Search Results (27)

Background/Objectives: Pulmonary lymphangitic carcinomatosis (PLC) is a rare, aggressive manifestation of metastatic cancer characterized by lymphatic infiltration of the lungs, typically indicating advanced disease and poor prognosis. Methods: This comprehensive narrative review evaluates the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging in assessing PLC. Results: Current evidence demonstrates that [18F]FDG PET/CT achieves high diagnostic accuracy, with sensitivity and specificity ranging from 86 to 97% and 84 to 100%, respectively, particularly when employing semiquantitative metrics such as peritumoral standardized uptake value (SUVmax) thresholds (e.g., ≥2.1). PET/CT surpasses high-resolution computed tomography (HRCT) in distinguishing PLC from mimics like pulmonary sarcoidosis by identifying distinct metabolic patterns: bronchovascular hypermetabolism in PLC versus subpleural nodular uptake in sarcoidosis. Prognostically, metabolic tumor burden (e.g., SUVmax × involved lobes) and novel cPLC classifications (localized to the ipsilateral or contralateral lung) independently predict progression-free survival. However, challenges persist, including non-specific tracer uptake in inflammatory conditions and variability in SUV measurements due to technical factors. Emerging digital PET/CT systems, with enhanced spatial resolution, may improve the detection of focal PLC and reduce false negatives. While [18F]FDG PET/CT is invaluable for whole-body staging, therapeutic monitoring and biopsy guidance, the standardization of protocols and multicenter validation of prognostic models are critical for clinical integration. Future research should explore novel tracers (e.g., PSMA for prostate cancer-related PLC) and machine learning approaches to refine diagnostic and prognostic accuracy. Conclusions: This review underscores the role and the transformative potential of [18F]FDG PET/CT in PLC management while advocating for rigorous standardization to maximize its clinical utility. Full article

RASopathies are a group of genetic syndromes caused by germline mutations in genes involved in the RAS/Mitogen-Activated Protein Kinase signaling pathway, which regulates cellular proliferation, differentiation, and angiogenesis. Despite their involvement at different levels of this pathway, RASopathies share overlapping clinical phenotypes. Noonan syndrome is the most prevalent RASopathy, with an estimated incidence of 1 in 2500 live births, and it is typically inherited in an autosomal dominant manner, with 50% of cases involving gain-of-function mutations in the PTPN11 gene. De novo mutations are common, accounting for 60% of cases. The phenotype of Noonan syndrome includes characteristic facial and physical features, congenital cardiac defects, lymphatic and cerebrovascular anomalies, renal malformations, hematological abnormalities, developmental issues, and an increased risk of cancer. Severe congenital cardiac defects and lymphatic abnormalities significantly impact prognosis, contributing to increased morbidity and mortality. Recent therapeutic advancements have introduced trametinib, an MEK1/2 inhibitor, for treating Noonan syndrome patients with severe cardiac and lymphatic complications. To assess its efficacy, here, we present a case of a newborn with Noonan syndrome who exhibited refractory chylothorax, ventricular hypertrophy, and pulmonary stenosis who was treated with trametinib. The patient demonstrated significant improvement in chylothorax and left ventricular hypertrophy, though pulmonary stenosis persisted. This case further confirms trametinib’s potential as a therapeutic option for severe Noonan syndrome complications, emphasizing the need for further clinical trials to optimize treatment protocols and evaluate long-term outcomes. Full article

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by nail bed changes, pulmonary involvement, and lymphatic drainage disorders. Pulmonary involvement usually manifests as bronchiectasis, bronchiolitis, and pleural effusion. There are few studies on yellow nail syndrome combined with opportunistic infection. Here, we report a case of clinically diagnosed YNS combined with Nocardia cyriacigeorgica infection and the course of treatment used, which can provide some useful information for clinicians to better understand this rare illness. Full article

