Surrounding Lung Tissue Research Articles

Clinicopathological and genetic analysis of interstitial disease-like pulmonary intravascular large B cell lymphoma

Objective: To investigate the clinicopathological features and genetic mutation status of pulmonary intravascular large B cell lymphoma. Methods: The clinicopathological data of eight patients diagnosed with pulmonary intravascular large B cell lymphoma, from April 2018 to May 2023, were retrospectively analyzed. The genetic profile of six patients was detected via next-generation sequencing (NGS) and followed up. Results: All patients included one male and seven females, with a median age of 64 years (ranging from 45 to 66 years). Respiratory symptoms were the most common (7 cases), B symptoms in two cases, hemophagocytic syndrome in two cases. Multiple diffuse ground-glass opacities in both lungs were observed based on the high-resolution chest CT scan. Six cases of mild to moderate ventilation or diffusion dysfunction were observed based on the pulmonary function tests. Moreover, two cases of hypoxemia and two cases with type Ⅰ respiratory failure were recorded. The serum lactate dehydrogenase level increased (7/8), β2-MG level increased (2/8), neuron-specific enolase level increased (7/8), total number of peripheral blood lymphocytes decreased (7/8), and clinical stages were all stage Ⅳ. The neoplastic lymphoid cells were lodged in the lumina of venules and capillaries of the alveolar septum; the tumor cells were large, with prominent nucleoli and frequent mitotic figures. The malignant cells were detected in the extravascular surrounding lung tissue in all cases. The tumor cells expressed mature B cell-associated antigens CD20 and CD79a, and the vascular endothelial markers CD31 and CD34 showed that the tumor cells were filled in the blood vessels, infiltrated blood vessel walls, and perivascular areas. One case was germinal center-type, seven cases were non-germinal center-type, two cases were double-expressing lymphoma, and all cases were EBER-negative. Furthermore, the top five genes with mutation frequencies detected by NGS were MYD88 (5/6), PIM1 (5/6), CD79B (4/6), TCF3 (4/6), and TP53 (3/6). Of the eight cases, seven patients received R-CHOP-based chemotherapy, six cases had complete remission after chemotherapy, one case died, and one case was lost to follow-up. Conclusions: Pulmonary vascular large B cell lymphoma is rare, which shares similar patterns with interstitial lung disease on imaging. Transbronchial lung biopsy is an effective method to confirm the diagnosis. Immunochemotherapy with BTK inhibitors can provide a survival advantage for patients in the future based on molecular typing.

Identification of pathological characteristics in pulmonary tuberculosis using polarization-sensitive optical coherence tomography

The low detection rate of Mycobacterium tuberculosis in clinical practice leads to a high rate of missed diagnosis for pulmonary tuberculosis (PTB). As a noninvasive, high-resolution, real-time imaging technology, polarization-sensitive optical coherence tomography (PS-OCT) may be feasible for the rapid identification of pathological feature. This study aimed to explore the feasibility of using PS-OCT to identify pathological features of PTB. In the experiments, PTB samples containing some surrounding lung tissues were imaged using PS-OCT. It is demonstrated that PS-OCT images showed good consistency with the corresponding pathological images and were able to identify PTB-related characteristic pathological regions. We think PS-OCT can serve as an effective supplement for the diagnosis of PTB, enabling rapid and accurate diagnosis, and aiding in the understanding of the pathological characteristics and pathophysiological processes of PTB.

