A Case of Incidentally Discovered Congenital Complete Pericardial Defect during Lobectomy for Lung Cancer: A Case Report and Literature Review.

An 82-year-old male patient underwent a left upper lobectomy with anterolateral thoracotomy for lung cancer. Although a complete left-pericardial defect was observed during surgery, the pericardial repair was not performed because the left lower lobe remained and the heart was considered stable. Postoperative pathological examination revealed primary synchronous double-lung squamous-cell carcinoma (pathological stage pT2a(2)N0M0 stage IB). He was discharged without complications on postoperative day 8. Leftward displacement of the heart and left diaphragmatic elevation, suspected of phrenic-nerve paralysis, were found in the chest X-ray after discharge. However, the patient's overall condition remained unaffected at the 5-month postoperative follow-up. To assess the need for pericardial repair, we compared cases of complete pericardial defects observed during lobectomy or pneumonectomy reported in the literature. Only one of 12 cases occurred postoperative death despite pericardial repair, and that case combined pectus excavatum and pericardial defects. Our assessment indicated that pericardial repair might not be necessary, excluding complex cases.

CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma.

Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identification of those in an early stage who would likely benefit from adjuvant chemotherapy. To identify circulating miRNAs useful for predicting recurrence in early-stage LUAD, we performed miRNA microarray analysis with pools of pretreatment plasma samples from patients with stage I LUAD who developed recurrence or remained recurrence-free during the follow-up period. Subsequent validation in 85 patients with stage I LUAD resulted in the development of a circulating miRNA panel comprising miR-23a-3p, miR-320c, and miR-125b-5p and yielding an area under the curve (AUC) of 0.776 in predicting recurrence. Furthermore, the three-miRNA panel yielded an AUC of 0.804, with a sensitivity of 45.8% at 95% specificity in the independent test set of 57 stage I and II LUAD patients. The miRNA panel score was a significant and independent factor for predicting disease-free survival (p < 0.001, hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.51-4.22) and overall survival (p = 0.001, HR = 1.51, 95% CI = 1.17-1.94). This circulating miRNA panel is a useful noninvasive tool to stratify early-stage LUAD patients and determine an appropriate treatment plan with maximal efficacy.

Thoracoscopic Wedge Resection for Low-Grade Fibromyxoid Sarcoma (Evans Tumor) with Massive Calcification and Originating from the Lung: A Rare Case in an Unexpected Location.

We encountered a rare case of low-grade fibromyxoid sarcoma, which is generally known as Evans tumor, with massive calcification originating from the lung. The patient was a 22-year-old man with Duchenne muscular dystrophy who was referred for a detailed investigation of an intrathoracic tumor with massive calcification. Although our preoperative diagnosis was a solitary fibrous tumor originating from the mediastinum or diaphragm, intraoperative thoracoscopy revealed the tumor arising from the left lower lobe without adhesion to the other organs. Considering his medical history, we aimed to preserve lung function and chose wedge resection, which completely removed the tumor. Based on the pathological findings, the tumor was diagnosed as low-grade fibromyxoid sarcoma with massive calcification originating from the lung. Although extremely rare, this tumor should be considered as a differential diagnosis for a solitary lung mass with massive calcification in young adults.

Immunosuppressive treatment for myasthenia gravis crises improve the taste disorder in patients with thymoma: two case reports.

Background: Taste disorders in patients with thymoma accompanied by myasthenia gravis (MG) is rare. Case Description: The first case was a male in his 50s who underwent surgery for Masaoka stage III type B3 thymoma. He experienced a loss of taste before surgery, which showed no improvement after surgery. Due to a MG crisis 44 days after surgery, the patient underwent intensive treatment with mechanical ventilation, steroid pulse therapy, and intravenous immunoglobulin (IVIG) therapy. The patient recovered taste when he started oral food intake after the treatment for the MG crisis (about 3 months after surgery). Despite the recovery of taste after steroid pulse therapy and IVIG therapy, taste disorder gradually worsened about 1 year and 9 months after surgery, resulting in an almost complete loss of sweet taste 2 years after surgery. The second case was a male in his 60s who underwent surgery for Masaoka stage II type B1 thymoma. He experienced loss of taste before surgery, which showed no improvement after surgery. Five years and two months after surgery, the patient was diagnosed with a MG crisis and underwent steroid pulse therapy. Along with improvements in MG symptoms, taste disorders gradually improved. After 6 years and 10 months of surgery, the patient is still alive without MG symptoms (only pyridostigmine, 180 mg/body/day), taste disorder, and thymoma recurrence. Conclusions: The autoimmune mechanism may contribute to taste disorders in patients with thymoma, which can be recovered by immunosuppressive treatment in our cases.

