FGF21 Signaling Exerts Antifibrotic Properties during Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal disease with limited therapeutic options. FGF21 (fibroblast growth factor 21), an endocrine fibroblast growth factor that acts through the FGFR1 (fibroblast growth factor receptor 1)/KLB (β-Klotho) pathway, mitigates liver fibrosis. We hypothesized that FGF21 could exert antifibrotic properties in the lung.

Identification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited therapeutic options. Fibroblast growth factor receptor-4 (FGFR4) is a known receptor for several paracrine fibroblast growth factors (FGFs). FGFR4 is also the main receptor for FGF19, an endocrine FGF that was demonstrated by our group to have antifibrotic properties in the lung.

Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip.

There is a compelling need for approaches to predict the efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate simplified tumor ecosystems. Here, we present the development and validation of lung tumor-on-chip platforms to quickly and precisely measure ex vivo the effects of immune checkpoint inhibitors on T cell-mediated cancer cell death by exploiting the power of live imaging and advanced image analysis algorithms.

[Infectious pneumonia favored by paraneoplastic Cushing syndrome in a pulmonary carcinoid tumor].

Introduction: Ectopic Cushing's syndrome (CS) is a rare condition nevertheless well-known to endocrinologists. The pneumologist may be called upon to treat CS not only because bronchial carcinoid tumors are the most frequent source of ectopic ACTH secretion, but also due to the fact that the immunosuppression induced by hypercorticism favors lower respiratory tract infections.

Case Report: We report the case of a female patient presenting with acute respiratory failure secondary to Enterobacter cloacae pneumonia exacerbated by SC.

Borderline Hepatocellular Adenomas: A Practical Diagnostic Approach Based on Pathologic and Molecular Features.

Borderline hepatocellular adenomas (BL-HCA) are characterized by focal architectural/cytologic atypia and reticulin loss, features that are insufficient for a definitive diagnosis of hepatocellular carcinoma (HCC). The diagnosis and management of BL-HCA are challenging as their biological behavior, especially in terms of malignant potential, is still debated. We aimed to compare the clinicopathologic and molecular features of BL-HCA with those of typical HCA (T-HCA), HCA with malignant transformation (HCC on HCA), and HCC to assess the risk of malignancy.

Platelet Satellitism in a Patient with Bronchial Asthma.

Platelet satellitism is uncommon phenomenon characterized by formation of platelet rosette around polymorphonuclear leucocytes in blood smear prepared from Ethylenediaminetetraacetic acid anticoagulated blood. This phenomenon may cause reporting of spurious thrombocytopenia unless proper examination of blood smears. Here we describe a case of platelet satellitism in a 29 year old female which has been incidentally found on evaluation of eosinophilia in a bronchial asthma patient.

[Digestive infectious pathology: Diagnoses not to be missed].

The recent context of COVID-19 has renewed the interest of pathologists in diseases of infectious origin. This interest is even stronger in the gastrointestinal tract where symptoms are aspecific, often frustrating with a normal endoscopic appearance sometimes leading to diagnostic erraticity. In this context, systematic biopsies performed by the clinician are sometimes the only way to reach a diagnosis.

[Lymphocytic "…itis", from esophagus to large bowel].

Intra-epithelial lymphocytosis is an elementary lesion frequently observed in the gastrointestinal tract, which can be found from the esophagus to the colon. Many conditions of a varied nature (dysimmunitary diseases, drugs, infections…) are associated with intra-epithelial lymphocytosis, and the etiological diagnosis most often requires an anatomo-clinical correlation. The pathologist will have to identify histological lesions associated with intra-epithelial lymphocytosis allowing the diagnosis to be oriented in order to propose appropriate treatment.

[Adipocytes, adipokines and metabolic alterations in pulmonary fibrosis].

Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by severe remodeling of the lung parenchyma, with an accumulation of activated myofibroblasts and extracellular matrix, along with aberrant cellular differentiation. Within the subpleural fibrous zones, ectopic adipocyte deposits often appear. In addition, alterations in lipid homeostasis have been associated with IPF pathophysiology.

Grade 3-4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study.

Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3−4 irAEs on overall survival (OS).

Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut-like profile.

