Lymphatic Vessels Research Articles

Benign Tumors and Tumor-Like Conditions of Ampulla and Small Intestine: The PathologyOutlines.com Review.

Small intestine and ampulla can be involved in a heterogeneous group of benign tumors and tumor-like diseases, potentially mimicking malignant neoplasms. In-depth knowledge of them is critical for practicing pathologists since they represent potential pitfalls in routine diagnostic activity. Such conditions include the following: (1) Brunner gland lesions, including Brunner gland hyperplasia and hamartoma; (2) polyps, such as adenoma, hyperplastic, hamartomatous, and inflammatory; (3) mesenchymal proliferations encompassing inflammatory fibroid polyp, inflammatory myofibroblastic tumor, leiomyomas, lipomas, and lipomatosis of the ileocecal valve; (4) fibrosis-associated diseases, such as idiopathic retroperitoneal fibrosis, reactive nodular fibrous pseudotumor, and sclerosing peritonitis; (5) disorders of lymphatic vessels, including lymphangiectasia and lymphangiomas; and (6) other rare conditions/miscellanea, such as enteritis cystica profunda, intussusception, ischemia, and pneumatosis cystoides intestinalis. This review, inspired by the content of the PathologyOutlines website (https://www.pathologyoutlines.com), aims to provide a reference point in this complex scenario, summarizing the essential histopathological features of all these entities for better addressing routine practice and differential diagnoses.

Molecular Mechanism of lncRNAs in Regulation of Breast Cancer Metastasis; a Comprehensive Review.

Although the number of breast cancer deaths has decreased, and there have been developments in targeted therapies and combination treatments for the management of metastatic illness, metastatic breast cancer is still the second most common cause of cancer-related deaths in U.S. women. Numerous phases and a vast number of proteins and signaling molecules are involved in the invasion-metastasis cascade. The tumor cells penetrate and enter the blood or lymphatic vessels, and travel to distant organs via the lymphatic or blood vessels. Tumor cells enter cell cycle arrest, adhere to capillary beds in the target organ, and then disseminate throughout the organ's parenchyma, proliferating and enhancing angiogenesis. Each of these processes is regulated by changes in the expression of different genes, in which lncRNAs play a role in this regulation. Transcripts that are longer than 200 nucleotides and do not translate into proteins are called RNAs. LncRNA molecules, whose function depends on their unique molecular structure, play significant roles in controlling the expression of genes at various epigenetic levels, transcription, and so on. LncRNAs have essential functions in regulating the expression of genes linked to cell development in healthy and pathological processes, specialization, programmed cell death, cell division, invasion, DNA damage, and spread to other parts of the body. A number of cancer types have been shown to exhibit aberrant expression of lncRNAs. In this review, we describe the general characteristics, potential molecular mechanisms and targeted therapy of lncRNAs and discuss the emerging functions of lncRNAs in breast cancer.

Genomic landscape and preclinical models of angiosarcoma.

Angiosarcoma is a cancer that develops in blood or lymphatic vessels that presents a significant clinical challenge due to its rarity and aggressive features. Clinical outcomes have not improved in decades, highlighting a need for innovative therapeutic strategies to treat the disease. Genetically, angiosarcomas exhibit high heterogeneity and complexity with many recurrent mutations. However, recent studies have identified some common features within anatomic and molecular subgroups. To identify potential therapeutic vulnerabilities, it is essential to understand and integrate the mutational landscape of angiosarcoma with the models that exist to study the disease. In this review, we will summarize the insights gained from reported genomic alterations in molecular and anatomic subtypes of angiosarcoma, discuss several potential actionable targets, and highlight the preclinical disease models available in the field.