Influencing Factors on Intersegmental Identification Adequacy in Segmentectomy with Intraoperative Indocyanine Green (ICG) Intravenous Administration.

Accurate identification of the intersegmental plane is essential in segmentectomy, and Indocyanine Green (ICG) assists in visualizing lung segments. Various factors, including patient-related, intraoperative, and technical issues, can influence boundary delineation. This study aims to assess the rate of unsuccessful intersegmental identification and identify the contributing factors. We analyzed cases of lung segmentectomy from April 2020 to March 2023, where intraoperative ICG was intravenously administered during robot-assisted or video-assisted thoracoscopic surgery. Cases where fluorescence extended beyond expected boundaries within 30 s were classified as the "unclear boundary group". This group was then compared to the "clear boundary group". The study encompassed 111 cases, 104 (94%) of which were classified under the "clear boundary group" and 7 (6%) under the "unclear boundary group". The "unclear boundary group" had a significantly lower DLCO (15.7 vs. 11.8, p = 0.03) and DLCO/VA (4.3 vs. 3.0, p = 0.01) compared to the "clear boundary group". All cases in the "unclear boundary group" underwent lower lobe segmentectomy. ICG administration effectively outlines pulmonary segments. Challenges in segment demarcation may occur in cases with low DLCO and DLCO/VA values, particularly during lower lobe segmentectomy.

Complete visualization using indocyanine green in thoracic surgery for pulmonary sequestration.

Preoperative three-dimensional computed tomography (CT) facilitates accurate identification of aberrant systemic arteries in thoracic surgery for pulmonary sequestration (PS). Furthermore, the boundary between normal and sequestrated lungs can be visualized using the spread of fluorescent indocyanine green (ICG) when performing surgery for PS. This study aimed to determine how to completely visualize anatomical variations, safely treat aberrant arteries, remove only sequestrated lungs, and perform minimally invasive surgery for PS. Seventeen patients underwent lung resection for intralobar PS at our institution between 2009 and 2022. We retrospectively reviewed the surgical outcomes and intraoperative images using ICG to assess the efficacy and feasibility of near-infrared fluorescence imaging. Since 2019, intraoperative near-infrared fluorescence imaging with ICG has been used in six patients, including four females and two males (median age, 56 years), to visualize the boundary between normal and sequestrated lungs. Aberrant arteries were identified using preoperative three-dimensional CT, and the boundary between sequestrated and normal lungs could be clearly delineated intraoperatively using ICG in all cases. The median operative time was 145 min (range, 88-167 min), and the median blood loss was 5 mL (range, 1-191 mL). The overlay mode using near-infrared thoracoscopy, which merges visible light images with fluorescent images, was safer and more useful than conventional thoracoscopy for delineating boundaries with electrocautery. No intraoperative or postoperative complications occurred. The median postoperative hospital stay was 5 days (range, 3-7 days). Intraoperative identification of the boundary between normal and sequestrated lungs using ICG was simple and feasible. We suggested that this technique was effective for lesion resection and normal lung preservation during surgery for intralobar PS.

Prognostic impact of highly solid component in early-stage solid lung adenocarcinoma.

