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.
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.
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.
The detectability of somatic mutations in cfDNA obtained from lung cancer patients at earlier stages. Detection of the mutations relies on the tumor burden in the patients. Deep sequencing as well as digital PCR is reliable technology for detection of somatic mutations in serum.
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.
The aim of this study was to evaluate the effectiveness of 3-dimensional computed tomography (3D-CT) software in short-term surgical outcomes and the assessment of variations of pulmonary vessel ...branching patterns on performing video-assisted thoracic surgery (VATS).
The study included 179 consecutive patients who had undergone VATS anatomical lung resection, of which 172 were lobectomies (96%) and 7 were segmentectomies (4%), from May 2011 through January 2013. There were 124 patients (69%) in whom 3D-CT was performed and 55 patients (31%) who had not undergone 3D-CT. Observed actual pulmonary vessel branching patterns by intraoperative findings or footage were compared with the 3D image findings. Various surgical outcomes, including the occurrence of postoperative complications, in this study defined as those of Grade 2 or above under the Clavien-Dindo classification system, and total operative time, were retrieved from available clinical records.
Among the 124 patients with preoperative 3D imaging, there were 5 (4%) conversions from VATS to thoracotomy. The incidence rate of patients with postoperative complications was 8% (n = 10), and there were no 30-day or 90-day mortalities. Pulmonary artery (PA) branches were precisely identified for 97.8% (309 of 316) of branches on 3D images, and the sizes of the seven undetected branches (five in the right upper lobe, two in the left upper lobe) ranged from 1 to 2 mm. The 3D images accurately revealed 15 cases (12%) of anomalous or unusual PA branches and 5 cases (4%) of variant pulmonary veins. Multivariate logistic regression analysis of the association with postoperative complications and operative time in 165 lung cancer patients demonstrated that male gender was the only statistically significant independent predictor of complications (risk ratio: 5.432, P = 0.013), and patients without 3D imaging tended to have operative complications (risk ratio: 2.852, P = 0.074), whereas conducting the 3D-CT (risk ratio: 2.282, P = 0.021) as well as intraoperative bleeding amount (risk ratio: 1.005, P = 0.005) had significant association with operative time.
High-quality 3D-CT images clearly revealed the anatomies of pulmonary vessels, which could play important roles in safe and efficient VATS anatomical resection.
Background
Mediastinal teratomas occasionally rupture into the thoracic cavity, which induces mediastinitis or various other severe complications. Surgical treatment is crucial for ruptured ...teratomas; however, few literature reviews to date have addressed the characteristics of ruptured mediastinal teratomas.
Case presentation
We report a 29-year-old woman with severe mediastinitis owing to a mediastinal mature teratoma that ruptured into the mediastinum and right pleural cavity. Surgical resection by median sternotomy was performed within 24 hours after emergency admission. Intraoperative findings demonstrated the ruptured wall of the tumor with exposure of its white contents, which appeared similar to skin and fat, and necrotic tissue in the anterior mediastinum. The tumor was adhered to the right upper lobe, the ascending aorta, and pericardium. Owing to the severe adhesion of the tumor caused by inflammation in the surrounding tissues, a small portion of the tumor could not be removed, and hence complete resection with a sufficient surgical margin was not achieved. Pathologically, the tumor consisted of a solid mass and a cystic mass with severe adhesion to the resected portion of the lung, which included skin and lipid tissue. The tumor was concluded to be a mature teratoma as neither an immature component nor malignant transformation was observed. The patient had an uneventful postoperative course.
Conclusions
To our knowledge, this is the report of successful surgical resection of a ruptured mediastinal teratoma causing severe mediastinitis, with the first literature review of ruptured mediastinal teratomas. We also discuss relevant findings from reports in the literature.
The number of minimally invasive operations, such as video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy, has enormously increased in recent years. These operations require extreme ...knowledge of the anatomy of pulmonary vessels and bronchi in each patient, and surgeons must carefully dissect the branches of pulmonary vessels during operation. Thus, foreknowledge of the anatomy of each patient would greatly contribute to the safety and accuracy of the operation. The development of multi-detector computed tomography (MDCT) has promoted three dimensional (3D) images of lung structures. It is possible to see the vascular and bronchial structures from the view of the operator; therefore, it is employed for preoperative simulation as well as navigation during operation. Due to advances in software, even small vessels can be accurately imaged, which is useful in performing segmentectomy. Surgical simulation and navigation systems based on high quality 3D lung modeling, including vascular and bronchial structures, can be used routinely to enhance the safety operation, education of junior staff, as well as providing a greater sense of security to the operators.
•Solid-part volume of lung adenocarcinoma is a powerful predictor of prognosis.•The integration of solid-part volume and SUVmax of FDG is also highly useful.•Three-dimensional lung tumor analysis is ...beneficial for understanding lung cancer biology.
The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis).
We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUVmax) of F18-fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes.
Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p < .001). The receiver operating characteristic curves for pathological invasiveness, determined using the variables dichotomized at each cut-off level (SUVmax 2.4; solid-part size 1.23 cm; solid-part volume 779 mm3), showed that all were significantly correlated with pathological invasiveness and prognosis, whereas the combination of SUVmax and the solid-part volume was the most powerful predictor of survival and pathological invasiveness compared to any other parameters: the 4-year DFS and proportion of pathological invasiveness in patients with SUVmax > 2.4 and solid-part volume > 779 mm3 versus those with SUVmax ≤ 2.4 or solid-part volume ≤779 mm3 were 81.2% versus 98.3% (p < .001) and 84.3% versus 15.1% (p < .001), respectively.
In c-IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUVmax was highly beneficial for the prediction of survival and pathological invasiveness.
Background Microscopic vascular invasion (MVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong predictor of poor outcomes but it has not been a descriptor of the ...TNM classification. The purposes of this study were to determine whether the presence of MVI is related to a predictor of poor outcomes and to explore the degree of MVI according to tumor size. Methods A total of 1,884 patients with stage pT1-4N0-2 NSCLC who underwent complete resection comprised the study sample. Overall survival (OS) and recurrence-free proportion were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess independent predictors of poor outcomes. Results Of 1,884 patients, 1,097 (58.2%) had MVI. Multivariate analysis showed MVI was a significant independent predictor of unfavorable OS (hazard ratio, 1.666; P < .001) and recurrence (hazard ratio, 2.268; P < .001). The frequency of MVI varied according to tumor size, and in each cohort of tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm, there were significant differences in survival outcome by MVI status. The proportions of patients with a 5-year recurrence-free period with tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm between MVI (+) and MVI (–) were 93.0% and 72.5% ( P < .001), 90.8% and 63.3% ( P < .001), and 86.4% and 59.9% ( P < .001), respectively. Conclusions This study demonstrated that MVI was a strong predictor of poor outcomes and that the effect is more prominent in patients with tumor sizes ≤ 5 cm. Further analysis of survival and MVI should be collected for future revision of the TNM system.
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