Isolated hepatic localizations of neuroendocrine tumors (NETs) are generally considered as metastatic NETs of unknown primary but could correspond to primary hepatic NETs (PHNETs), a poorly explored entity. We aimed to describe the clinicopathological and molecular features of PHNETs and compare them with other primary NETs. We assembled a retrospective cohort of patients managed for hepatic localization of NET without extra-hepatic primary tumor after exhaustive clinical, imaging, and immunohistochemical characterization.

Autofluorescence imaging within the liver: a promising tool for the detection and characterization of primary liver tumors.

Objectives: To assess the performance of 405 nm-induced autofluorescence for the characterization of primary liver nodules on ex vivo resected specimens.

Materials And Methods: Forty resected liver specimens bearing 53 primary liver nodules were included in this IRB-approved prospective study. Intratissular spectroscopic measurements were performed using a 25-G fibered-needle on all ex vivo specimens: 5 autofluorescence measurements were performed in both nodules and adjacent parenchyma.

Gene expression signature as a surrogate marker of microvascular invasion on routine hepatocellular carcinoma biopsies.

Background & Aims: Microvascular invasion (MVI), a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma (HCC), is only detectable by microscopic examination of the surgical specimen. We aimed to define a transcriptomic signature associated with MVI in HCC than can be applied to formalin-fixed paraffin-embedded (FFPE) biopsies for use in clinical practice.

Methods: To identify a gene expression signature related to MVI by using NanoString technology, we selected a set of 200 genes according to the literature and RNA-sequencing data obtained from a cohort of 150 frozen HCC samples previously published.

Blood fibrocytes are associated with severity and prognosis in COVID-19 pneumonia.

Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45/CD15/CD34/collagen-1 cells in patients hospitalized for COVID-19 pneumonia.

Poor performance status patient with long-lasting major response to pembrolizumab in advanced non-small-cell lung cancer with coexisting POLE mutation and deficient mismatch repair pathway.

Immunotherapy with immune checkpoint inhibitors (ICIs) represents a major breakthrough in lung cancer treatment. For patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status (PS), the availability of sensitivity markers to immune-checkpoint inhibitors (ICI) would be useful for attending physicians and assist them in their decision-making process. Deficient mismatch repair (dMMR) can lead to high microsatellite instability (MSI-H) and coexist with mutations in polymerase proofreading (DNA polymerase Epsilon POLE and delta 1 POLD1) with a specific mutational signature.

Long-term outcomes following resection of hepatocellular adenomas with small foci of malignant transformation or malignant adenomas.

Background & Aims: Malignant transformation of hepatocellular adenoma (MT-HCA) may occur in up to 5% of tumours. However, the prognostic value of this event remains poorly described. In this study, we aimed to analyse the long-term outcomes of patients undergoing liver resection (LR) for MT-HCA compared to those of patients resected for hepatocellular carcinoma (HCC) occurring on normal liver parenchyma (NP-HCC).

Smooth muscular layer: A new helpful criterion to reclassify tumor deposits into metastatic lymph nodes in patients with colo-rectal adenocarcinoma.

Context: The origin of tumor deposit in colorectal cancer is still unknown, and currently there is no single morphological feature to distinguish a metastatic lymph node from a tumor deposit. Histologically, the normal lymph node capsule and trabeculae contain a smooth muscular layer, which when present in extramural deposits would strongly suggest their lymph node origin.

Objective: We analyze the value of the smooth muscular layer criterion in reclassifying tumor deposit into metastatic lymph node.

Prevalence and prognosis of microsatellite instability in oesogastric adenocarcinoma, NORDICAP 16-01.

Background: The prevalence and prognosis association of microsatellite instability (MSI) in oesogastric junction and gastric adenocarcinoma (OGC) have been reported with conflicting results.

Methods: Patients with OGC from 2010 to 2015 were enrolled in this retrospective multicenter study. MSI was determined by genotyping.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

Background: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases.

Materials And Methods: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019.

Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass.

The exact mechanisms underlying the metabolic effects of bariatric surgery remain unclear. Here, we demonstrate, using a combination of direct and indirect calorimetry, an increase in total resting metabolic rate (RMR) and specifically anaerobic RMR after Roux-en-Y gastric bypass (RYGB), but not sleeve gastrectomy (SG). We also show an RYGB-specific increase in splanchnic sympathetic nerve activity and "browning" of visceral mesenteric fat.