Background: Based on computed tomography (CT) findings of lung cancer, solid nodules have a much worse prognosis than subsolid nodules, even if the nodules are subcentimeter in size. There is, however, no systematic method for determining the prognosis of solid tumors on CT. This study aimed to discover the prognostic factor of early-stage solid lung adenocarcinoma using three-dimensional CT volumetry. Methods: Patients with pathological stage I solid lung adenocarcinoma who underwent complete resection between 2007 and 2012 were selected in this retrospective study. Clinicopathological data and preoperative multidetector CT findings, such as tumor size on the two-dimensional axial image, three-dimensional tumor volume between -600 and 199 HU, and three-dimensional solid volume between 0 and 199 HU, which corresponded to highly solid components, were compared between recurrence and non-recurrence. Furthermore, these radiological values were compared to pathological invasive volume (PIV). Results: During this time, 709 patients had their lung cancer completely removed. From this cohort, 90 patients with pathological stage I solid lung adenocarcinoma were selected. In addition, recurrence was found in 26 patients (28.9%). Although two-dimensional axial image, serum carcinoembryonic antigen (CEA) level, and SUVmax on 18F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) did not differ statistically between recurrent and non-recurrent patients, three-dimensional tumor and solid tumor volume did. Multivariate analysis indicated that three-dimensional solid tumor volume [hazard ratio: 2.440; 95% confidence interval (CI): 1.110-5.361, P=0.026] and epidermal growth factor receptor (EGFR) mutation (hazard ratio: 4.307; 95% CI: 1.328-13.977, P=0.015) were significantly associated with disease-free survival (DFS). When three-dimensional tumor and solid tumor volume were compared to PIV, three-dimensional solid tumor volume (3,091 mm3 on average) showed a highly similar value with PIV (2,930 mm3 on average), whereas three-dimensional tumor volume (6,175 mm3 on average) was significantly larger than PIV (P<0.001). Conclusions: In patients with early-stage solid lung adenocarcinoma, the measurement of three-dimensional solid tumor volume, which is correlated with PIV, accurately predicted the postoperative outcome.

[Robot-assisted Extended Thymectomy via a Bilateral Approach for Patients with Myasthenia Gravis].

Extended thymectomy is a procedure to remove the thymus gland and surrounding adipose tissue, while the traditional approach via a median sternotomy, minimally invasive approaches such as video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracoscopic surgery (RATS) have been adopted. This report described the technique of bilateral approach for extended thymectomy in patients with myasthenia gravis (MG) by robot-assisted thoracoscopic surgery, and also showed the perioperative outcomes and postoperative exacerbation rates of 11 patients. In most patients, score of MG symptom were reduced and levels of anti-acetylcholine receptor antibodies declined postoperatively. In a small number of cases, the safety and efficacy of a RATS bilateral approach for extended thymectomy were confirmed.

Lingular-segment torsion after extended left-upper division segmentectomy by video-assisted thoracic surgery with indocyanine green fluorescence imaging.

Lingular-segment torsion after left-upper division segmentectomy (LUDS) is a rare complication, and the cause remains unclear. Here we report the case of a patient who developed lingular-segment torsion after LUDS for multiple lung metastases of breast cancer. One lung nodule was located in the S1 + 2 segment and another between the upper lobe and S6 on an incomplete interlobar fissure. The lung metastases were resected by extended LUDS using video-assisted thoracic surgery with indocyanine green fluorescence imaging. The staple line on the lingular segment was vertically tilted against the interlobar line because of the atypical defect of the fluorescence plane and nodule position. Chest X-ray and contrast-enhanced computed tomography indicated ischemia and torsion of the lingular segment on the second postoperative day, and completion of lingular segmentectomy was performed. This case showed the vertical intersegment staple line during LUDS was one of the important causes of postoperative torsion of the lingular segment.

Real-world evidence of safety and influence for lung cancer surgery under COVID-19 pandemic in Japan.

