1681 patients between January 2000 and December 2013. Of these patients, 936 who survived 5 years or longer after surgery were identified, and factors associated with OS and CSS were determined using the Cox proportional hazard model. RESULTS: Multivariable analysis demonstrated that lymph node metastasis (p < 0.01) and absence of GGO components (p < 0.01) were independently associated with OS and CSS for the 5-year survivors. The absence of GGO components was significantly associated with OS (p < 0.01) and CSS (p < 0.01) also for the 5-year survivors with stage 1 disease (n = 782) and for the 5-year survivors without recurrence (n = 809). The incidence of recurrence anytime during the 10-year postoperative follow-up period differed significantly between the 5-year survivors with and without GGO components. CONCLUSIONS: The absence of GGO components was significantly associated with an unfavorable prognosis for the 5-year survivors with completely resected lung adenocarcinoma regardless whether they had recurrences not.

The Correlation Between Fissureless Technique and Prolonged Air Leak for Patients Undergoing Video-Assisted Right Upper Lobectomy.

PURPOSE: We aimed to assess the clinical usefulness of the fissureless technique, which avoided dissection of the lung parenchyma over the pulmonary artery, in preventing prolonged air leak after video-assisted thoracic surgery right upper lobectomy (VATS RUL). METHODS: Perioperative outcomes, including the frequency of prolonged air leak after fissureless technique or traditional fissure dissection technique, which dissected the lung parenchyma through the fissure, were compared in patients who underwent VATS RUL (n = 213) between January 2016 and March 2020. We adopted our fissural grade to evaluate the degree of fused fissure ranging from II (light incomplete fissure) to IV (severe incomplete fissure), which covered all fissural grades in 213 patients. RESULTS: Fifty-four and 159 patients underwent fissureless and traditional techniques, respectively. Significant differences in the incidence of prolonged air leak (p = 0.037), time to air leak cessation (p = 0.047), and duration of chest tube placement (p = 0.017) were observed between fissureless and traditional technique groups. On multivariable analysis, traditional technique (p = 0.005), and greater fissural grade (III vs II, p = 0.020; IV vs II, p = 0.001) were significantly associated with prolonged air leak. CONCLUSIONS: Fissureless technique during VATS RUL can be a superior alternative to the traditional technique to prevent prolonged air leak in treating incomplete fissures.

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.

Tumor volume determines the feasibility of cell-free DNA sequencing for mutation detection in non-small cell lung cancer.

Next-generation sequencing (NGS) and digital PCR technologies allow analysis of the mutational profile of circulating cell-free DNA (cfDNA) in individuals with advanced lung cancer. We have now evaluated the feasibility of cfDNA sequencing for mutation detection in patients with non-small cell lung cancer at earlier stages. A total of 150 matched tumor and serum samples were collected from non-small cell lung cancer patients at stages IA-IIIA. Amplicon sequencing with DNA extracted from tumor tissue detected frequent mutations in EGFR (37% of patients), TP53 (39%), and KRAS (10%), consistent with previous findings. In contrast, NGS of cfDNA identified only EGFR, TP53, and PIK3CA mutations in three, five, and one patient, respectively, even though adequate amounts of cfDNA were extracted (median of 4936 copies/mL serum). Next-generation sequencing showed a high accuracy (98.8%) compared with droplet digital PCR for cfDNA mutation detection, suggesting that the low frequency of mutations in cfDNA was not due to a low assay sensitivity. Whereas the yield of cfDNA did not differ among tumor stages, the cfDNA mutations were detected in seven patients at stages IIA-IIIA and at T2b or T3. Tumor volume was significantly higher in the cfDNA mutation-positive patients than in the negative patients at stages T2b-T4 (159.1 ± 58.0 vs. 52.5 ± 9.9 cm3 , P = 0.014). Our results thus suggest that tumor volume is a determinant of the feasibility of mutation detection with cfDNA as the analyte.

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.

Prognostic significance of immunotherapy in postoperative recurrent non-small cell lung cancer without EGFR mutations or ALK rearrangements.

