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Lymphatic Research and Biology Feb 2021It has now been ∼20 years since the original Lymphatic Continuum conference was convened, and this continuum has transitioned from a compelling concept to a reality....
It has now been ∼20 years since the original Lymphatic Continuum conference was convened, and this continuum has transitioned from a compelling concept to a reality. The explosive growth in our comprehension of lymphatic genetics, development, and function has expanded and modified our traditional views regarding what is, and is not, lymphatic disease. Groundbreaking investigations over the past decade have now defined a large and growing list of pathological conditions in which morphological or function lymphatic alterations can be identified. This list includes atherosclerosis and dyslipidemia, hypertension and other cardiovascular diseases, inflammation and inflammatory bowel disease, obesity, narrow angle glaucoma, and, most recently and compellingly, neurodegenerative disease. The sometimes overlapping but largely disparate nature of these various aforementioned disease categories suggests that the presence, or absence, of structural or functional lymphatic derangements may represent a previously unrecognized unifying influence in the maintenance of health and the promotion of disease. Future investigation of lymphatic mechanisms in disease will likely continue to elucidate the influences of lymphatic dysfunction, perhaps subtle, that can invest other, seemingly unrelated, diseases. In future, such discoveries will provide mechanistic insights and may potentiate the development of a new lymphatic-based approach to human disease diagnosis and therapeutics.
Topics: Comorbidity; Humans; Inflammation; Lymphatic Diseases; Lymphatic Vessels; Neurodegenerative Diseases
PubMed: 33625889
DOI: 10.1089/lrb.2021.0001 -
European Radiology Jan 2022To characterize hepatic to systemic lymphatic connections in patients with systemic lymphatic disease using intra-hepatic lymphangiography and to compare outcomes after...
OBJECTIVES
To characterize hepatic to systemic lymphatic connections in patients with systemic lymphatic disease using intra-hepatic lymphangiography and to compare outcomes after lymphatic intervention.
METHODS
In this retrospective study, patients with intra-hepatic lymphangiography from May 2014 - April 2019 at our institution were included. Imaging review was performed and hepatic lymphatic connections and flow patterns were characterized. Clinical data were reviewed and comparisons between patients undergoing lymphatic intervention with or without abnormal hepatic lymphatics were performed.
RESULTS
During the study period, 105 patients underwent intra-hepatic lymphangiography. Primary clinical presentation included ascites (19/105), chylothorax (27/105), plastic bronchitis (PB) (17/105), and protein losing enteropathy (PLE) (42/105). Five categories of hepatic lymphatic connections and flow patterns were identified (%): normal (25%, 26/105), hepatoperitoneal (12%, 13/105), hepatopulmonary (10.5%, 11/105), hepatomesenteric (7.5%, 8/105), and hepatoduodenal (41%, 43/105) with four patients having more than one abnormal pattern. A comparison between clinical presentation and imaging category revealed an increased likelihood of having ascites with hepatoperitoneal (p < .0001), chylothorax/PB with hepatopulmonary (p = .01), and PLE with hepatoduodenal (p < .001) connections. Seventy-six patients had a lymphatic intervention, 24% with normal, and 76% with abnormal liver lymphatics. There was no difference in length of hospital stay or mortality between the two groups, but there was a prolonged time to symptom resolution (p = .006) and persistent symptoms after 6 months (5% vs 44%, p = .002) in the group with abnormal liver lymphatics.
CONCLUSION
We identified five liver lymphatic imaging categories with a substantial correlation to presenting lymphatic disease. Abnormal imaging patterns correlated with increased morbidity. Evaluation of liver lymphatics should be considered in patients with a systemic lymphatic disease if central lymphatic imaging is normal.
KEY POINTS
• We identified five liver lymphatic imaging patterns: normal, hepatoperitoneal, hepatomesenteric, hepatopulmonary, and hepatoduodenal. • Imaging patterns were correlated with disease presentation (normal - chylothorax/PB, hepatoperitoneal - ascites/chylothorax, hepatopulmonary - chylothorax/PB, hepatoduodenal - PLE). • Abnormal imaging patterns correlated with increased morbidity.