Case report: video-assisted thoracoscopic surgery for pulmonary arteriovenous malformation using near-infrared fluorescence with indocyanine green

BackgroundPulmonary arteriovenous malformation (PAVM) is an abnormal communication between pulmonary vasculatures and has an unclear boundary with surrounding lung tissues. At present, surgeons can only determine its location by preoperative imaging and intraoperative palpation, despite its soft texture. Indocyanine green(ICG), a near-infrared fluorophore, has been demonstrated useful in the accurate identification of vascular tissue. Therefore, we explored its application in PAVM cases.Case presentationWe present two PAVM cases using near-infrared fluorescence (NIF) with 25 mg ICG at 5 mg/ml to achieve intraoperative visualization of the lesion in video-assisted thoracoscopic surgery (VATS). Under the NIF mode, ICG systemic injection led to successive signaling of the anomaly and normal tissues in merely 10 s, which helped us distinguish them efficiently and precisely. A peak signal-to-background ratio of 2.2 confirmed the significant fluorescence difference and excluded interference from carbon dust.ConclusionsWe are the first to report the use of such an approach in delineating the margin of vascular malformation with high contrast, and this new finding may help minimize the damage to lung function in PAVM treatment. Further exploration and validation are needed to determine its role.

Three-Dimensional Reconstruction for the Whole Lung with Early Multiple Pulmonary Nodules.

For patients with early multiple pulmonary nodules, it is essential, from a diagnostic perspective, to determine the spatial distribution, size, location, and relationship with surrounding lung tissue of these nodules throughout the entire lung. This is crucial for identifying the primary lesion and developing more scientifically grounded treatment plans for doctors. However, pattern recognition methods based on machine vision are susceptible to false positives and false negatives and, therefore, cannot fully meet clinical demands in this regard. Visualization methods based on maximum intensity projection (MIP) can better illustrate local and individual pulmonary nodules but lack a macroscopic and holistic description of the distribution and spatial features of multiple pulmonary nodules. Therefore, this study proposes a whole-lung 3D reconstruction method. It extracts the 3D contour of the lung using medical image processing technology against the background of the entire lung and performs 3D reconstruction of the lung, pulmonary artery, and multiple pulmonary nodules in 3D space. This method can comprehensively depict the spatial distribution and radiological features of multiple nodules throughout the entire lung, providing a simple and convenient means of evaluating the diagnosis and prognosis of multiple pulmonary nodules.

Hybrid deep learning model for detection and classification of lung cancer fusion images using MCNet

Lung cancer is a dangerous tumor that requires accurate diagnosis for effective treatment. Traditional diagnosis involves invasive and time-consuming histologic examination, and radiologists face challenges in localizing lung tumors. Deep neural convolutional networks are frequently used to locate lung cancer, but this is still difficult when not accounting for surrounding lung tissue. Despite progress in research, healthcare still uses deep learning models to improve the precision and sensitivity of large datasets. CNN (Convolutional Neural Network) accuracy standards are adequate, but image properties such as flips, construction, and other uncommon alignments diminish its efficiency. CNN also does not store the geometric distribution between scanned picture features. CT (Computed Tomography) and PET (Positron Emission Tomography) scans require a method that takes into consideration the spatial information of picture characteristics, as they are vulnerable to alignment problems during the perusing process. To address these issues, the authors propose MCNet (MobileNetV2 with Capsule Network), a hybrid network that adopts feature extraction and categorization from MobileNetV2, and capsule network is used to overcome the limitations of convolutional neural networks (CNNs) when it comes to processing images with abnormal orientations, such as tilting or rotation. Although CNNs are effective in processing images presented in a standard orientation, they have difficulty handling variations in image orientation. In this work, MobileNetV2 serves as a backbone network for Capsule Networks in lung cancer diagnosis. The lung image collection dataset verifies the effectiveness of MCNet, and experimental results show that MCNet technology performs better than previous state-of-the-art techniques. The proposed hybrid MCNet architecture achieves the clinical goal of lung cancer diagnosis with a lower computational cost, reducing processing time complexity and false positive rates compared to current techniques.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide.