Background: The COVID-19 pandemic has affected the clinical practice of lung cancer surgery in Japan, but few studies have revealed the real situation of surgical practice for lung cancer in this country. This latest information will help us to decide the future direction of lung cancer surgery under pandemic circumstances. Methods: We collected data from patients with primary lung cancer who underwent thoracic surgery between 2018 and 2021. To investigate the impact of the COVID-19 pandemic on lung cancer surgery, we compared between 2018-2019 (prepandemic group) and 2020-2021 (pandemic group) in the respect of patient characteristics, pathological findings, and short-term outcome after lung cancer resection by Mann-Whitney and Fisher's exact tests. Moreover, the monthly number of surgeries for lung cancer in our institution during 2020-2021 was compared with the number of newly diagnosed COVID-19 patients in Japan by Spearman correlation analysis. Results: From 2018 through 2021, 936 patients with primary lung cancer underwent surgical intervention in our institute and were included in this study. The number of surgeries did not decrease in the pandemic group (n=443) compared with that in the prepandemic group (n=493). Tumor and invasive size in stage I which was measured by pathologist were significantly larger in the pandemic group than in the prepandemic group (tumor size: P=0.031, invasive size: P<0.001). In terms of postoperative short-term outcome, the median hospital stay was 6 days, 30-day mortality was 2, and morbidity was around 20% in both groups. Only one patient suffered from COVID-19 infection 5 months after right upper lobectomy. An increased ratio of newly diagnosed COVID-19 cases in Japan was negatively correlated with the number of surgeries for lung cancer in our institution in the next month (r=-0.393, P=0.007), although there was no correlation in the present or the month after next. Conclusions: Even during the COVID-19 pandemic period, lung cancer surgery could be performed safely and in a sustainable manner. However, pathological findings of lung cancer tended to be progressive in early-stage lung cancer.

Setting a quality indicator for actual surgery time relative to scheduled surgery time in the context of increasing robotic-assisted thoracic surgery cases.

OBJECTIVE: This study aimed to demonstrate to the involved departments the goal of increasing the number of robotic-assisted thoracic surgery (RATS) cases/surgeons and acceptable surgery times. METHODS: This retrospective study included 1572 patients who underwent thoracic surgery from fiscal year (FY) 2018 to FY 2021. The factors evaluated included the number of surgery cases and actual and scheduled surgery times. RESULTS: The total number of RATS and total surgery cases increased after the quality indicator (QI) setting (n = 363, 360, 417, and 432 in FY 2018, 2019, 2020, and 2021, respectively). In FY 2020, 93.3% of the QI target was achieved, while in FY 2021, 88% was achieved. The number of RATS lobectomy/segmentectomy increased as the FY progressed (n = 31, 47, 58, and 116 in FY 2018, 2019, 2020, and 2021, respectively). The mean surgical time by RATS starters decreased in FY 2020 and 2021 (171.4 min.; 74 cases; seven RATS starters) compared with those in FY 2018 and 2019 (198.0 min.; 57 cases; six RATS starters) (P = 0.002). CONCLUSIONS: The goal of increasing the number of surgery cases and RATS cases/surgeons within the given framework was achieved by setting the QI.

Impact of Pleural Thickness on Occurrence of Postoperative Complications in Patients with Malignant Pleural Mesothelioma.

OBJECTIVES: The rates of postoperative mortality and morbidity are high in patients with malignant pleural mesothelioma (MPM). Therefore, it is important to identify variables that increase the risk of postoperative complications. Pleural thickness has recently been identified as a prognostic indicator in patients with MPM. The aim of this study was to investigate clinical variables, including pleural thickness, that contribute to postoperative complications in patients with MPM. PATIENTS AND METHODS: A total of 47 patients who underwent surgical excision of MPM between 2005 and 2021 were enrolled in this study. Correlations between postoperative complications within 90 days of surgery and preoperative clinical factors were investigated. RESULTS: A total of 27 patients underwent extrapleural pneumonectomy (EPP), and the remaining 20 underwent pleurectomy/decortication (P/D). Macroscopic complete resections were obtained in all but three patients. Of the 47 patients, 23 (49%) experienced postoperative complications of grade 3 or worse. The major complication in patients with EPP was respiratory failure (n = 6), whereas the major complication in patients with P/D was prolonged air leakage (n = 7). Univariate logistic regression analysis found a correlation between postoperative complications and age, surgical side, and pleural thickness, while multivariate logistic regression analysis found surgical side (p = 0.04, 95% Cl 1.10-21.71, OR 4.90) and pleural thickness (p = 0.03, 95% Cl 1.21-23.00, OR 5.26) to significantly influence the occurrence of postoperative complications. CONCLUSIONS: Pleural thickness has a significant effect on the occurrence of postoperative complications. Patients with thick pleura on the right side are at greater risk of postoperative complications.

