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Cells Mar 2021Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and... (Review)
Review
Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans and Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age. Intrathoracic involvement occurs in 90% of patients with symmetrical bilateral hilar adenopathy and/or diffuse lung micronodules, mainly along the lymphatic structures which are the most affected system. Among extrapulmonary manifestations, skin lesions, uveitis, liver or splenic involvement, peripheral and abdominal lymphadenopathy and peripheral arthritis are the most frequent with a prevalence of 25-50%. Finally, cardiac and neurological manifestations which can be the initial manifestation of sarcoidosis, as can be bilateral parotitis, nasosinusal or laryngeal signs, hypercalcemia and renal dysfunction, affect less than 10% of patients. The diagnosis is not standardized but is based on three major criteria: a compatible clinical and/or radiological presentation, the histological evidence of non-necrotizing granulomatous inflammation in one or more tissues and the exclusion of alternative causes of granulomatous disease. Certain clinical features are considered to be highly specific of the disease (e.g., Löfgren's syndrome, lupus pernio, Heerfordt's syndrome) and do not require histological confirmation. New diagnostic guidelines were recently published. Specific clinical criteria have been developed for the diagnosis of cardiac, neurological and ocular sarcoidosis. This article focuses on the clinical presentation and the common differentials that need to be considered when appropriate.
Topics: Diagnosis, Differential; Humans; Organ Specificity; Phenotype; Sarcoidosis
PubMed: 33807303
DOI: 10.3390/cells10040766 -
Wounds : a Compendium of Clinical... Mar 2020The lymphatic system is arguably the most neglected bodily system. As a result, its contribution to human health and disease is not well understood. In this review, the... (Review)
Review
The lymphatic system is arguably the most neglected bodily system. As a result, its contribution to human health and disease is not well understood. In this review, the clinical approaches based on new knowledge and developments of the lymphatic system are covered. The lymphatic system has 3 major functions: (1) the preservation of fluid balance; (2) a nutritional function, as intestinal lymphatics are responsible for fat absorption; and (3) host defense. Lymph vessels return the capillary ultrafiltrate and escaped plasma proteins from most tissues back, ultimately, to the blood circulation. Hence, lymphatics are responsible for maintaining tissue (and plasma) volume homeostasis. Impaired lymph drainage results in peripheral edema (lymphedema) and may have more far-reaching effects on cardiovascular disease, in particular hypertension and atherosclerosis. Lymphatics have an important immune surveillance function, as they represent the principal route of transport from tissues for antigen and immune cells. Intestinal lymphatics (lacteals) are responsible for most fat absorption, first documented by Gaspare Aselli in 1627, when the lymphatic system was discovered. A relationship between fat and lymphatics may exist well beyond the gut alone. Fat deposition is a defining clinical characteristic of lymphedema. Suction-assisted lipectomy of lymphedema has shown the swelling is not just fluid but is dominated by fat. Lymphatics are the preferred route for the metastatic spread of cancer. Accordingly, the lymphatic system may be important for defense against cancer by generating immune responses to malignant cell antigens. Preventing lymphatic entry and propagation of malignant metastasis would effectively render the cancer nonfatal. As one can see, the lymphatic circulation is fundamentally important to cardiovascular disease, infection and immunity, cancer, and, in all likelihood, obesity - 4 of the major challenges to health care in the 21st century.