To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide

Pulmonary papillary adenoma with malignant potential: a case report and literature review

BackgroundPulmonary papillary adenoma is a rare benign tumor in the periphery of the lung. We report a 66-year-old female patient with a tumor in the lower lobe of the right lung and present the clinicopathological features and review the literature.Case presentationA tumor in the lower lobe of the right lung was found incidentally on chest X-ray during the physical examination of the patient, and the patient occasionally had a dry cough that was not treated. The tumor was clearly demarcated and lobulated on CT scan. After 2 years of follow-up, the boundary of the tumor was still clear, with more lobulations and the enhanced scan showed uniform enhancement. Grossly, the tumor had a granular cut surface and was easy to fall off, which was helpful for the diagnosis of papillary adenoma during intraoperative frozen examination. Under the microscope, most areas of the tumor had the typical morphological structure of papillary adenoma. However, the tumor locally protruded into the surrounding lung tissue, accompanied by crowded cells and high cell proliferation index. It was suggested that this case of papillary adenoma had malignant potential and needed active intervention and treatment.ConclusionPulmonary papillary adenoma is a rare epithelial tumor with malignant potential. Surgical treatment should be performed as soon as possible after diagnosis to prevent malignant transformation.

Pneumothorax and Intrapulmonary Hemorrhage in CT-Guided Transthoracic Biopsy

Objective: To study the frequency of pneumothorax and intrapulmonary haemorrhage in computed tomography (CT) guided transthoracic needle lung biopsy (NLB) and the factors that affect the development of these complications in Pakistan through a representative limited data obtained from a tertiary care centre.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Armed Forces Institute of Radiology and Imaging, Rawalpindi, from Jan 2018 to Feb 2019.&#x0D; Methodology: A total of 68 patients who underwent CT-guided transthoracic biopsy were evaluated for intra- and immediate (within 04 hours) post-procedural pneumothorax and pulmonary haemorrhage. The factors affecting the development of these complications were evaluated.&#x0D; Results: Complications developed in 30 patients with the frequency of pneumothorax at 26.5 % and frequency of pulmonary haemorrhage at 19.1%. Significant risk factors for the development of pneumothorax were small lesions less than 2.5 cm in diameter (p-value &lt;0.05), increased needle track path within the lung tissue of more than 21 mm (p-value = 0.05), and presence of emphysema in the surrounding lung tissue (p-value &lt;0.05). In addition, smaller lesion size (p-value &lt;0.05) and increased traversed lung parenchyma (p-value &lt;0.05) were also significant factors in the development of intrapulmonary haemorrhage.&#x0D; Conclusion: Significant risk factors for pneumothorax and intrapulmonary haemorrhage are smaller lesion size and length of puncture path. The presence of emphysema is related to the development of pneumothorax.

Novel light delivery method for performing transbronchial photodynamic therapy ablation to treat peripheral lung cancer: A pilot study

BackgroundPhotodynamic therapy involves using a photosensitizer with l illumination and is recommended for treating early, centrally located lung cancers, but it is not a standard treatment for peripheral lung tumor.. We previously proposed a novel light delivery method, in which lipiodol is perfused into the bronchial tree to increase the scope of illumination via the fiber effect. Herein, we attempted this novel technique under electromagnetic bronchoscope guidance in a hybrid operation room where lipiodol facilitated light diffusion, and evaluated the effectiveness and feasibility of this technique for peripheral lung cancers. MethodsThis phase 0 pilot study included three patients with peripheral lung cancers (primary tumors ≤20-mm diameter). The photodynamic therapy was administered using Porfimer sodium as the photosensitizer, and an electromagnetic navigation bronchoscope in a hybrid operating room to guide the catheter to the tumor. This facilitated lipiodol infusion to encase the tumor and permit the transbronchial photodynamic therapy ablation. ResultsAdministering 630 nm 200 J/cm (400mW/500sec) energy through a 3-cm cylindrical diffusing laser fiber was safe; no significant acute complications were observed. Although the treatment outcome was unsatisfactory due to the low light dose, tumor pathology in one case revealed tumor necrosis, with no significant damage to the surrounding lung tissue. ConclusionsNovel light delivery transbronchial photodynamic therapy ablation for peripheral lung tumors is feasible and safe. Additional clinical trials may help determine the best illumination plan and light dose through multiple deliveries from multiple angles.

CD4 Tcells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection.

HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 Tcells, raising the possibility that HIV co-infection leads to CD4 Tcell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 Tcells are dramatically depleted from granulomas, before CD4 Tcell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 Tcells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 Tcell motility is reduced after SIV co-infection. Thus, granuloma CD4 Tcells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection.

How to optimize your set-up for a VATS right upper lobectomy

A 77-year-old woman with multiple ground-glass opacities, the largest of which measured 21 mm, has a biopsy-proven primary lung adenocarcinoma in her right upper lobe. We performed a 3-port right-sided VATS using the Copenhagen approach. There was no pleural effusion or evidence of pleural metastatic spread. A tumor was identified in the upper lobe. The surrounding lung tissue appeared normal. We performed a multilevel intercostal block using 0.25% levobupivacaine. The inferior pulmonary ligament was divided. The superior pulmonary vein and 2 branches of the pulmonary artery to the right upper lobe were dissected, encircled, and divided using tan reloads of the Endo GIA stapler. The right upper lobe bronchus was dissected, encircled, and divided in a similar fashion using a purple reload of the Endo GIA stapler following a successful test inflation of the lower and middle lobes. The horizontal fissure was completed with further firings of the stapler. Lymph nodes from stations 2, 4, 7, 8, 9, 10, and 11 were sampled and sent separately for histological analysis. There was no parenchymal or stump leak to 20 cm H20 on the test inflation. Hemostasis and pneumostasis were checked and ensured. A single 24 Fr drain was placed in the apex. Hemostasis was complete. The incision was closed in layers.

