Impact of Implementing a Grossing Tumor-margin Distance Threshold for Frozen Section in Oncologic Lung Surgery.

Intraoperative frozen section (FS) examination of oncologic surgical specimens is frequently performed to ensure complete surgical resection. Data on the gross evaluation of surgical margins are limited. We recently published a study suggesting the use of a macroscopic 2.

Cell states and neighborhoods in distinct clinical stages of primary and metastatic esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a highly lethal cancer of the upper gastrointestinal tract with rising incidence in western populations. To decipher EAC disease progression and therapeutic response, we performed multiomic analyses of a cohort of primary and metastatic EAC tumors, incorporating single-nuclei transcriptomic and chromatin accessibility sequencing, along with spatial profiling. We identified tumor microenvironmental features previously described to associate with therapy response.

Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens: Examination of Clinical Impact.

Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined.

Pulmonary Adenocarcinoma In Situ and Minimally Invasive Adenocarcinomas in European Patients Have Less and More Mutations Compared to Advanced Adenocarcinomas.

Pulmonary adenocarcinoma (ADC) is a very diverse disease, both genetically and histologically, which displays extensive intratumor heterogeneity with numerous acquired mutations. ADC is the most common type of lung cancer and is believed to arise from adenocarcinoma in situ (AIS) which then progresses to minimally invasive adenocarcinoma (MIA). In patients of European ethnicity, we analyzed genetic mutations in AIS ( = 10) and MIA ( = 18) and compared the number of genetic mutations with advanced ADC ( = 2419).

CXCL13 Positive Cells Localization Predict Response to Anti-PD-1/PD-L1 in Pulmonary Non-Small Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancers (NSCLCs) treatment, but only 20-30% of patients benefit from these treatments. Currently, PD-L1 expression in tumor cells is the only clinically approved predictor of ICI response in lung cancer, but concerns arise due to its low negative and positive predictive value. Recent studies suggest that CXCL13+ T cells in the tumor microenvironment (TME) may be a good predictor of response.

Clinical Outcomes of Resected Pure Ground-Glass, Heterogeneous Ground-Glass, and Part-Solid Pulmonary Nodules.

Increased (but not definitively solid) attenuation within pure ground-glass nodules (pGGNs) may indicate invasive adenocarcinoma and the need for resection rather than surveillance. The purpose of this study was to compare the clinical outcomes among resected pGGNs, heterogeneous ground-glass nodules (GGNs), and part-solid nodules (PSNs). This retrospective study included 469 patients (335 female patients and 134 male patients; median age, 68 years [IQR, 62.

Amplification of Wild-Type Represents a Novel Molecular Subtype of Several Cancer Types With Clinical Response to Selpercatinib.

Purpose: rearrangements and activating point mutations represent targetable genomic alterations in advanced solid tumors. However, the frequency and clinicopathologic characteristics of wild-type amplification in cancer and its potential role as a targetable oncogenic driver are not well-characterized.

Methods: In two institutional cohorts of patients with solid cancers from the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC) whose tumors underwent next-generation sequencing (NGS), the frequency and clinicopathologic features of wild-type amplification in the absence of rearrangements or activating mutations was assessed.

Generalization optimizing machine learning to improve CT scan radiomics and assess immune checkpoint inhibitors' response in non-small cell lung cancer: a multicenter cohort study.

Background: Recent developments in artificial intelligence suggest that radiomics may represent a promising non-invasive biomarker to predict response to immune checkpoint inhibitors (ICIs). Nevertheless, validation of radiomics algorithms in independent cohorts remains a challenge due to variations in image acquisition and reconstruction. Using radiomics, we investigated the importance of scan normalization as part of a broader machine learning framework to enable model external generalizability to predict ICI response in non-small cell lung cancer (NSCLC) patients across different centers.

A Simplified Version of the IASLC Grading System for Invasive Pulmonary Adenocarcinomas With Improved Prognosis Discrimination.

Tumor grading enables better management of patients and treatment options. The International Association for the Study of Lung Cancer (IASLC) Pathology Committee has recently released a 3-tier grading system for invasive pulmonary adenocarcinoma consisting of predominant histologic patterns plus a cutoff of 20% of high-grade components including solid, micropapillary, and complex glandular patterns. The goal of this study was to validate the prognostic value of the new IASLC grading system and to compare its discriminatory performance to the predominant pattern-based grading system and a simplified version of the IASLC grading system without complex glandular patterns.

Single-cell spatial landscapes of the lung tumour immune microenvironment.

Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution. Most clinical strategies rely on histopathological stratification of tumour subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns.

Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity.