Multi-parameter tunable synthetic matrix for engineering lymphatic vessels

Controlling the formation of new lymphatic vessels has been postulated as an innovative therapeutic strategy for various disease phenotypes, including neurodegenerative diseases, metabolic syndrome, cardiovascular disease, and lymphedema. Yet, compared to the blood vascular system, little is known about the molecular regulation that controls lymphatic tube formation in a synthetic matrix. In this study, we utilize hyaluronic acid (HA)-hydrogels to design a novel platform for decoupled investigation into how mechanical and biochemical cues regulate lymphatic vessel formation in a synthetic matrix. Using HA and controlling the degree of modification provides a method to preserve and modulate key lymphatic markers Prox1, LYVE-1, and Pdpn. The chemistry of the system allows for spatial and temporal patterning of specific peptides and substrate stiffnesses, and an MMP-sensitive crosslinker allowed cells to degrade and remodel their matrix. Through systematic optimization of multiple parameters, we have designed a system that allows human lymphatic endothelial cells (LECs) to self-assemble into vessels in vitro within 3 days. These engineered vessels can be cultured for up to 3 weeks and can be used for high-throughput mechanistic studies, or can be implanted into immunodeficient mice where they have demonstrated the ability to integrate and mature. Collectively, these studies report a novel, fully-defined 3D synthetic matrix system capable of generating lymphatic vessels in vitro that provide promise as an in vitro screening platform and as a therapeutic vessel transplant, which to our knowledge, is the first ever 3D lymphatic tissue engineering approach to not require the use of support cells.

Enhanced lymphangiogenesis in the left lateral segment of a biopsied liver during portoenterostomy for biliary atresia

PurposeWe investigate the histopathology of the portal vein branches and lymphatic vessels to elucidate the mechanism of atrophy of the left lateral segment (LLS) of the liver in biliary atresia (BA).MethodsLLS and right anterior segment (RAS) liver biopsy samples obtained during Kasai portoenterostomy (KPE) from ten consecutive patients with BA underwent histopathological investigation of the portal vein and lymphatic vessels using double chromogenic immunostaining for CD31/D2-40 and the hepatitis-like findings (HLF) score. Each parameter and clinical data were compared between prognostic groups.ResultsHLF scores in the LLS were always higher than those in the RAS. There was no difference in portal vein and lymphatic vascular morphology, whereas the number of lymphatic vessels was correlated with the fibrotic area of all specimen areas. Left-to-right ratio of the number of lymphatic vessels was correlated with the age at KPE (r = 0.784, p = 0.007) and the pre-KPE CRP value (r = 0.723, p = 0.018).ConclusionsLymphangiogenesis on the LLS compared to the RAS was significantly correlated with the degree of fibrosis and the age at KPE. Further investigation is warranted to clarify the causes of LLS atrophy and lymphangiogenesis relevant to immune dysregulation.

Characterization of the cellular components of mouse collecting lymphatic vessels reveals that lymphatic muscle cells are the innate pacemaker cells regulating lymphatic contractions.

Collecting lymphatic vessels (cLVs) exhibit spontaneous contractions with a pressure-dependent frequency, but the identity of the lymphatic pacemaker cell is still debated. By analogy to pacemakers in the GI and lower urinary tracts, proposed cLV pacemaker cells include interstitial cells of Cajal like cells (ICLC) or the lymphatic muscle (LMCs) cells themselves. Here we combined immunofluorescence and scRNAseq analyses with electrophysiological methods to examine the cellular constituents of the mouse cLV wall and assess whether any cell type exhibited morphological and functional processes characteristic of pacemaker cells: a continuous if not contiguous network integrated into the electrical syncytium; spontaneous Ca2+ transients; and depolarization-induced propagated contractions. We employed inducible Cre (iCre) mouse models routinely used to target these specific cell populations including: c-kitCreER T2 to target ICLC; PdgfrβCreER T2 to target pericyte-like cells; PdgfrαCreER ™ to target CD34+ adventitial cells and ICLC; and Myh11CreER T2 to target LMCs directly. These specific inducible Cre lines were crossed to the fluorescent reporter ROSA26mT/mG, the genetically encoded Ca2+ sensor GCaMP6f, and the light-activated cation channel rhodopsin2 (ChR2). c-KitCreER T2 labeled both a sparse population of LECs and round adventitial cells that responded to the mast cell activator compound 48-80. PdgfrβCreER T2 drove recombination in both adventitial cells and LMCs, limiting its power to discriminate a pericyte-specific population. PdgfrαCreER ™ labeled a large population of interconnected, oak leaf-shaped cells primarily along the adventitial surface of the vessel. Of these cells, only LMCs consistently, but heterogeneously, displayed spontaneous Ca2+ events during the diastolic period of the contraction cycle, and whose frequency was modulated in a pressure-dependent manner. Optogenetic depolarization through the expression of ChR2 under control of Myh11CreER T2 , but not PdgfrαCreER ™ or c-KitCreER T2 , resulted in propagated contractions upon photo-stimulation. Membrane potential recordings in LMCs demonstrated that the rate of diastolic depolarization significantly correlated with contraction frequency. These findings support the conclusion that LMCs, or a subset of LMCs, are responsible for mouse cLV pacemaking.