TRANSPARENCHYMAL MICROWAVE ABLATION ASSESSMENT IN A SURVIVAL PORCINE LUNG MODEL

TOPIC: Procedures TYPE: Original Investigations PURPOSE: Percutaneous microwave ablation (MWA) is an established approach for CT-guided treatment of pulmonary tumors. A percutaneous approach for pulmonary MWA limits potential targets to peripheral lesions, and pneumothorax, hemorrhage, and fistula are some of the common complications. We have developed a system for bronchoscopic transparenchymal MWA of pulmonary tumors. Integration of the MWA system with virtual bronchoscopy and transparenchymal nodule access offers potential to enable minimally invasive diagnosis, staging, and treatment of peripheral lung nodules in a single session. In a survival porcine model, we assessed the feasibility of safely delivering MWA by introducing the applicator into lung targets via transparenchymal tunnel through the airway wall. METHODS: A total of 8 MWAs (90 W, 5 min) were performed in 4 pigs with a custom water-cooled, microwave catheter operating at 2.45 GHz. The catheter was introduced into multiple regions of the normal lung parenchyma via tunnels that extended 2.5–4 cm from the airway wall, guided by virtual bronchoscopy (Archimedes, Broncus Medical). Animals were euthanized at 2 (n=2) and 13 days (n=2) post-ablation. CT images were acquired immediately post-ablation and on the day of euthanasia. At necropsy, ablated and surrounding lung tissue was excised. Fresh tissue was used to assess the macroscopic extent of the ablation zones following viability staining. Formalin fixed tissue was processed into paraffin for thin sectioning and stained with hematoxylin and eosin for histopathologic examination. RESULTS: No pneumothorax, major bleeding or fistula were observed during and after ablation procedures. All pigs maintained normal appetite and behavior throughout the survival period. On day 2, ablation zone diameters on CT imaging were in the range 18–47 mm, as compared to 10–18 mm on macroscopic analysis. This discrepancy was likely due to edema, inflammation and/or hemorrhage obscuring the ablation boundary on CT assessment. At day 13, ablation zone diameters on CT imaging and macroscopic analysis were in the ranges 16–21 mm and 14–20 mm, respectively. On day 13, the ablation zone was separated from adjacent, aerated, pulmonary parenchyma by a 1-2 mm wide band of granulation tissue (fibrous connective tissue, fibrocytes, and vessels with macrophages and lymphoplasmacytic infiltrates). One of the animals in the 13-day group developed a severe suppurative bronchopneumonia attributed to secondary bacterial infection (the protocol did not include antibiotics). No evidence of emphysema was observed along the transparenchymal tunnels. CONCLUSIONS: We have demonstrated the feasibility of safely delivering virtual bronchoscopy guided transparenchymal MWA in a survival porcine model. CLINICAL IMPLICATIONS: Further evaluation of virtual-bronchoscopy guided transbronchial MWA in human patients in an ablate-and-resect study to assess safety and feasibility is warranted and planned for 2022. DISCLOSURES: No relevant relationships by Warren Beard, source=Web Response No relevant relationships by David Biller, source=Web Response No relevant relationships by Faraz Chamani, source=Web Response No relevant relationships by Pegah Faridi, source=Web Response Employee relationship with phenoMapper Please note: 09/01/2020-now Added 04/30/2021 by Steven Goh, source=Web Response, value=Salary No relevant relationships by Nicholas Hemphill, source=Web Response No relevant relationships by Margaret Highland, source=Web Response No relevant relationships by David Hodgson, source=Web Response No relevant relationships by Stephen Lam, source=Web Response PI ofan investigator-initiated study relationship with Medtronic Please note: >$100000 by Fabien Maldonado, source=Web Response, value=Grant/Research Supportco-I on investigator-initiated studies relationship with Janssen Please note: $20001 - $100000 by Fabien Maldonado, source=Web Response, value=Grant/Research Support Removed 04/19/2021 by Fabien Maldonado, source=Web Response PI on investigator-initiated relationship with Erbe Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Grant/Research Support Consulting relationship with Medtronic Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Honorariaco-I industry-sponsored trial relationship with Lung Therapeutics Please note: $5001 - $20000 by Fabien Maldonado, source=Web Response, value=Grant/Research Supportspeaker relationship with Longitudinal lung nodule fellows program - Please note: $1001 - $5000 by Fabien Maldonado, source=Web Response, value=Honoraria Removed 04/19/2021 by Fabien Maldonado, source=Web Response Board of director member relationship with AABIP Please note: $1-$1000 by Fabien Maldonado, source=Web Response, value=Travel No relevant relationships by Renelle Myers, source=Web Response No relevant relationships by Punit Prakash, source=Web Response No relevant relationships by Jan Sebek, source=Web Response No relevant relationships by Abbe Smith, source=Web Response No relevant relationships by Zixuan Wang, source=Web Response Owner/Founder relationship with phenoMapper, LLC Please note: 01/2021-12/2021 Added 04/30/2021 by Henky Wibowo, source=Web Response, value=Grant/Research Support No relevant relationships by Kun-Chang Yu, source=Web Response

Changes in the SARS-CoV-2 cellular receptor ACE2 levels in cardiovascular patients: a potential biomarker for the stratification of COVID-19 patients

Angiotensin-converting enzyme 2 (ACE2) is essential for SARS-CoV-2 cellular entry. Here we studied the effects of common comorbidities in severe COVID-19 on ACE2 expression. ACE2 levels (by enzyme activity and ELISA measurements) were determined in human serum, heart and lung samples from patients with hypertension (n = 540), heart transplantation (289) and thoracic surgery (n = 49). Healthy individuals (n = 46) represented the controls. Serum ACE2 activity was increased in hypertensive subjects (132%) and substantially elevated in end-stage heart failure patients (689%) and showed a strong negative correlation with the left ventricular ejection fraction. Serum ACE2 activity was higher in male (147%), overweight (122%), obese (126%) and elderly (115%) hypertensive patients. Primary lung cancer resulted in higher circulating ACE2 activity, without affecting ACE2 levels in the surrounding lung tissue. Male sex resulted in elevated serum ACE2 activities in patients with heart transplantation or thoracic surgery (146% and 150%, respectively). Left ventricular (tissular) ACE2 activity was unaffected by sex and was lower in overweight (67%), obese (62%) and older (73%) patients with end-stage heart failure. There was no correlation between serum and tissular (left ventricular or lung) ACE2 activities. Neither serum nor tissue (left ventricle or lung) ACE2 levels were affected by RAS inhibitory medications. Abandoning of ACEi treatment (non-compliance) resulted in elevated blood pressure without effects on circulating ACE2 activities. ACE2 levels associate with the severity of cardiovascular diseases, suggestive for a role of ACE2 in the pathomechanisms of cardiovascular diseases and providing a potential explanation for the higher mortality of COVID-19 among cardiovascular patients. Abandoning RAS inhibitory medication worsens the cardiovascular status without affecting circulating or tissue ACE2 levels.