Indocyanine green (ICG) fluorescence imaging has revolutionized surgical practice across various medical and surgical specialties. This article reviews the clinical applications of ICG in abdominal, urological, thoracic, and gynecological surgery. ICG fluorescence imaging has been widely adopted in general surgery for various applications, including perfusion assessment, intraoperative visualization of the ureter, and tumor localization. It is particularly valuable in evaluating anastomotic leaks and aiding in precise tumor resection during minimally invasive surgeries. Studies have shown mixed results on its effectiveness in reducing anastomotic leak rates, highlighting the need for further research. In thoracic surgery, ICG facilitates the identification and resection of pulmonary bullae, as well as the precise localization of pulmonary nodules during video-assisted surgery. In urology, ICG aids in localizing renal tumors and guiding selective arterial occlusion during partial nephrectomy. Its role in identifying the lymphatic pathway in prostate cancer and sentinel lymph node biopsy in gynecological cancer is also discussed. Despite its benefits, the use of ICG fluorescence faces challenges such as limited tissue penetration, the potential for false results, a lack of standardized protocols, and high equipment costs. Nonetheless, it remains a powerful tool that could improve surgical outcomes. Full article

Over the past five decades, the Fontan procedure has been developed to improve the life expectancy of patients with congenital heart defects characterized by a functionally single ventricle. The Fontan circulation aims at redirecting systemic venous return to the pulmonary circulation in the absence of an impelling subpulmonary ventricle, which makes this physiology quite fragile and leads to several long-term complications. Despite the importance of hemodynamic assessment through cardiac catheterization in the management and follow-up of these patients, a thorough understanding of the ultimate functioning of this type of circulation is lacking, and the interpretation of the hemodynamic data is often complex. In recent years, new tools such as combined catheterization with cardiopulmonary exercise testing have been incorporated to improve the understanding of the hemodynamic profile of these patients. Furthermore, extensive percutaneous treatment options have been developed, addressing issues ranging from obstructive problems in Fontan pathway and acquired shunts through compensatory collaterals to the percutaneous treatment of lymphatic circulation disorders and transcatheter edge-to-edge repair of atrioventricular valves. The aim of this review is to detail the various tools used in cardiac catheterization for patients with Fontan circulation, analyze different percutaneous treatment strategies, and discuss the latest advancements in this field. Full article

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15–20 min) and intratracheal administration (6–50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 10⁸ CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP. Full article

Excessive alcohol consumption increases the severity and worsens outcomes of pulmonary infections, often due to oxidative stress and tissue damage. While the mechanism behind this relationship is multifaceted, recent evidence suggests ethanol-induced changes to the gut microbiome impact the gut–lung axis. To assess this, a chronic–binge ethanol feeding mouse model was used to determine how ethanol altered the gut microbiome, small intestinal epithelial barrier, and immune responses, as well as neutrophil abundance and oxidative stress in the lungs, and how supporting gut health with tributyrin supplementation during chronic–binge ethanol exposure affected these responses. We found that ethanol consumption altered gut bacterial taxa and metabolic processes, distorted small intestinal immune responses, and induced both bacteria and endotoxin translocation into the lymphatic and circulatory systems. These changes were associated with increased neutrophil (Ly6G) presence and markers of oxidative stress, lipocalin-2 and myeloperoxidase, in the lungs. Importantly, tributyrin supplementation during ethanol exposure rescued gut bacterial function (p < 0.05), small intestinal barrier integrity, and immune responses, as well as reducing both Ly6G mRNA (p < 0.05) and lipocalin-2 mRNA (p < 0.01) in the lungs. These data suggest ethanol-associated disruption of gut homeostasis influenced the health of the lungs, and that therapeutics supporting gut health may also support lung health. Full article

Pulmonary fibrosis results from the deposition and proliferation of extracellular matrix components in the lungs. Despite being an airway disorder, pulmonary fibrosis also has notable effects on the pulmonary vasculature, with the development and severity of pulmonary hypertension tied closely to patient mortality. Furthermore, the anatomical proximity of blood vessels, the alveolar epithelium, lymphatic tissue, and airway spaces highlights the need to identify shared pathogenic mechanisms and pleiotropic signaling across various cell types. Sensory nerves and their transmitters have a variety of effects on the various cell types within the lungs; however, their effects on many cell types and functions during pulmonary fibrosis have not yet been investigated. This review highlights the importance of gaining a new understanding of sensory nerve function in the context of pulmonary fibrosis as a potential tool to limit airway and vascular dysfunction. Full article