Background: Limited reports exist regarding postoperative recurrent non-small cell lung cancer (NSCLC) without major driver mutations [epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements] treated with immune checkpoint inhibitors (ICIs) when programmed cell death ligand 1 (PD-L1) is expressed in a real-world setting. The aim of this study was to evaluate the effect of ICIs for those NSCLC. Methods: We enrolled 255 patients with postoperative recurrent NSCLC lacking EGFR mutations or ALK rearrangements who underwent lobectomy or more extensive resection between 2012 and 2021. Factors associated with post-recurrence survival (PRS) were determined using the Cox proportional hazards model. PRS was analyzed using Kaplan-Meier curves and compared using the log-rank test. Results: Multivariable analysis demonstrated that squamous cell carcinoma, pathological stage III, and an Eastern Cooperative Oncology Group (ECOG) performance status ≥2 were significantly associated with worse PRS. Conversely, ICI use at first line was associated with improved PRS. Patients who used ICIs during the first line and subsequent therapies had better PRS than those who received chemotherapy alone. Among patients who used ICIs, there was no significant difference in response rate at the first line, nor in PRS among those with PD-L1 expression ≥50%, 1-49%, and <1% in surgically resected specimens. Conclusions: ICI use at any treatment line improved the PRS of NSCLC patients without major driver mutations, irrespective of PD-L1 expression, in a real-world setting.

Intrathoracic Needle Migration from the Mediastinum into the Thoracic Cavity.

Intrathoracic needles are rarely used in clinical practice. They can migrate within the body, injure large blood vessels and other organs, and cause severe complications. We report an interesting case of intrathoracic needle removal using video-assisted thoracoscopic surgery. The needle was inserted under the left clavicle, penetrated the mediastinum, and migrated into the right thoracic cavity. Although pneumothorax developed during the disease course, no severe complications were observed. This rare case illustrates the course of needle migration from the mediastinum into the thoracic cavity. Prompt imaging and surgical removal of foreign bodies are necessary in cases of intrathoracic foreign bodies.

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.

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.

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.

Retrospective analysis of nodal spread patterns according to tumor location in pathological N2 non-small cell lung cancer.

BACKGROUND: The purpose of the present study was to determine the nodal spread patterns of pN2 non-small cell lung cancer (NSCLC) according to tumor location, and to attempt to evaluate the possible indications of selective lymph node dissection (SLND). METHODS: We retrospectively analyzed nodal spread patterns in 207 patients with NSCLC of less than 5 cm with N2 involvement. RESULTS: The tumor location was right upper lobe (RUL) in 79, middle lobe in 12, right lower lobe (RLL) in 40, left upper division (LUD) in 41, lingular division in 11, and left lower lobe (LLL) in 24. Both RUL and LUD tumors showed a higher incidence of upper mediastinal (UM) involvement (96 and 100%, respectively) and a lower incidence of subcarinal involvement (15 and 10%, respectively) than lower lobe tumors (UM; RLL 60%, LLL 42%; subcarinal: RLL 60%, LLL 46%, respectively). Among the patients with 24 right UM-positive RLL and 10 left UM-positive LLL tumors, 2 showed negative hilar, subcarinal, and lower mediastinal involvement, and cT1, suggesting that UM dissection may be unnecessary in lower lobe tumors with no metastasis to hilar, subcarinal, and lower mediastinal nodes on frozen sections according to the preoperative T status. Among the patients with 12 subcarinal-positive RUL and 4 subcarinal-positive LUD tumors, one showed negative hilar or UM involvement, suggesting that subcarinal dissection may be unnecessary in RUL or LUD tumors with no metastasis to hilar and UM nodes on frozen sections. CONCLUSIONS: The present study appears to provide one of the supportive results regarding the treatment strategies for tumor location-specific SLND.

A case of paravertebral mediastinal chordoma without bone destruction.

We report a unique case of mediastinal paravertebral chordoma without bone destruction in a 47-year-old Japanese woman. She was admitted to hospital after a tumor was incidentally detected on a chest radiograph. The tumor was located in the paravertebral region of the mediastinum and did not show any destruction of the thoracic vertebra radiologically. The tumor was clinically diagnosed as a benign neurogenic tumor and the tumor was easily removed surgically. Microscopically, the tumor mainly consisted of tumor cells with extensively vacuolated cytoplasm, arranged in cord- and nest-like fashion against a myxoid matrix background. Immunohistochemically, the tumor cells showed diffuse positivity for pancytokeratin (AE1/AE3) and vimentin. The tumor cell nuclei were positive for brachyury, which is a key transcription factor of notochordal development. These results confirmed the tumor to be an extraosseous chordoma in the paravertebral mediastinal region, which is an extremely rare location for a chordoma.

