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Frontiers in Immunology 2022Lymphatic vasculature is a network of capillaries and vessels capable of draining extracellular fluid back to blood circulation and to facilitate immune cell migration....
Lymphatic vasculature is a network of capillaries and vessels capable of draining extracellular fluid back to blood circulation and to facilitate immune cell migration. Although the role of the lymphatic vasculature as coordinator of fluid homeostasis has been extensively studied, the consequences of abnormal lymphatic vasculature function and impaired lymph drainage have been mostly unexplored. Here, by using the mice with defective lymphatic vasculature and lymphatic leakage, we provide evidence showing that lymph leakage induces an immunosuppressive environment by promoting anti-inflammatory M2 macrophage polarization in different inflammatory conditions. In fact, by using a mouse model of tail lymphedema where lymphatic vessels are thermal ablated leading to lymph accumulation, an increasing number of anti-inflammatory M2 macrophages are found in the lymphedematous tissue. Moreover, RNA-seq analysis from different human tumors shows that reduced lymphatic signature, a hallmark of lymphatic dysfunction, is associated with increased M2 and reduced M1 macrophage signatures, impacting the survival of the patients. In summary, we show that lymphatic vascular leakage promotes an immunosuppressive environment by enhancing anti-inflammatory macrophage differentiation, with relevance in clinical conditions such as inflammatory bowel diseases or cancer.
Topics: Anti-Inflammatory Agents; Humans; Immunosuppression Therapy; Lymphatic Vessels; Lymphedema; Macrophages
PubMed: 35663931
DOI: 10.3389/fimmu.2022.841641 -
Nature Reviews. Endocrinology Dec 2021
Topics: Humans; Insulin Resistance; Obesity
PubMed: 34663931
DOI: 10.1038/s41574-021-00588-w -
Immunity Dec 2021Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn's disease. Here, we examined the genesis of these TLOs and their...
Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn's disease. Here, we examined the genesis of these TLOs and their impact on disease progression. Whole-mount and intravital imaging of the ileum and ileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodes from TNF mice, a model of ileitis, revealed TLO formation at valves of CLVs. TLOs obstructed cellular and molecular outflow from the gut and were sites of lymph leakage and backflow. Tumor necrosis factor (TNF) neutralization begun at early stages of TLO formation restored lymph transport. However, robustly developed, chronic TLOs resisted regression and restoration of flow after TNF neutralization. TNF stimulation of cultured lymphatic endothelial cells reprogrammed responses to oscillatory shear stress, preventing the induction of valve-associated genes. Disrupted transport of immune cells, driven by loss of valve integrity and TLO formation, may contribute to the pathology of Crohn's disease.
Topics: Animals; Cell Movement; Cells, Cultured; Crohn Disease; Disease Models, Animal; Endothelial Cells; Humans; Ileitis; Ileum; Lymph; Lymphangitis; Lymphatic Vessels; Mesentery; Mice; Mice, Knockout; Stress, Mechanical; Tertiary Lymphoid Structures; Tumor Necrosis Factor-alpha
PubMed: 34788601
DOI: 10.1016/j.immuni.2021.10.003 -
The Breast Journal May 2018
Review
Topics: Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Chyle; Drainage; Female; Humans; Lymph Node Excision; Lymph Nodes; Male; Mastectomy; Middle Aged; Postoperative Care; Postoperative Complications
PubMed: 29063644
DOI: 10.1111/tbj.12934 -
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke... Aug 2019To analyze the clinical characteristics, treatment and prognosis of chyle leakage after central lymph node dissection for thyroid cancer. A retrospective analysis was...
To analyze the clinical characteristics, treatment and prognosis of chyle leakage after central lymph node dissection for thyroid cancer. A retrospective analysis was made of 985 patients who underwent surgical for thyroid carcinoma plus central lymph node dissection from January 2017 to June 2018 in Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University. Patients were divided into those without (group A, 973) and with (group B, 12) chyle leakage. Patients with chyle leakage who underwent left central lymph node dissection were divided into group B1 (5) and right central lymph node dissection into group B2 (7). Patients with chyle leakage were treated with fat-free diet and negative pressure drainage. SPSS 20.0 software was used to analyze the general condition, surgical pathology, postoperative drainage, hospitalization days, treatment and prognosis of patients in B1 and B2 groups. The incidence of chyle leakage after central lymph node dissection for thyroid cancer was 1.2% (12/985). There were no significant differences in age, sex, size of primary lesion, number of lymph node dissection in central area and number of lymph node metastasis in central area between group A and group B (all 0.05). The drainage volume on the first day after operation [((51.7±26.7)) ml] and the average hospitalization days [(3.4±0.8) d] in group A were significantly lower than those in group B ([131.3±56.0)]ml, [10.4±2.6)]d). The differences were statistically significant ( value was -5.442, -11.238, respectively, both 0.001). There were no significant differences in age, size of primary lesion, number of lymph node dissection, number of lymph node metastasis, drainage volume on the first day after operation and average hospitalization days between group B1 and group B2 (all 0.05). All chyle leakages in group B stopped after conservative management without surgical intervention. The occurrence of chyle leakage after central lymph node dissection is a rare complication. It can be cured by conservative treatment such as diet control, pressure bandaging and negative pressure drainage, and generally does not require secondary surgery.