Disease-Specific Alteration of Cardiac Lymphatics: A Review from Animal Disease Models to Clinics.

For many years, the significance of cardiac lymphatic vessels was largely overlooked in clinical practice, with little consideration given to their role in the pathophysiology or treatment of cardiac diseases. However, recent research has brought renewed attention to these vessels, progressively illuminating their function and importance within the realm of cardiovascular science. Experimental studies, particularly those utilizing animal models of cardiac disease, have demonstrated a clear relationship between cardiac lymphatic vessels and both the pathogenesis and progression of these conditions. These findings have prompted a growing interest in potential therapeutic applications that specifically target the cardiac lymphatic system. Conversely, while clinical investigations into cardiac lymphatics remain limited, recent studies have begun to explore their identification through specific surface markers, as well as the expression dynamics of lymphangiogenic factors. These studies have increasingly highlighted associations of lymphatic dysfunction with inflammation and fibrosis, both of which negatively impact cardiac function and remodeling across various pathological states. Despite these advances, comprehensive reviews of the current knowledge regarding the cardiac lymphatic vasculature, particularly within specific disease contexts, remain scarce. This review aims to address this gap by providing a detailed synthesis of existing reports, encompassing both animal model research and studies on human clinical specimens, with a special focus on the role of cardiac lymphatic vessels in different disease states.

Cell-cell contact-dependent secretion of large-extracellular vesicles from EFNBhigh cancer cells accelerates peritoneal dissemination.

Large non-apoptotic vesicles released from the plasma membrane protrusions are classified as large-EVs (LEVs). However, the triggers of LEV secretion and their functions in tumors remain unknown. Coculture system of cancer cells, peritoneal mesothelial cells (PMCs), and macrophages (MΦs) was conducted to observe cell-cell contact-mediated LEV secretion. Lineage tracing of PMCs was performed using Wt1CreERT2-tdTnu mice to explore the effects of LEVs on PMCs in vivo, and lymphangiogenesis was assessed by qRT-PCR and flow-cytometry. In peritoneal dissemination, cancer cells expressing Ephrin-B (EFNB) secreted LEVs upon the contact with PMCs expressing ephrin type-B (EphB) receptors, which degraded mesothelial barrier by augmenting mesothelial-mesenchymal transition. LEVs were incorporated in subpleural MΦs, and these MΦs transdifferentiated into lymphatic endothelial cells (LEC) and integrated into the lymphatic vessels. LEC differentiation was also induced in PMCs by interacting with LEV-treated MΦs, which promoted lymphangiogenesis. Mechanistically, activation of RhoA-ROCK pathway through EFNB reverse signaling induced LEV secretion. EFNBs on LEVs activated EphB forward signaling in PMC and MΦs, activating Akt, ERK and TGF-β1 pathway, which were indispensable for causing MMT and LEC differentiation. LEVs accelerated peritoneal dissemination and lymphatic invasions by cancer cells. Blocking of EFNBs on LEVs using EphB-Fc-fusion protein attenuated these events. EFNBhigh cancer cells scattered LEVs when they attached to PMCs, which augmented the local reactions of PMC and MΦ (MMT and lymphangiogenesis) and exaggerated peritoneal dissemination.

Rare Yet Relevant: Adult Onset Cervical Lymphangioma - Our Experience and Comprehensive Review.