Prognostic impact of artificial intelligence-based volumetric quantification of the solid part of the tumor in clinical stage 0-I adenocarcinoma.

INTRODUCTION: The size of the solid part of a tumor, as measured using thin-section computed tomography, can help predict disease prognosis in patients with early-stage lung cancer. Although three-dimensional volumetric analysis may be more useful than two-dimensional evaluation, measuring the solid part of some lesions is difficult using this methods. We developed an artificial intelligence-based analysis software that can distinguish the solid and non-solid parts (ground-grass opacity). This software calculates the solid part volume in a totally automated and reproducible manner. The predictive performance of the artificial intelligence software was evaluated in terms of survival or recurrence-free survival. METHODS: We analyzed the high-resolution computed tomography images of the primary lesion in 772 consecutive patients with clinical stage 0-I adenocarcinoma. We performed automated measurement of the solid part volume using an artificial intelligence-based algorithm in collaboration with FUJIFILM Corporation. The solid part size, the solid part volume based on traditional three-dimensional volumetric analysis, and the solid part volume based on artificial intelligence were compared. RESULTS: Higher areas under the curve related to the solid part volume were provided by the artificial intelligence-based method (0.752) than by the solid part size (0.722) and traditional three-dimensional volumetric analysis-based method (0.723). Multivariate analysis demonstrated that the solid part volume based on artificial intelligence was independently correlated with overall survival (P = 0.019) and recurrence-free survival (P < 0.001). CONCLUSION: The solid part volume measured by artificial intelligence was superior to conventional methods in predicting the prognosis of clinical stage 0-I adenocarcinoma.

Effect of photodynamic therapy (PDT) on a rat model of bleomycin-induced interstitial pneumonia.

BACKGROUND: Even if lung cancer is detected at an early stage, surgery may be difficult in patients with severe comorbidities, like interstitial pneumonia (IP). Radiation therapy cannot be performed due to the high risk of acute IP exacerbation. Therefore, an effective alternative, such as photodynamic therapy (PDT), is required. To prove that acute exacerbation is not induced after PDT in peripheral lung cancer, we investigated the effects of PDT on IP rat models. METHODS: Bleomycin (BLM) was administered intratracheally. Seven days after administration, left thoracotomy was performed. Talaporfin sodium was injected, and diode laser irradiation (664 nm, 150mW, 100J/cm2) was performed. Seven days after PDT, the whole blood and left lungs were collected. A total of 23 rats, comprising BLM + PDT (n = 4), BLM + non-PDT (n = 10), non-BLM + PDT (n = 2), non-BLM + non-PDT (n = 5), and two rats that died immediately after PDT were observed. Serum levels of Krebs von den Lungen-6, surfactant protein-D, lactate dehydrogenase, and serum C-reactive protein were measured. Fibrosis and macrophage scorings, and the ​​collagen fibers percentage were examined by staining with hematoxylin and eosin, Elastica van Gieson, anti-α smooth muscle antibody, and anti-CD68 antibodies. RESULTS: There was no remarkable difference in the values of each marker in fibrosis and macrophage scores with or without PDT. In case of death, fibrosis was mild, and PDT was not affected. CONCLUSIONS: In IP rat models, PDT did not induce lung fibrosis or acute exacerbation.

Artificial intelligence analysis of three-dimensional imaging data derives factors associated with postoperative recurrence in patients with radiologically solid-predominant small-sized lung cancers.