Topics: China; Chyle; Humans; Lymphatic Diseases; Lymphatic System; Neck Dissection; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy
PubMed: 31434373
DOI: 10.3760/cma.j.issn.1673-0860.2019.08.007 -
Oncotarget Sep 2017Lymphatic complications are rare, but well-known phenomena, and have been described by many researchers. However, many diagnoses of lymphatic complications are found... (Review)
Review
Lymphatic complications are rare, but well-known phenomena, and have been described by many researchers. However, many diagnoses of lymphatic complications are found confusing due to different definition. A literature search in Pubmed was performed for studies postoperative lympatic complications. These complications divided into two parts: lymphatic leakage and lymphatic stasis. This review is about lymphatic leakage, especially, postoperative lymphatic leakage due to the injury of lymphatic channels in surgical procedures. According to polytrophic consequences, many types of postoperative lymphatic leakage have been presented, including lymph ascites, lymphocele, lymphorrhea, lymphatic fistula, chylous ascites, chylothorax, chyloretroperitoneum and chylorrhea. In this review, we focus on the definition, incidence and treatment about most of these forms of lymphatic complications to depict a comprehensive view of postoperative lymphatic leakage. We hold the idea that the method of treatment should be individual and personal according to manifestation and tolerance of patient. Meanwhile, conservative treatment is suitable and should be considered first.
PubMed: 28978181
DOI: 10.18632/oncotarget.17297 -
Academic Radiology Apr 1995Disturbances in blood capillary exchange of fluid, macromolecules, and cells across intact and abnormal microvessels and deranged lymphatic transport are integral,... (Review)
Review
Disturbances in blood capillary exchange of fluid, macromolecules, and cells across intact and abnormal microvessels and deranged lymphatic transport are integral, interacting components in disorders of tissue swelling. Lymphedema or low-output failure of the lymph circulation is often indolent for many years before lymphatic insufficiency (failure) and tissue swelling emerge and persist. Superimposed occult or overt infection (lymphangitis) are probably major contributors to progressive limb deformity (elephantiasis). Long-standing lymphedema is characterized by trapping in the skin and subcutaneous tissue of fluid, extravasated plasma proteins, and other macromolecules: impaired immune cell trafficking; abnormal processing of autologous and foreign antigens; heightened susceptibility to superimposed infection; local immunodysregulation; defective lymphatic (lymphangion) propulsion from an imbalance of mediators regulating vasomotion; soft-tissue overgrowth; scarring and hypertrophy; and exuberant angiogenesis occasionally culminating in vascular tumors (Fig. 8). In contrast to the blood circulation, where flow depends primarily on the propulsive force of the myocardium, lymph propulsion depends predominately on intrinsic truncal contraction, a phylogenetic vestige of amphibian lymph hearts. Whereas venous "plasma" flows rapidly (2-3 l/min) against low vascular resistance, lymph flows slowly (1-2 ml/min) against high vascular resistance. On occasion, impaired transport of intestinal lymph may be associated with reflux and accumulation and leakage of intestinal chyle in a swollen leg. Although the term "lymphedema" is usually reserved for extremity swelling, the pathogenesis of a wide variety of visceral disorders also may be traceable to defective tissue fluid and macromolecular circulation and impaired cell trafficking of lymphocytes and macrophages. Thus, lymph stasis, with impaired tissue fluid flow, underlies or complicates an indolent subclinical course with a long latent period and sporadic episodes of lymphangitis, which culminates in intense scarring. Examples are pulmonary fibrosis (e.g., pneumoconiosis), regional enteritis, retroperitoneal fibrosis, and perhaps chronic pancreatitis and cirrhosis of the liver. Transdifferentiation and ultimately transformation of endothelial and other vascular accessory cells during lymph stasis also may be pivotal to a wide range of dysplastic and neoplastic vascular disorders, including Stewart-Treves angiosarcoma, AIDS-associated Kaposi's sarcoma, and lymphangitic metastatic carcinomatosis. Lymphscintigraphy has now replaced conventional lymphography as the procedure of choice to corroborate the diagnosis of peripheral lymphedema, whereas MR imaging using paramagnetic and superparamagnetic contrast agents has the potential to yield huge dividends in furthering understanding of a variety of enigmatic edematous states, including lymphedema. Not only are better explanations and insights into swelling disorders likely to be forthcoming, but, equally important, these new, safe, noninvasive imaging techniques can and should be used to monitor the evolution and document the efficacy of commonly advocated operations and nonoperative remedies for defective lymph transport and function.
Topics: Diagnostic Imaging; Humans; Lymph; Lymphatic Diseases; Lymphatic System
PubMed: 9419570
DOI: 10.1016/s1076-6332(05)80193-x -
European Journal of Pharmaceutics and... Nov 2022Dietary lipids, highly lipophilic drugs, antigens and immune cells are transported from the intestine to the mesenteric lymph nodes (MLNs) via mesenteric lymphatic...