Spatial analysis of the T-cell repertoire in non-small cell lung cancer reveals a clonality gradient from the tumor to the distal lung.

e20544 Background: The immunomodulatory effects of the tumor microenvironment (TME) significantly impact the T cell repertoire resulting in different anti-tumor immune responses. Previous work by our group and others has highlighted intratumor heterogeneity in T cell clonality, spatial distribution, and diversity, as well as infiltration of bystander T cells in early-stage non-small cell lung cancer (NSCLC). However, little is known about how the TME impacts the T cell repertoire in distant or surrounding adjacent uninvolved lung tissue. Methods: We investigated the interplay between tumor and surrounding lung tissues by investigating the T cell repertoire at the tumor site, tumor margin, and 1cm, 2cm, 5cm, and 10cm away from the tumor as well as in peripheral blood in 21 NSCLC patients with a total of 123 samples undergoing T cell receptor (TCR) CDR3b sequencing using the Geneplus technology. Differences in regional T cell repertoires were analyzed based on clonality, diversity, and Morisita Overlap Index (MOI). GLIPH was utilized to identify motifs associated with pathogen specificity in each region. Results: Clonality was lowest within the tumor and progressively increases from tumor margin to tumor adjacent lung toward distant lung with “hot spot” regions of T cell expansion located in adjacent lung tissue proximal to the tumor, namely 2cm away (p = 0.0025). Dominant T cell populations were better conserved between the tumor margins and “hot regions” of high clonality compared to the tumors (p = 0.0009) highlighting the differences between these environments and possible T cell exclusion in immunosuppressive TME. GLIPH analysis revealed an inverse correlation between clonality and the proportion of pathogen-associated TCR motifs (r = -0.83, p = 0.0195). Interestingly, tumor tissue contained the highest proportion of predicted pathogen TCRs whereas regions of high clonality contained the lowest (p &lt; 0.0001), suggesting the antigen-independent nature of T cell trafficking. Conclusions: Combined, these results highlight isolated pockets of T cell expansion in the lungs outside the tumor and potential immune evasion mechanisms in NSCLC.

A 3D image segmentation for lung cancer using V.Net architecture based deep convolutional networks

Lung segmentation of chest CT scan is utilised to identify lung cancer and this step is also critical in other diagnostic pathways. Therefore, powerful algorithms to accomplish this accurate segmentation task are highly needed in the medical imaging domain, where the tumours are required to be segmented with the lung parenchyma. Also, the lung parenchyma needs to be detached from the tumour regions that are often confused with the lung tissue. Recently, lung semantic segmentation is more suitable to allocate each pixel in the image to a predefined class based on fully convolutional networks (FCNs). In this paper, CT cancer scans from the Task06_Lung database were applied to FCN that was inspired by V.Net architecture for efficiently selecting a region of interest (ROI) using the 3D segmentation. This lung database is segregated into 64 training images and 32 testing images. The proposed system is generalised by three steps including data preprocessing, data augmentation and neural network based on the V-Net model. Then, it was evaluated by dice score coefficient (DSC) to calculate the ratio of the segmented image and the ground truth image. This proposed system outperformed other previous schemes for 3D lung segmentation with an average DCS of 80% for ROI and 98% for surrounding lung tissues. Moreover, this system demonstrated that 3D views of lung tumours in CT images precisely carried tumour estimation and robust lung segmentation.