Currently, the treatment of malignant melanoma offers the longest and the most studied experience of innovative treatments in malignant pathology. The algorithm of the therapeutic decision in advanced or metastatic melanoma must comprise: the timing of the therapeutic initiation, the sequencing of the specific oncological treatment (radiotherapy and chemotherapy still being therapeutic alternatives in selected cases), the diagnosis and the management of adverse reactions. We present the case of a patient diagnosed with metastatic malignant melanoma in November 2019, who progressed successively under new systemic treatment throughout the 3 years of treatment and experienced skin reactions of various degrees of severity. The comprehensive response to secondary hilar pulmonary lymphatic determinations under subsequent chemotherapy was specific to the presented case. The occurrence of vitiligo secondary to immunotherapy is a favorable prognostic factor, but the occurrence of secondary cerebral determinations is an extremely severe prognostic factor in malignant melanoma and a challenge in making the therapeutic decision. Previous treatment with immune checkpoint inhibitors may trigger a favorable response to systemic chemotherapy. The early and accurate diagnosis of the adverse events of the new therapies requires a multidisciplinary approach, because it can radically change the therapeutic decision. Full article

Due to the rich vascularization and lymphatic drainage of the pulmonary tissue, lung metastases (LM) are not uncommon in patients with cancer. Radiomics is an active research field aimed at the extraction of quantitative data from diagnostic images, which can serve as useful imaging biomarkers for a more effective, personalized patient care. Our purpose is to illustrate the current applications, strengths and weaknesses of radiomics for lesion characterization, treatment planning and prognostic assessment in patients with LM, based on a systematic review of the literature. Full article

Occult micrometastases can be missed by routine pathological analysis. Mapping of the pulmonary lymphatic system by near-infrared (NIR) fluorescence imaging can identify the first lymph node relay. This sentinel lymph node (SLN) can be analyzed by immunohistochemistry (IHC), which may increase micrometastasis detection and improve staging. This study analyzed the feasibility and safety of identifying SLNs in thoracic surgery by NIR fluorescence imaging in non-small cell lung cancer (NSCLC). This was a prospective, observational, single-center study. Eighty adult patients with suspected localized stage NSCLC (IA1 to IIA) were included between December 2020 and May 2022. All patients received an intraoperative injection of indocyanine green (ICG) directly in the peri tumoural area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed using an infrared fluorescence camera. SLN was identified in 60 patients (75%). Among them, 36 SLNs associated with a primary lung tumor were analyzed by IHC. Four of them were invaded by micrometastases (11.1%). In the case of pN0 SLN, the rest of the lymphadenectomy was cancer free. The identification of SLNs in thoracic surgery by NIR fluorescence imaging seems to be a feasible technique for improving pathological staging. Full article

Background: Electromagnetic navigation bronchoscopy (ENB) and robotic-assisted bronchoscopy (RAB) systems are used for pulmonary lesion sampling, and utilize a pre-procedural CT scan where an airway, or “bronchus sign”, is used to map a pathway to the target lesion. However, up to 40% of pre-procedural CT’s lack a “bronchus sign” partially due to surrounding emphysema or limitation in CT resolution. Recognizing that the branches of the pulmonary artery, lymphatics, and airways are often present together as the bronchovascular bundle, we postulate that a branch of the pulmonary artery (“artery sign”) could be used for pathway mapping during navigation bronchoscopy when a “bronchus sign” is absent. Herein we describe the navigation success and safety of using the “artery sign” to create a pathway for pulmonary lesion sampling. Methods: We reviewed data on consecutive cases in which the “artery sign” was used for pre-procedural planning for conventional ENB (superDimension™, Medtronic) and RAB (Monarch™, Johnson & Johnson). Patients who underwent these procedures from July 2020 until July 2021 at the University of Minnesota Medical Center and from June 2018 until December 2019 at the University of Chicago Medical Center were included in this analysis (IRB #19-0011 for the University of Chicago and IRB #00013135 for the University of Minnesota). The primary outcome was navigation success, defined as successfully maneuvering the bronchoscope to the target lesion based on feedback from the navigation system. Secondary outcomes included navigation success based on radial EBUS imaging, pneumothorax, and bleeding rates. Results: A total of 30 patients were enrolled in this analysis. The median diameter of the lesions was 17 mm. The median distance of the lesion from the pleura was 5 mm. Eleven lesions were solid, 15 were pure ground glass, and 4 were mixed. All cases were planned successfully using the “artery sign” on either the superDimension™ ENB (n = 15) or the Monarch™ RAB (n = 15). Navigation to the target was successful for 29 lesions (96.7%) based on feedback from the navigation system (virtual target). Radial EBUS image was acquired in 27 cases (90%) [eccentric view in 13 (43.33%) and concentric view in 14 patients (46.66%)], while in 3 cases (10%) no r-EBUS view was obtained. Pneumothorax occurred in one case (3%). Significant airway bleeding was reported in one case (3%). Conclusions: We describe the concept of using the “artery sign” as an alternative for planning EMN and RAB procedures when “bronchus sign” is absent. The navigation success based on virtual target or r-EBUS imaging is high and safety of sampling of such lesions compares favorably with prior reports. Prospective studies are needed to assess the impact of the “artery sign” on diagnostic yield. Full article