Topics: Chylothorax; Humans; Liver; Lymphatic Diseases; Lymphatic Vessels; Lymphography; Retrospective Studies
PubMed: 34165621
DOI: 10.1007/s00330-021-08098-z -
Phlebology Apr 2018Objective Medical compression stockings are a standard, non-invasive treatment option for all venous and lymphatic diseases. The aim of this consensus document is to... (Review)
Review
Objective Medical compression stockings are a standard, non-invasive treatment option for all venous and lymphatic diseases. The aim of this consensus document is to provide up-to-date recommendations and evidence grading on the indications for treatment, based on evidence accumulated during the past decade, under the auspices of the International Compression Club. Methods A systematic literature review was conducted and, using PRISMA guidelines, 51 relevant publications were selected for an evidence-based analysis of an initial 2407 unrefined results. Key search terms included: 'acute', CEAP', 'chronic', 'compression stockings', 'compression therapy', 'lymph', 'lymphatic disease', 'vein' and 'venous disease'. Evidence extracted from the publications was graded initially by the panel members individually and then refined at the consensus meeting. Results Based on the current evidence, 25 recommendations for chronic and acute venous disorders were made. Of these, 24 recommendations were graded as: Grade 1A (n = 4), 1B (n = 13), 1C (n = 2), 2B (n = 4) and 2C (n = 1). The panel members found moderately robust evidence for medical compression stockings in patients with venous symptoms and prevention and treatment of venous oedema. Robust evidence was found for prevention and treatment of venous leg ulcers. Recommendations for stocking-use after great saphenous vein interventions were limited to the first post-interventional week. No randomised clinical trials are available that document a prophylactic effect of medical compression stockings on the progression of chronic venous disease (CVD). In acute deep vein thrombosis, immediate compression is recommended to reduce pain and swelling. Despite conflicting results from a recent study to prevent post-thrombotic syndrome, medical compression stockings are still recommended. In thromboprophylaxis, the role of stockings in addition to anticoagulation is limited. For the maintenance phase of lymphoedema management, compression stockings are the most important intervention. Conclusion The beneficial value of applying compression stockings in the treatment of venous and lymphatic disease is supported by this document, with 19/25 recommendations rated as Grade 1 evidence. For recommendations rated with Grade 2 level of evidence, further studies are needed.
Topics: Clinical Trials as Topic; Consensus; Humans; Lymphatic Diseases; Postthrombotic Syndrome; Practice Guidelines as Topic; Stockings, Compression
PubMed: 28549402
DOI: 10.1177/0268355516689631 -
Clinical and Translational Medicine Apr 2022The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In...
BACKGROUND
The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies.
METHODS
We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise co-occurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease-disease interrelationships.
RESULTS
Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease-disease interrelationships was noted in all three lymphatic categories when compared to the control population.
CONCLUSIONS
The presence or absence of a lymphatic disease significantly influences disease interrelationships in the study cohorts. As a physiologic substrate, the lymphatic circulation may be an underappreciated participant in disease pathogenesis. These relationships warrant further, prospective scrutiny and study.
Topics: Humans; Lipedema; Lymphatic Diseases; Lymphedema; Prospective Studies; Retrospective Studies
PubMed: 35452183
DOI: 10.1002/ctm2.760 -
Annals of the New York Academy of... 2008Lymphatic disease is quite prevalent, and often not well clinically characterized. Beyond lymphedema, there is a broad array of human disease that directly or indirectly... (Review)
Review
Lymphatic disease is quite prevalent, and often not well clinically characterized. Beyond lymphedema, there is a broad array of human disease that directly or indirectly alters lymphatic structure and function. The symptomatic and objective presentation of these patients can be quite diverse. In this review, we have attempted to provide a systematic overview of the subjective and objective spectrum of lymphatic disease, with consideration of all of the categories of disease that primarily or secondarily impair the functional integrity of the lymphatic system. Lymphedema is discussed, along with chromosomal disorders, lymphangioma, infectious diseases, lymphangioleiomyomatosis, lipedema, heritable genetic disorders, complex vascular malformations, protein-losing enteropathy, and intestinal lymphangiectasia.