Cervical lymphangiomas are anomalies that arise from lymphatic vessels, characterized by gradual and painless growth. While predominantly located in the neck, they may also manifest in the axilla, mediastinum, groin, and abdominal organs. Cervical lymphangioma usually occurs in children and is relatively rare in adults. The purpose of this study was to investigate the characteristics of cervical lymphangiomas in adults. We reviewed the medical records and analysed clinical data obtained from fifteen adult patients who suffered from cervical lymphangioma and were operated from January 2021 to January 2023. Out of 15 cases, 73.3% were females and 26.7% were males. All tumours were unilaterally located. Five patients had prior history of associated dyspnoea / dysphagia. All 15 cervical lymphangiomas (100%) were adjacent to the carotid sheath .Tumour size ranged from 6cm to 15cm, with the maximum diameter of ≥ 15cm in two cases, between 6cm and 10cm in eight cases and less than 6cm in five cases. Further, in this study all cervical lymphangiomas were surgically excised. Postoperative courses were uneventful, and histo-pathological examinations confirmed all cases to be cystic lymphangiomas. A 6 -month follow-up in all 15 cases showed no recurrences. Overall, this study underscores the importance of a multidisciplinary approach involving clinicians, radiologists, and surgeons in the management of adult cervical lymphangiomas, with an emphasis on accurate diagnosis, appropriate classification, and tailored treatment strategies to optimize patient outcomes and minimize complications.

A New Approach to Ultra-Low Anterior Resection-Intersphincteric Dissection With Total Hiatal Ligament Excision for Very Low Rectal Cancer Located in the Posterior Wall of the Rectum: A More Satisfactory Technique for Local Recurrence Control.

The hiatal ligament, as the anatomical landmark for the completion of total mesorectal excision (TME) for ultra-low rectal cancer, represents a continuation of the longitudinal muscle of the rectum. It receives vascular supply from the median sacral artery and contains lymphatic vessels. In cases where ultra-low rectal cancer is located in the posterior rectal wall, the hiatal ligament may theoretically serve as an anatomical region susceptible to direct tumor cell spread or distant metastasis. To evaluate the effect of circumferential tumor location (CTL) on postoperative survival of low rectal cancer and to determine the effect of total hiatal ligament excision (THLE) on the prognosis of patients with posterior rectal cancer. Patients with ultra-low rectal cancer who underwent laparoscopic surgery between March 2014 and October 2021 were enrolled in this study. Propensity score matching (PSM) analysis was used to compare the clinicopathological characteristics and prognosis of patients in the posterior group and the non-posterior group. Prognostic factors were identified using COX regression. PSM analysis was also used in the posterior tumor subgroup to compare the clinicopathological characteristics and prognosis of patients in the hiatal ligament traditional transection (HLTT) and THLE groups. After PSM, OS, and DFS were comparable between the posterior and non-posterior groups. Similarly, no difference was noted in the local recurrence rate between the two groups (p = 0.23). The prognosis of ultra-low rectal cancer was not affected by CTL. However, the local recurrence rate was significantly lower in the THLE group compared with the HLTT group (p = 0.023). Multivariate analysis of the posterior group identified CRM, TNM stage III, and HLTT as independent risk factors for local recurrence-free survival. CTL is not a prognostic risk factor for low rectal cancer. In posterior wall tumors, THLE significantly reduces the local recurrence rate for low rectal cancer.

Glucocorticoid Receptor Signaling Is Critical for Mouse Corneal Development, Inhibition of Inflammatory Response, and Neovascularization of the Cornea

The cornea protects the interior of the eye from external agents such as bacteria, viruses, and debris. Synthetic glucocorticoids are widely prescribed in the treatment of ocular infections and disorders. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR); however, the molecular and physiological functions of GR signaling in the cornea are poorly understood. This study found that treatment of mice with glucocorticoid eye drops led to a profound regulation of the corneal transcriptome. These glucocorticoid-regulated genes were associated with multiple biological functions, including the immune response. To understand the direct role of GR signaling in the cornea, mice with conditional knockout of GRs in the corneal epithelium were generated. Mice lacking corneal GRs exhibited microphthalmia, loss of pupils, a deformed and opaque lens, and mislocalization of key structural proteins within the corneal epithelial layers. Global transcriptomic approaches revealed that loss of GR signaling in the cornea also resulted in the dysregulation of a large cohort of genes strongly associated with an enhanced inflammatory response. Finally, corneal GR signaling was required for preventing neovascularization of blood and lymphatic vessels and thereby immune cell infiltration of the cornea. These results reveal that corneal GR signaling plays a critical role in ocular development and in maintaining the homeostasis of the eye.