Neoadjuvant Therapy for Patients With Non-small Cell Lung Cancer Complicated With Chest Wall Invasion.

BACKGROUND/AIM: Multidisciplinary treatment including anatomical pulmonary and chest wall resection is recommended for lung cancer complicated by chest wall invasion. The present study aimed to investigate the survival benefit and safety of preoperative therapy followed by surgery for non-small cell lung cancer with chest wall invasion. PATIENTS AND METHODS: Sixty-five patients who underwent surgical excision of lung cancer complicated with chest wall invasion between 2009 and 2020 were enrolled in this study. RESULTS: The median age was 65 (37-81) years old, with 59 males and 6 females. Histological types included squamous cell carcinoma (n=32) and adenocarcinoma (n=21). The median tumor diameter was 5.5 cm (2.3-12.5 cm). The clinical nodal status was N0 in 49 cases and N positive in 16 cases. Of the 65 eligible patients, 5- and 10-year overall survival (OS) rates were 58.4% and 46.0%, respectively, and 5- and 10-year progression-free survival (PFS) rates were 54.2% and 41.7%, respectively. For patients receiving preoperative therapy followed by surgery (Pre-Tx), 5- and 10-year OS survival rates were 69.2% and 62.9%, and among patients receiving up-front surgery (UFS) were 48.5% and 29.1%, respectively (p=0.03). The 5- and 10-year PFS rates for pre-Tx were 65.8% and 59.2%, respectively, and 44.7% and 26.8% for UFS, respectively (p=0.02). Cox regression analysis preoperative therapy was significantly associated with OS and PFS. CONCLUSION: We demonstrate the survival benefit of preoperative therapy followed by surgery for patients with lung cancer and chest wall invasion.

A Comprehensive Search of Non-Canonical Proteins in Non-Small Cell Lung Cancer and Their Impact on the Immune Response.

There is substantial interest in mining neoantigens for cancer applications. Non-canonical proteins resulting from frameshift mutations have been identified as neoantigens in cancer. We investigated the landscape of non-canonical proteins in non-small cell lung cancer (NSCLC) and their induced immune response in the form of autoantibodies. A database of cryptoproteins was computationally constructed and comprised all alternate open reading frames (altORFs) and ORFs identified in pseudogenes, noncoding RNAs, and untranslated regions of mRNAs that did not align with known canonical proteins. Proteomic profiles of seventeen lung adenocarcinoma (LUAD) cell lines were searched to evaluate the occurrence of cryptoproteins. To assess the immunogenicity, immunoglobulin (Ig)-bound cryptoproteins in plasmas were profiled by mass spectrometry. The specimen set consisted of plasmas from 30 newly diagnosed NSCLC cases, pre-diagnostic plasmas from 51 NSCLC cases, and 102 control plasmas. An analysis of LUAD cell lines identified 420 cryptoproteins. Plasma Ig-bound analyses revealed 90 cryptoproteins uniquely found in cases and 14 cryptoproteins that had a fold-change >2 compared to controls. In pre-diagnostic samples, 17 Ig-bound cryptoproteins yielded an odds ratio ≥2. Eight Ig-bound cryptoproteins were elevated in both pre-diagnostic and newly diagnosed cases compared to controls. Cryptoproteins represent a class of neoantigens that induce an autoantibody response in NSCLC.

Extracellular Vesicles in Lung Cancer: Prospects for Diagnostic and Therapeutic Applications.

Extracellular vesicles (EVs) are nano-sized lipid-bound particles containing proteins, nucleic acids and metabolites released by cells. They have been identified in body fluids including blood, saliva, sputum and pleural effusions. In tumors, EVs derived from cancer and immune cells mediate intercellular communication and exchange, and can affect immunomodulatory functions. In the context of lung cancer, emerging evidence implicates EV involvement during various stages of tumor development and progression, including angiogenesis, epithelial to mesenchymal transformation, immune system suppression, metastasis and drug resistance. Additionally, tumor-derived EVs (TDEs) have potential as a liquid biopsy source and as a means of therapeutic targeting, and there is considerable interest in developing clinical applications for EVs in these contexts. In this review, we consider the biogenesis, components, biological functions and isolation methods of EVs, and the implications for their clinical utility for diagnostic and therapeutic applications in lung cancer.