Topics: Humans; Lymphatic System; Lymphedema; Lymphoscintigraphy
PubMed: 32163039
DOI: No ID Found -
Circulation Research Jun 2021Lymphatic vessels maintain tissue fluid homeostasis by returning to blood circulation interstitial fluid that has extravasated from the blood capillaries. They provide a... (Review)
Review
Lymphatic vessels maintain tissue fluid homeostasis by returning to blood circulation interstitial fluid that has extravasated from the blood capillaries. They provide a trafficking route for cells of the immune system, thus critically contributing to immune surveillance. Developmental or functional defects in the lymphatic vessels, their obstruction or damage, lead to accumulation of fluid in tissues, resulting in lymphedema. Here we discuss developmental lymphatic anomalies called lymphatic malformations and complex lymphatic anomalies that manifest as localized or multifocal lesions of the lymphatic vasculature, respectively. They are rare diseases that are caused mostly by somatic mutations and can present with variable symptoms based upon the size and location of the lesions composed of fluid-filled cisterns or channels. Substantial progress has been made recently in understanding the molecular basis of their pathogenesis through the identification of their genetic causes, combined with the elucidation of the underlying mechanisms in animal disease models and patient-derived lymphatic endothelial cells. Most of the solitary somatic mutations that cause lymphatic malformations and complex lymphatic anomalies occur in genes that encode components of oncogenic growth factor signal transduction pathways. This has led to successful repurposing of some targeted cancer therapeutics to the treatment of lymphatic malformations and complex lymphatic anomalies. Apart from the mutations that act as lymphatic endothelial cell-autonomous drivers of these anomalies, current evidence points to superimposed paracrine mechanisms that critically contribute to disease pathogenesis and thus provide additional targets for therapeutic intervention. Here, we review these advances and discuss new treatment strategies that are based on the recently identified molecular pathways.
Topics: Animals; Disease Models, Animal; Genetic Predisposition to Disease; Humans; Lymphangiogenesis; Lymphatic Abnormalities; Lymphatic Vessels; Mutation; Phenotype; Signal Transduction
PubMed: 34166072
DOI: 10.1161/CIRCRESAHA.121.318142 -
Nature Reviews. Disease Primers Oct 2021The historic term 'histiocytosis' meaning 'tissue cell' is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological... (Review)
Review
The historic term 'histiocytosis' meaning 'tissue cell' is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological features with macrophages or dendritic cells. These cells may arise from the embryonic yolk sac, fetal liver or postnatal bone marrow. Prior classification schemes align disease designation with terminal phenotype: for example, Langerhans cell histiocytosis (LCH) shares CD207 antigen with physiological epidermal Langerhans cells. LCH, Erdheim-Chester disease (ECD), juvenile xanthogranuloma (JXG) and Rosai-Dorfman disease (RDD) are all characterized by pathological ERK activation driven by activating somatic mutations in MAPK pathway genes. The title of this Primer (Histiocytic disorders) was chosen to differentiate the above diseases from Langerhans cell sarcoma and malignant histiocytosis, which are hyperproliferative lesions typical of cancer. By comparison LCH, ECD, RDD and JXG share some features of malignant cells including activating MAPK pathway mutations, but are not hyperproliferative. 'Inflammatory myeloproliferative neoplasm' may be a more precise nomenclature. By contrast, haemophagocytic lymphohistiocytosis is associated with macrophage activation and extreme inflammation, and represents a syndrome of immune dysregulation. These diseases affect children and adults in varying proportions depending on which of the entities is involved.
Topics: Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Inflammation; Xanthogranuloma, Juvenile
PubMed: 34620874
DOI: 10.1038/s41572-021-00307-9 -
Cell Jul 2020Mammals have two specialized vascular circulatory systems: the blood vasculature and the lymphatic vasculature. The lymphatic vasculature is a unidirectional conduit... (Review)
Review
Mammals have two specialized vascular circulatory systems: the blood vasculature and the lymphatic vasculature. The lymphatic vasculature is a unidirectional conduit that returns filtered interstitial arterial fluid and tissue metabolites to the blood circulation. It also plays major roles in immune cell trafficking and lipid absorption. As we discuss in this review, the molecular characterization of lymphatic vascular development and our understanding of this vasculature's role in pathophysiological conditions has greatly improved in recent years, changing conventional views about the roles of the lymphatic vasculature in health and disease. Morphological or functional defects in the lymphatic vasculature have now been uncovered in several pathological conditions. We propose that subtle asymptomatic alterations in lymphatic vascular function could underlie the variability seen in the body's response to a wide range of human diseases.