Background: Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression and response to immune checkpoint inhibitors (ICI). As such, there is an unmet need to elucidate the spatially defined single-cell landscape of the lung cancer microenvironment to understand the mechanisms of disease progression and identify biomarkers of response to ICI.

Prognostic value of complex glandular patterns in invasive pulmonary adenocarcinomas.

Prognostic stratification of patients surgically resected with invasive pulmonary adenocarcinoma must be improved. Previous studies reported that complex glandular patterns (CGPs), cribriform and fused gland growth patterns, are associated with unfavorable prognosis. The goal of this study is to evaluate the prognostic value of CGPs in patients with resected stage I-IV lung adenocarcinoma.

Wait Times and Survival in Lung Cancer Patients across the Province of Quebec, Canada.

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017.

Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota.

Profiles of teacher-child interaction quality in groups of 3-year-old children in Quebec and France.

Theory and studies support that educational quality may differ according to socio-political context even in states with similar cultures. Based on a secondary analysis of data, this study aims at identifying latent profiles of adult-child interaction quality in groups of three-year-old children in Quebec's (Canada) early childhood centers and France's kindergarten classrooms using the CLASS Pre-K. This study also aims to explore existing associations between identified profiles, socio-political contexts, and structural characteristics (staff qualifications, ages, group size).

ZNF768 Expression Associates with High Proliferative Clinicopathological Features in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and a leading cause of cancer-related deaths worldwide. Despite important recent advances, the prognosis for LUAD patients is still unfavourable, with a 5 year-survival rate close to 15%. Improving the characterization of lung tumors is important to develop alternative options for the diagnosis and the treatment of this disease.

ZNF768 links oncogenic RAS to cellular senescence.

RAS proteins are GTPases that lie upstream of a signaling network impacting cell fate determination. How cells integrate RAS activity to balance proliferation and cellular senescence is still incompletely characterized. Here, we identify ZNF768 as a phosphoprotein destabilized upon RAS activation.

Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study.

Objectives: Venous thrombotic events (VTEs) are a frequent complication of non-small cell lung cancer (NSCLC) and are associated with increased morbidity. Immune checkpoint inhibitors (ICIs) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of VTEs in NSCLC patients receiving these treatments.

Unravelling actionable biology using transcriptomic data to integrate mitotic index and Ki-67 in the management of lung neuroendocrine tumors.

Pulmonary neuroendocrine tumors (NETs) are a heterogeneous family of malignancies whose classification relies on morphology and mitotic rate, unlike extrapulmonary neuroendocrine tumors that require both mitotic rate and Ki-67. As mitotic count is proportional to Ki-67, it is crucial to understand if Ki-67 can complement the existing diagnostic guidelines, as well as discover the benefit of these two markers to unravel the biological heterogeneity. In this study, we investigated the association of mitotic rate and Ki-67 at gene- and pathway-level using transcriptomic data in lung NET malignancies.

Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage.

Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Mice bearing harboring this prophage mounted a TMP-specific H-2K-restricted CD8 T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice.

Comprehensive assessment of PD-L1 immunohistochemistry on paired tissue and cytology specimens from non-small cell lung cancer.

Objectives: PD-L1 staining assessed by immunohistochemistry (IHC) is a predictive biomarker used to select advanced stage non-small cell lung carcinoma (NSCLC) patients who are likely to respond to PD-1/PD-L1 inhibitors. Cytology specimens represent a significant percentage of the diagnostic samples and additional data are required to show that they provide reliable PD-L1 results when compared to tissue specimens. We aimed to compare PD-L1 staining obtained from patient-matched tissue and cytology specimens.

Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in LDLrApoB mice.

Background And Aims: Poor dietary habits contribute to the obesity pandemic and related cardiovascular diseases but the respective impact of high saturated fat versus added sugar consumption remains debated. Herein, we aimed to disentangle the individual role of dietary fat versus sugar in cardiometabolic disease progression.

Methods: We fed pro-atherogenic LDLrApoB mice either a low-fat/high-sucrose (LFHS) or a high-fat/low-sucrose (HFLS) diet for 24 weeks.

Efficacy of immune checkpoint inhibitors in older patients with non-small cell lung cancer: Real-world data from multicentric cohorts in Canada and France.

Background: Age-related immune remodelling is thought to be associated with resistance to immune checkpoint inhibitors (ICIs) in cancer. Patients older than 70 years, representing >50% of the population with non-small cell lung cancer (NSCLC) according to SEER database, are underrepresented in clinical trials exploring ICIs. The objective of this study was to determine if patients with NSCLC older than ≥70 years had inferior clinical outcomes with ICIs.