Topics: Chromosome Disorders; Communicable Diseases; Humans; Lymphangioleiomyomatosis; Lymphangioma; Lymphatic Diseases; Lymphedema; Parasitic Diseases; Protein-Losing Enteropathies; Subcutaneous Fat
PubMed: 18519969
DOI: 10.1196/annals.1413.015 -
American Journal of Respiratory and... Feb 2007
Review
Topics: Anti-Infective Agents; Bone Diseases; Clinical Laboratory Techniques; Disease Outbreaks; Drug Resistance, Bacterial; Genotype; Humans; Infection Control; Lung Diseases; Lymphatic Diseases; Mycobacterium Infections, Nontuberculous; Skin Diseases
PubMed: 17277290
DOI: 10.1164/rccm.200604-571ST -
Annals of Vascular Surgery Jan 2023Malpractice claims involving nonthrombotic venous and lymphatic diseases and interventions have not been reported previously. We investigated common reasons for... (Review)
Review
BACKGROUND
Malpractice claims involving nonthrombotic venous and lymphatic diseases and interventions have not been reported previously. We investigated common reasons for litigation, medical specialties involved, patient injuries, and case outcomes in malpractice litigation involving venous and lymphatic disease.
METHODS
Litigation cases entered into the Westlaw database from June 8th, 1984 to February 15th, 2018 were analyzed. Search terms included relevant words and phrases related to nonthrombotic venous, thoracic outlet syndrome, and lymphatic disease and treatment. Data on physician specialty, malpractice claims, and patient injuries jury outcomes, amount awarded to the plaintiff, and jury fees were collected and compared for each category.
RESULTS
A total of 144 cases were identified. 41 cases involved varicose veins, 11 spider veins, 35 thoracic outlet syndrome (TOS), 17 other venous diseases, and 40 lymphatic diseases. Physician defendants were frequently vascular surgeons (23%) and general surgeons (15%). The majority of litigation claims involved "post-procedure complication" (77%), "lack of informed consent" (25%), "failure to diagnose & treat" (15%), and "intraoperative complications" (13%). The most common injuries were skin damage (27.8%), nerve damage (25%), and lymphedema (24%). Patient death occurred in 6% of cases. Out of venous malpractice cases with post-procedure complications, stab phlebectomy (27%) was the most common intervention followed by foam sclerotherapy (21%), rib resection (21%), laser spider vein removal (5%), and endovenous laser ablation therapy (EVLT)(3%). Of varicose vein cases, 15% included deep vein thrombosis or pulmonary embolism as post-procedure complications. In TOS rib resections, 65% of cases referenced nerve damage and 12% involved arterial injury. For lymphatic disease cases, general surgeons were frequently identified defendants (25%). Lymphedema (93%) and lymphangitis (7%) occurred as post-procedure complications after breast, gynecologic, orthopedic, and radiation procedures. A majority of complications occurred after breast cases (40%). Verdicts overall ruled in favor of the defendant in 71% (102/144) of cases and the plaintiff in 20% (29/144) of cases. Out of cases ruled in favor of the plaintiff, 31% were lymphatics, 24% varicose veins, and 24% TOS cases. Only 8% (12/144) of cases were settled and one outcome was unknown. The mean award was $820,193 (standard deviation SD $1,226,008, Range $12,853 - $6,500,000).
CONCLUSIONS
The majority of venous and lymphatic litigation cases involve claims of post-procedure complications. Venous complications occurred after open and endovascular treatment of varicose veins, spider vein treatment, and surgical management of TOS. Lymphedema occurred after breast, oncology, and orthopedic procedures. These cases reflect opportunities for intervention to help potentially prevent litigation.