Plasma Based Protein Signatures Associated with Small Cell Lung Cancer.

Small-cell-lung cancer (SCLC) is associated with overexpression of oncogenes including Myc family genes and YAP1 and inactivation of tumor suppressor genes. We performed in-depth proteomic profiling of plasmas collected from 15 individuals with newly diagnosed early stage SCLC and from 15 individuals before the diagnosis of SCLC and compared findings with plasma proteomic profiles of 30 matched controls to determine the occurrence of signatures that reflect disease pathogenesis. A total of 272 proteins were elevated (area under the receiver operating characteristic curve (AUC) ≥ 0.60) among newly diagnosed cases compared to matched controls of which 31 proteins were also elevated (AUC ≥ 0.60) in case plasmas collected within one year prior to diagnosis. Ingenuity Pathway analyses of SCLC-associated proteins revealed enrichment of signatures of oncogenic MYC and YAP1. Intersection of proteins elevated in case plasmas with proteomic profiles of conditioned medium from 17 SCLC cell lines yielded 52 overlapping proteins characterized by YAP1-associated signatures of cytoskeletal re-arrangement and epithelial-to-mesenchymal transition. Among samples collected more than one year prior to diagnosis there was a predominance of inflammatory markers. Our integrated analyses identified novel circulating protein features in early stage SCLC associated with oncogenic drivers.

Extracellular Vesicles Mediate B Cell Immune Response and Are a Potential Target for Cancer Therapy.

Extracellular vesicles (EVs) are increasingly understood to participate directly in many essential aspects of host antitumor immune response. Tumor- and immune-cell-derived EVs function in local and systemic contexts with roles in immune processes including cancer antigen conveyance, immune cell priming and activation, as well as immune escape. Current practice of cancer immunotherapy has de facto focused on eliciting T-cell-mediated cytotoxic responses. Humoral immunity is also known to exert antitumor effects, and B cells have been demonstrated to have functions that extend beyond antibody production to include antigen presentation and activation and modulation of T cells and innate immune effectors. Evidence of B cell response against tumor-associated antigens (TAAs) is observed in early stages of tumorigenesis and in most solid tumor types. It is known that EVs convey diverse TAAs, express antigenic-peptide-loaded MHCs, and complex with circulating plasma antitumoral autoantibodies. In this review, we will consider the relationships between EVs, B cells, and other antigen-presenting cells, especially in relation to TAAs. Understanding the intersection of EVs and the cancer immunome will enable opportunities for developing tumor antigen targets, antitumor vaccines and harnessing the full potential of multiple immune system components for next-generation cancer immunotherapies.

Plasma-Derived Extracellular Vesicles Convey Protein Signatures that Reflect Pathophysiology in Lung and Pancreatic Adenocarcinomas.

Using a combination of mass-spectrometry and aptamer array-based proteomics, we characterized the protein features of circulating extracellular vesicles (EVs) in the context of lung (LUAD) and pancreatic ductal (PDAC) adenocarcinomas. We profiled EVs isolated from conditioned media of LUAD and PDAC cell lines to identify EV-associated protein cargoes released by these cancer cell types. Analysis of the resulting data identified LUAD and PDAC specific and pan-adenocarcinoma EV protein signatures. Bioinformatic analyses confirmed enrichment of proteins annotated to vesicle-associated processes and intracellular compartments, as well as representation of cancer hallmark functions and processes. Analysis of upstream regulator networks indicated significant enrichment of TP53, MYC, TGFB1 and KRAS-driven network effectors (p = 1.69 × 10-77-2.93 × 10-49) manifest in the adenocarcinoma sEV protein cargoes. We extended these findings by profiling the proteome of EVs isolated from lung (N = 15) and pancreatic ductal (N = 6) adenocarcinoma patient plasmas obtained at time of diagnosis, along with EVs derived from matched healthy controls (N = 21). Exploration of these proteomic data revealed abundant protein features in the plasma EVs with capacity to distinguish LUAD and PDAC cases from controls, including features yielding higher performance in the plasma EV isolates relative to unfractionated plasmas.