Dietary lipids, highly lipophilic drugs, antigens and immune cells are transported from the intestine to the mesenteric lymph nodes (MLNs) via mesenteric lymphatic vessels. Recently our lab reported that the mesenteric lymphatic vessels become highly branched and leak lymph to the surrounding mesenteric adipose tissue (MAT) in mice and humans with obesity, promoting insulin resistance. This study aimed to investigate the impact of obesity-associated mesenteric lymph leakage on the trafficking of a dietary lipid (oleic acid), lipophilic drug (cyclosporin A) and antigen (ovalbumin) from the intestine to MLNs. C57BL/6J mice were fed a control fat diet (CFD), or a high fat diet (HFD) for up to 35 weeks leading to obesity and impaired glucose tolerance. C-oleic acid, H-cyclosporin or Cy5.5-ovalbumin were administered orally, and blood plasma and tissues collected to measure radioactivity or fluorescence levels. The accumulation of C-oleic acid, H-cyclosporin and Cy5.5-ovalbumin in MAT was significantly increased in HFD compared to CFD fed mice, whereas in the MLNs there was less accumulation (H-cyclosporin and Cy5.5-ovalbumin) or no significant difference (for C-oleic acid). The mass ratio of these molecules in MLNs compared to MAT was thus significantly decreased. Obesity-associated mesentery lymph leakage appears to divert dietary lipids, lipophilic drugs and antigens away from their normal lymphatic trafficking pathways from the intestine to MLNs and instead results in leakage into MAT. This is likely to contribute to known detrimental changes to lipid metabolism, immunotherapy and mucosal immunity in obesity.
Topics: Humans; Mice; Animals; Ovalbumin; Oleic Acid; Mice, Inbred C57BL; Mesentery; Lymph Nodes; Obesity; Intestines; Cyclosporins
PubMed: 36283633
DOI: 10.1016/j.ejpb.2022.10.019 -
Langenbeck's Archives of Surgery Aug 2020Lymphatic complications occur frequently after radical inguinal lymph node dissection (RILND). The incidence of lymphatic leakage varies considerably among different...
PURPOSE
Lymphatic complications occur frequently after radical inguinal lymph node dissection (RILND). The incidence of lymphatic leakage varies considerably among different studies due to the lack of a consistent definition. The aim of the present study is to propose a standardized definition and grading of different types of lymphatic leakage after groin dissection.
METHODS
A bicentric retrospective analysis of 82 patients who had undergone RILND was conducted. A classification of postoperative lymphatic leakage was developed on the basis of the daily drainage output, any necessary postoperative interventions and reoperations, and any delay in adjuvant treatment.
RESULTS
In the majority of cases, RILND was performed in patients with inguinal metastases of malignant melanoma (n = 71). Reinterventions were necessary in 15% of the patients and reoperations in 32%. A new classification of postoperative lymphatic leakage was developed. According to this definition, grade A lymphatic leakage (continued secretion of lymphatic fluid from the surgical drains without further complications) occurred in 13% of the patients, grade B lymphatic leakage (persistent drainage for more than 10 postoperative days or the occurrence of a seroma after the initial removal of the drain that requires an intervention) in 28%, and grade C lymphatic leakage (causing a reoperation or a subsequent conflict with medical measures) in 33%. The drainage volume on the second postoperative day was a suitable predictor for a complicated lymphatic leakage (grades B and C) with a cutoff of 110 ml.
CONCLUSION
The proposed definition is clinically relevant, is easy to employ, and may serve as the definition of a standardized endpoint for the assessment of lymphatic morbidity after RILND in future studies.
Topics: Adult; Aged; Aged, 80 and over; Drainage; Female; Humans; Inguinal Canal; Lymph Node Excision; Lymphatic Metastasis; Lymphocele; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Severity of Illness Index
PubMed: 32816115
DOI: 10.1007/s00423-020-01927-7 -
Annali Italiani Di Chirurgia 2020To explore the treatment strategies of chylous leakage after dissection of central lymph nodes in thyroid cancer.
OBJECTIVE
To explore the treatment strategies of chylous leakage after dissection of central lymph nodes in thyroid cancer.
METHODS
Patients with chylous leakage after dissection of central lymph nodes in thyroid cancer were recruited in this study. All participants adopted a conservative treatment method of external fixation of neck brace + cotton ball packing and compression bandage + adequate negative pressure drainage and assisted low-fat diet.
RESULTS
A total of two patients were included in this study. The results showed that the drainage rate of these two patients was reduced to less than 10 ml after 1-2 days of drainage. The maintenance treatment was continued for 10 days. The drainage volume of the patient did not increase during the three days after returning to normal diet. There was no recurrence of posterior lymphatic leakage.
CONCLUSION
External fixation of neck brace + cotton ball packing and compression bandage + adequate negative pressure drainage is important for the treatment of mild to moderate chylotrhea after thyroid cancer surgery which was worthy of clinical application.
KEY WORDS
Chylous leakage; Dissection of lymph nodes; Thyroid cancer; External fixation of neck brace; Postoperative complication.
Topics: Chyle; Drainage; Humans; Lymph Nodes; Neck Dissection; Thyroid Neoplasms
PubMed: 33554938
DOI: No ID Found