Topics: Female; Humans; Databases, Factual; Lymphatic Diseases; Lymphedema; Malpractice; Surgeons; Telangiectasis; Thoracic Outlet Syndrome; Treatment Outcome; Varicose Veins
PubMed: 35926792
DOI: 10.1016/j.avsg.2022.07.002 -
Annals of the New York Academy of... Dec 2002The hereditary lymphedemas provide an opportunity to identify genes involved in normal and deranged lymphatic development. Genetic analysis of families with Milroy's... (Review)
Review
The hereditary lymphedemas provide an opportunity to identify genes involved in normal and deranged lymphatic development. Genetic analysis of families with Milroy's disease identified mutations in VEGFR3 as a cause of congenital lymphedema, confirming the importance of VEGFC/VEGFR3 signaling in lymphatic development. These observations led to the identification of a mouse model for primary lymphedema, and subsequent analysis of this mouse model, using transgenic and gene transfer techniques, has provided initial clues to the development of a biologically based therapy for primary lymphedema. Of more importance from a public health perspective is the fact that manipulation of this pathway may lead to effective therapies for the more prevalent forms of secondary lymphedema. Identification of FOXC2 as the gene mutated in the lymphedema-distichiasis syndrome has revealed new molecular insight into lymphatic development. Molecular analysis of the FOXC2 pathway may provide clues to developmental pathways shared by the lymphatic system and the other developmental abnormalities associated with this complex syndrome. With improving knowledge of the human genome, genetic analysis of families with lymphedema continues to offer one of the most promising approaches to identifying genes influencing lymphatic development.
Topics: DNA-Binding Proteins; Endothelial Growth Factors; Forkhead Transcription Factors; Humans; Lymphatic Diseases; Lymphedema; Noonan Syndrome; Research; Syndrome; Transcription Factors; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3
PubMed: 12543715
DOI: 10.1111/j.1749-6632.2002.tb04866.x -
Journal of the American College of... Sep 2008The lymphatic vasculature is comprised of a network of vessels that is essential both to fluid homeostasis and to the mediation of regional immune responses. In health,... (Review)
Review
The lymphatic vasculature is comprised of a network of vessels that is essential both to fluid homeostasis and to the mediation of regional immune responses. In health, the lymphatic vasculature possesses the requisite transport capacity to accommodate the fluid load placed upon it. The most readily recognizable attribute of lymphatic vascular incompetence is the presence of the characteristic swelling of tissues, called lymphedema, which arises as a consequence of insufficient lymph transport. The diagnosis of lymphatic vascular disease relies heavily upon the physical examination. If the diagnosis remains in question, the presence of lymphatic vascular insufficiency can be ascertained through imaging, including indirect radionuclide lymphoscintigraphy. Beyond lymphoscintigraphy, clinically-relevant imaging modalities include magnetic resonance imaging and computerized axial tomography. The state-of-the-art therapeutic approach to lymphatic edema relies upon physiotherapeutic techniques. Complex decongestive physiotherapy is an empirically-derived, effective, multicomponent technique designed to reduce limb volume and maintain the health of the skin and supporting structures. The application of pharmacological therapies has been notably absent from the management strategies for lymphatic vascular insufficiency states. In general, drug-based approaches have been controversial at best. Surgical approaches to improve lymphatic flow through vascular reanastomosis have been, in large part, unsuccessful, but controlled liposuction affords lasting benefit in selected patients. In the future, specifically engineered molecular therapeutics may be designed to facilitate the controlled regrowth of damaged, dysfunctional, or obliterated lymphatic vasculature in order to circumvent or mitigate the vascular insufficiency that leads to edema and tissue destruction.
Topics: Cardiovascular Diseases; Humans; Lymphangiogenesis; Lymphatic Diseases; Lymphedema; Physical Therapy Modalities; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor A
PubMed: 18755341
DOI: 10.1016/j.jacc.2008.06.005 -
Molecular Diagnosis & Therapy 2007Substantial advances have accrued over the last decade in the identification of the processes that contribute to lymphatic vascular development in health and disease.... (Review)
Review
Substantial advances have accrued over the last decade in the identification of the processes that contribute to lymphatic vascular development in health and disease. Identification of distinct regulatory milestones, from a variety of genetic models, has led to a stepwise chronology of lymphatic development. Several molecular species have been identified as important tissue biomarkers of lymphatic development and function. At present, vascular endothelial growth-factor receptor (VEGFR)-3/VEGF-C/VEGF-D signaling has proven useful in the identification of clinical lymphatic metastatic potential and the assessment of cancer prognosis. Similar biomarkers, to be utilized as surrogates for the assessment of inherited and acquired diseases of the lymphatic circulation, are actively sought, and will represent a signal advance in biomedical investigation.
Topics: Animals; Biomarkers; Humans; Lymphangiogenesis; Lymphatic Diseases; Lymphatic System; Lymphedema
PubMed: 17705577
DOI: 10.1007/BF03256244