LYVE1 Ectodomain Shedding Promotes Renal Interstitial Retention of Macrophages Cleared by Lymphatic Vessels and Kidney Fibrosis

LYVE1 Ectodomain Shedding Promotes Renal Interstitial Retention of Macrophages Cleared by Lymphatic Vessels and Kidney Fibrosis

The Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain.

The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain. We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis. Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures. The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.

The“Overlapping”Lymphaticovenous Anastomosis: an overlapped end-to-end anastomosis supermicrosurgical technique

ObjectiveLymphaticovenular anastomosis (LVA) is increasingly utilized in the treatment of lymphedema. This study aims to assess the efficacy and safety of the “Overlapping” LVA technique, which addresses the size mismatch between lymphatic and venous vessels in lymphedema treatment.MethodsBetween August 2022 and April 2023, seventeen patients diagnosed with lymphedema were enrolled in this study. The severity of lymphedema in these patients was classified according to the International Society of Lymphology (ISL) staging system.All patient underwent LVA procedures, anastomosis techniques including the Overlapping, end-to-end and octopus anastomosis. The techniques of anastomosis, anastomosis time, patency rate, and volume of limb lymphedema were evaluated.ResultsOur study enrolled 17 lymphedema patients who underwent the LVA procedure. All patients showed significant postoperative improvement in limb edema. The mean drainage volume was 472.29 ml. The Overlapping technique demonstrated a 100% success rate as assessed by clinical observation and intraoperative Indocyanine Green (ICG) lymphography. The average anastomosis time was 5.3 min, reducing operative time compared to traditional methods.ConclusionsThese findings suggest that the Overlapping technique could serve as a valuable addition to the current LVA technique. This Overlapping anastomosis technique provides a wide range of applications for lymphatic anastomosis treatment and prevention of lymphedema.

Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151.

Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre-metastatic "niches" in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high-resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue-derived EVs to identify a novel subset of tumour-derived EVs that contain integrin α6 (ITGA6+EVs) and revealed the positive correlation of ITGA6+EVs with the formation of pre-metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820-case BCa patients. BCa-derived ITGA6+EVs induced E-selectin (SELE)-marked lymphatic remodelling pre-metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA-LIPAR to lymphatic endothelial cells in vivo and in vitro. Mechanistically, LIPAR linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP-bound activated state, thus maintaining the production of ITGA6+EVs loaded with LIPAR through endosomal trafficking. ITGA6+EVs targeted lymphatic vessels through ITGA6-CD151 interplay and released LIPAR to induce SELE overexpression-marked lymphatic remodelling pre-metastatic niche. Importantly, we constructed engineered-ITGA6 EVs to inhibit lymphatic pre-metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa-derived ITGA6+EVs mediating pre-metastatic niche and provides an engineered-EV-based strategy against BCa lymphatic metastasis.

Matrix Stiffness of GelMA Hydrogels Regulates Lymphatic Endothelial Cells toward Enhanced Lymphangiogenesis.