Noonan syndrome (NS) is a multisystemic disorder caused by germline mutations in the Ras/MAPK cascade, causing a broad spectrum of phenotypical abnormalities, including abnormal facies, developmental delay, bleeding diathesis, congenital heart disease (mainly pulmonary stenosis and hypertrophic cardiomyopathy), lymphatic disorders, and uro-genital abnormalities. Multifocal atrial tachycardia has been associated with NS, where it may occur independently of hypertrophic cardiomyopathy. Trametinib, a highly selective MEK1/2 inhibitor currently approved for the treatment of cancer, has been shown to reverse left ventricular hypertrophy in two RIT1-mutated newborns with NS and severe hypertrophic cardiomyopathy. Severe lymphatic abnormalities may contribute to decreased pulmonary compliance in NS, and pulmonary lymphangiectasias should be included in the differential diagnosis of a newborn requiring prolonged oxygen administration. Herein we report the case of a pre-term newborn who was admitted to our unit for the occurrence of severe respiratory distress and subentrant MAT treated with trametinib. Full article

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, predominantly affecting the lung parenchyma and peripheral airways, that results in progressive and irreversible airflow obstruction. COPD development is promoted by persistent pulmonary inflammation in response to several stimuli (e.g., cigarette smoke, bacterial and viral infections, air pollution, etc.). Angiogenesis, the formation of new blood vessels, and lymphangiogenesis, the formation of new lymphatic vessels, are features of airway inflammation in COPD. There is compelling evidence that effector cells of inflammation (lung-resident macrophages and mast cells and infiltrating neutrophils, eosinophils, basophils, lymphocytes, etc.) are major sources of a vast array of angiogenic (e.g., vascular endothelial growth factor-A (VEGF-A), angiopoietins) and/or lymphangiogenic factors (VEGF-C, -D). Further, structural cells, including bronchial and alveolar epithelial cells, endothelial cells, fibroblasts/myofibroblasts, and airway smooth muscle cells, can contribute to inflammation and angiogenesis in COPD. Although there is evidence that alterations of angiogenesis and, to a lesser extent, lymphangiogenesis, are associated with COPD, there are still many unanswered questions. Full article

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is increasingly recognized as the consequence of a pathological reparative response of the developing lung to both antenatal and postnatal injury. According to this view, the pathogenesis of BPD is multifactorial and heterogeneous with different patterns of antenatal stress (endotypes) that combine with varying postnatal insults and might distinctively damage the development of airways, lung parenchyma, interstitium, lymphatic system, and pulmonary vasculature. This results in different clinical phenotypes of BPD. There is no clear consensus on which are the endotypes of prematurity but the combination of clinical information with placental and bacteriological data enables the identification of two main pathways leading to birth before 32 weeks of gestation: (1) infection/inflammation and (2) dysfunctional placentation. Regarding BPD phenotypes, the following have been proposed: parenchymal, peripheral airway, central airway, interstitial, congestive, vascular, and mixed phenotype. In line with the approach of personalized medicine, endotyping prematurity and phenotyping BPD will facilitate the design of more targeted therapeutic and prognostic approaches. Full article