Abstract PO-123: Distinct subpopulations of osteosarcoma cells cooperate to establish lung metastases

Abstract Four decades of intense multinational efforts to improve outcomes for children and teenagers with osteosarcoma have failed. Today, we still treat patients with a regimen first developed in 1982. The same 35-40% of young people diagnosed with osteosarcoma die from their disease, almost always from complications related to lung metastasis. Believing that therapies targeting lung metastasis could dramatically improve outcomes, we have sought to understand the mechanisms that drive lung colonization in this disease. We previously found that interactions with lung epithelium cause osteosarcoma cells to produce IL6 and CXCL8 and that this activity is necessary for metastasis. Inhibiting IL6 and CXCL8 signaling prevents metastasis entirely in 85% of mice with osteosarcoma. While conducting these studies, we learned that individual tumor cells react differently to signals from lung epithelium. Nearly all the IL6 and CXCL8 produced by osteosarcoma cells come from a small subset of cells. Interactions with pulmonary epithelium cause this discrete subset of tumor cells to produce large quantities of inflammatory cytokines, become strongly p21+, and stop proliferating. Early metastatic lesions consist almost entirely of cells with this phenotype, positioning them to orchestrate the development of the metastatic niche. Thus, we call these hypo-proliferative, cytokine-producing cells that survive early attrition "anchor cells." In the initial stages of metastasis, anchor cells alter the surrounding lung tissue in ways that facilitate subsequent colonization by tumor cells with proliferating phenotypes ("growth cells"). Growth cells then divide to create expanding, clinically-relevant metastasis. Importantly, one can leverage the biology of these anchor cells to develop rational targeting strategies. Anchor cells exhibit profound sensitivity to known senolytic agents. Combining these with conventional therapies (which effectively target growth cells) can eradicate established metastatic lesions and prevent new metastases from forming. These novel findings fundamentally alter our understanding of osteosarcoma and metastasis biology and have direct implications for approaches to treatment. Citation Format: James B. Reinecke, John M. Hinckley, Amy C. Gross, Maren Cam, Sanjana Rajan, Ryan D. Roberts. Distinct subpopulations of osteosarcoma cells cooperate to establish lung metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-123.

Interobserver agreement of the visual Herder scale for the assessment of solitary pulmonary nodules on 18F Fluorodeoxyglucose PET/computed tomography.

British Thoracic Society guidelines recommend 18F Fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) for solitary pulmonary nodule (SPN) follow-up in high-risk individuals or if the CT Brock score is >10%. Nodule tracer uptake is assessed visually in comparison to the surrounding lung tissue and mediastinal blood pool (Herder score). This score is used to calculate the risk of malignancy and guide patient management. Despite its widespread use, there have been no studies to date looking at interobserver agreement using the Herder scale. F-FDG PET/CT studies of 100 consecutive patients imaged for the evaluation of SPN were retrospectively analysed. Anonymized images were reviewed independently by three Consultant Nuclear Medicine Radiologists and the Herder score was documented, along with a confidence score graded 1-3, where 1 indicated 'not at all confident' and 3 indicated 'very confident'. Interobserver agreement was assessed using interclass correlation coefficient modelling. There was complete reviewer agreement in 81% cases, and interclass correlation with Cronbach's alpha was excellent at 0.973 (95% confidence interval, 0.962-0.981). The agreement between pairs of reviewers was good and confidence scores using the Herder scale were high, with reviewers giving a confidence score of 3 in an average of 78% of cases. Our study suggests excellent interobserver agreement for use of the Herder scale in evaluating SPNs. Reviewer confidence scores were high reflecting high confidence in the use of the Herder scale for evaluating SPN.

MRIgRT dynamic lung motion thorax anthropomorphic QA phantom: Design, development, reproducibility, and feasibility study.