Topics: Cardiovascular Diseases; History, 21st Century; Humans; Lymph Nodes; Lymphangiogenesis; Lymphatic Diseases; Lymphatic Metastasis; Lymphatic Vessels; Neoplasms; Vascular Endothelial Growth Factor Receptor-3
PubMed: 32707093
DOI: 10.1016/j.cell.2020.06.039 -
Cancer Journal (Sudbury, Mass.) 2019Bruton tyrosine kinase (BTK) is a nonreceptor tyrosine kinase that plays a central role in the signal transduction of the B-cell antigen receptor and other cell surface... (Review)
Review
Bruton tyrosine kinase (BTK) is a nonreceptor tyrosine kinase that plays a central role in the signal transduction of the B-cell antigen receptor and other cell surface receptors, both in normal and malignant B lymphocytes. B-cell antigen receptor signaling is activated in secondary lymphatic organs and drives the proliferation of malignant B cells, including chronic lymphocytic leukemia (CLL) cells. During the last 10 years, BTK inhibitors (BTKis) are increasingly replacing chemotherapy-based regimen, especially in patients with CLL and mantle cell lymphoma (MCL). Bruton tyrosine kinase inhibitors are particularly active in patients with CLL and MCL, but also received approval for Waldenström macroglobulinemia, small lymphocytic lymphoma, marginal zone lymphoma, and chronic graft-versus-host disease. Current clinical practice is continuous long-term administration of BTKi, which can be complicated by adverse effects or the development of drug resistance. Alternatives to long-term use of BTKi are being developed, such as combination therapies, permitting for limited duration therapy. Second-generation BTKis are under development, which differ from ibrutinib, the first-in-class BTKi, in their specificity for BTK, and therefore may differentiate themselves from ibrutinib in terms of adverse effects or efficacy.
Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; B-Lymphocytes; Clinical Trials as Topic; Drug Resistance, Neoplasm; Humans; Invasive Fungal Infections; Leukemia, B-Cell; Lymphoma, B-Cell; Molecular Targeted Therapy; Protein Kinase Inhibitors; Signal Transduction; Treatment Outcome
PubMed: 31764119
DOI: 10.1097/PPO.0000000000000412 -
Journal of Cancer Research and Clinical... Jun 2022Water therapies as hydrotherapy, balneotherapy or aqua therapy are often used in the relief of disease- and treatment-associated symptoms of cancer patients. Yet, a... (Review)
Review
BACKGROUND
Water therapies as hydrotherapy, balneotherapy or aqua therapy are often used in the relief of disease- and treatment-associated symptoms of cancer patients. Yet, a systematic review for the evidence of water therapy including all cancer entities has not been conducted to date.
PURPOSE
Oncological patients often suffer from symptoms which in patients with other diseases are successfully treated with water therapy. We want to gather more information about the benefits and risks of water therapy for cancer patients.
METHOD
In May 2020, a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychInfo, CINAHL and PubMed) to find studies concerning the use, effectiveness and potential harm of water therapy on cancer patients.
RESULTS
Of 3165 search results, 10 publications concerning 12 studies with 430 patients were included in this systematic review. The patients treated with water therapy were mainly diagnosed with breast cancer. The therapy concepts included aqua lymphatic therapy, aquatic exercises, foot bathes and whole-body bathes. Outcomes were state of lymphedema, quality of life, fatigue, BMI, vital parameters, anxiety and pain. The quality of the studies was assessed with the AMSTAR2-instrument, the SIGN-checklist and the IHE-Instruments. The studies had moderate quality and reported heterogeneous results. Some studies reported significantly improved quality of life, extent of lymphedema, neck and shoulder pain, fatigue and BMI while other studies did not find any changes concerning these endpoints.