Lymphatic vessel regeneration is crucial for various tissue engineering strategies, particularly in resolving inflammation and restoring tissue homeostasis. In our study, we focused on investigating how hydrogel matrix stiffness influences lymphatic endothelial cells (LECs) in promoting lymphatic vessel regeneration. Gelatin methacrylate (GelMA) was chosen as our biomaterial due to its versatility in tissue engineering and biofabrication. We fabricated GelMA hydrogels at concentrations of 5, 7.5, and 15% (w/v) with corresponding Young's modulus values of 1.55 kPa (soft matrix), 12.02 kPa (medium matrix), and 48.50 kPa (stiff matrix). Among these, the 7.5% GelMA hydrogel exhibited optimal stiffness for promoting lymphangiogenesis. LECs seeded either on the hydrogel surface or within spontaneously formed a more stable lymphatic capillary network compared with other GelMA formulations. Furthermore, we investigated the enhancement of lymphangiogenesis by incorporating VEGF-C into the GelMA hydrogel, leveraging the synergistic effects of mechanical and chemical cues. Our results underscored the critical role of FAK-phosphorylation in this process; treatment with an FAK-specific inhibitor prevented the formation of tube-like structures by LECs and attenuated the expression of lymphatic markers. Overall, our findings highlight how the mechanical and chemical cues provided by GelMA hydrogels can effectively regulate LEC behavior toward enhanced lymphangiogenesis via the integrin/FAK mechanotransduction pathway. This study proposes a promising strategy for developing hydrogel-based scaffolds or bioinks tailored to promote lymphatic vessel regeneration in therapeutic applications.

Understanding The Role Of Exercise In Lymphatic Vessel Regulation In Melanoma

Understanding The Role Of Exercise In Lymphatic Vessel Regulation In Melanoma

The lymphatic vessels of the liver observed by Frederik Ruysch.

The lymphatic vessels of the liver observed by Frederik Ruysch.

Lymphatic Fistula Treatment: Indocyanine Green Lymphography-guided Microsurgery

Background: Lymphatic fistulas are a common complication from surgery or interventional procedures resulting in persistent lymphatic leakage and delayed wound healing. The management of lymphatic fistula remains a subject of debate, ranging from conservative treatment to surgical lymphatic ligation. The implementation of a novel microsurgical approach involving lymphatic fistula ligation and/or lymphovenous anastomosis (LVA) using indocyanine green (ICG) lymphography is expected to decrease occurrence and complications. In this study, we share our experience in treating lymphatic fistula–guided microsurgical treatment. Methods: A total of 13 patients from our hospital with persistent lymphatic fistula were enrolled in this retrospective study. Lymphatic fistulas and their leakages were identified and ligated by using ICG lymphography and a surgical microscope. In two cases, additional LVA surgery was performed. Results: We were able to precisely identify lymphatic fistulas and treat them in all 13 patients. Lymph ligation was performed in all 13 cases, with additional distal LVA in two cases. In all patients, wound healing occurred following lymphatic ligation, except in one patient due to persistent infection. Patients with a lymphatic fistula were referred to our unit within 3 weeks to 1 year after onset, with an average consultation occurring after 5 months of persistent lymphatic fistula. Conclusions: Targeted lymphatic vessel ligation with or without LVA with ICG-guided surgical microscope represents a promising highly efficacious therapy for persistent lymphatic fistula. This technique may accelerate wound healing and reduce hospitalization duration, thus advocating for its preferential use in managing lymphatic fistulas.

The Lymphatic Highway: How Lymphatics Drive Lung Health and Disease.

The pulmonary lymphatic system has emerged as a critical regulator of lung homeostasis and a key contributor to the pathogenesis of respiratory diseases. As the primary conduit responsible for maintaining fluid balance and facilitating immune cell trafficking, the integrity of lymphatic vessels is essential for preserving normal pulmonary structure and function. Lymphatic abnormalities manifest across a broad spectrum of pulmonary disorders, underscoring their significance in respiratory health and disease. This review provides an overview of pulmonary lymphatic biology and delves into the involvement of lymphatics in four major lung diseases: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung transplant rejection. We examine how lymphatic abnormalities manifest in each of these conditions and investigate the mechanisms through which lymphatic remodeling and dysfunction contribute to disease progression. Furthermore, we explore the therapeutic potential of targeting the lymphatic system to ameliorate these debilitating respiratory conditions. Despite the current knowledge, several crucial questions remain unanswered, such as the spatial and temporal dynamics of lymphatic changes, the molecular crosstalk between lymphatics and the lung microenvironment, and the distinction between protective versus detrimental lymphatic phenotypes. Unraveling these mysteries holds the promise of identifying novel molecular regulators, characterizing lymphatic endothelial phenotypes, and uncovering bioactive mediators. By harnessing this knowledge, we can pave the way for the development of innovative disease-modifying therapies targeting the lymphatic highway in lung disorders.