To design, manufacture, and evaluate a dynamic magnetic resonance imaging/computed tomography (MRI/CT)-compatible anthropomorphic thorax phantom used to credential MR image-guided radiotherapy (MRIgRT) systems participating in NCI-sponsored clinical trials. The dynamic anthropomorphic thorax phantom was constructed from a water-fillable acrylic shell that contained several internal structures representing radiation-sensitive organs within the thoracic region. A custom MR/CT visible cylindrical insert was designed to simulate the left lung with a centrally located tumor target. The surrounding lung tissue was constructed from a heterogeneous in-house mixture using petroleum jelly and miniature (2-4mm diameter) styrofoam balls and the tumor structure was manufactured from liquid PVC plastic. An MR conditional pneumatic system was developed to allow the MRIgRT insert to move in similar inhale/exhale motions. TLDs and radiochromic EBT3 film were inserted into the phantom to measure absolute point doses and dose distributions, respectively. The dynamic MRIgRT thorax phantom was evaluated through a reproducibility study and a feasibility study. Comprehensive end-to-end examinations were done where the phantom was imaged on a CT, an IMRT treatment plan was created and an MR image was captured to verify treatment setup. Then, the phantom was treated on an MRIgRT system. The reproducibility study evaluated how well the phantom could be reproduced in an MRIgRT system by irradiating three times on an Elekta's 1.5T Unity system. The phantom was shipped to three independent institutions and was irradiated on either an MRIdian cobalt-60 (60 Co) or an MRIdian linear accelerator system. Treatment evaluations used TLDs and radiochromic film to compare the planned treatment reported on the treatment planning software against the measured dose on the dosimeters. The phantom on the Unity system had reproducible TLD doses measurements (SD<1.5%). The measured TLD to calculated dose ratios from the reproducibility and feasibility studies ranged from 0.93 to 1.01 and 0.96 to 1.03, respectively. Using a 7%/5mm gamma analysis criteria, the reproducibility and feasibility studies resulted in an average passing rate of 93.3% and 96.8%, respectively. No difference was noted in the results between the MRIdian 60 Co and MRIdian 6MV linac delivery to the phantom and all treatment evaluations were within IROC-Houston's acceptable criterion. A dosimetrically tissue equivalent, CT/MR visible, motion-enabled anthropomorphic MRIgRT thorax phantom was constructed to simulate a lung cancer patient and was evaluated as an appropriate NIH credentialing tool used for MRIgRT systems.

Ectopic prolactin production by lung cancer cells as an indicator of aggressive nature of tumors.

e20021 Background: Cancer cells use many unexpected molecular mechanisms to ensure their malignancy, and a comprehensive understanding of cancer cannot be achieved without a global consideration of all oncogenic events. Ectopic activation of tissue-specific hormones accompanies malignant transformation in many cancers. The aim of the study was to determine prolactin (PRL) levels in the blood, tumor and surrounding lung tissues in lung cancer patients of both sexes. Methods: Levels of PRL were measured in the blood and 10% homogenates of the tumor, perifocal tissues and intact lung tissues by radioimmune method using Immunotech kits (Czech Republic). The study included 33 men and 22 women with central and peripheral lung adenocarcinomas (T2-3N0-1M0), mean age 62±3.4 years, all women were menopausal. The comparison group included non-cancer patients (13 men and 12 women) operated on for chronic inflammatory lung diseases. Results: PRL levels in peripheral blood in 74% of men were increased by 3.7 times, and in 85% of women by 5.7 times. Peripheral cancer in men and women had no significant differences in prolactin levels; the hormone distribution was similar in the tumor, perifocal and intact tissues and was on average 1.5 times higher than in lung tissues in patients with inflammatory processes. Women with central cancer were characterized by higher tumor levels of PRL compared to men. In general, both in men and women, PRL levels in perifocal tissues and in intact lung tissue distant from the tumor focus were similar to tumor levels, which could indicate a general change in the organ metabolism, and not a local hormone synthesis by tumor tissues. Conclusions: The detected increase in the PRL content in lung tissues and in the blood may indicate the dysfunction of central regulatory mechanisms and a change in lung metabolism, being one of the links in the causal mechanisms of tumor development.