OBJECTIVES: Indications of limited resection, such as segmentectomy, have recently been reported for patients with solid-predominant lung cancers ≤2 cm. This study aims to identify unfavourable prognostic factors using three-dimensional imaging analysis with artificial intelligence (AI) technology. METHODS: A total of 157 patients who had clinical N0 non-small cell lung cancer with a radiological size ≤2 cm, and a consolidation tumour ratio > 0.5, who underwent anatomical lung resection between 2011 and 2017 were enrolled. To evaluate the three-dimensional structure, the ground-glass nodule/Solid Automatic Identification AI software Beta Version (AI software; Fujifilm Corporation, Japan) was used. RESULTS: Maximum standardized uptake value (SUVmax) and solid-part volume measured by AI software (AI-SV) showed significant differences between the 139 patients with adenocarcinoma and the 18 patients with non-adenocarcinoma. Among the adenocarcinoma patients, 42 patients (30.2%) were found to be pathological upstaging. Multivariable analysis demonstrated that high SUVmax, high carcinoembryonic antigen level and high AI-SV were significant prognostic factors for recurrence-free survival (RFS; P < 0.05). The 5-year RFS was compared between patients with tumours showing high SUVmax and those showing low SUVmax (67.7% vs 95.4%, respectively, P < 0.001). The 5-year RFS was 91.0% in patients with small AI-SV and 68.1% in those with high AI-SV (P = 0.001). CONCLUSIONS: High AI-SV, high SUVmax and abnormal carcinoembryonic antigen level were unfavourable prognostic factors of patients with solid-predominant lung adenocarcinoma with a radiological size ≤2 cm. Our results suggest that lobectomy should be preferred to segmentectomy for patients with these prognostic factors.

Clinical usefulness of the 3-tier classification according to the proportion of morphological patterns for patients with pathological stage I invasive lung adenocarcinoma.

OBJECTIVES: We classified pathological stage I invasive lung adenocarcinomas according to our 3-tier classification, which was based on the proportion of invasive morphological patterns as follows: (1) patients with each predominant subtype, (2) those with a minor histological subtype, even not the predominant subtype and (3) those without each invasive component. We aimed to evaluate the classification's clinical impact in survival, recurrence, malignant grade, and epidermal growth factor receptor (EGFR) mutational status. MATERIALS AND METHODS: A total of 1,269 patients with p-stage I lung adenocarcinoma underwent curative surgical resection between January 2008 and December 2017. Of these, 620 patients (48.9%) met the inclusion criteria of this study. RESULTS: Postoperative recurrence was observed in 81 patients (13.1%). Multivariate analysis showed that vascular invasion (hazard ratio, 2.61; p < 0.001) and p-stage IB (hazard ratio, 2.19; p = 0.001) were significantly associated with an unfavorable RFS, while the presence of acinar component (hazard ratio, 1.64; p = 0.052) or solid component (hazard ratio, 1.60; p = 0.074) were marginally significant. The presence of lepidic or papillary component and the absence of acinar or solid component significantly correlated with an increased proportion of lung adenocarcinomas harboring EGFR mutations. CONCLUSION: In patients with p-stage I invasive lung adenocarcinoma, it is beneficial to use not only the predominant subtype but analyzing the extent of each histological component based on our classification to predict patient prognoses and form appropriate postoperative follow-up methods.

Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer.

PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome's surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I-III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8+ TILs (p = 0.001). Patients with exosomal PD-L1 ≥ 166 pg/mL tended to have a worse RFS than those with < 166 pg/mL in all stage (p = 0.163) and stage I patients (p = 0.116). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment. The disease control rate of patients with exosomal PD-L1 ≥ 166 pg/mL was 100%. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and clinical outcomes in patients with NSCLC.

Comparative analysis of the results of video-assisted thoracic surgery lobectomy simulation using the three-dimensional-printed Biotexture wet-lung model and surgeons' experience.

OBJECTIVES: We performed a comparative analysis of the performance of video-assisted thoracic surgery (VATS) lobectomy simulation using three-dimensional-printed Biotexture lung models by surgeons classified according to their level of expertise. The aim of this study was to investigate the association between surgeons' experience and time to complete the VATS lobectomy simulation. METHODS: Participants were divided into 3 groups: group A included those who had no experience of actual VATS lobectomy (n = 11), group B included those who had performed 5-10 VATS lobectomies (n = 12) and group C included those who had performed >100 VATS lobectomies (n = 6). Their performances were assessed based on total procedure time, duration to the exposure of the vessels, ligation of the arteries and stapling of the fissures. After the simulation, a questionnaire survey was performed. RESULTS: The median total procedure time was significantly shorter in the group of surgeons with more experience (A vs B, P < 0.001; B vs C, P = 0.034; A vs C, P < 0.001). Regarding 'the exposure of all the vessels to be resected' and 'ligation of the arteries', group B completed these steps in less time than group A (P = 0.024 and P = 0.012, respectively). In the questionnaire, all groups answered that this simulation was useful for novices to improve their skills. CONCLUSIONS: Although time to complete the VATS lobectomy simulation is only a part of evaluation points for real skills, this model can facilitate basic skill acquisitions for novices.