Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5−/KRT17+ pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis.
Highlights d Integrated proteogenomic characterization in 103 ccRCC cases d Delineation of chromosomal translocation events leading to chromosome 3p loss d Tumor-specific proteomic/phosphoproteomic alterations unrevealed by mRNA analysis d Immune-based subtypes of ccRCC defined by mRNA, proteome, and phosphoproteome
In the originally published version of this article, Daniel Geiszler's last name was misspelled. This error has now been corrected in the article online.
When managing nonseminomatous germ cell tumors, contralateral lung abnormalities ≤ 10 mm can be observed if histology of unilateral PM demonstrates complete tumor necrosis. 17. When managing nonseminomatous germ cell tumors, PM is indicated for select patients with limited number of lung abnormalities after first or second-line platin-based chemotherapy suspected of containing viable nonseminomatous cancer and/or malignant transformation of teratoma into non-germ cell cancer. 18. In breast cancer patients, PM can be considered within a MDT construct. Pulmonary metastasectomy literature characteristics Since 1980, greater than 1000 publications addressed pulmonary metastasectomy, without a single randomized controlled trial (RCT). The overwhelming majority is surgical series, usually single institution, and includes single or multiple pathologies. The pool of patients from which metastasectomy patients derive is not reported, allowing no comparative survival analysis. Historical controls are used or metastatic disease survival is assumed to be zero, a contention not supported by the literature. Yet metastasectomy is infrequently performed (1-6.5%) when sizable populations of cancer patients are reported. [1-3] Thus surgical case series manifest inherent selection bias and do not clarify the role of metastasectomy in prolongation of survival or cure. The literature is further hampered by inconsistent or absent description of other local or systemic therapies and variable length of follow up. Finally, the literature fails to distinguish between prognostic (indolent disease which will do well with any or no treatment) or predictive
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