CONCLUSION
Due to the very heterogeneous results and methodical limitations of the included studies, a clear statement regarding the effectiveness of water therapy on cancer patients is not possible.
Topics: Balneology; Breast Neoplasms; Fatigue; Female; Humans; Hydrotherapy; Lymphedema; Quality of Life; Water
PubMed: 35171330
DOI: 10.1007/s00432-022-03947-w -
Neuro-oncology Sep 2021Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The... (Review)
Review
Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The identification of the pivotal role of the mitogen-activated protein kinase (MAPK) pathway has opened new avenues of research and therapeutic approaches. We review the neurologic manifestations of 3 histiocytic disorders with frequent involvement of the brain and spine: Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman-Destombes disease (RDD). Central nervous system (CNS) manifestations occur in 10%-25% of LCH cases, with both tumorous or neurodegenerative forms. These subtypes differ by clinical and radiological presentation, pathogenesis, and prognosis. Tumorous or degenerative neurologic involvement occurs in 30%-40% of ECD patients and affects the hypothalamic-pituitary axis, meninges, and brain parenchyma. RDD lesions are typically tumorous with meningeal or parenchymal masses with strong contrast enhancement. Unlike LCH and ECD, neurodegenerative lesions or syndromes have not been described with RDD. Familiarity with principles of evaluation and treatment both shared among and distinct to each of these 3 diseases is critical for effective management. Refractory or disabling neurohistiocytic involvement should prompt the consideration for use of targeted kinase inhibitor therapies.
Topics: Central Nervous System; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Prognosis
PubMed: 33993305
DOI: 10.1093/neuonc/noab107 -
Phlebology Oct 2020Patients with lower limb edema are frequently referred to vascular specialists for evaluation. Multiple etiologies must be considered and often more than one cause may...
Patients with lower limb edema are frequently referred to vascular specialists for evaluation. Multiple etiologies must be considered and often more than one cause may be present. Notably, the role of lymphatic system regardless of the underlying pathology has been underestimated. A thorough history and physical examination and a carefully considered laboratory and imaging evaluation are critical in differentiating causes. In this opinion article, we propose a diagnostic algorithm that incorporates a systematic approach to the patient with leg swelling and provides an efficient pathway for the differential diagnosis for this problem.
Topics: Diagnosis, Differential; Diagnostic Imaging; Edema; Humans; Leg; Lymphedema
PubMed: 32631171
DOI: 10.1177/0268355520938283 -
Journal of B.U.ON. : Official Journal... 2021Cancer-related lymphedema is the result of surgical operation or radiation therapy of the corresponding lymph nodes and is due to the obstruction of the lymphatic... (Review)
Review
Cancer-related lymphedema is the result of surgical operation or radiation therapy of the corresponding lymph nodes and is due to the obstruction of the lymphatic drainage in the affected area. In lymphedema the lymphatic stasis causes an inflammatory reaction that leads to the proliferation of adipose tissue and fibrosis, resulting in mild to severe permanent swelling of the affected part of the body. It is more often found in the upper extremities of women with breast cancer. It may, however, appear at one or more extremities and may include the corresponding quadrant of the trunk. It may also affect head and neck, breast, genitals and lower extremities, depending on the surgery the patient has undergone. It is often associated with obesity (BMI>40). Early diagnosis and treatment of lymphedema is related with better therapeutic outcome. Women with breast cancer confront more problems with lymphedema than with mastectomy. Its effect on patients' quality of life is relevant to changes in body image, self-esteem, feelings of weakness, fear and anxiety about disease progression, financial costs, and reduced limb function. More recent studies support the effectiveness of contemporary surgical techniques in lymphedema's treatment. In conservative management, CDT remains the treatment of choice and in combination with exercise, weight control programs and self-care training seems to significantly improve patients' quality of life.
Topics: Female; Humans; Lymphedema; Male; Quality of Life
PubMed: 34761576
DOI: No ID Found